Subjects -> MEDICAL SCIENCES (Total: 8196 journals)
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MEDICAL SCIENCES (2241 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 601 - 800 of 3562 Journals sorted alphabetically
Extreme Physiology & Medicine     Open Access   (Followers: 1)
F&S Reports     Open Access  
F&S Science : Official journal of the American Society for Reproductive Medicine     Open Access  
Facial Plastic Surgery & Aesthetic Medicine     Full-text available via subscription   (Followers: 7)
Facta Universitatis, Series : Medicine and Biology     Open Access  
Family Medicine and Community Health     Open Access   (Followers: 8)
Family Practice     Hybrid Journal   (Followers: 17)
Family Practice & Palliative Care     Open Access   (Followers: 5)
Family Practice Management     Full-text available via subscription   (Followers: 4)
Faridpur Medical College Journal     Open Access  
FEM : Revista de la Fundación Educación Médica     Open Access  
Finlay : Revista de Enfermedades no Transmisibles     Open Access  
Fisioterapia     Full-text available via subscription   (Followers: 2)
Fisioterapia & Saúde Funcional     Open Access  
Flugmedizin · Tropenmedizin · Reisemedizin - FTR     Hybrid Journal  
FMC - Formación Médica Continuada en Atención Primaria     Full-text available via subscription  
Folia Medica     Open Access  
Folia Medica Indonesiana     Open Access  
Folia Morphologica     Full-text available via subscription  
Folia Phoniatrica et Logopaedica     Full-text available via subscription   (Followers: 1)
Fontanus     Open Access   (Followers: 1)
Food Hydrocolloids for Health     Open Access  
Foodborne Pathogens and Disease     Hybrid Journal   (Followers: 11)
Foot & Ankle Specialist     Hybrid Journal   (Followers: 4)
Foot and Ankle Clinics     Full-text available via subscription   (Followers: 12)
Foot and Ankle Online Journal     Full-text available via subscription   (Followers: 6)
Forensic Science International : Mind and Law     Open Access   (Followers: 4)
Forum Medycyny Rodzinnej     Hybrid Journal  
Forum Zaburzeń Metabolicznych     Hybrid Journal  
Frontières     Full-text available via subscription   (Followers: 3)
Frontiers in Digital Health     Open Access   (Followers: 4)
Frontiers in Medical Technology     Open Access  
Frontiers in Medicine     Open Access   (Followers: 2)
Frontiers in Network Physiology     Open Access   (Followers: 2)
Frontiers in Neuroprosthetics     Open Access   (Followers: 6)
Frontiers in Synaptic Neuroscience     Open Access   (Followers: 2)
Frontiers in Tropical Diseases     Open Access  
Frontiers of Medical and Biological Engineering     Hybrid Journal  
Frontiers of Medicine     Hybrid Journal   (Followers: 2)
Fuss & Sprunggelenk     Hybrid Journal  
Future Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Future Prescriber     Hybrid Journal  
Future Science OA     Open Access  
Gaceta Médica Boliviana     Open Access  
Gaceta Médica Espirituana     Open Access  
Galen Medical Journal     Open Access  
Galician Medical Journal     Open Access   (Followers: 1)
Galle Medical Journal     Open Access  
Gefäßmedizin Scan     Hybrid Journal  
Gender and the Genome     Open Access   (Followers: 1)
Gene Expression     Full-text available via subscription   (Followers: 1)
General Reanimatology     Open Access  
Genes     Open Access   (Followers: 2)
Genome Instability & Disease     Hybrid Journal  
Geoforum     Hybrid Journal   (Followers: 25)
Gestão e Desenvolvimento     Open Access  
Ghana Medical Journal     Open Access   (Followers: 1)
GigaScience     Open Access   (Followers: 4)
Gimbernat : Revista d’Història de la Medicina i de les Ciències de la Salut     Open Access  
Glia     Hybrid Journal   (Followers: 5)
Global Advances in Health and Medicine     Open Access  
Global Bioethics     Open Access   (Followers: 5)
Global Health : Science and Practice     Open Access   (Followers: 7)
Global Health Journal     Open Access   (Followers: 2)
Global Journal of Integrated Chinese Medicine and Western Medicine     Open Access  
Global Journal of Cancer Therapy     Open Access  
Global Journal of Fertility and Research     Open Access  
Global Journal of Health Science     Open Access   (Followers: 5)
Global Journal of Infectious Diseases and Clinical Research     Open Access   (Followers: 1)
Global Journal of Medical and Clinical Case Reports     Open Access  
Global Journal of Obesity, Diabetes and Metabolic Syndrome     Open Access   (Followers: 2)
Global Journal of Perioperative Medicine     Open Access  
Global Journal of Rare Diseases     Open Access  
Global Medical & Health Communication     Open Access   (Followers: 1)
Global Reproductive Health     Open Access  
Grande Medical Journal     Open Access  
Growth Factors     Hybrid Journal   (Followers: 2)
GSTF Journal of Advances in Medical Research     Open Access  
Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi     Open Access  
Hamdan Medical Journal     Open Access  
Hämostaseologie     Hybrid Journal   (Followers: 4)
Hämostaseologie     Open Access  
Hand     Hybrid Journal   (Followers: 4)
Hand Clinics     Full-text available via subscription   (Followers: 6)
Hand Therapy     Hybrid Journal   (Followers: 11)
Hard Tissue     Open Access  
Head & Face Medicine     Open Access   (Followers: 1)
Head and Neck Cancer Research     Open Access  
Head and Neck Tumors     Open Access  
Health Information : Jurnal Penelitian     Open Access  
Health Matrix : The Journal of Law-Medicine     Open Access  
Health Notions     Open Access  
Health Science Journal of Indonesia     Open Access  
Health Science Reports     Open Access   (Followers: 1)
Health Sciences and Disease     Open Access   (Followers: 1)
Health Sciences Review     Open Access  
Health Security     Hybrid Journal   (Followers: 1)
Healthcare Technology Letters     Open Access  
Hearing, Balance and Communication     Hybrid Journal   (Followers: 6)
Hearts     Open Access   (Followers: 1)
HEC Forum     Hybrid Journal   (Followers: 1)
Heighpubs Otolaryngology and Rhinology     Open Access  
Heilberufe     Hybrid Journal  
HeilberufeSCIENCE     Hybrid Journal  
Heilpflanzen     Hybrid Journal   (Followers: 8)
Helicobacter     Hybrid Journal  
HemaSphere     Open Access   (Followers: 2)
Hemoglobin     Hybrid Journal  
Hepatology, Medicine and Policy     Open Access  
HERALD of North-Western State Medical University named after I.I. Mechnikov     Open Access  
Herald of the Russian Academy of Sciences     Full-text available via subscription  
Herzschrittmachertherapie + Elektrophysiologie     Hybrid Journal  
Highland Medical Research Journal     Full-text available via subscription  
Hipertensión y Riesgo Vascular     Full-text available via subscription  
HIV Australia     Full-text available via subscription   (Followers: 3)
Homeopathy     Hybrid Journal   (Followers: 1)
Homoeopathic Links     Hybrid Journal  
Hong Kong Physiotherapy Journal     Open Access   (Followers: 14)
Horizonte Medico     Open Access  
Hormones : International Journal of Endocrinology and Metabolism     Hybrid Journal  
Hospital a Domicilio     Open Access  
Hospital Practices and Research     Open Access  
Hospital Topics     Hybrid Journal   (Followers: 1)
Hua Hin Sook Jai Klai Kangwon Journal     Open Access  
Huisarts en wetenschap     Hybrid Journal   (Followers: 4)
Human & Veterinary Medicine - International Journal of the Bioflux Society     Open Access   (Followers: 4)
Human Factors in Healthcare     Open Access   (Followers: 2)
Human Fertility     Hybrid Journal   (Followers: 4)
Humanidades Médicas     Open Access  
I.P. Pavlov Russian Medical Biological Herald     Open Access  
Iatreia     Open Access  
Ibnosina Journal of Medicine and Biomedical Sciences     Open Access  
IDCases     Open Access  
IEEE Journal of Biomedical and Health Informatics     Hybrid Journal   (Followers: 14)
IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology     Hybrid Journal  
IEEE Journal of Translational Engineering in Health and Medicine     Open Access   (Followers: 5)
IEEE Open Journal of Engineering in Medicine and Biology     Open Access   (Followers: 1)
IEEE Transactions on Medical Robotics and Bionics     Hybrid Journal   (Followers: 3)
IEEE/ACM Transactions on Computational Biology and Bioinformatics     Hybrid Journal   (Followers: 18)
IJID Regions     Open Access   (Followers: 1)
IJS Global Health     Open Access  
IJU Case Reports     Open Access  
iLiver     Open Access   (Followers: 6)
Im OP     Hybrid Journal  
Image Analysis & Stereology     Open Access   (Followers: 1)
IMAGING     Full-text available via subscription   (Followers: 1)
Imaging in Medicine     Open Access  
Imaging Journal of Clinical and Medical Sciences     Open Access   (Followers: 1)
Imam Journal of Applied Sciences     Open Access  
Indian Journal of Ayurveda and lntegrative Medicine Klue     Open Access   (Followers: 4)
Indian Journal of Burns     Open Access   (Followers: 2)
Indian Journal of Clinical Medicine     Open Access  
Indian Journal of Community and Family Medicine     Open Access   (Followers: 3)
Indian Journal of Community Medicine     Open Access   (Followers: 1)
Indian Journal of Health Sciences and Biomedical Research KLEU     Open Access   (Followers: 2)
Indian Journal of Medical Microbiology     Open Access   (Followers: 1)
Indian Journal of Medical Research     Open Access   (Followers: 3)
Indian Journal of Medical Sciences     Open Access   (Followers: 2)
Indian Journal of Medical Specialities     Hybrid Journal  
Indian Journal of Otology     Open Access   (Followers: 1)
Indian Journal of Public Health     Open Access   (Followers: 1)
Indian Journal of Transplantation     Open Access  
Indian Spine Journal     Open Access  
Indo-Pacific Journal of Phenomenology     Open Access   (Followers: 1)
Indonesia Journal of Biomedical Science     Open Access   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Indonesian Journal for Health Sciences     Open Access   (Followers: 1)
Indonesian Journal of Medicine     Open Access  
Indonesian Journal of Tropical and Infectious Disease     Open Access  
Infant Observation: International Journal of Infant Observation and Its Applications     Hybrid Journal   (Followers: 1)
Inflammation     Hybrid Journal   (Followers: 3)
Inflammation Research     Hybrid Journal   (Followers: 4)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
Infodir : Revista de Información científica para la Dirección en Salud     Open Access  
Informatics in Medicine Unlocked     Open Access  
Injury Prevention     Hybrid Journal   (Followers: 6)
InnovAiT     Hybrid Journal   (Followers: 1)
Innovare Journal of Health Science     Open Access  
Innovare Journal of Medical Science     Open Access  
Innovation in Aging     Open Access   (Followers: 1)
Inside Precision Medicine     Full-text available via subscription   (Followers: 6)
Insights in Biology and Medicine     Open Access  
Integrative and Complementary Therapies     Full-text available via subscription   (Followers: 6)
Integrative Medicine Insights     Open Access   (Followers: 1)
Integrative Medicine International     Open Access   (Followers: 1)
Integrative Medicine Research     Open Access   (Followers: 3)
Intellectual Disability Australasia     Full-text available via subscription   (Followers: 12)
Intelligence-Based Medicine     Open Access  
Intelligent Medicine     Open Access   (Followers: 1)
intensiv     Hybrid Journal   (Followers: 1)
interactive Journal of Medical Research     Open Access  
Interdisciplinary Perspectives on Infectious Diseases     Open Access   (Followers: 1)
Interdisciplinary Sciences : Computational Life Sciences     Hybrid Journal   (Followers: 2)
Internal Medicine     Open Access   (Followers: 1)
International Biomechanics     Open Access   (Followers: 1)
International Health     Hybrid Journal   (Followers: 5)
International Health Trends and Perspectives     Open Access  
International Journal for Numerical Methods in Biomedical Engineering     Hybrid Journal   (Followers: 2)
International Journal for Vitamin and Nutrition Research     Hybrid Journal   (Followers: 10)
International Journal of Academic Medicine     Open Access   (Followers: 1)

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Journal Prestige (SJR): 1.82
Citation Impact (citeScore): 3
Number of Followers: 2  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2073-4425
Published by MDPI Homepage  [84 journals]
  • Genes, Vol. 13, Pages 1103: Genome-Wide Analysis of the GDSL Genes in
           Pecan (Carya illinoensis K. Koch): Phylogeny, Structure, Promoter
           Cis-Elements, Co-Expression Networks, and Response to Salt Stresses

    • Authors: Yun Jiao, Jianhong Zhang, Cunde Pan
      First page: 1103
      Abstract: The Gly-Asp-Ser-Leu (GDSL)-lipase family is a large subfamily of lipolytic enzymes that plays an important role in plant growth and defense against environmental stress. However, little is known about their function in pecans (Carya illinoensis K. Koch). In this study, 87 CilGDSLs were identified and divided into 2 groups and 12 subgroups using phylogenetic analysis; members of the same sub-branch had conserved gene structure and motif composition. The majority of the genes had four introns and were composed of an α-helix and a β-strand. Subcellular localization analysis revealed that these genes were localized in the extracellular matrix, chloroplasts, cytoplasm, nucleus, vacuole, and endoplasmic reticulum, and were validated by transient expression in tobacco mesophyll cells. Furthermore, the analysis of the promoter cis-elements for the CilGDSLs revealed the presence of plant anaerobic induction regulatory, abscisic acid response, light response elements, jasmonic acid (JA) response elements, etc. The qRT-PCR analysis results in “Pawnee” with salt treatment showed that the CilGDSL42.93 (leaf) and CilGDSL39.88 (root) were highly expressed in different tissues. After salt stress treatment, isobaric tags for relative and absolute quantitation (iTRAQ) analysis revealed the presence of a total of ten GDSL proteins. Moreover, the weighted gene co-expression network analysis (WGCNA) showed that one set of co-expressed genes (module), primarily CilGDSL41.11, CilGDSL39.49, CilGDSL34.85, and CilGDSL41.01, was significantly associated with salt stress in leaf. In short, some of them were shown to be involved in plant defense against salt stress in this study.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071103
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1104: A Formative Study of the Implementation of
           Whole Genome Sequencing in Northern Ireland

    • Authors: Katie Kerr, Caoimhe McKenna, Shirley Heggarty, Caitlin Bailie, Julie McMullan, Ashleen Crowe, Jill Kilner, Michael Donnelly, Saralynne Boyle, Gillian Rea, Cheryl Flanagan, Shane McKee, Amy Jayne McKnight
      First page: 1104
      Abstract: Background: The UK 100,000 Genomes Project was a transformational research project which facilitated whole genome sequencing (WGS) diagnostics for rare diseases. We evaluated experiences of introducing WGS in Northern Ireland, providing recommendations for future projects. Methods: This formative evaluation included (1) an appraisal of the logistics of implementing and delivering WGS, (2) a survey of participant self-reported views and experiences, (3) semi-structured interviews with healthcare staff as key informants who were involved in the delivery of WGS and (4) a workshop discussion about interprofessional collaboration with respect to molecular diagnostics. Results: We engaged with >400 participants, with detailed reflections obtained from 74 participants including patients, caregivers, key National Health Service (NHS) informants, and researchers (patient survey n = 42; semi-structured interviews n = 19; attendees of the discussion workshop n = 13). Overarching themes included the need to improve rare disease awareness, education, and support services, as well as interprofessional collaboration being central to an effective, mainstreamed molecular diagnostic service. Conclusions: Recommendations for streamlining precision medicine for patients with rare diseases include administrative improvements (e.g., streamlining of the consent process), educational improvements (e.g., rare disease training provided from undergraduate to postgraduate education alongside genomics training for non-genetic specialists) and analytical improvements (e.g., multidisciplinary collaboration and improved computational infrastructure).
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071104
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1105: Use of Publication Dynamics to Distinguish
           Cancer Genes and Bystander Genes

    • Authors: László Bányai, Mária Trexler, László Patthy
      First page: 1105
      Abstract: de Magalhães has shown recently that most human genes have several papers in PubMed mentioning cancer, leading the author to suggest that every gene is associated with cancer, a conclusion that contradicts the widely held view that cancer is driven by a limited number of cancer genes, whereas the majority of genes are just bystanders in carcinogenesis. We have analyzed PubMed to decide whether publication metrics supports the distinction of bystander genes and cancer genes. The dynamics of publications on known cancer genes followed a similar pattern: seminal discoveries triggered a burst of cancer-related publications that validated and expanded the discovery, resulting in a rise both in the number and proportion of cancer-related publications on that gene. The dynamics of publications on bystander genes was markedly different. Although there is a slow but continuous time-dependent rise in the proportion of papers mentioning cancer, this phenomenon just reflects the increasing publication bias that favors cancer research. Despite this bias, the proportion of cancer papers on bystander genes remains low. Here, we show that the distinctive publication dynamics of cancer genes and bystander genes may be used for the identification of cancer genes.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071105
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1106: A Possible Cause for the Differential
           Expression of a Subset of miRNAs in Mesenchymal Stem Cells Derived from
           Myometrium and Leiomyoma

    • Authors: Mariangela Di Vincenzo, Concetta De Quattro, Marzia Rossato, Raffaella Lazzarini, Giovanni Delli Carpini, Andrea Ciavattini, Monia Orciani
      First page: 1106
      Abstract: The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, we try to elucidate whether these differentially regulated 15 miRNAs arise as a conversion of M-MSCs along the differentiation process or whether they may originate from divergent cell commitment. To trace the origin of the dysregulation, a comparison was made of the expression of miRNAs previously identified as differentially regulated in M-MSCs and L-MSCs with that detected in MSCs from amniotic fluid (considered as a substitute for embryonic cells). The results do not allow for a foregone conclusion: the miRNAs converging to the adherens junction pathway showed a gradual change along the differentiation process, and the miRNAs which coincided with the other three pathways (ECM-receptor interaction, TGFβ and cell cycle) showed a complex, not linear, regulation and, therefore, a trend along the hypothetical differentiation process was not deduced. However, the role of miRNAs appears to be predominant in the onset of leiomyoma and may follow two different mechanisms (early commitment; exacerbation); furthermore, miRNAs can support the observed (epigenetic) predisposition.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071106
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1107: Mutation of foxl1 Results in Reduced Cartilage
           Markers in a Zebrafish Model of Otosclerosis

    • Authors: Alexia Hawkey-Noble, Justin A. Pater, Roshni Kollipara, Meriel Fitzgerald, Alexandre S. Maekawa, Christopher S. Kovacs, Terry-Lynn Young, Curtis R. French
      First page: 1107
      Abstract: Bone diseases such as otosclerosis (conductive hearing loss) and osteoporosis (low bone mineral density) can result from the abnormal expression of genes that regulate cartilage and bone development. The forkhead box transcription factor FOXL1 has been identified as the causative gene in a family with autosomal dominant otosclerosis and has been reported as a candidate gene in GWAS meta-analyses for osteoporosis. This potentially indicates a novel role for foxl1 in chondrogenesis, osteogenesis, and bone remodelling. We created a foxl1 mutant zebrafish strain as a model for otosclerosis and osteoporosis and examined jaw bones that are homologous to the mammalian middle ear bones, and mineralization of the axial skeleton. We demonstrate that foxl1 regulates the expression of collagen genes such as collagen type 1 alpha 1a and collagen type 11 alpha 2, and results in a delay in jawbone mineralization, while the axial skeleton remains unchanged. foxl1 may also act with other forkhead genes such as foxc1a, as loss of foxl1 in a foxc1a mutant background increases the severity of jaw calcification phenotypes when compared to each mutant alone. Our zebrafish model demonstrates atypical cartilage formation and mineralization in the zebrafish craniofacial skeleton in foxl1 mutants and demonstrates that aberrant collagen expression may underlie the development of otosclerosis.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071107
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1108: Development of Transformation for Genome
           Editing of an Emerging Model Organism

    • Authors: Yutaka Yamamoto, Susan A. Gerbi
      First page: 1108
      Abstract: With the advances in genomic sequencing, many organisms with novel biological properties are ripe for use as emerging model organisms. However, to make full use of them, transformation methods need to be developed to permit genome editing. Here, we present the development of transformation for the fungus fly Bradysia (Sciara) coprophila; this may serve as a paradigm for the development of transformation for other emerging systems, especially insects. Bradysia (Sciara) has a variety of unique biological features, including locus-specific developmentally regulated DNA amplification, chromosome imprinting, a monopolar spindle in male meiosis I, non-disjunction of the X chromosome in male meiosis II, X chromosome elimination in early embryogenesis, germ-line-limited (L) chromosomes and high resistance to radiation. Mining the unique biology of Bradysia (Sciara) requires a transformation system to test mutations of DNA sequences that may play roles for these features. We describe a Bradysia (Sciara) transformation system using a modified piggyBac transformation vector and detailed protocols we have developed to accommodate Bradysia (Sciara) specific requirements. This advance will provide a platform for us and others in the growing Bradysia (Sciara) community to take advantage of this unique biological system. In addition, the versatile piggyBac vectors described here and transformation methods will be useful for other emerging model systems.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071108
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1109: Identification of COVID-19-Associated DNA
           Methylation Variations by Integrating Methylation Array and scRNA-Seq Data
           at Cell-Type Resolution

    • Authors: Guoliang Wang, Zhuang Xiong, Fei Yang, Xinchang Zheng, Wenting Zong, Rujiao Li, Yiming Bao
      First page: 1109
      Abstract: Single-cell transcriptome studies have revealed immune dysfunction in COVID-19 patients, including lymphopenia, T cell exhaustion, and increased levels of pro-inflammatory cytokines, while DNA methylation plays an important role in the regulation of immune response and inflammatory response. The specific cell types of immune responses regulated by DNA methylation in COVID-19 patients will be better understood by exploring the COVID-19 DNA methylation variation at the cell-type level. Here, we developed an analytical pipeline to explore single-cell DNA methylation variations in COVID-19 patients by transferring bulk-tissue-level knowledge to the single-cell level. We discovered that the methylation variations in the whole blood of COVID-19 patients showed significant cell-type specificity with remarkable enrichment in gamma-delta T cells and presented a phenomenon of hypermethylation and low expression. Furthermore, we identified five genes whose methylation variations were associated with several cell types. Among them, S100A9, AHNAK, and CX3CR1 have been reported as potential COVID-19 biomarkers previously, and the others (TRAF3IP3 and LFNG) are closely associated with the immune and virus-related signaling pathways. We propose that they might serve as potential epigenetic biomarkers for COVID-19 and could play roles in important biological processes such as the immune response and antiviral activity.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071109
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1110: Genetic Analyses of Discrete Geographic
           Samples of a Golden Chanterelle in Canada Reveal Evidence for Recent
           Regional Differentiation

    • Authors: Zhao, Korfanty, Xu, Thorn
      First page: 1110
      Abstract: The wild edible mushroom Cantharellus enelensis is a recently described species of the golden chanterelles found in eastern North America. At present, the genetic diversity and population structure of C. enelensis are not known. In this study, we analyzed a total of 230 fruiting bodies of C. enelensis that were collected from three regions of Canada: near the east and west coasts of Newfoundland (NFLD), with 110 fruiting bodies each, and around Hamilton, Ontario (10 fruiting bodies). Among the 110 fruiting bodies from each coast in NFLD, 10 from 2009 were without specific site information, while 100 sampled in 2010 were from each of five patches separated by at least 100 m from each other. Each fruiting body was genotyped at three microsatellite loci. Among the total 28 multilocus genotypes (MLGs) identified, 2 were shared among all three regions, 4 were shared between 2 of the t3hree regions, and the remaining 22 were each found in only 1 region. Minimal spanning network analyses revealed several region-specific MLG clusters, consistent with geographic specific mutation and expansion. Though the most frequently observed MLGs were shared among local (patch) and regional populations, population genetic analyses revealed that both local and regional geographic separations contributed significantly to the observed genetic variation in the total sample. All three regional populations showed excess heterozygosity; for the eastern NFLD population, we reject the null hypothesis of Hardy–Weinberg equilibrium (HWE) at all three loci. However, the analyses of clone-corrected samples revealed that most loci were in HWE. Together, our results suggest that the three discrete regional populations of C. enelensis were likely colonized from a common refugium since the last ice age. However, the local and regional populations are diverging from each other through mutation, drift, and selection at least partly due to heterozygous advantage.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071110
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1111: The Role of ACE, ACE2, and AGTR2 Polymorphisms
           in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy

    • Authors: Kristina Jevnikar, Luka Lapajne, Daniel Petrovič, Andrej Meglič, Mateja Logar, Nataša Vidovič Valentinčič, Mojca Globočnik Petrovič, Ines Cilenšek, Polona Jaki Mekjavić
      First page: 1111
      Abstract: The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50; No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males; hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071111
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1112: Characterization of Expression and Epigenetic
           Features of Core Genes in Common Wheat

    • Authors: Dongyang Zheng, Wenli Zhang
      First page: 1112
      Abstract: The availability of multiple wheat genome sequences enables us to identify core genes and characterize their genetic and epigenetic features, thereby advancing our understanding of their biological implications within individual plant species. It is, however, largely understudied in wheat. To this end, we reanalyzed genome sequences from 16 different wheat varieties and identified 62,299 core genes. We found that core and non-core genes have different roles in subgenome differentiation. Meanwhile, according to their expression profiles, these core genes can be classified into genes related to tissue development and stress responses, including 3376 genes highly expressed in both spikelets and at high temperatures. After associating with six histone marks and open chromatin, we found that these core genes can be divided into eight sub-clusters with distinct epigenomic features. Furthermore, we found that ca. 51% of the expressed transcription factors (TFs) were marked with both H3K27me3 and H3K4me3, indicative of the bivalency feature, which can be involved in tissue development through the TF-centered regulatory network. Thus, our study provides a valuable resource for the functional characterization of core genes in stress responses and tissue development in wheat.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071112
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1113: Characterization of Chicken
           α2A-Adrenoceptor: Molecular Cloning, Functional Analysis, and Its
           Involvement in Ovarian Follicular Development

    • Authors: Biying Jiang, Baolong Cao, Zhichun Zhou, Zejiao Li, Can Lv, Jiannan Zhang, Heyuan Zhang, Yajun Wang, Juan Li
      First page: 1113
      Abstract: Adrenoceptors are suggested to mediate the functions of norepinephrine (NE) and epinephrine (EPI) in the central nervous system (CNS) and peripheral tissues in vertebrates. Compared to mammals, the functionality and expression of adrenoceptors have not been well characterized in birds. Here, we reported the structure, expression, and functionality of chicken functional α2A-adrenoceptor, named ADRA2A. The cloned chicken ADRA2A cDNA is 1335 bp in length, encoding the receptor with 444 amino acids (a.a.), which shows high amino acid sequence identity (63.4%) with its corresponding ortholog in humans. Using cell-based luciferase reporter assays and Western blot, we demonstrated that the ADRA2A could be activated by both NE and EPI through multiple signaling pathways, including MAPK/ERK signaling cascade. In addition, the mRNA expression of ADRA2A is found to be expressed abundantly in adult chicken tissues including thyroid, lung, ovary and adipose from the reported RNA-Seq data sets. Moreover, the mRNA expression of ADRA2A is also found to be highly expressed in the granulosa cells of 6–8 mm and F5 chicken ovarian follicles, which thus supports that ADRA2A signaling may play a role in ovarian follicular growth and differentiation. Taken together, our data provide the first proof that the α2A-adrenoceptor is functional in birds involving avian ovarian follicular development.
      Citation: Genes
      PubDate: 2022-06-21
      DOI: 10.3390/genes13071113
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1114: Nucleosome-Omics: A Perspective on the
           Epigenetic Code and 3D Genome Landscape

    • Authors: Siyuan Kong, Yuhui Lu, Shuhao Tan, Rongrong Li, Yan Gao, Kui Li, Yubo Zhang
      First page: 1114
      Abstract: Genetic information is loaded on chromatin, which involves DNA sequence arrangement and the epigenetic landscape. The epigenetic information including DNA methylation, nucleosome positioning, histone modification, 3D chromatin conformation, and so on, has a crucial impact on gene transcriptional regulation. Out of them, nucleosomes, as basal chromatin structural units, play an important central role in epigenetic code. With the discovery of nucleosomes, various nucleosome-level technologies have been developed and applied, pushing epigenetics to a new climax. As the underlying methodology, next-generation sequencing technology has emerged and allowed scientists to understand the epigenetic landscape at a genome-wide level. Combining with NGS, nucleosome-omics (or nucleosomics) provides a fresh perspective on the epigenetic code and 3D genome landscape. Here, we summarized and discussed research progress in technology development and application of nucleosome-omics. We foresee the future directions of epigenetic development at the nucleosome level.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071114
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1115: Genome-Wide Identification of NRT Gene Family
           and Expression Analysis of Nitrate Transporters in Response to Salt Stress
           in Poncirus trifoliata

    • Authors: Zeqi Zhao, Mengdi Li, Weiwei Xu, Ji-Hong Liu, Chunlong Li
      First page: 1115
      Abstract: The uptake and transportation of nitrate play a crucial role in plant growth and development. These processes mostly depend on nitrate transporters (NRT), which guarantee the supplement of nutrition in the plant. In this study, genes encoding NRT with Major Facilitator Superfamily (MFS) domain were identified in trifoliate orange (Poncirus trifoliata (L.) Raf.). Totally, 56 NRT1s, 6 NRT2s, and 2 NAR2s were explored. The bioinformation analysis, including protein characteristics, conserved domain, motif, phylogenetic relationship, cis-acting element, and synteny correlation, indicated the evolutionary conservation and functional diversity of NRT genes. Additionally, expression profiles of PtrNRTs in different tissues demonstrated that NRT genes possessed spatio-temporal expression specificity. Further, the salt condition was certified to induce the expression of some NRT members, like PtrNPF2.1, PtrNPF7.4, and PtrNAR2.1, proposing the potential role of these NRTs in salt stress response. The identification of NRT genes and the expression pattern analysis in various tissues and salt stress lay a foundation for future research between nitrogen transport and salt resistance in P. trifoliata.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071115
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1116: Mitochondrial Genome of Strophopteryx fasciata
           (Plecoptera: Taeniopterygidae), with a Phylogenetic Analysis of

    • Authors: Xuan Guo, Caiyue Guo, Xiaojiao Dong, Heng Zhang, Dávid Murányi, Weihai Li, Ying Wang
      First page: 1116
      Abstract: Taeniopterygidae is a medium-sized family of stoneflies. The phylogeny of Taeniopterygidae was widely accepted based on the morphological analyses. However, there are different opinions based on molecular data. To date, only two taeniopterygid mitochondrial genomes (mitogenomes) were available, and more sampling is needed to obtain precise phylogenetic relationships. In this research, the Strophopteryx fasciata mitogenome was sequenced and analyzed. The complete mitogenome of S. fasciata was 15,527 bp in length and contained 37 genes and a non-coding control region. Among taeniopterygid mitogenomes, the length variation was minimal in protein-coding genes (PCGs), transfer RNA genes (tRNAs) and ribosomal RNA genes (rRNAs), but very different in the control region. Similar to mitogenomes of other taeniopterygid species, the S. fasciata mitogenome was consistently AT biased and displayed positive AT- and negative GC-skews of the whole mitogenome. Most PCGs used ATN as the start codon and TAA/TAG as the stop codon. The stop codons were far less variable than the start codons in taeniopterygid mitogenomes. All Ka/Ks ratios were less than 1, indicating the presence of purifying selection in these genes. The secondary structures of transfer and ribosomal RNA genes of S. fasciata mitogenome are highly conserved with other taeniopterygid species. In the control region of the S. fasciata mitogenome, some essential elements (tandem repeats, stem–loop structures, and poly−N stretch, etc.) were observed. Two phylogenetic trees were inferred from Bayesian inference (BI) and Maximum Likelihood (ML) methods generated the identical topology across the PCGR dataset. The relationships of five families in Nemouroidea were recovered as Leuctridae + ((Capniidae + Taeniopterygidae) + (Nemouridae + Notonemouridae)). These results will help us understand the mitogenome structure of taeniopterygid species and the evolutionary relationship within Plecoptera.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071116
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1117: Cell Subsampling Recovers Probative DNA
           Profile Information from Unresolvable/Undetectable Minor Donors in

    • Authors: Kaitlin Huffman, Erin Hanson, Jack Ballantyne
      First page: 1117
      Abstract: When a minor DNA component to a binary mixture is present at a weight ratio of approximately 1:50 or less, the presence of this minor donor is undetectable (or barely detectable) by standard mixture deconvolution approaches. In an attempt to retrieve probative minor donor DNA profile information, multiple quintuple cell subsamples were collected from a 1:50 DNA mixture using direct single cell subsampling (DSCS) paired with probabilistic genotyping (PG), the latter validated for use with single or few cells. DSCS employs a simplified micromanipulation technique paired with an enhanced DNA profiling approach, involving direct cell lysis and a sensitive PCR process, to genotype individual cells. Multiple five-cell subsamples were used to interrogate sufficient cells from the mixture such that some of the created 5-cell “mini-mixture” subsamples contained a cell from the minor donor. The latter mini-mixture subsamples, which now comprised weight ratios of 1:4 as opposed to the bulk mixture 1:50, were analyzed with the PG systems STRmixTM and EuroForMix resulting in a significant probative gain of information, (LR ≅ 1011, compared to standard bulk mixture PG methods, LR ≅ 101–102).
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071117
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1118: The Genetic Diversity of Bletilla spp. Based
           on SLAF-seq and Oligo-FISH

    • Authors: Jie Huan, Zhoujian He, Yuting Lei, Wenjun Li, Liqiong Jiang, Xiaomei Luo
      First page: 1118
      Abstract: Bletilla spp.Rchb. F. is a traditional Chinese medicinal material. In this study, Bletilla striata (Thunb. ex A. Murray) Rchb F, Bletilla formosana (Hayata) Schltr, and Bletilla ochracea Schltr were collected to analyze the genetic diversity of 16 materials using specific site-amplified fragment sequencing (SLAF-seq) and fluorescence in situ hybridization (FISH). The results showed that the phylogenetic tree of the single-nucleotide polymorphism (SNP) data rendering system was correlated with the shape and geographical distribution of the material. The results of the population structural analysis showed that all the materials containing yellow labellum came from the same ancestor. The results of the principal component analysis were able to preliminarily judge the genetic distance and provided a reference for the selection of hybrid parents. The FISH analysis showed that the chromosomes of B. striata were 2n = 32 and the chromosomes of the B. striata (safflower) mutant were 2n = 34 and the chromosomes of B. ochracea and B. formosana were 2n = 34–36. The (AG3T3)3 non-terminal signal was different from the 5S rDNA signal. These results revealed that the 16 materials had rich genetic diversity, which can provide molecular and cytogenetic data for the study of the genus and its relatives and serve as a reference for the breeding of new genus varieties and improve breeding efficiency and cost.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071118
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1119: Integrated sRNA-seq and RNA-seq Analyses
           Reveal a microRNA Regulation Network Involved in Cold Response in Pisum
           sativum L.

    • Authors: Mélanie Mazurier, Jan Drouaud, Nasser Bahrman, Andrea Rau, Isabelle Lejeune-Hénaut, Bruno Delbreil, Sylvain Legrand
      First page: 1119
      Abstract: (1) Background: Cold stress affects growth and development in plants and is a major environmental factor that decreases productivity. Over the past two decades, the advent of next generation sequencing (NGS) technologies has opened new opportunities to understand the molecular bases of stress resistance by enabling the detection of weakly expressed transcripts and the identification of regulatory RNAs of gene expression, including microRNAs (miRNAs). (2) Methods: In this study, we performed time series sRNA and mRNA sequencing experiments on two pea (Pisum sativum L., Ps) lines, Champagne frost-tolerant and Térèse frost-sensitive, during a low temperature treatment versus a control condition. (3) Results: An integrative analysis led to the identification of 136 miRNAs and a regulation network composed of 39 miRNA/mRNA target pairs with discordant expression patterns. (4) Conclusions: Our findings indicate that the cold response in pea involves 11 miRNA families as well as their target genes related to antioxidative and multi-stress defense mechanisms and cell wall biosynthesis.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071119
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1120: Gene-Based Association Tests Using New
           Polygenic Risk Scores and Incorporating Gene Expression Data

    • Authors: Shijia Yan, Qiuying Sha, Shuanglin Zhang
      First page: 1120
      Abstract: Recently, gene-based association studies have shown that integrating genome-wide association studies (GWAS) with expression quantitative trait locus (eQTL) data can boost statistical power and that the genetic liability of traits can be captured by polygenic risk scores (PRSs). In this paper, we propose a new gene-based statistical method that leverages gene-expression measurements and new PRSs to identify genes that are associated with phenotypes of interest. We used a generalized linear model to associate phenotypes with gene expression and PRSs and used a score-test statistic to test the association between phenotypes and genes. Our simulation studies show that the newly developed method has correct type I error rates and can boost statistical power compared with other methods that use either gene expression or PRS in association tests. A real data analysis Figurebased on UK Biobank data for asthma shows that the proposed method is applicable to GWAS.
      Citation: Genes
      PubDate: 2022-06-22
      DOI: 10.3390/genes13071120
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1121: The Effect of Angiotensin Converting Enzyme
           (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and
           Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease:
           The Mediating Role of Plasma ACE Level

    • Authors: Hendri Susilo, Budi Susetyo Pikir, Mochammad Thaha, Mochamad Yusuf Alsagaff, Satriyo Dwi Suryantoro, Citrawati Dyah Kencono Wungu, Ifan Ali Wafa, Cennikon Pakpahan, Delvac Oceandy
      First page: 1121
      Abstract: The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071121
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1122: Identification and Functional Analysis of
           Individual-Specific Subpathways in Lung Adenocarcinoma

    • Authors: Jingya Fang, Zutan Li, Mingmin Xu, Jinwen Ji, Yanru Li, Liangyun Zhang, Yuanyuan Chen
      First page: 1122
      Abstract: Small molecular networks within complex pathways are defined as subpathways. The identification of patient-specific subpathways can reveal the etiology of cancer and guide the development of personalized therapeutic strategies. The dysfunction of subpathways has been associated with the occurrence and development of cancer. Here, we propose a strategy to identify aberrant subpathways at the individual level by calculating the edge score and using the Gene Set Enrichment Analysis (GSEA) method. This provides a novel approach to subpathway analysis. We applied this method to the expression data of a lung adenocarcinoma (LUAD) dataset from The Cancer Genome Atlas (TCGA) database. We validated the effectiveness of this method in identifying LUAD-relevant subpathways and demonstrated its reliability using an independent Gene Expression Omnibus dataset (GEO). Additionally, survival analysis was applied to illustrate the clinical application value of the genes and edges in subpathways that were associated with the prognosis of patients and cancer immunity, which could be potential biomarkers. With these analyses, we show that our method could help uncover subpathways underlying lung adenocarcinoma.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071122
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1123: From First to Second: How Stickler’s
           Diagnostic Genetics Has Evolved to Match Sequencing Technologies

    • Authors: Howard Martin, Allan J. Richards, Martin P. Snead
      First page: 1123
      Abstract: Diagnostic genetics within the United Kingdom National Health Service (NHS) has undergone many stepwise improvements in technology since the completion of the human genome project in 2003. Although Sanger sequencing has remained a cornerstone of the diagnostic sequencing arena, the human genome reference sequence has enabled next-generation sequencing (more accurately named ‘second-generation sequencing’), to rapidly surpass it in scale and potential. This mini review discusses such developments from the viewpoint of the Stickler’s higher specialist service, detailing the considerations and improvements to diagnostic sequencing implemented since 2003.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071123
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1124: Validation of a Chromosome 14 Risk Haplotype
           for Idiopathic Epilepsy in the Belgian Shepherd Dog Found to Be Associated
           with an Insertion in the RAPGEF5 Gene

    • Authors: Janelle M. Belanger, Tiina Heinonen, Thomas R. Famula, Paul J. J. Mandigers, Peter A. Leegwater, Marjo K. Hytönen, Hannes Lohi, Anita M. Oberbauer
      First page: 1124
      Abstract: An idiopathic epilepsy (IE) risk haplotype on canine chromosome (CFA) 14 has been reported to interact with the CFA37 common risk haplotype in the Belgian shepherd (BS). Additional IE cases and control dogs were genotyped for the risk haplotypes to validate these previous findings. In the new cohort, the interaction between the two regions significantly elevated IE risk. When the haplotypes were analyzed individually, particular haplotypes on both CFA14 (ACTG) and 37 (GG) were associated with elevated IE risk, though only the CFA37 AA was significantly associated (p < 0.003) with reduced risk in the new cohort. However, the CFA14 ACTG risk was statistically significant when the new and previous cohort data were combined. The frequency of the ACTG haplotype was four-fold higher in BS dogs than in other breeds. Whole genome sequence analysis revealed that a 3-base pair predicted disruptive insertion in the RAPGEF5 gene, which is adjacent to the CFA14 risk haplotype. RAPGEF5 is involved in the Wnt-β-catenin signaling pathway that is crucial for normal brain function. Although this risk variant does not fully predict the likelihood of a BS developing IE, the association with a variant in a candidate gene may provide insight into the genetic control of canine IE.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071124
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1125: Specific Irreversible Cell-Cycle Arrest and
           Depletion of Cancer Cells Obtained by Combining Curcumin and the
           Flavonoids Quercetin and Fisetin

    • Authors: Viviana Barra, Roberta Flavia Chiavetta, Simona Titoli, Ivana Maria Provenzano, Pietro Salvatore Carollo, Aldo Di Leonardo
      First page: 1125
      Abstract: Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined the cellular senescence induced by curcumin and whether it could be targeted by fisetin and quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number and structure, and heterochromatin markers were evaluated via flow cytometry, metaphase spreads, and immunofluorescence, respectively. The activation of p21waf1/cip1 was assessed via RT-qPCR and immunoblotting. Senescent cells were detected via SA-β-Galactosidase staining. Results: We report that curcumin treatment specifically triggers senescence in cancer cells by inducing mitotic slippage and DNA damage. We show that curcumin-induced senescence is p21waf1/cip1-dependent and characterized by heterochromatin loss. Finally, we found that flavonoids clear curcumin-induced senescent cancer cells. Conclusions: Our findings expand the characterization of curcumin-induced cellular senescence in cancer cells and lay the foundation for the combination of curcumin and flavonoids as a possible anti-cancer therapy.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071125
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1126: PromoterLCNN: A Light CNN-Based Promoter
           Prediction and Classification Model

    • Authors: Daryl Hernández, Nicolás Jara, Mauricio Araya, Roberto E. Durán, Carlos Buil-Aranda
      First page: 1126
      Abstract: Promoter identification is a fundamental step in understanding bacterial gene regulation mechanisms. However, accurate and fast classification of bacterial promoters continues to be challenging. New methods based on deep convolutional networks have been applied to identify and classify bacterial promoters recognized by sigma (σ) factors and RNA polymerase subunits which increase affinity to specific DNA sequences to modulate transcription and respond to nutritional or environmental changes. This work presents a new multiclass promoter prediction model by using convolutional neural networks (CNNs), denoted as PromoterLCNN, which classifies Escherichia coli promoters into subclasses σ70, σ24, σ32, σ38, σ28, and σ54. We present a light, fast, and simple two-stage multiclass CNN architecture for promoter identification and classification. Training and testing were performed on a benchmark dataset, part of RegulonDB. Comparative performance of PromoterLCNN against other CNN-based classifiers using four parameters (Acc, Sn, Sp, MCC) resulted in similar or better performance than those that commonly use cascade architecture, reducing time by approximately 30–90% for training, prediction, and hyperparameter optimization without compromising classification quality.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071126
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1127: The First Complete Mitochondrial Genome of
           Eucrate crenata (Decapoda: Brachyura: Goneplacidae) and Phylogenetic
           Relationships within Infraorder Brachyura

    • Authors: Xiaoke Pang, Chenglong Han, Biao Guo, Kefeng Liu, Xiaolong Lin, Xueqiang Lu
      First page: 1127
      Abstract: Characterizing the complete mitochondrial genome (mitogenome) of an organism is useful for genomic studies in taxonomy and evolution. The mitogenomic characteristics of Eucrate crenata (Decapoda: Brachyura: Goneplacidae) have never been studied. The present study decodes the first mitogenome of E. crenata by high-throughput sequencing (HTS). The length of the mitogenome is 15,597 bp, and it contains 13 protein-coding genes, 2 ribosomal RNA genes (rrnS and rrnL), and 22 transfer RNA genes. There are 14 and 23 genes observed on the heavy and light strands, respectively. E. crenata possesses a trnH-cac translocation, with the trnH-cac shifted between trnE-gaa and trnF-ttc instead of the usual location between nad5 and nad4 in decapods. Phylogenetic analyses based on the current dataset of 33 Brachyuran mitogenomes indicate that E. crenata. is closely related to Ashtoret lunaris of Matutidae. The similar codon usage and rearrangements in the two species provide evidence for their close phylogenetic relationship. Positive selection analysis showed that one residue located in cox1 was identified as a positively selected site with high BEB value (>95%), indicating that this gene was under positive selection pressure. This study is the first complete mitogenome record for the family Goneplacidae, and the results obtained may improve the understanding of the phylogeny of Goneplacidae in Brachyura.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071127
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1128: A Novel 90-kbp Deletion of RUNX2 Associated
           with Cleidocranial Dysplasia

    • Authors: Yanli Zhang, Xiaohong Duan
      First page: 1128
      Abstract: Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia caused by runt-related transcription factor 2 (RUNX2) mutations. In addition to the regular missense, small or large fragment deletions are the common mutation types of RUNX2. This study aimed to find the rules of deletions in RUNX2. the clinical information of one Chinese CCD family was collected. Genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatics analyzed the pathogenicity of the variants. Polymerase chain reaction (PCR) and Sanger sequencing were carried out using specific primers. RT-PCR and Q-PCR were also used to detect the mRNA level of RUNX2. The CCD studies related with deletions in RUNX2 from 1999 to 2021 from HGMD and PubMed were collected and analyzed for the relationship between the phenotypes and the length of deleted fragments. the proband presented typical CCD features, including delayed closure of cranial sutures, clavicle dysplasia, abnormal teeth. WES, PCR with specific primers and Sanger sequencing revealed a novel heterozygous 90-kbp deletion in RUNX2 (NG_008020.2 g.103671~193943), which caused a substitution (p.Asn183Ile) and premature termination (p.Asp184*). In addition, the mRNA expression of RUNX2 was decreased by 75.5% in the proband. Herein, 31 types of deletions varying from 2 bp to 800 kbp or covering the whole gene of RUNX2 were compared and the significant phenotypic difference was not found among these deletions. the CCD phenotypes were related with the final effects of RUNX2 mutation instead of the length of deletion. WES has the defects in identifying large indels, and direct PCR with specific primers and Sanger sequencing could make up for the shortcoming.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071128
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1129: The Relative Power of Structural Genomic
           Variation versus SNPs in Explaining the Quantitative Trait Growth in the
           Marine Teleost Chrysophrys auratus

    • Authors: Mike Ruigrok, Bing Xue, Andrew Catanach, Mengjie Zhang, Linley Jesson, Marcus Davy, Maren Wellenreuther
      First page: 1129
      Abstract: Background: Genetic diversity provides the basic substrate for evolution. Genetic variation consists of changes ranging from single base pairs (single-nucleotide polymorphisms, or SNPs) to larger-scale structural variants, such as inversions, deletions, and duplications. SNPs have long been used as the general currency for investigations into how genetic diversity fuels evolution. However, structural variants can affect more base pairs in the genome than SNPs and can be responsible for adaptive phenotypes due to their impact on linkage and recombination. In this study, we investigate the first steps needed to explore the genetic basis of an economically important growth trait in the marine teleost finfish Chrysophrys auratus using both SNP and structural variant data. Specifically, we use feature selection methods in machine learning to explore the relative predictive power of both types of genetic variants in explaining growth and discuss the feature selection results of the evaluated methods. Methods: SNP and structural variant callers were used to generate catalogues of variant data from 32 individual fish at ages 1 and 3 years. Three feature selection algorithms (ReliefF, Chi-square, and a mutual-information-based method) were used to reduce the dataset by selecting the most informative features. Following this selection process, the subset of variants was used as features to classify fish into small, medium, or large size categories using KNN, naïve Bayes, random forest, and logistic regression. The top-scoring features in each feature selection method were subsequently mapped to annotated genomic regions in the zebrafish genome, and a permutation test was conducted to see if the number of mapped regions was greater than when random sampling was applied. Results: Without feature selection, the prediction accuracies ranged from 0 to 0.5 for both structural variants and SNPs. Following feature selection, the prediction accuracy increased only slightly to between 0 and 0.65 for structural variants and between 0 and 0.75 for SNPs. The highest prediction accuracy for the logistic regression was achieved for age 3 fish using SNPs, although generally predictions for age 1 and 3 fish were very similar (ranging from 0–0.65 for both SNPs and structural variants). The Chi-square feature selection of SNP data was the only method that had a significantly higher number of matches to annotated genomic regions of zebrafish than would be explained by chance alone. Conclusions: Predicting a complex polygenic trait such as growth using data collected from a low number of individuals remains challenging. While we demonstrate that both SNPs and structural variants provide important information to help understand the genetic basis of phenotypic traits such as fish growth, the full complexities that exist within a genome cannot be easily captured by classical machine learning techniques. When using high-dimensional data, feature selection shows some increase in the prediction accuracy of classification models and provides the potential to identify unknown genomic correlates with growth. Our results show that both SNPs and structural variants significantly impact growth, and we therefore recommend that researchers interested in the genotype–phenotype map should strive to go beyond SNPs and incorporate structural variants in their studies as well. We discuss how our machine learning models can be further expanded to serve as a test bed to inform evolutionary studies and the applied management of species.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071129
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1130: Genotype-Phenotype Correlations in
           Neurofibromatosis Type 1: Identification of Novel and Recurrent NF1 Gene
           Variants and Correlations with Neurocognitive Phenotype

    • Authors: Filomena Napolitano, Milena Dell’Aquila, Chiara Terracciano, Giuseppina Franzese, Maria Teresa Gentile, Giulio Piluso, Claudia Santoro, Davide Colavito, Anna Patanè, Paolo De Blasiis, Simone Sampaolo, Simona Paladino, Mariarosa Anna Beatrice Melone
      First page: 1130
      Abstract: Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the NF1. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases). Clinical data were collected at the time of the mutation analysis and reviewed for accuracy in this investigation. An internal phenotypic categorization was applied. The 94% of the patients enrolled showed a severe phenotype with at least one systemic complication and a wide range of associated malignancies. Spine deformities were the most common complications in this cohort. We also reported 66 different NF1 mutations, of which 7 are novel mutations. Correlation analysis identified a slight significant inverse correlation between age at diagnosis and delayed acquisition of psychomotor skills with residual multi-domain cognitive impairment. Odds ratio with 95% confidence interval showed a higher prevalence of learning disabilities in patients carrying frameshift mutations. Overall, our results aim to offer an interesting contribution to studies on the genotype–phenotype of NF1 and in genetic management and counselling.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071130
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1131: Mapping‑by‑Sequencing Reveals

    • Authors: Hanna Marie Schilbert, Boas Pucker, David Ries, Prisca Viehöver, Zeljko Micic, Felix Dreyer, Katrin Beckmann, Benjamin Wittkop, Bernd Weisshaar, Daniela Holtgräwe
      First page: 1131
      Abstract: Rapeseed (Brassica napus L.) is an important oil crop and has the potential to serve as a highly productive source of protein. This protein exhibits an excellent amino acid composition and has high nutritional value for humans. Seed protein content (SPC) and seed oil content (SOC) are two complex quantitative and polygenic traits which are negatively correlated and assumed to be controlled by additive and epistatic effects. A reduction in seed glucosinolate (GSL) content is desired as GSLs cause a stringent and bitter taste. The goal here was the identification of genomic intervals relevant for seed GSL content and SPC/SOC. Mapping by sequencing (MBS) revealed 30 and 15 new and known genomic intervals associated with seed GSL content and SPC/SOC, respectively. Within these intervals, we identified known but also so far unknown putatively causal genes and sequence variants. A 4 bp insertion in the MYB28 homolog on C09 shows a significant association with a reduction in seed GSL content. This study provides insights into the genetic architecture and potential mechanisms underlying seed quality traits, which will enhance future breeding approaches in B. napus.
      Citation: Genes
      PubDate: 2022-06-23
      DOI: 10.3390/genes13071131
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1132: Efficient Editing of the ZBED6-Binding Site in
           Intron 3 of IGF2 in a Bovine Model Using the CRISPR/Cas9 System

    • Authors: Huiying Zou, Dawei Yu, Shun Yao, Fangrong Ding, Junliang Li, Ling Li, Xue Li, Shanjiang Zhao, Yunwei Pang, Haisheng Hao, Weihua Du, Xueming Zhao, Yunping Dai, Huabin Zhu
      First page: 1132
      Abstract: Background: Insulin-like growth factor 2 is a growth-promoting factor that plays an important role in the growth and development of mammals. A nucleotide substitution in intron 3 of IGF2—which disrupts the ZBED6-binding site—affects muscle mass, organ size, and fat deposition in pigs. The ZBED6-binding site is also conserved in cattle. Methods: In the present study, we introduced mutations in the ZBED6-binding site in intron3 of IGF2 in bovine fetal fibroblasts using the CRISPR/Cas9 system, and investigated the effect of disruption of ZBED6 binding on IGF2 expression. Results: Eleven biallelic-mutant single-cell clones were established, three of which contained no foreign DNA residues. Single-cell clones 93 and 135 were used to produce cloned embryos. Dual-luciferase reporter assay in C2C12 cells demonstrated that the mutation in the ZBED6-binding site increases the promoter 3 activity of bovine IGF2. A total of 49 mutant cloned embryos were transplanted into surrogate cows. Unfortunately, all cloned embryos died before birth. IGF2 was found to be hypomethylated in the only fetus born (stillborn), which may have been due to the incomplete reprogramming. Conclusions: We efficiently constructed IGF2-edited cell lines and cloned embryos, which provided a theoretical basis and experimental materials for beef cattle breeding.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071132
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1133: Identification of Novel Circular RNAs of the
           Human Protein Arginine Methyltransferase 1 (PRMT1) Gene, Expressed in
           Breast Cancer Cells

    • Authors: Maria Papatsirou, Marios A. Diamantopoulos, Katerina Katsaraki, Dimitris Kletsas, Christos K. Kontos, Andreas Scorilas
      First page: 1133
      Abstract: Circular RNAs (circRNAs) constitute a type of RNA formed through back-splicing. In breast cancer, circRNAs are implicated in tumor onset and progression. Although histone methylation by PRMT1 is largely involved in breast cancer development and metastasis, the effect of circular transcripts deriving from this gene has not been examined. In this study, total RNA was extracted from four breast cancer cell lines and reversely transcribed using random hexamer primers. Next, first- and second-round PCRs were performed using gene-specific divergent primers. Sanger sequencing followed for the determination of the sequence of each novel PRMT1 circRNA. Lastly, bioinformatics analysis was conducted to predict the functions of the novel circRNAs. In total, nine novel circRNAs were identified, comprising both complete and truncated exons of the PRMT1 gene. Interestingly, we demonstrated that the back-splice junctions consist of novel splice sites of the PRMT1 exons. Moreover, the circRNA expression pattern differed among these four breast cancer cell lines. All the novel circRNAs are predicted to act as miRNA and/or protein sponges, while five circRNAs also possess an open reading frame. In summary, we described the complete sequence of nine novel circRNAs of the PRMT1 gene, comprising distinct back-splice junctions and probably having different molecular properties.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071133
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1134: NtDREB-1BL1 Enhances Carotenoid Biosynthesis
           by Regulating Phytoene Synthase in Nicotiana tabacum

    • Authors: Chen Dong, Qingdong Wang, Yubo Wang, Lili Qin, Yongchun Shi, Xiaoran Wang, Ran Wang
      First page: 1134
      Abstract: As one of the most imperative antioxidants in higher plants, carotenoids serve as accessory pigments to harvest light for photosynthesis as well as photoprotectors for plants to adapt to high light stress. Phytoene synthase (PSY) is the entry enzyme and also the major rate-limiting enzyme in the carotenoid pathway. Here, we report a dehydration-responsive element-binding protein (DREB) transcription factor member in Nicotiana tabacum K326, NtDREB-1BL1, which regulates carotenoids biosynthesis by binding to the NtPSY promoter. The NtDREB-1BL1 transcript was widely distributed in leaves by Real-time PCR. Confocal image revealed that NtDREB-1BL1 was localized in the nucleus. The chromatin immunoprecipitation (ChIP) with the qPCR technique indicated that NtDREB-1BL1 could anchor the promoter region of NtPSY. Overexpression (NtDREB-1BL1 OE) and RNA interference (NtDREB-1BL1 RNAi) of NtDREB-1BL1 were performed to evaluate its biological function in N. tabacum. Both carotenoid and chlorophyll contents increased in transgenic plants of NtDREB-1BL1 OE compared with wild-type (WT) plants, with the augment of the genes involved in carotenoid biosynthesis. In contrast, the contents of carotenoid and chlorophyll significantly decreased in transgenic plants of NtDREB-1BL1 RNAi compared to WT, along with the decline in the expression of genes related to carotenoid biosynthesis. Moreover, transgenic plants of NtDREB-1BL1 OE exhibited enhanced tolerance under drought stress, with the weakened tolerance of drought stress in transgenic plants of NtDREB-1BL1 RNAi. In conclusion, our results illustrated the new role of transcription factor NtDREB-1BL1 in improving carotenoid biosynthesis through regulating NtPSY expression.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071134
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1135: Autosomal Recessive Stickler Syndrome

    • Authors: Thomas R. W. Nixon, Allan J. Richards, Howard Martin, Philip Alexander, Martin P. Snead
      First page: 1135
      Abstract: Stickler syndrome (SS) is a genetic disorder with manifestations in the eye, ear, joints, face and palate. Usually inherited in a dominant fashion due to heterozygous pathogenic variants in the collagen genes COL2A1 and COL11A1, it can rarely be inherited in a recessive fashion from variants in COL9A1, COL9A2, and COL9A3, COL11A1, as well as the non-collagen genes LRP2, LOXL3 and GZF1. We review the published cases of recessive SS, which comprise 40 patients from 23 families. Both homozygous and compound heterozygous pathogenic variants are found. High myopia is near-universal, and sensorineural hearing loss is very common in patients with variants in genes for type IX or XI collagen, although hearing appears spared in the LRP2 and LOXL3 patients and is variable in GZF1. Cleft palate is associated with type XI collagen variants, as well as the non-collagen genes, but is so far unreported with type IX collagen variants. Retinal detachment has occurred in 18% of all cases, and joint pain in 15%. However, the mean age of this cohort is 11 years old, so the lifetime incidence of both problems may be underestimated. This paper reinforces the importance of screening for SS in congenital sensorineural hearing loss, particularly when associated with myopia, and the need to warn patients and parents of the warning signs of retinal detachment, with regular ophthalmic review.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071135
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1136: Gene–Environment Correlation over Time: A
           Longitudinal Analysis of Polygenic Risk Scores for Schizophrenia and Major
           Depression in Three British Cohorts Studies

    • Authors: Sandra Machlitt-Northen, Robert Keers, Patricia Munroe, David Howard, Michael Pluess
      First page: 1136
      Abstract: Research suggests that both genetic and environmental risk factors are involved in the aetiology of schizophrenia (SCZ) and major depressive disorder (MDD). Importantly, environmental and genetic risk factors are often related as evidenced in gene–environment correlation (rGE), which describes the observation that genetic and environmental factors are associated with each other. It is understood that rGE gets stronger over time as individuals select their environments more actively based on their genetic propensities. However, little is known whether rGEs remain stable over time or change across different development periods. Using data from three British longitudinal cohorts, we investigated whether rGE patterns of polygenic risk scores (PRS) for SCZ and MDD changed over time across childhood and adulthood, as well as across both from birth to age 55 and whether results differed between SCZ and MDD. Overall, the majority of rGEs remained stable across the investigated development periods. Furthermore, the few detected rGE changes which did differ between SCZ and MDD, could not be explained by the confounding of clinical cases and are therefore likely the result of actual changes in environmental and cultural risk factors with genetic susceptibility to SCZ and MDD likely playing a less significant role.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071136
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1137: Group II Intron-Encoded Proteins
           (IEPs/Maturases) as Key Regulators of Nad1 Expression and Complex I
           Biogenesis in Land Plant Mitochondria

    • Authors: Ron Mizrahi, Sofia Shevtsov-Tal, Oren Ostersetzer-Biran
      First page: 1137
      Abstract: Mitochondria are semi-autonomous organelles that produce much of the energy required for cellular metabolism. As descendants of a bacterial symbiont, most mitochondria harbor their own genetic system (mtDNA/mitogenome), with intrinsic machineries for transcription and protein translation. A notable feature of plant mitochondria involves the presence of introns (mostly group II-type) that reside in many organellar genes. The splicing of the mtRNAs relies on the activities of various protein cofactors, which may also link organellar functions with cellular or environmental signals. The splicing of canonical group II introns is aided by an ancient class of RT-like enzymes (IEPs/maturases, MATs) that are encoded by the introns themselves and act specifically on their host introns. The plant organellar introns are degenerated in structure and are generally also missing their cognate intron-encoded proteins. The factors required for plant mtRNA processing are mostly nuclearly-encoded, with the exception of a few degenerated MATs. These are in particular pivotal for the maturation of NADH-dehydrogenase transcripts. In the following review we provide an update on the non-canonical MAT factors in angiosperm mitochondria and summarize the current knowledge of their essential roles in regulating Nad1 expression and complex I (CI) biogenesis during embryogenesis and early plant life.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071137
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1138: QTL Mapping for Age-Related Eye Pigmentation
           in the Pink-Eyed Dilution Castaneus Mutant Mouse

    • Authors: Takaya Nakano, Momoko Takenaka, Makoto Sugiyama, Akira Ishikawa
      First page: 1138
      Abstract: Pink-eyed dilution castaneus (Oca2p-cas) is a mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus. Homozygotes for Oca2p-cas exhibit pink eyes and a light gray coat throughout life. In an ordinary mutant strain carrying Oca2p-cas, we previously discovered a novel spontaneous mutation that gradually increases melanin pigmentation in the eyes and coat with aging, and we developed a novel mutant strain that was fixed for the novel phenotype. The purpose of this study was to map major quantitative trait loci (QTLs) for the novel pigmentation phenotype and for expression levels of four important melanogenesis genes, microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1) and dopachrome tautomerase (Dct). We developed 69 DNA markers and created 303 F2 mice from two reciprocal crosses between novel and ordinary mutant strains. The QTL analysis using a selective genotyping strategy revealed a significant QTL for eye pigmentation between 34 and 64 Mb on chromosome 13. This QTL explained approximately 20% of the phenotypic variance. The QTL allele derived from the novel strain increased pigmentation. Although eye pigmentation was positively correlated with Dct expression, no expression QTLs were found, suggesting that the pigmentation QTL on chromosome 13 may not be directly in the pathway of any of the four melanogenesis genes. This study is the first step toward identifying a causal gene for the novel spontaneous phenotype in mice and is expected to discover a new regulatory mechanism for complex melanin biosynthesis during aging.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071138
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1139: Principal Amalgamation Analysis for Microbiome

    • Authors: Yan Li, Gen Li, Kun Chen
      First page: 1139
      Abstract: In recent years microbiome studies have become increasingly prevalent and large-scale. Through high-throughput sequencing technologies and well-established analytical pipelines, relative abundance data of operational taxonomic units and their associated taxonomic structures are routinely produced. Since such data can be extremely sparse and high dimensional, there is often a genuine need for dimension reduction to facilitate data visualization and downstream statistical analysis. We propose Principal Amalgamation Analysis (PAA), a novel amalgamation-based and taxonomy-guided dimension reduction paradigm for microbiome data. Our approach aims to aggregate the compositions into a smaller number of principal compositions, guided by the available taxonomic structure, by minimizing a properly measured loss of information. The choice of the loss function is flexible and can be based on familiar diversity indices for preserving either within-sample or between-sample diversity in the data. To enable scalable computation, we develop a hierarchical PAA algorithm to trace the entire trajectory of successive simple amalgamations. Visualization tools including dendrogram, scree plot, and ordination plot are developed. The effectiveness of PAA is demonstrated using gut microbiome data from a preterm infant study and an HIV infection study.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071139
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1140: Overexpression of an Inositol
           Phosphorylceramide Glucuronosyltransferase Gene IbIPUT1 Inhibits Na+
           Uptake in Sweet Potato Roots

    • Authors: Chong Liu, Mingku Zhu, Jian Sun
      First page: 1140
      Abstract: IPUT1 is a glycosyltransferase capable of synthesizing the glycosyl inositol phosphorylceramide (GIPC) sphingolipid. The GIPC sphingolipid is a Na+ receptor on cell membranes which can sense extracellular Na+ concentrations, promote the increase in intracellular Ca2+ concentrations, and plays critical roles in maintaining intracellular Na+ balance. Therefore, the IPUT1 gene plays an important role in the genetic improvement of crop salt tolerance. Herein, the IbIPUT1 gene, which encodes an ortholog of Arabidopsis AtIPUT1, from sweet potato was cloned. Agrobacterium rhizogenes-mediated in vivo transgenic technology, non-invasive micro-measuring technology (NMT) and Na+ fluorescence imaging technology were then combined to quickly study the potential function of IbIPUT1 in salt tolerance. The data showed that IbIPUT1 was involved in the regulation of root cell Na+ balance, and the overexpression of IbIPUT1 could not promote sweet potato root cell Na+ efflux under salt stress, but it could significantly inhibit the Na+ absorption of root cells, thereby reducing the accumulation of Na+ in root cells under salt stress. Additionally, Ca2+ efflux in transgenic root cells was slightly higher than that in control roots under salt stress. Collectively, an efficient transgenic method for gene function studies was established, and our results suggested that IbIPUT1 acts as a candidate gene for the genetic enhancement of sweet potato salt tolerance.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071140
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1141: RNAi Mediated Gene Silencing of Detoxification
           Related Genes in the Ectropis oblique

    • Authors: Cui Peng, Heng Yin, Yang Liu, Xin-Fang Mao, Zhong-Yuan Liu
      First page: 1141
      Abstract: Ectropis oblique is one of the main pests that feed on tea leaves. At present, the main control method is chemical control, but the long-term use of insecticides has been related to the development of insect resistance. One of the resistance mechanisms is the upregulation of relevant detoxification enzymes for defense. In this study, four genes with increased expression were screened from the gene sequences annotated from the transcriptome data of deltamethrin-treated larvae of E. oblique, which are acid phosphatase EoACP138, and cytochrome P450 EoCYP316, carboxylesterase EoCarE592 and acetylcholine esterase EoAchE989, respectively. The fourth instar larvae of E. oblique were stimulated by deltamethrin, chlorpyrifos and fenpropathrin respectively, and the expression levels of the genes were detected by qRT-PCR. The result showed that all four genes’ expression had significantly increased under the stimulation of three insecticides. RNAi technology was used to silence the expression of genes of EoACP138, EoCYP316, EoCarE592 and EoAchE989 in the fourth instar larvae of E. oblique. The change in the expression levels of the above genes in the larvae treated with dsRNA and stimulated with pesticides was determined by qRT-PCR. The target genes have been effectively silenced after feeding on dsRNA and higher sensitivity with higher mortality to pesticides was observed in the larvae interfered with dsRNA. The above genes are related to the detoxification and metabolism of resistance of E. oblique, which lays a foundation for further study on the mechanism of insecticide resistance in E. oblique.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071141
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1142: Ginsenoside Rg5 Sensitizes
           Paclitaxel—Resistant Human Cervical-Adeno-Carcinoma Cells to
           Paclitaxel—And Enhances the Anticancer Effect of Paclitaxel

    • Authors: Janani Ramesh, Rejani Chalikkaran Thilakan, Raja Mohan Gopalakrishnan, Singaravel Vijayapoopathi, Arianna Dorschel, Bhuvarahamurthy Venugopal
      First page: 1142
      Abstract: In cervical cancer chemotherapy, paclitaxel (PTX) chemoresistance has become a major difficulty, and it also affects the survival rate of numerous tumor patients. Thus, for the reversal of chemoresistance, it is imperative to develop combinatory drugs with petite or almost no side effects to sensitize cells to paclitaxel. Ginsenoside Rg5 (GRg5) may act as a chemosensitizer by reversing multidrug resistance. The present study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). MTT assay was carried out to assess whether GRg5 can potentiate the cytotoxic effect of PTX in PTX- resistant HeLa cells; using flow cytometry-based annexin V-FITC assay, cellular apoptosis was analyzed; the rate of expression of the cell cycle, apoptosis and major cell-survival-signaling-related genes and its proteins were examined using RT-PCR and Western blotting technique. We found increased mRNA expression of Bak, Bax, Bid, and PUMA genes, whereas the mRNA expression of Bcl2, Bcl-XL, c-IAP-1, and MCL-1 were low; GRg5 combination triggered the efficacy of paclitaxel, which led to increased expression of Bax with an enhanced caspase-9/-3 activation, and apoptosis. Moreover, the study supports GRg5 as an inhibitor of two key signaling proteins, Akt and NF-κB, by which GRg5 augments the susceptibility of cervical cancer cells to PTX chemotherapy. GRg5 drastically potentiated the antiproliferative and pro-apoptotic activity of paclitaxel in PTX-resistant human cervical cancer cells in a synergistic mode. Moreover, in the clinical context, combining paclitaxel with GRg5 may prove to be a new approach for enhancing the efficacy of the paclitaxel.
      Citation: Genes
      PubDate: 2022-06-24
      DOI: 10.3390/genes13071142
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1143: Involvement of MicroRNA-27a-3p in the
           Licorice-Induced Alteration of Cd28 Expression in Mice

    • Authors: Gang Feng, Guozheng Liang, Yaqian Zhang, Jicong Hu, Chuandong Zhou, Jiawen Li, Wenfeng Zhang, Han Shen, Fenglin Wu, Changli Tao, Yan Liu, Hongwei Shao
      First page: 1143
      Abstract: Licorice has previously been shown to affect gene expression in cells; however, the underlying mechanisms remain to be clarified. We analyzed the microRNA expression profile of serum from mice treated by gavage with licorice decoction, and obtained 11 differentially expressed microRNAs (DEmiRNAs). We also screened differentially expressed genes (DEgenes) based on RNA-Seq data, and 271 common genes were identified by intersection analysis of the predicted target genes of 11 DEmiRNAs and the DEgenes. The miRNA–gene network showed that most of the hub genes were immune-related. KEGG enrichment analysis of the 271 genes identified three significant pathways, and the 21 genes involved in these three pathways, and the 11 DEmiRNAs, were constructed into a miRNA pathway–target gene network, in which mmu-miR-27a-3p stood out. Compared to ImmPort, there were 13 immune genes within the above group of 21 genes, and three intersected with the mmu-miR-27a-3p predicted target genes, Cd28, Grap2 and Cxcl12, of which the expression of Cd28 changed most significantly. We confirmed the regulation of Cd28 by mmu-miR-27a-3p using a dual-luciferase assay, and further confirmed that overexpression of mmu-miR-27a-3p could significantly downregulate the expression of Cd28 in lymphocytes. These results indicate that mmu-miR-27a-3p could be involved in the licorice-mediated regulation of the expression of Cd28 in mice.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071143
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1144: Targeting a Novel G-Quadruplex in the CARD11
           Oncogene Promoter with Naptho(2,1-b)furan-1-ethanol,2-nitro- Requires the
           Nitro Group

    • Authors: Kennith Swafford, Baku Acharya, Ying-Zhi Xu, Thomas Raney, Mason McCrury, Debasmita Saha, Brendan Frett, Samantha Kendrick
      First page: 1144
      Abstract: The aggressive nature of the activated B cell such as (ABC) subtype of diffuse large B cell (DLBCL) is frequently associated with altered B cell Receptor (BCR) signaling through the activation of key components including the scaffolding protein, CARD11. Most inhibitors, such as ibrutinib, target downstream BCR kinases with often modest and temporary responses for DLBCL patients. Here, we pursue an alternative strategy to target the BCR pathway by leveraging a novel DNA secondary structure to repress transcription. We discovered that a highly guanine (G)-rich element within the CARD11 promoter forms a stable G-quadruplex (G4) using circular dichroism and polymerase stop biophysical techniques. We then identified a small molecule, naptho(2,1-b)furan-1-ethanol,2-nitro- (NSC373981), from a fluorescence-resonance energy transfer-based screen that stabilized CARD11 G4 and inhibited CARD11 transcription in DLBCL cells. In generating and testing analogs of NSC373981, we determined that the nitro group is likely essential for the downregulation of CARD11 and interaction with CARD11 G4, and the removal of the ethanol side chain enhanced this activity. Of note, the expression of BCL2 and MYC, two other key oncogenes in DLBCL pathology with known promoter G4 structures, were often concurrently repressed with NSC373981 and the highly potent R158 analog. Our findings highlight a novel approach to treat aggressive DLBCL by silencing CARD11 gene expression that warrants further investigation.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071144
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1145: Internal Introns Promote Backsplicing to
           Generate Circular RNAs from Spinal Muscular Atrophy Gene

    • Authors: Diou Luo, Natalia Nikolaevna Singh, Ravindra Narayan Singh
      First page: 1145
      Abstract: Human survival motor neuron 1 (SMN1) codes for SMN, an essential housekeeping protein involved in most aspects of RNA metabolism. Deletions or mutations of SMN1 lead to spinal muscular atrophy (SMA), a devastating neurodegenerative disease linked to a high rate of infant mortality. SMN2, a near identical copy of SMN1 present in humans, cannot compensate for the loss of SMN1 due to predominant skipping of SMN2 exon 7. Restoration of SMN by splicing modulation of SMN2 exon 7 or gene replacement are currently approved therapies of SMA. Human SMN genes produce a vast repertoire of circular RNAs (circRNAs). However, the mechanism of SMN circRNA generation has not yet been examined in detail. For example, it remains unknown if forward splicing impacts backsplicing that generates circRNAs containing multiple exons. Here, we employed SMN as a model system to examine the impact of intronic sequences on the generation of circRNAs. We performed our experiments in HeLa cells transiently transfected with minigenes expressing three abundantly represented circRNAs containing two or more SMN exons. We observed an enhanced rate of circRNA generation when introns joining exons to be incorporated into circRNAs were present as compared to the intronless context. These results underscore the stimulatory effect of forward splicing in the generation of circRNAs containing multiple exons. These findings are consistent with the reported low abundance of SMN circRNAs comprised of single exons. We confirmed our findings using inducible HEK 293 cells stably expressing the SMN circRNAs. Our results support the role of the exon junction complex in the generation of the exon-only-containing circRNAs. We showed that SMN circRNAs were preferentially localized in the cytoplasm. These findings provide new insights regarding our understanding of circRNA generation and open avenues to uncover novel functions of the SMN genes.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071145
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1146: The Effect of Host miRNAs on Prognosis in
           COVID-19: miRNA-155 May Promote Severity via Targeting Suppressor of
           Cytokine Signaling 1 (SOCS1) Gene

    • Authors: Asuman Gedikbasi, Gokhan Adas, Nilgun Isiksacan, Kadriye Kart Kart Yasar, Esra Canbolat Canbolat Unlu, Rabia Yilmaz, Gulsum Oya Hergunsel, Zafer Cukurova
      First page: 1146
      Abstract: The epigenetic features contribute to variations in host susceptibility to SARS-CoV-2 infection and severity of symptoms. This study aimed to evaluate the relationship between the relative expression of microRNAs (miRNAs) and the severity of the disease in COVID-19 patients. The miRNA profiles were monitored during the different stages of the disease course using reverse transcription–quantitative polymerase chain reaction (RT-qPCR). The expression levels of the selected 11 miRNAs were measured in the blood samples collected from 73 patients (moderate, n = 37; severe, n = 25; critically ill, n = 11, a total of 219 longitudinal samples) on hospitalization day and days 7 and 21. Expression changes were expressed as “fold change” compared to healthy controls (n = 10). Our study found that several miRNAs differed according to disease severity, with the miR-155-5p the most strongly upregulated (p = 0.0001). A statistically significant negative correlation was observed between the expression of miR-155-5p and its target gene, the suppressor of cytokine signaling 1 (SOCS1). The relative expression of miR-155-5p was significantly increased and SOCS1 was significantly decreased with the disease progression (r = −0.805 p = 0.0001, r = −0.940 p = 0.0001, r = −0.933 p = 0.0001 for admission, day 7, and day 21, respectively). The overexpression of miR-155-5p has significantly increased inflammatory cytokine production and promoted COVID-19 progression. We speculated that microRNA-155 facilitates immune inflammation via targeting SOCS1, thus establishing its association with disease prognosis.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071146
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1147: iPBS-Retrotransposon Markers in the Analysis
           of Genetic Diversity among Common Bean (Phaseolus vulgaris L.) Germplasm
           from Türkey

    • Authors: Kamil Haliloğlu, Aras Türkoğlu, Halil Ibrahim Öztürk, Güller Özkan, Erdal Elkoca, Peter Poczai
      First page: 1147
      Abstract: Beans are legumes that play extremely important roles in human nutrition, serving as good sources of protein, vitamins, minerals, and antioxidants. In this study, we tried to elucidate the genetic diversity and population structure of 40 Turkish bean (Phaseolus vulgaris L.) local varieties and 5 commercial cultivars collected from 8 different locations in Erzurum-Ispir by using inter-primary binding site (iPBS) retrotransposon markers. For molecular characterization, the 26 most polymorphic iPBS primers were used; 52 bands per primer and 1350 bands in total were recorded. The mean polymorphism information content was 0.331. Various diversity indices, such as the mean effective allele number (0.706), mean Shannon’s information index (0.546), and gene diversity (0.361) revealed the presence of sufficient genetic diversity in the germplasm examined. Molecular analysis of variance (AMOVA) revealed that 67% of variation in bean germplasm was due to differences within populations. In addition, population structure analysis exposed all local and commercial bean varieties from five sub-populations. Expected heterozygosity values ranged between 0.1567 (the fourth sub-population) and 0.3210 (first sub-population), with an average value of 0.2103. In contrary, population differentiation measurement (Fst) was identified as 0.0062 for the first sub-population, 0.6372 for the fourth subpopulations. This is the first study to investigate the genetic diversity and population structure of bean germplasm in Erzurum-Ispir region using the iPBS-retrotransposon marker system. Overall, the current results showed that iPBS markers could be used consistently to elucidate the genetic diversity of local and commercial bean varieties and potentially be included in future studies examining diversity in a larger collection of local and commercial bean varieties from different regions.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071147
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1148: Epidermal Patterning Factor 2-Like (McEPFL2):
           A Putative Candidate for the Continuous Ridge (cr) Fruit Skin Locus in
           Bitter Gourd (Momordica charantia L.)

    • Authors: Jing Yang, Yiqun Weng, Huihong Li, Qiusheng Kong, Weiluan Wang, Chenghuan Yan, Liping Wang
      First page: 1148
      Abstract: Bitter gourd (Momordica charantia L.) is an economically important vegetable and medicinal crop in many Asian countries. Limited work has been conducted in understanding the genetic basis of horticulturally important traits in bitter gourd. Bitter gourd is consumed primarily for its young, immature fruit, and fruit appearance plays an important role in market acceptability. One such trait is the ridges on the fruit skin. In the present study, molecular mapping of a locus underlying fruit ridge continuity was conducted. Genetic analysis in segregating populations, derived from the crosses between two inbred lines Y1 with continuous ridges (CR) and Z-1-4 with discontinuous ridges (DCR), suggested that CR was controlled by a single recessive gene (cr). High-throughput genome sequencing of CR and DCR bulks combined with high-resolution genetic mapping in an F2 population delimited cr into a 108 kb region with 16 predicted genes. Sequence variation analysis and expression profiling supported the epidermal patterning factor 2-like (McEPFL2) gene as the best candidate of the cr locus. A 1 bp deletion in the first exon of McEPFL2 in Y1 which would result in a truncated McEPFL2 protein may be the causal polymorphism for the phenotypic difference between Y1 and Z-1-4. The association of this 1 bp deletion with CR was further supported by gDNA sequencing of McEPFL2 among 31 bitter gourd accessions. This work provides a foundation for understanding the genetic and molecular control of fruit epidermal pattering and development, which also facilitates marker-assisted selection in bitter melon breeding.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071148
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1149: Genetic Diversity and Population Genetic
           Analysis of Plasmodium falciparum Thrombospondin Related Anonymous Protein
           (TRAP) in Clinical Samples from Saudi Arabia

    • Authors: Saad M. Bin Dajem, Md Atique Ahmed, Fatimah F. Alghnnam, Shouq F. Alghannam, Gauspasha Yusuf Deshmukh, Rehan Haider Zaidi, Marie Fe F. Bohol, Syeda Sabiha Salam, Syeda Wasfeea Wazid, Mohammed I. Shafeai, Fuad H. Rudiny, Ali M. Motaen, Kareem Morsy, Ahmed A. Al-Qahtani
      First page: 1149
      Abstract: The thrombospondin related anonymous protein (TRAP) is considered one of the most important pre-erythrocytic vaccine targets. Earlier population genetic studies revealed the TRAP gene to be under strong balancing natural selection. This study is the first attempt to analyze genetic diversity, natural selection, phylogeography and population structure in 199 clinical samples from Saudi Arabia using the full-length PfTRAP gene. We found the rate of nonsynonymous substitutions to be significantly higher than that of synonymous substitutions in the clinical samples, indicating a strong positive or diversifying selection for the full-length gene and the Von Willebrand factor (VWF). The nucleotide diversity was found to be π~0.00789 for the full-length gene; however, higher nucleotide diversity was observed for the VWF compared to the thrombospondin repeat region (TSP). Deduction of the amino acid sequence alignment of the PNP repeat region in the Saudi samples revealed six genotypes characterized by tripeptide repeat motifs (PNP, ANP, ENP and SNP). Haplotype network, population structure and population differentiation analyses indicated four distinct sub-populations in spite of the low geographical distance between the sampling sites. Our results suggest the likeliness of independent parasite evolution, creating opportunities for further adaptation, including host transition, and making malaria control even more challenging.
      Citation: Genes
      PubDate: 2022-06-25
      DOI: 10.3390/genes13071149
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1150: Prevention of Blindness in Stickler Syndrome

    • Authors: Philip Alexander, Martin P. Snead
      First page: 1150
      Abstract: Stickler syndromes are inherited conditions caused by abnormalities of structural proteins in the eye, inner ear and cartilage. The risk of retinal detachment, particularly due to the development of giant retinal tears, is high. Stickler syndrome is the most common cause of childhood retinal detachment. Although retinal detachment surgery in the general population has a high success rate, outcomes from surgical repair in Stickler syndrome patients are notoriously poor, providing a strong argument for prophylactic intervention. Variable case selection, absence of molecular genetic sub-typing and inconsistent treatment strategies have all contributed to the historic uncertainty regarding the safety and efficacy of prophylactic treatment. This paper reviews the major published clinical studies that have evaluated different methods and strategies for prophylaxis. Based on the current body of literature, there is extremely strong evidence from cohort comparison studies demonstrating the efficacy and safety of prophylactic retinopexy to reduce, but not eliminate, the risk of retinal detachment in Stickler syndrome patients. It is vital that this body of evidence is provided to Stickler syndrome patients, to enable them to make their own fully informed choice about whether to receive prophylaxis for themselves and particularly on behalf of their affected children, to reduce the risk of retinal detachment.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071150
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1151: Integrated Analyses of DNA Methylation and
           Gene Expression of Rainbow Trout Muscle under Variable Ploidy and Muscle
           Atrophy Conditions

    • Authors: Mohamed Salem, Rafet Al-Tobasei, Ali Ali, Brett Kenney
      First page: 1151
      Abstract: Rainbow trout, Oncorhynchus mykiss, is an important cool, freshwater aquaculture species used as a model for biological research. However, its genome reference has not been annotated for epigenetic markers affecting various biological processes, including muscle growth/atrophy. Increased energetic demands during gonadogenesis/reproduction provoke muscle atrophy in rainbow trout. We described DNA methylation and its associated gene expression in atrophying muscle by comparing gravid, diploid females to sterile, triploid females. Methyl Mini-seq and RNA-Seq were simultaneously used to characterize genome-wide DNA methylation and its association with gene expression in rainbow trout muscle. Genome-wide enrichment in the number of CpGs, accompanied by depleted methylation levels, was noticed around the gene transcription start site (TSS). Hypermethylation of CpG sites within ±1 kb on both sides of TSS (promoter and gene body) was weakly/moderately associated with reduced gene expression. Conversely, hypermethylation of the CpG sites in downstream regions of the gene body +2 to +10 kb was weakly associated with increased gene expression. Unlike mammalian genomes, rainbow trout gene promotors are poor in CpG islands, at <1% compared to 60%. No signs of genome-wide, differentially methylated (DM) CpGs were observed due to the polyploidy effect; only 1206 CpGs (0.03%) were differentially methylated, and these were primarily associated with muscle atrophy. Twenty-eight genes exhibited differential gene expression consistent with methylation levels of 31 DM CpGs. These 31 DM CpGs represent potential epigenetic markers of muscle atrophy in rainbow trout. The DM CpG-harboring genes are involved in apoptosis, epigenetic regulation, autophagy, collagen metabolism, cell membrane functions, and Homeobox proteins. Our study also identified genes explaining higher water content and modulated glycolysis previously shown as characteristic biochemical signs of rainbow trout muscle atrophy associated with sexual maturation. This study characterized DNA methylation in the rainbow trout genome and its correlation with gene expression. This work also identified novel epigenetic markers associated with muscle atrophy in fish/lower vertebrates.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071151
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1152: Structural Analysis of microRNAs in Myeloid
           Cancer Reveals Consensus Motifs

    • Authors: Senol Dogan, Emrulla Spahiu, Anis Cilic
      First page: 1152
      Abstract: MicroRNAs (miRNAs) are short non-coding RNAs that function in post-transcriptional gene silencing and mRNA regulation. Although the number of nucleotides of miRNAs ranges from 17 to 27, they are mostly made up of 22 nucleotides. The expression of miRNAs changes significantly in cancer, causing protein alterations in cancer cells by preventing some genes from being translated into proteins. In this research, a structural analysis of 587 miRNAs that are differentially expressed in myeloid cancer was carried out. Length distribution studies revealed a mean and median of 22 nucleotides, with an average of 21.69 and a variance of 1.65. We performed nucleotide analysis for each position where Uracil was the most observed nucleotide and Adenine the least observed one with 27.8% and 22.6%, respectively. There was a higher frequency of Adenine at the beginning of the sequences when compared to Uracil, which was more frequent at the end of miRNA sequences. The purine content of each implicated miRNA was also assessed. A novel motif analysis script was written to detect the most frequent 3–7 nucleotide (3–7n) long motifs in the miRNA dataset. We detected CUG (42%) as the most frequent 3n motif, CUGC (15%) as a 4n motif, AGUGC (6%) as a 5n motif, AAGUGC (4%) as a 6n motif, and UUUAGAG (4%) as a 7n motif. Thus, in the second part of our study, we further characterized the motifs by analyzing whether these motifs align at certain consensus sequences in our miRNA dataset, whether certain motifs target the same genes, and whether these motifs are conserved within other species. This thorough structural study of miRNA sequences provides a novel strategy to study the implications of miRNAs in health and disease. A better understanding of miRNA structure is crucial to developing therapeutic settings.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071152
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1153: Primitive Cutaneous (P)erivascular
           (E)pithelioid (C)ell Tumour (PEComa): A New Case Report of a Rare
           Cutaneous Tumor

    • Authors: Gerardo Cazzato, Anna Colagrande, Lucia Lospalluti, Lucia Pacello, Teresa Lettini, Francesca Arezzo, Vera Loizzi, Carmelo Lupo, Nadia Casatta, Gennaro Cormio, Eugenio Maiorano, Giuseppe Ingravallo, Leonardo Resta
      First page: 1153
      Abstract: Perivascular epithelioid cell tumours (PEComas) are a growing family of tumours composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. Cutaneous primitive PEComas (cPEComas) are very rare, with 65 cases described in the English literature, and occur as a painless lesion predominantly in female patients, with a wide age range. We present a new case of cPEComa found on the left thigh of a 53-year-old patient with histopathological, immunohistochemical, and molecular information. The lesion was positive for HMB-45 and focal for smooth muscle actin and desmin but negative for melan-A, S-100 protein, CD31, and CD34. Next generation sequencing (NGS) analysis demonstrated the presence of genomic aberration for baculoviral IAP repeats containing BIRC3 splice site 1622-27_1631del37. Although there are little molecular data regarding this entity, our case adds to this knowledge, considering the importance of detecting genomic aberrations in the context of specific therapies such as mTOR inhibitors.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071153
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1154: Satellite DNAs in Health and Disease

    • Authors: Đurđica Ugarković, Antonio Sermek, Sven Ljubić, Isidoro Feliciello
      First page: 1154
      Abstract: Tandemly repeated satellite DNAs are major components of centromeres and pericentromeric heterochromatin which are crucial chromosomal elements responsible for accurate chromosome segregation. Satellite DNAs also contribute to genome evolution and the speciation process and are important for the maintenance of the entire genome inside the nucleus. In addition, there is increasing evidence for active and tightly regulated transcription of satellite DNAs and for the role of their transcripts in diverse processes. In this review, we focus on recent discoveries related to the regulation of satellite DNA expression and the role of their transcripts, either in heterochromatin establishment and centromere function or in gene expression regulation under various biological contexts. We discuss the role of satellite transcripts in the stress response and environmental adaptation as well as consequences of the dysregulation of satellite DNA expression in cancer and their potential use as cancer biomarkers.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071154
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1155: Research on Potential Network Markers and
           Signaling Pathways in Type 2 Diabetes Based on Conditional Cell-Specific

    • Authors: Yuke Xie, Zhizhong Cui, Nan Wang, Peiluan Li
      First page: 1155
      Abstract: Traditional methods concerning type 2 diabetes (T2D) are limited to grouped cells instead of each single cell, and thus the heterogeneity of single cells is erased. Therefore, it is still challenging to study T2D based on a single-cell and network perspective. In this study, we construct a conditional cell-specific network (CCSN) for each single cell for the GSE86469 dataset which is a single-cell transcriptional set from nondiabetic (ND) and T2D human islet samples, and obtain a conditional network degree matrix (CNDM). Since beta cells are the key cells leading to T2D, we search for hub genes in CCSN of beta cells and find that ATP6AP2 is essential for regulation and storage of insulin, and the renin-angiotensin system involving ATP6AP2 is related to most pathological processes leading to diabetic nephropathy. The communication between beta cells and other endocrine cells is performed and three gene pairs with obvious interaction are found. In addition, different expression genes (DEGs) are found based on CNDM and the gene expression matrix (GEM), respectively. Finally, ‘dark’ genes are identified, and enrichment analysis shows that NFATC2 is involved in the VEGF signaling pathway and indirectly affects the production of Prostacyclin (PGI2), which may be a potential biomarker for diabetic nephropathy.
      Citation: Genes
      PubDate: 2022-06-26
      DOI: 10.3390/genes13071155
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1156: Comparative Transcriptome Profiling Reveals
           the Genes Involved in Storage Root Expansion in Sweetpotato (Ipomoea
           batatas (L.) Lam.)

    • Authors: Weihan Song, Hui Yan, Meng Ma, Meng Kou, Chen Li, Wei Tang, Yicheng Yu, Qixian Hao, Thanhliem Nguyen, Xin Wang, Zhenyi Zhang, Chang You, Runfei Gao, Yungang Zhang, Qiang Li
      First page: 1156
      Abstract: Sweetpotato (Ipomoea batatas [L.] Lam.) is recognized as one of the most important root crops in the world by the Food and Agriculture Organization of the United Nations. The yield of sweetpotato is closely correlated with the rate of storage root (SR) formation and expansion. At present, most of the studies on sweetpotato SR expansion are focused on the physiological mechanism. To explore the SR expansion mechanism of sweetpotato, we performed transcriptome sequencing of SR harvested at 60, 90, 120, and 150 days after planting (DAP) to analyze two sweetpotato lines, Xuzishu 8 and its crossing progenies named Xu 18-192, which were selected from an F1 segregation population of Xuzishu 8 and Meiguohong, in which SR expansion was delayed significantly. A total of 57,043 genes were produced using transcriptome sequencing, of which 1312 were differentially expressed genes (DEGs) in four SR growth periods of the sweetpotato lines. The combination of the KEGG and trend analysis revealed several key candidate genes involved in SR expansion. The SBEI gene involved in starch metabolism, and transcription factors ARF6, NF-YB3 and NF-YB10 were all significantly up-regulated during SR expansion. The data from this study provide insights into the complex mechanisms of SR formation and expansion in sweetpotato and identify new candidate genes for increasing the yield of sweetpotato.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071156
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1157: Dynamic Features of Chromosomal Instability
           during Culture of Induced Pluripotent Stem Cells

    • Authors: Casey O. DuBose, John R. Daum, Christopher L. Sansam, Gary J. Gorbsky
      First page: 1157
      Abstract: Induced pluripotent stem cells (iPSCs) hold great potential for regenerative medicine. By reprogramming a patient′s own cells, immunological rejection can be avoided during transplantation. For expansion and gene editing, iPSCs are grown in artificial culture for extended times. Culture affords potential danger for the accumulation of genetic aberrations. To study these, two induced pluripotent stem (iPS) cell lines were cultured and periodically analyzed using advanced optical mapping to detect and classify chromosome numerical and segmental changes that included deletions, insertions, balanced translocations and inversions. In one of the lines, a population trisomic for chromosome 12 gained dominance over a small number of passages. This appearance and dominance of the culture by chromosome 12 trisomic cells was tracked through intermediate passages by the analysis of chromosome spreads. Mathematical modeling suggested that the proliferation rates of diploid versus trisomic cells could not account for the rapid dominance of the trisomic population. In addition, optical mapping revealed hundreds of structural variations distinct from those generally found within the human population. Many of these structural variants were detected in samples obtained early in the culturing process and were maintained in late passage samples, while others were acquired over the course of culturing.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071157
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1158: Clinical Aspects of Genetic and Non-Genetic
           Cardiovascular Risk Factors in Familial Hypercholesterolemia

    • Authors: Eszter Berta, Noémi Zsíros, Miklós Bodor, István Balogh, Hajnalka Lőrincz, György Paragh, Mariann Harangi
      First page: 1158
      Abstract: Familial hypercholesterolemia (FH) is the most common monogenic metabolic disorder characterized by considerably elevated low-density lipoprotein cholesterol (LDL-C) levels leading to enhanced atherogenesis, early cardiovascular disease (CVD), and premature death. However, the wide phenotypic heterogeneity in FH makes the cardiovascular risk prediction challenging in clinical practice to determine optimal therapeutic strategy. Beyond the lifetime LDL-C vascular accumulation, other genetic and non-genetic risk factors might exacerbate CVD development. Besides the most frequent variants of three genes (LDL-R, APOB, and PCSK9) in some proband variants of other genes implicated in lipid metabolism and atherogenesis are responsible for FH phenotype. Furthermore, non-genetic factors, including traditional cardiovascular risk factors, metabolic and endocrine disorders might also worsen risk profile. Although some were extensively studied previously, others, such as common endocrine disorders including thyroid disorders or polycystic ovary syndrome are not widely evaluated in FH. In this review, we summarize the most important genetic and non-genetic factors that might affect the risk prediction and therapeutic strategy in FH through the eyes of clinicians focusing on disorders that might not be in the center of FH research. The review highlights the complexity of FH care and the need of an interdisciplinary attitude to find the best therapeutic approach in FH patients.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071158
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1159: Whole Transcriptome Sequencing Reveals Drought
           Resistance-Related Genes in Upland Cotton

    • Authors: Juyun Zheng, Zeliang Zhang, Yajun Liang, Zhaolong Gong, Nala Zhang, Allah Ditta, Zhiwei Sang, Junduo Wang, Xueyuan Li
      First page: 1159
      Abstract: China, particularly the cotton-growing province of Xinjiang, is experiencing acute agricultural water shortages, stifling the expansion of the cotton sector. Discovering drought resistance genes in cotton and generating high-quality, drought-resistant cotton varieties through molecular breeding procedures are therefore critical to the cotton industry’s success. The drought-resistant cotton variety Xinluzhong No. 82 and the drought-sensitive cotton variety Kexin No. 1 were utilised in this study to uncover a batch of drought-resistant candidate genes using whole transcriptome sequencing. The following are the key research findings: A competing endogenous RNA network (ceRNA) was built using complete transcriptional sequencing to screen the core genes in the core pathway, and two drought-related candidate genes were discovered. It was found that γ-aminobutyric acid aminotransferase (GhGABA-T, Gohir.A11G156000) was upregulated at 0 h vs. 12 h and downregulated at 12 h vs. 24 h. L-Aspartate oxidase (GhAO, Gohir.A07G220600) was downregulated at 0 h vs. 12 h and upregulated at 12 h vs. 24 h. GABA-T is analogous to a pyridoxal phosphate-dependent transferase superfamily protein (POP2) in Arabidopsis thaliana and influences plant drought resistance by controlling γ-aminobutyric acid (GABA) concentration. The analogue of GhAO in A. thaliana is involved in the early steps of nicotinamide adenine dinucleotide (NAD) production as well as in plant antioxidant responses. This study revealed that gene expression regulatory networks can be used for rapid screening of reliable drought resistance genes and then utilised to validate gene function.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071159
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1160: Circulating microRNAs as the Potential
           Diagnostic and Prognostic Biomarkers for Nasopharyngeal Carcinoma

    • Authors: Thuy Ai Huyen Le, Thuan Duc Lao
      First page: 1160
      Abstract: microRNAs are endogenous non-coding miRNAs, 19–25 nucleotides in length, that can be detected in the extracellular environment in stable forms, named circulating miRNAs (CIR-miRNAs). Since the first discovery of CIR-miRNAs, a large number of studies have demonstrated that the abnormal changes in its expression could be used to significantly distinguish nasopharyngeal carcinoma (NPC) from healthy cells. We herein reviewed and highlighted recent advances in the study of CIR-miRNAs in NPC, which pointed out the main components serving as promising and effective biomarkers for NPC diagnosis and prognosis. Furthermore, brief descriptions of its origin and unique characteristics are provided.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071160
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1161: Mother and Daughter Carrying of the Same
           Pathogenic Variant in FGFR2 with Discordant Phenotype

    • Authors: Filomena Lo Vecchio, Elisabetta Tabolacci, Veronica Nobile, Maria Grazia Pomponi, Roberta Pietrobono, Giovanni Neri, Simona Amenta, Ettore Candida, Cristina Grippaudo, Ettore Lo Cascio, Alessia Vita, Federica Tiberio, Alessandro Arcovito, Wanda Lattanzi, Maurizio Genuardi, Pietro Chiurazzi
      First page: 1161
      Abstract: Craniosynostosis are a heterogeneous group of genetic conditions characterized by the premature fusion of the skull bones. The most common forms of craniosynostosis are Crouzon, Apert and Pfeiffer syndromes. They differ from each other in various additional clinical manifestations, e.g., syndactyly is typical of Apert and rare in Pfeiffer syndrome. Their inheritance is autosomal dominant with incomplete penetrance and one of the main genes responsible for these syndromes is FGFR2, mapped on chromosome 10, encoding fibroblast growth factor receptor 2. We report an FGFR2 gene variant in a mother and daughter who present with different clinical features of Crouzon syndrome. The daughter is more severely affected than her mother, as also verified by a careful study of the face and oral cavity. The c.1032G>A transition in exon 8, already reported as a synonymous p.Ala344 = variant in Crouzon patients, also activates a new donor splice site leading to the loss of 51 nucleotides and the in-frame removal of 17 amino acids. We observed lower FGFR2 transcriptional and translational levels in the daughter compared to the mother and healthy controls. A preliminary functional assay and a molecular modeling added further details to explain the discordant phenotype of the two patients.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071161
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1162: The New Variation in the Promoter Region of
           FLOWERING LOCUS T Is Involved in Flowering in Brassica rapa

    • Authors: Qingzhen Wei, Tianhua Hu, Xinfeng Xu, Zhen Tian, Chonglai Bao, Jinglei Wang, Hongtao Pang, Haijiao Hu, Yaqin Yan, Tongkun Liu, Wuhong Wang
      First page: 1162
      Abstract: Flowering time is an important agronomic trait in Brassica rapa and has a wide range of variation. The change from vegetative to reproductive development is a major transition period, especially in flowering vegetable crops. In this study, two non-heading Chinese cabbage varieties with significantly different flowering times, Pak-choi (B. rapa var. communis Tesn et Lee) and Caitai (B. rapa var. tsaitai Hort.), were used to construct segregated F2 populations. The bulk-segregant approach coupled with whole genome re-sequencing was used for QTL sequencing (QTL-seq) analysis to map flowering time traits. The candidate genes controlling flowering time in B. rapa were predicted by homologous gene alignment and function annotation. The major-effect QTL ft7.1 was detected on chromosome A07 of B. rapa, and the FT family gene BrFT was predicted as the candidate gene. Moreover, a new promoter regional difference of 1577 bp was revealed by analyzing the sequence of the BrFT gene. The promoter region activity analysis and divergent gene expression levels indicated that the difference in the promoter region may contribute to different flowering times. These findings provide insights into the mechanisms underlying the flowering time in Brassica and the candidate genes regulating flowering in production.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071162
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1163: Methionine Adenosyltransferase I/III
           Deficiency Detected by Newborn Screening

    • Authors: Vanessa Hübner, Luciana Hannibal, Nils Janzen, Sarah Catharina Grünert, Peter Freisinger
      First page: 1163
      Abstract: Methionine adenosyltransferase I/III deficiency is an inborn error of metabolism due to mutations in the MAT1A gene. It is the most common cause of hypermethioninemia in newborn screening. Heterozygotes are often asymptomatic. In contrast, homozygous or compound heterozygous individuals can develop severe neurological symptoms. Less than 70 cases with biallelic variants have been reported worldwide. A methionine-restricted diet is recommended if methionine levels are above 500–600 µmol/L. In this study, we report on a female patient identified with elevated methionine concentrations in a pilot newborn screening program. The patient carries a previously described variant c.1132G>A (p.Gly378Ser) in homozygosity. It is located at the C-terminus of MAT1A. In silico analysis suggests impaired protein stability by β-turn disruption. On a methionine-restricted diet, her serum methionine concentration ranged between 49–605 µmol/L (median 358 µmol/L). Her clinical course was characterized by early-onset muscular hypotonia, mild developmental delay, delayed myelination and mild periventricular diffusion interference in MRI. At 21 months, the girl showed age-appropriate neurological development, but progressive diffusion disturbances in MRI. Little is known about the long-term outcome of this disorder and the necessity of treatment. Our case demonstrates that neurological symptoms can be transient and even patients with initial neurologic manifestations can show normal development under dietary management.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071163
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1164: The Dct−/− Mouse Model to Unravel
           Retinogenesis Misregulation in Patients with Albinism

    • Authors: Angèle Tingaud-Sequeira, Elina Mercier, Vincent Michaud, Benoît Pinson, Ivet Gazova, Etienne Gontier, Fanny Decoeur, Lisa McKie, Ian J. Jackson, Benoît Arveiler, Sophie Javerzat
      First page: 1164
      Abstract: We have recently identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism (OCA). Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy. Here we investigate the eye phenotype in Dct−/− mice. We show that their retinal pigmented epithelium (RPE) is severely hypopigmented from early stages, contrasting with the darker melanocytic tissues. Multimodal imaging reveals specific RPE cellular defects. Melanosomes are fewer with correct subcellular localization but disrupted melanization. RPE cell size is globally increased and heterogeneous. P-cadherin labeling of Dct−/− newborn RPE reveals a defect in adherens junctions similar to what has been described in tyrosinase-deficient Tyrc/c embryos. The first intermediate of melanin biosynthesis, dihydroxyphenylalanine (L-Dopa), which is thought to control retinogenesis, is detected in substantial yet significantly reduced amounts in Dct−/− postnatal mouse eyecups. L-Dopa synthesis in the RPE alone remains to be evaluated during the critical period of retinogenesis. The Dct−/− mouse should prove useful in understanding the molecular regulation of retinal development and aging of the hypopigmented eye. This may guide therapeutic strategies to prevent vision deficits in patients with albinism.
      Citation: Genes
      PubDate: 2022-06-27
      DOI: 10.3390/genes13071164
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1165: Novel Genetic Diagnoses in Septo-Optic

    • Authors: Linda M. Reis, Sarah Seese, Mohit Maheshwari, Donald Basel, LuAnn Weik, Julie McCarrier, University of Washington Center for Mendelian Genomics University of Washington Center for Mendelian Genomics, Elena V. Semina
      First page: 1165
      Abstract: Septo-optic dysplasia (SOD) is a developmental phenotype characterized by midline neuroradiological anomalies, optic nerve hypoplasia, and pituitary anomalies, with a high degree of variability and additional systemic anomalies present in some cases. While disruption of several transcription factors has been identified in SOD cohorts, most cases lack a genetic diagnosis, with multifactorial risk factors being thought to play a role. Exome sequencing in a cohort of families with a clinical diagnosis of SOD identified a genetic diagnosis in 3/6 families, de novo variants in SOX2, SHH, and ARID1A, and explored variants of uncertain significance in the remaining three. The outcome of this study suggests that investigation for a genetic etiology is warranted in individuals with SOD, particularly in the presence of additional syndromic anomalies and when born to older, multigravida mothers. The identification of causative variants in SHH and ARID1A further expands the phenotypic spectra associated with these genes and reveals novel pathways to explore in septo-optic dysplasia.
      Citation: Genes
      PubDate: 2022-06-28
      DOI: 10.3390/genes13071165
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1166: Association of CX36 Protein Encoding Gene GJD2
           with Refractive Errors

    • Authors: Edita Kunceviciene, Tomas Muskieta, Margarita Sriubiene, Rasa Liutkeviciene, Alina Smalinskiene, Ingrida Grabauskyte, Ruta Insodaite, Dovile Juoceviciute, Laimutis Kucinskas
      First page: 1166
      Abstract: Purpose: This study aimed to evaluate the associations of GJD2 (rs634990, rs524952) and RASGRF1 (rs8027411, rs4778879, rs28412916) gene polymorphisms with refractive errors. Methods: The study included 373 subjects with refractive errors (48 myopia, 239 myopia with astigmatism, 14 hyperopia, and 72 hyperopia with astigmatism patients) and 104 ophthalmologically healthy subjects in the control group. A quantitative real-time polymerase chain reaction (qPCR) method was chosen for genotyping. Statistical calculations and analysis of results were performed with IBM SPSS Statistics 27 software. Results: The correlations in monozygotic (MZ) twin pairs were higher compared to DZ pairs, indicating genetic effects on hyperopia and astigmatism. The heritability (h2) of hyperopia and astigmatism was 0.654 for the right eye and 0.492 for the left eye. The GJD2 rs634990 TT genotype increased the incidence of hyperopia with astigmatism by 2.4-fold and the CT genotype decreased the incidence of hyperopia with astigmatism by 0.51-fold (p < 0.05). The GJD2 rs524952 AT genotype reduced the incidence of hyperopia with astigmatism by 0.53-fold (p < 0.05). Haplotype analysis of SNPs in the GJD2 gene revealed two statistically significant haplotypes: ACTAGG for rs634990 and TTTAGA for rs524952, which statistically significantly reduced the incidence of hyperopia and hyperopia with astigmatism by 0.41-fold (95% CI: 0.220–0.765) and 0.383-fold (95% CI: 0.199–0.737), respectively (p < 0.05). It was also found that, in the presence of haplotypes ACTAGG for rs634990 and TATAGA for rs524952, the possibility of hyperopia was reduced by 0.4-fold (p < 0.05). Conclusions: the heritability of hyperopia and hyperopia with astigmatism was 0.654–0.492, according to different eyes in patients between 20 and 40 years. The GJD2 rs634990 was identified as an SNP, which has significant associations with the co-occurrence of hyperopia and astigmatism. Patients with the GJD2 gene rs634990 TT genotype were found to have a 2.4-fold higher risk of develop hyperopia with astigmatism.
      Citation: Genes
      PubDate: 2022-06-28
      DOI: 10.3390/genes13071166
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1167: Phylogenomic Coalescent Analyses of Avian
           Retroelements Infer Zero-Length Branches at the Base of Neoaves, Emergent
           Support for Controversial Clades, and Ancient Introgressive Hybridization
           in Afroaves

    • Authors: John Gatesy, Mark S. Springer
      First page: 1167
      Abstract: Retroelement insertions (RIs) are low-homoplasy characters that are ideal data for addressing deep evolutionary radiations, where gene tree reconstruction errors can severely hinder phylogenetic inference with DNA and protein sequence data. Phylogenomic studies of Neoaves, a large clade of birds (>9000 species) that first diversified near the Cretaceous–Paleogene boundary, have yielded an array of robustly supported, contradictory relationships among deep lineages. Here, we reanalyzed a large RI matrix for birds using recently proposed quartet-based coalescent methods that enable inference of large species trees including branch lengths in coalescent units, clade-support, statistical tests for gene flow, and combined analysis with DNA-sequence-based gene trees. Genome-scale coalescent analyses revealed extremely short branches at the base of Neoaves, meager branch support, and limited congruence with previous work at the most challenging nodes. Despite widespread topological conflicts with DNA-sequence-based trees, combined analyses of RIs with thousands of gene trees show emergent support for multiple higher-level clades (Columbea, Passerea, Columbimorphae, Otidimorphae, Phaethoquornithes). RIs express asymmetrical support for deep relationships within the subclade Afroaves that hints at ancient gene flow involving the owl lineage (Strigiformes). Because DNA-sequence data are challenged by gene tree-reconstruction error, analysis of RIs represents one approach for improving gene tree-based methods when divergences are deep, internodes are short, terminal branches are long, and introgressive hybridization further confounds species–tree inference.
      Citation: Genes
      PubDate: 2022-06-28
      DOI: 10.3390/genes13071167
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1168: Genes and Diseases: Insights from
           Transcriptomics Studies

    • Authors: Dmitry S. Kolobkov, Darya A. Sviridova, Serikbai K. Abilev, Artem N. Kuzovlev, Lyubov E. Salnikova
      First page: 1168
      Abstract: Results of expression studies can be useful to clarify the genotype-phenotype relationship. However, according to data from recent literature, there is a large group of genes that are revealed as differentially expressed (DE) in many studies, regardless of the biological context. Additional analyses could shed more light on the relationships between genes, their differential expression, and diseases. We generated a set of 9972 disease genes from five gene-phenotype databases (OMIM, ORPHANET, DDG2P, DisGeNet and MalaCards) and a report of the International Union of Immunological Societies. To study transcriptomics of disease and non-disease genes in healthy tissues, we obtained data from the Human Protein Atlas (HPA) website. We analyzed the dependency between expression in healthy tissues and gene occurrence in Gene Expression Omnibus series using tools within the Enrichr libraries. The results of expression studies were annotated with Gene Ontology (GO) and Human Phenotype Ontology (HPO) terms. Using transcriptomics analysis of healthy tissues, we validated the previous findings of higher expression levels of disease genes in pathologically linked tissues compared to other tissues. Preferentially DE genes were generally highly expressed in one or multiple tissues and were enriched for disease genes. According to the results of GO enrichment analyses, both down- and up-regulated DE genes most often took part in immune response, translation and tissue-specific processes. A connection between DE-related pathology and the diversity of HPO terms was found. Investigating a link between expression and phenotype contributes to understanding the mode of development and progression of human diseases.
      Citation: Genes
      PubDate: 2022-06-28
      DOI: 10.3390/genes13071168
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1169: Expression of Modified Snowdrop Lectin
           (Galanthus nivalis Agglutinin) Protein Confers Aphids and Plutella
           xylostella Resistance in Arabidopsis and Cotton

    • Authors: Peng He, Huanhuan Jia, Hui Xue, Yuechen Zeng, Lili Tian, Xiaoli Hu, Shufen Chang, Yanli Jiang, Jianing Yu
      First page: 1169
      Abstract: Cotton is a major fiber crop in the world that can be severely infested by pests in agricultural fields. Identifying new insect-resistance genes and increasing the expression of known insect-resistance genes are imperative in cultivated cotton. Galanthus nivalis agglutinin (GNA), a lectin that is toxic to both chewing and sucking pests, is mainly expressed in monocotyledons. It is necessary to improve the expression of the GNA protein and to test whether the lectin confers insect resistance to dicotyledons plants. We report a modified GNA gene (ASGNA) via codon optimization, its insertion into Arabidopsis thaliana, and transient expression in cotton to test its efficacy as an insect-resistance gene against cotton aphids and Plutella xylostella. The amount of ASGNA in transgenic plants reached approximately 6.5 μg/g of fresh weight. A feeding bioassay showed that the survival rate of aphids feeding on the leaves of ASGNA transgenic plants was lower than those of aphids feeding on the leaves of non-optimized GNA (NOGNA) transgenic plants and wild-type plants. Meanwhile, the fertility rate was 36% when fed on the ASGNA transgenic plants, while the fertility was 70% and 95% in NOGNA transgenic plants and wild-type plants. Correspondingly, the highest mortality of 55% was found in ASGNA transgenic lines, while only 35% and 20% mortality was observed in NOGNA transgenic plants and wild-type plants, respectively. Similar results were recorded for aphids feeding on cotton cotyledons with transient expression of ASGNA. Taken together, the results show that ASGNA exhibited high insecticidal activity towards sap-sucking insects and thus is a promising candidate gene for improving insect resistance in cotton and other dicotyledonous plants.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071169
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1170: Chromosomal Translocations Detection in Cancer
           Cells Using Chromosomal Conformation Capture Data

    • Authors: Muhammad Muzammal Adeel, Khaista Rehman, Yan Zhang, Yibeltal Arega, Guoliang Li
      First page: 1170
      Abstract: Complex chromosomal rearrangements such as translocations play a critical role in oncogenesis. Translocation detection is vital to decipher their biological role in activating cancer-associated mechanisms. High-throughput chromosomal conformations capture (Hi-C) data have shown promising progress in unveiling the genome variations in a disease condition. Until now, multiple structural data (Hi-C)-based methods are available that can detect translocations in cancer genomes. However, the consistency and specificity of Hi-C-based translocation results still need to be validated with conventional methods. This study used Hi-C data of cancerous cell lines, namely lung cancer (A549), Chronic Myelogenous Leukemia (K562), and Acute Monocytic Leukemia (THP-1), to detect the translocations. The results were cross-validated through whole-genome sequencing (WGS) and paired-read analysis. Moreover, PCR amplification validated the presence of translocated reads in different chromosomes. By integrating different data types, we showed that the results of Hi-C data are as reliable as WGS and can be utilized as an assistive method for detecting translocations in the diseased genome. Our findings support the utility of Hi-C technology to detect the translocations and study their effects on the three-dimensional architecture of the genome in cancer condition.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071170
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1171: Genome-Wide Evolutionary Analysis of Putative
           Non-Specific Herbicide Resistance Genes and Compilation of Core Promoters
           between Monocots and Dicots

    • Authors: Saket Chandra, Ramon G. Leon
      First page: 1171
      Abstract: Herbicides are key weed-control tools, but their repeated use across large areas has favored the evolution of herbicide resistance. Although target-site has been the most prevalent and studied type of resistance, non-target-site resistance (NTSR) is increasing. However, the genetic factors involved in NTSR are widely unknown. In this study, four gene groups encoding putative NTSR enzymes, namely, cytochrome-P450, glutathione-S-transferase (GST), uridine 5′-diphospho-glucuronosyltransferase (UDPGT), and nitronate monooxygenase (NMO) were analyzed. The monocot and dicot gene sequences were downloaded from publicly available databases. Phylogenetic trees revealed that most of the CYP450 resistance-related sequences belong to CYP81 (5), and in GST, most of the resistance sequences belonged to GSTU18 (9) and GSTF6 (8) groups. In addition, the study of upstream promoter sequences of these NTSR genes revealed stress-related cis-regulatory motifs, as well as eight transcription factor binding sites (TFBS) were identified. The discovered TFBS were commonly present in both monocots and dicots, and the identified motifs are known to play key roles in countering abiotic stress. Further, we predicted the 3D structure for the resistant CYP450 and GST protein and identified the substrate recognition site through the homology approach. Our description of putative NTSR enzymes may be used to develop innovative weed control techniques to delay the evolution of NTSR.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071171
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1172: Genetic Analysis Algorithm for the Study of
           Patients with Multiple Congenital Anomalies and Isolated Congenital Heart

    • Authors: Marisol Delea, Lucia S. Massara, Lucia D. Espeche, María Paz Bidondo, Pablo Barbero, Jaen Oliveri, Paloma Brun, Mónica Fabro, Micaela Galain, Cecilia S. Fernández, Melisa Taboas, Carlos D. Bruque, Jorge E. Kolomenski, Agustín Izquierdo, Ariel Berenstein, Viviana Cosentino, Celeste Martinoli, Mariana Vilas, Mónica Rittler, Rodrigo Mendez, Lilian Furforo, Rosa Liascovich, Boris Groisman, Sandra Rozental, Liliana Dain, on behalf of the PID ACM-CC Group on behalf of the PID ACM-CC Group
      First page: 1172
      Abstract: Congenital anomalies (CA) affect 3–5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian patients with MCA and isolated CHD. We recruited 366 patients (172 with MCA and 194 with isolated CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was obtained from all patients, while karyotyping was performed in patients with MCA. Samples from patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA. Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation sequencing (NGS). A total of 240 patients were successfully studied using at least one technique. Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one presented a TBX1 gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071172
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1173: Transcriptome Profiling of a Common Mistletoe
           Species Parasitizing Four Typical Host Species in Urban Southwest China

    • Authors: Jingge Kuang, Yufei Wang, Kangshan Mao, Richard Milne, Mingcheng Wang, Ning Miao
      First page: 1173
      Abstract: Comparing gene expression among parasitic plants infecting different host species can have significant implications for understanding host-parasite interactions. Taxillus nigrans is a common hemiparasitic species in Southwest China that parasitizes a variety of host species. However, a lack of nucleotide sequence data to date has hindered transcriptome-level research on T. nigrans. In this study, the transcriptomes of T. nigrans individuals parasitizing four typical host species (Broussonetia papyrifera [Bpap] a broad-leaved tree species; Cryptomeria fortunei [Cfor] a coniferous tree species; Cinnamomum septentrionale [Csep] an evergreen tree species; and Ginkgo biloba [Gbil] a deciduous-coniferous tree species) were sequenced, and the expression profiles and metabolic pathways compared among hosts. A total of 40.06 Gb of clean sequence data were generated in nine cDNA libraries. These were de novo assembled into 293,823 transcripts with an N50 value of 1790 bp. A large number of differentially expressed genes (DEGs) were identified when comparing T. nigrans individuals on different host species: Bpap vs. Cfor (713 DEGs), Bpap vs. Csep (1219), Bpap vs. Gbil (1514), Cfor vs. Csep (1639), Cfor vs. Gbil (1722), and Csep vs. Gbil (1723). Three hundred and eighty-one unigenes were common to all six pairwise comparisons; these were primarily associated with carbohydrate metabolism and energy metabolism, as determined in a KEGG enrichment analysis. Specific involvements included: the TCA cycle, biosynthesis of secondary metabolites, carbon metabolism, biosynthesis of amino acids and glyoxylate/dicarboxylate metabolism. A total of 251 unique unigenes were also identified, specific to either the Bpap vs. Cfor (249 unigenes) or Csep vs. Gbil (two unigenes) comparisons; partial unigenes were associated with the plasma membrane, response to endogenous stimuli, ion binding, and organic hydroxy compound metabolic processes. These results provide a foundation for further explorations of the detailed molecular mechanisms involved in plant parasitism.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071173
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1174: Identification of the Key miRNAs and Genes
           Associated with the Regulation of Non-Small Cell Lung Cancer: A
           Network-Based Approach

    • Authors: Zoya Shafat, Mohd Murshad Ahmed, Fahad N. Almajhdi, Tajamul Hussain, Shama Parveen; Anwar Ahmed
      First page: 1174
      Abstract: Lung cancer is the major cause of cancer-associated deaths across the world in both men and women. Lung cancer consists of two major clinicopathological categories, i.e., small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Lack of diagnosis of NSCLC at an early stage in addition to poor prognosis results in ineffective treatment, thus, biomarkers for appropriate diagnosis and exact prognosis of NSCLC need urgent attention. The proposed study aimed to reveal essential microRNAs (miRNAs) involved in the carcinogenesis of NSCLC that probably could act as potential biomarkers. The NSCLC-associated expression datasets revealed 12 differentially expressed miRNAs (DEMs). MiRNA-mRNA network identified key miRNAs and their associated genes, for which functional enrichment analysis was applied. Further, survival and validation analysis for key genes was performed and consequently transcription factors (TFs) were predicted. We obtained twelve miRNAs as common DEMs after assessment of all datasets. Further, four key miRNAs and nine key genes were extracted from significant modules based on the centrality approach. The key genes and miRNAs reported in our study might provide some information for potential biomarkers profitable to increased prognosis and diagnosis of lung cancer.
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071174
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1175: Genetic Structure of Racing Pigeons (Columba
           livia) Kept in Poland Based on Microsatellite Markers

    • Authors: Angelika Podbielska, Anna Radko
      First page: 1175
      Abstract: Pigeons played a major role in communication before the invention of the telephone and the telegraph, as well as in wars, where they were used to carry information and orders over long distances. Currently, numerous sports competitions and races are held with their participation, and their breeding is demanding not only for breeders, but also for the birds themselves. Therefore, an analysis of the genetic structure of racing pigeons kept in Poland was undertaken on the basis of 16 microsatellite markers, as well as the evaluation of the microsatellite panel recommended by ISAG. For this purpose, Bayesian clustering, a dendrogram, and Principal Coordinate Analysis were conducted. In addition, statistical analysis was performed. Based on this research, it was observed that racing pigeons are genetically mixed, regardless of their place of origin. Moreover, genetic diversity was estimated at a relatively satisfactory level (Ho = 623, He = 0.684), and no alarmingly high inbreeding coefficient was observed (F = 0.088). Moreover, it was found that the panel recommended by ISAG can be successfully used in Poland for individual identification and parentage testing (PIC = 0.639, CE-1P = 0.9987233, CE-2P = 0.9999872, CE-PP = 0.99999999).
      Citation: Genes
      PubDate: 2022-06-29
      DOI: 10.3390/genes13071175
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1176: Overview of Transcriptomic Research on Type 2
           Diabetes: Challenges and Perspectives

    • Authors: Ziravard N. Tonyan, Yulia A. Nasykhova, Maria M. Danilova, Yury A. Barbitoff, Anton I. Changalidi, Anastasiia A. Mikhailova, Andrey S. Glotov
      First page: 1176
      Abstract: Type 2 diabetes (T2D) is a common chronic disease whose etiology is known to have a strong genetic component. Standard genetic approaches, although allowing for the detection of a number of gene variants associated with the disease as well as differentially expressed genes, cannot fully explain the hereditary factor in T2D. The explosive growth in the genomic sequencing technologies over the last decades provided an exceptional impetus for transcriptomic studies and new approaches to gene expression measurement, such as RNA-sequencing (RNA-seq) and single-cell technologies. The transcriptomic analysis has the potential to find new biomarkers to identify risk groups for developing T2D and its microvascular and macrovascular complications, which will significantly affect the strategies for early diagnosis, treatment, and preventing the development of complications. In this article, we focused on transcriptomic studies conducted using expression arrays, RNA-seq, and single-cell sequencing to highlight recent findings related to T2D and challenges associated with transcriptome experiments.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071176
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1177: Effect of Developmental Stages on Genes
           Involved in Middle and Downstream Pathway of Volatile Terpene Biosynthesis
           in Rose Petals

    • Authors: Ying Kong, Huan Wang, Lixin Lang, Xiaoying Dou, Jinrong Bai
      First page: 1177
      Abstract: Terpenoids are economically and ecologically important compounds, and they are vital constituents in rose flower fragrance and rose essential oil. The terpene synthase genes (TPSs), trans-prenyltransferases genes (TPTs), NUDX1 are involved in middle and downstream pathway of volatile terpene biosynthesis in rose flowers. We identified 7 complete RcTPTs, 49 complete RcTPSs, and 9 RcNUDX1 genes in the genome of Rosachinensis. During the flower opening process of butterfly rose (Rosachinensis ‘Mutabilis’, MU), nine RcTPSs expressed in the petals of opening MU flowers exhibited two main expression trends, namely high and low, in old and fresh petals. Five short-chain petal-expressed RcTPTs showed expression patterns corresponding to RcTPSs. Analysis of differential volatile terpenes and differential expressed genes indicated that higher emission of geraniol from old MU petals might be related to the RcGPPS expression. Comprehensive analysis of volatile emission, sequence structure, micro-synteny and gene expression suggested that RcTPS18 may encode (E,E)-α-farnesene synthase. These findings may be useful for elucidating the molecular mechanism of terpenoid metabolism in rose and are vital for future studies on terpene regulation.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071177
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1178: The Effects of Catabolism Relationships of
           Leucine and Isoleucine with BAT2 Gene of Saccharomyces cerevisiae on High
           Alcohols and Esters

    • Authors: Lin Zhang, Yiqian Zhang, Zhongqiu Hu
      First page: 1178
      Abstract: This study sought to provide a theoretical basis for effectively controlling the content of higher alcohols and esters in fermented foods. In this work, isoleucine (Ile) or leucine (Leu) at high levels was used as the sole nitrogen source for a BAT2 mutant and its parental Saccharomyces. cerevisiae 38 to investigate the effects of the addition of amounts of Ile or Leu and BAT2 on the aroma components in the flavor profile using gas chromatography mass spectrometer (GC-MS). The results showed that 2-methyl-butyraldehyde, 2-methyl-1-butanol, and 2-methylbutyl-acetate were the products positively correlated with the Ile addition amount. In addition, 3-methyl-butyraldehyde, 3-methyl-1-butanol, and 3-methylbutyl-acetate were the products positively correlated with Leu addition amount. BAT2 deletion resulted in a significant decline in the yields of 2-methyl-butyraldehyde, 3-methyl-butyraldehyde,2-methyl-1-butanol, and 3-methyl-1-butanol, but also an increase in the yields of 2-methylbutyl-acetate and 3-methylbutyl-acetate. We speculated that BAT2 regulated the front and end of this metabolite chain in a feedback manner. Improved metabolic chain analyses, including the simulated energy metabolism of Ile or Leu, indicated that reducing the added amount of branched-chain amino acids, BAT mutation, and eliminating the role of energy cofactors such as NADH/NAD+ were three important ways to control the content of high alcohols and esters in fermented foods.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071178
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1179: Genotype-Phenotype Correlation and Functional
           Insights for Two Monoallelic TREX1 Missense Variants Affecting the
           Catalytic Core

    • Authors: Giulia Amico, Wayne O. Hemphill, Mariasavina Severino, Claudio Moratti, Rosario Pascarella, Marta Bertamino, Flavia Napoli, Stefano Volpi, Francesca Rosamilia, Sara Signa, Fred Perrino, Marialuisa Zedde, Isabella Ceccherini, on behalf of the Gaslini Stroke Study Group on behalf of the Gaslini Stroke Study Group
      First page: 1179
      Abstract: The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi–Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.A136V and p.R174G TREX1 variants, respectively. Genetic findings, obtained by a customized panel including 183 genes associated with monogenic stroke, were combined with interferon signature testing and biochemical assays to determine the mutations’ effects in vitro. Our results for the p.A136V variant are inconsistent with prior biochemistry-pathology correlates for dominant AGS-causing TREX1 mutants. The p.R174G variant modestly altered exonuclease activity in a manner consistent with perturbation of substrate interaction rather than catalysis, which represents the first robust enzymological data for a TREX1 variant identified in a CADASIL-like patient. In conclusion, functional analysis allowed us to interpret the impact of TREX1 variants on patients’ phenotypes. While the p.A136V variant is unlikely to be causative for AGS in Patient A, Patient B’s phenotype is potentially related to the p.R174G variant. Therefore, further functional investigations of TREX1 variants found in CADASIL-like patients are warranted to determine any causal link and interrogate the molecular disease mechanism(s).
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071179
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1180: Improvement of Gene Delivery and Mutation
           Efficiency in the CRISPR-Cas9 Wheat (Triticum aestivum L.) Genomics System
           via Biolistics

    • Authors: Jaclyn Tanaka, Bastian Minkenberg, Snigdha Poddar, Brian Staskawicz, Myeong-Je Cho
      First page: 1180
      Abstract: Discovery of the CRISPR-Cas9 gene editing system revolutionized the field of plant genomics. Despite advantages in the ease of designing gRNA and the low cost of the CRISPR-Cas9 system, there are still hurdles to overcome in low mutation efficiencies, specifically in hexaploid wheat. In conjunction with gene delivery and transformation frequency, the mutation efficiency bottleneck has the potential to slow down advancements in genomic editing of wheat. In this study, nine bombardment parameter combinations using three gold particle sizes and three rupture disk pressures were tested to establish optimal stable transformation frequencies in wheat. Utilizing the best transformation protocol and a knockout cassette of the phytoene desaturase gene, we subjected transformed embryos to four temperature treatments and compared mutation efficiencies. The use of 0.6 μm gold particles for bombardment increased transformation frequencies across all delivery pressures. A heat treatment of 34 °C for 24 h resulted in the highest mutation efficiency with no or minimal reduction in transformation frequency. The 34 °C treatment produced two M0 mutant events with albino phenotypes, requiring biallelic mutations in all three genomes of hexaploid wheat. Utilizing optimal transformation and heat treatment parameters greatly increases mutation efficiency and can help advance research efforts in wheat genomics.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071180
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1181: Current Understanding of the Genetics and
           Molecular Mechanisms Regulating Wood Formation in Plants

    • Authors: Min-Ha Kim, Eun-Kyung Bae, Hyoshin Lee, Jae-Heung Ko
      First page: 1181
      Abstract: Unlike herbaceous plants, woody plants undergo volumetric growth (a.k.a. secondary growth) through wood formation, during which the secondary xylem (i.e., wood) differentiates from the vascular cambium. Wood is the most abundant biomass on Earth and, by absorbing atmospheric carbon dioxide, functions as one of the largest carbon sinks. As a sustainable and eco-friendly energy source, lignocellulosic biomass can help address environmental pollution and the global climate crisis. Studies of Arabidopsis and poplar as model plants using various emerging research tools show that the formation and proliferation of the vascular cambium and the differentiation of xylem cells require the modulation of multiple signals, including plant hormones, transcription factors, and signaling peptides. In this review, we summarize the latest knowledge on the molecular mechanism of wood formation, one of the most important biological processes on Earth.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071181
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1182: A Systematic Review of the Impact of
           Mitochondrial Variations on Male Infertility

    • Authors: Houda Amor, Mohamad Eid Hammadeh
      First page: 1182
      Abstract: According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only to the man or the woman. Up to 15% of infertility cases in men can be attributed to genetic factors that can lead to irreversible partial or complete spermatogenic arrest. The increased use of assisted reproductive technology (ART) has provided not only insights into the causes of male infertility but also afforded a diagnostic tool to detect and manage this condition among couples. Genes control a variety of physiological attributes, such as the hypothalamic–pituitary–gonadal axis, development, and germ cell differentiation. In the era of ART, it is important to understand the genetic basis of infertility so as to provide the most tailored therapy and counseling to couples. Genetic factors involved in male infertility can be chromosome abnormalities or single-gene disorders, mitochondrial DNA (mtDNA) mutations, Y-chromosome deletions, multifactorial disorders, imprinting disorders, or endocrine disorders of genetic origin. In this review, we discuss the role of mitochondria and the mitochondrial genome as an indicator of sperm quality and fertility.
      Citation: Genes
      PubDate: 2022-06-30
      DOI: 10.3390/genes13071182
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1183: A Distribution-Free Model for Longitudinal
           Metagenomic Count Data

    • Authors: Dan Luo, Wenwei Liu, Tian Chen, Lingling An
      First page: 1183
      Abstract: Longitudinal metagenomics has been widely studied in the recent decade to provide valuable insight for understanding microbial dynamics. The correlation within each subject can be observed across repeated measurements. However, previous methods that assume independent correlation may suffer from incorrect inferences. In addition, methods that do account for intra-sample correlation may not be applicable for count data. We proposed a distribution-free approach, namely CorrZIDF, which extends the current method to model correlated zero-inflated metagenomic count data, offering a powerful and accurate solution for detecting significance features. This method can handle different working correlation structures without specifying each margin distribution of the count data. Through simulation studies, we have shown the robustness of CorrZIDF when selecting a working correlation structure for repeated measures studies to enhance the efficiency of estimation. We also compared four methods using two real datasets, and the new proposed method identified more unique features that were reported previously on the relevant research.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071183
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1184: Complete Chloroplast Genome of an Endangered
           Species Quercus litseoides, and Its Comparative, Evolutionary, and
           Phylogenetic Study with Other Quercus Section Cyclobalanopsis Species

    • Authors: Yu Li, Tian-Rui Wang, Gregor Kozlowski, Mei-Hua Liu, Li-Ta Yi, Yi-Gang Song
      First page: 1184
      Abstract: Quercus litseoides, an endangered montane cloud forest species, is endemic to southern China. To understand the genomic features, phylogenetic relationships, and molecular evolution of Q. litseoides, the complete chloroplast (cp) genome was analyzed and compared in Quercus section Cyclobalanopsis. The cp genome of Q. litseoides was 160,782 bp in length, with an overall guanine and cytosine (GC) content of 36.9%. It contained 131 genes, including 86 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. A total of 165 simple sequence repeats (SSRs) and 48 long sequence repeats with A/T bias were identified in the Q. litseoides cp genome, which were mainly distributed in the large single copy region (LSC) and intergenic spacer regions. The Q. litseoides cp genome was similar in size, gene composition, and linearity of the structural region to those of Quercus species. The non-coding regions were more divergent than the coding regions, and the LSC region and small single copy region (SSC) were more divergent than the inverted repeat regions (IRs). Among the 13 divergent regions, 11 were in the LSC region, and only two were in the SSC region. Moreover, the coding sequence (CDS) of the six protein-coding genes (rps12, matK, atpF, rpoC2, rpoC1, and ndhK) were subjected to positive selection pressure when pairwise comparison of 16 species of Quercus section Cyclobalanopsis. A close relationship between Q. litseoides and Quercus edithiae was found in the phylogenetic analysis of cp genomes. Our study provided highly effective molecular markers for subsequent phylogenetic analysis, species identification, and biogeographic analysis of Quercus.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071184
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1185: Cytogenetic Analysis of the Members of the
           Snake Genera Cylindrophis, Eryx, Python, and Tropidophis

    • Authors: Tomáš Charvát, Barbora Augstenová, Daniel Frynta, Lukáš Kratochvíl, Michail Rovatsos
      First page: 1185
      Abstract: The recent discovery of two independently evolved XX/XY sex determination systems in the snake genera Python and Boa sparked a new drive to study the evolution of sex chromosomes in poorly studied lineages of snakes, where female heterogamety was previously assumed. Therefore, we examined seven species from the genera Eryx, Cylindrophis, Python, and Tropidophis by conventional and molecular cytogenetic methods. Despite the fact that these species have similar karyotypes in terms of chromosome number and morphology, we detected variability in the distribution of heterochromatin, telomeric repeats, and rDNA loci. Heterochromatic blocks were mainly detected in the centromeric regions in all species, although accumulations were detected in pericentromeric and telomeric regions in a few macrochromosomes in several of the studied species. All species show the expected topology of telomeric repeats at the edge of all chromosomes, with the exception of Eryx muelleri, where additional accumulations were detected in the centromeres of three pairs of macrochromosomes. The rDNA loci accumulate in one pair of microchromosomes in all Eryx species and in Cylindrophis ruffus, in one macrochromosome pair in Tropidophis melanurus and in two pairs of microchromosomes in Python regius. Sex-specific differences were not detected, suggesting that these species likely have homomorphic, poorly differentiated sex chromosomes.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071185
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1186: Genetic Demography of the Blue and Red Shrimp,
           Aristeus antennatus: A Female-Based Case Study Integrating Multilocus
           Genotyping and Morphometric Data

    • Authors: Alba Abras, Jose-Luis García-Marín, Sandra Heras, Melania Agulló, Manuel Vera, Laia Planella, María Inés Roldán
      First page: 1186
      Abstract: In this study, we quantified the three key biological processes, growth, recruitment, and dispersal pattern, which are necessary for a better understanding of the population dynamics of the blue and red shrimp Aristeus antennatus. This marine exploited crustacean shows sex-related distribution along the water column, being females predominate in the middle slope. The present study attempts to fill the existing gap in the females’ genetic demography, as scarce knowledge is available despite being the most abundant sex in catches. We analyzed morphometric data and genotyped 12 microsatellite loci in 655 A. antennatus females collected in two consecutive seasons, winter and summer 2016, at the main Mediterranean fishing ground as a model. Almost every female in summer was inseminated. Five modal groups were observed in both seasons, from 0+ to 4+ in winter and from 1+ to 5+ in summer. Commercial-sized sorting based on fishermen’s experience resulted in a moderate-to-high assertive method concerning cohort determination. Genetic data pointed out females’ horizontal movement between neighboring fishing grounds, explaining the low genetic divergence detected among western Mediterranean grounds. Our results could represent critical information for the future implementation of management measures to ensure long-time conservation of the A. antennatus populations.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071186
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1187: Genomics of Adaptation and Speciation

    • Authors: Walter W. Wolfsberger, Fabia U. Battistuzzi, Taras K. Oleksyk
      First page: 1187
      Abstract: The availability of genome data provides a unique window into speciation mechanisms with virtually infinite amounts of information, providing a pathway for a better understanding of major evolutionary questions [...]
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071187
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1188: Association of APOE Serum Levels and APOE
           ε2, ε3, and ε4 Alleles with Optic Neuritis

    • Authors: Liucija Momkute, Alvita Vilkeviciute, Greta Gedvilaite, Gabriele Dubinskaite, Loresa Kriauciuniene, Rasa Liutkeviciene
      First page: 1188
      Abstract: Optical neuritis (ON), otherwise known as optical nerve damage, is a term used to describe various environmental and body conditions that lead to optic nerve dysfunction. Neurologists are well aware of conditions that cause optic neuropathy, such as trauma, infections, malnutrition, and various toxins. As optic neuritis is a multifactorial demyelinating or infectious process, genetic predisposition may also influence the progression of optic neuritis. This study aimed to evaluate the association of ON (with and without multiple sclerosis) with APOE alleles and APOE serum levels. We found that the APOE ε3/ε3 genotype was statistically less common in the ON group of males than in the control group (p = 0.045). Moreover, the APOE ε3/ε3 genotype had a 3.7-fold increase in the odds of ON development in males (OR = 3.698; CI: 1.503–9.095; p = 0.004). In contrast, the APOE ε3/ε4 genotype had a 4.1-fold decrease in the odds of ON development in males (OR = 0.242; CI: 0.083–0.704; p = 0.009). APOE serum levels were statistically significantly higher in the ON group than in the control group (p = 0.042). The APOE ε3/ε3 genotype may increase males’ risk of developing ON, while the ε3/ε4 genotype may reduce males’ risk of developing ON.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071188
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1189: Identification and Characterization Roles of
           Phytoene Synthase (PSY) Genes in Watermelon Development

    • Authors: Xufeng Fang, Peng Gao, Feishi Luan, Shi Liu
      First page: 1189
      Abstract: Phytoene synthase (PSY) plays an essential role in carotenoid biosynthesis. In this study, three ClPSY genes were identified through the watermelon genome, and their full-length cDNA sequences were cloned. The deduced proteins of the three ClPSY genes were ranged from 355 to 421 amino acid residues. Phylogenetic analysis suggested that the ClPSYs are highly conserved with bottle gourd compared to other cucurbit crops PSY proteins. Variation in ClPSY1 expression in watermelon with different flesh colors was observed; ClPSY1 was most highly expressed in fruit flesh and associated with the flesh color formation. ClPSY1 expression was much lower in the white-fleshed variety than the colored fruits. Gene expression analysis of ClPSY genes in root, stem, leaf, flower, ovary and flesh of watermelon plants showed that the levels of ClPSY2 transcripts found in leaves was higher than other tissues; ClPSY3 was dominantly expressed in roots. Functional complementation assays of the three ClPSY genes suggested that all of them could encode functional enzymes to synthesize the phytoene from Geranylgeranyl Pyrophosphate (GGPP). Some of the homologous genes clustered together in the phylogenetic tree and located in the synteny chromosome region seemed to have similar expression profiles among different cucurbit crops. The findings provide a foundation for watermelon flesh color breeding with regard to carotenoid synthesis and also provide an insight for the further research of watermelon flesh color formation.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071189
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1190: Verification of Candidate SNP Effects Reveals
           Two QTLs on BTA7 for Beef Marbling in Two Japanese Black Cattle

    • Authors: Sasazaki, Yamamoto, Toyomoto, Kondo, Akiyama, Kohama, Yoshida, Kawaguchi, Oyama, Mannen
      First page: 1190
      Abstract: In our previous study, we used genome resequencing to detect all candidate polymorphisms within a quantitative trait loci (QTL) region for beef marbling reported previously at 10–30 Mbp on bovine chromosome 7, and we selected 6044 polymorphisms as candidate quantitative trait nucleotides (QTNs). In the present study, we aimed to identify quantitative trait genes (QTGs) and QTNs in this QTL region by verifying the effect of SNPs on beef marbling in two Japanese Black cattle populations using a Dynamic Array integrated fluidic circuit. In total, 96 selected SNPs were genotyped in 441 and 529 animals in Hyogo and Miyazaki cattle populations, respectively. The most significant p-values were detected in a SNP in a splice region of ALDH7A1 (SNP93_ALDH7A1; p = 3.46 × 10−5) in Hyogo cattle and a missense polymorphism of intercellular adhesion molecule-1 (ICAM1) (SNP37_ICAM1; p = 3.33 × 10−4) in Miyazaki cattle. Interestingly, SNP93_ALDH7A1 was not significant (p = 0.459) in Miyazaki cattle, and SNP37_ICAM1 showed a weakly significant association (p = 0.043) in Hyogo cattle. Thus, each population would likely have different QTGs and QTNs for beef marbling in the QTL region. In the Hyogo population, it was not possible to determine the accurate range of the linkage disequilibrium (LD) block in LD block analysis because of a strong LD structure throughout the assessed region. In Miyazaki cattle, however, an LD block containing SNP37_ICAM1 had a range of 15.8–16.1 Mbp, suggesting that QTNs would be located within this region. The functions of 19 genes in the LD block were investigated. ICAM1 is known to play an important role in adipocyte differentiation; given this function and the effect of amino acid substitution, SNP37_ICAM1 was identified as a promising candidate QTN for beef marbling. Further research on the effect of SNP37_ICAM1 on adipocyte differentiation is expected to provide insights into the mechanism underlying beef marbling formation.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071190
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1191: TTC30A and TTC30B Redundancy Protects IFT
           Complex B Integrity and Its Pivotal Role in Ciliogenesis

    • Authors: Hoffmann, Bolz, Junger, Klose, Schubert, Woerz, Boldt, Ueffing, Beyer
      First page: 1191
      Abstract: Intraflagellar transport (IFT) is a microtubule-based system that supports the assembly and maintenance of cilia. The dysfunction of IFT leads to ciliopathies of variable severity. Two of the IFT-B components are the paralogue proteins TTC30A and TTC30B. To investigate whether these proteins constitute redundant functions, CRISPR/Cas9 was used to generate single TTC30A or B and double-knockout hTERT-RPE1 cells. Ciliogenesis assays showed the redundancy of both proteins while the polyglutamylation of cilia was affected in single knockouts. The localization of other IFT components was not affected by the depletion of a single paralogue. A loss of both proteins led to a severe ciliogenesis defect, resulting in no cilia formation, which was rescued by TTC30A or B. The redundancy can be explained by the highly similar interaction patterns of the paralogues; both equally interact with the IFT-B machinery. Our study demonstrates that a loss of one TTC30 paralogue can mostly be compensated by the other, thus preventing severe ciliary defects. However, cells assemble shorter cilia, which are potentially limited in their function, especially because of impaired polyglutamylation. A complete loss of both proteins leads to a deficit in IFT complex B integrity followed by disrupted IFT and subsequently no cilia formation.
      Citation: Genes
      PubDate: 2022-07-01
      DOI: 10.3390/genes13071191
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1192: Testing Efficacy of Assembly-Free and
           Alignment-Free Methods for Species Identification Using Genome Skims, with
           Patellogastropoda as a Test Case

    • Authors: Tao Xu, Lingfeng Kong, Qi Li
      First page: 1192
      Abstract: Most recently, species identification has leaped from DNA barcoding into shotgun sequencing-based “genome skimming” alternatives. Genome skims have mainly been used to assemble organelle genomes, which discards much of the nuclear genome. Recently, an alternative approach was proposed for sample identification, using unassembled genome skims, which can effectively improve phylogenetic signal and identification resolution. Studies have shown that the software Skmer and APPLES work well at estimating genomic distance and performing phylogenetic placement in birds and insects using low-coverage genome skims. In this study, we use Skmer and APPLES based on genome skims of 11 patellogastropods to perform assembly-free and alignment-free species identification and phylogenetic placement. Whether or not data corresponding to query species are present in the reference database, Skmer selects the best matching or closest species with COI barcodes under different sizes of genome skims except lacking species belonging to the same family as a query. APPLES cannot place patellogastropods in the correct phylogenetic position when the reference database is sparse. Our study represents the first attempt at assembly-free and alignment-free species identification of marine mollusks using genome skims, demonstrating its feasibility for patellogastropod species identification and flanking the necessity of establishing a database to share genome skims.
      Citation: Genes
      PubDate: 2022-07-02
      DOI: 10.3390/genes13071192
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1193: Microarray-Based Prediction of Polycythemia
           after Exposure to High Altitudes

    • Authors: Haijing Wang, Daoxin Liu, Pengfei Song, Feng Jiang, Tongzuo Zhang
      First page: 1193
      Abstract: In high-altitude environments, the prevalence of high-altitude polycythemia (HAPC) ranges between 5 and 18 percent. However, there is currently no effective treatment for this condition. Therefore, disease prevention has emerged as a critical strategy against this disease. Here, we looked into the microarray profiles of GSE135109 and GSE29977, linked to either short- or long-term exposure to the Qinghai Tibet Plateau (QTP). The results revealed inhibition in the adaptive immune response during 30 days of exposure to QTP. Following a gene set enrichment analysis (GSEA) discovered that genes associated with HAPC were enriched in Cluster1, which showed a dramatic upregulation on the third day after arriving at the QTP. We then used GeneLogit to construct a logistic prediction model, which allowed us to identify 50 genes that classify HAPC patients. In these genes, LRRC18 and HCAR3 were also significantly altered following early QTP exposure, suggesting that they may serve as hub genes for HAPC development. The in-depth study of a combination of the datasets of transcriptomic changes during exposure to a high altitude and whether diseases occur after long-term exposure in Hans can give us some inspiration about genes associated with HAPC development during adaption to high altitudes.
      Citation: Genes
      PubDate: 2022-07-02
      DOI: 10.3390/genes13071193
      Issue No: Vol. 13, No. 7 (2022)
  • Genes, Vol. 13, Pages 1094: Integrated Analysis of a Ferroptosis-Related
           LncRNA Signature for Evaluating the Prognosis of Patients with Colorectal

    • Authors: Shaohua Xu, Yanjie Zhou, Junyun Luo, Su Chen, Jiahui Xie, Hui Liu, Yirong Wang, Zhaoyong Li
      First page: 1094
      Abstract: LncRNAs have been well known for their multiple functions in the tumorigenesis, development, and relapse of colorectal cancer (CRC). Accumulating studies demonstrated that the expression of lncRNAs can be regulated by ferroptosis, a biological process that has been revealed to suppress CRC progression. However, the functions and clinical implications of ferroptosis-associated lncRNAs in CRC remain largely unknown. We, herein, aim to construct a prognostic signature with ferroptosis-related lncRNAs for the prognostic estimation of CRC patients. Firstly, we identified the lncRNAs related to ferroptosis based on the RNA-Seq data of CRC from the TCGA database. The univariate and multivariate Cox analyses were then performed to establish a prognostic signature composed of eight ferroptosis-related lncRNAs (AL161729.4, AC010973.2, CCDC144NL-AS1, AC009549.1, LINC01857, AP003555.1, AC099850.3, and AC008494.3). Furthermore, we divided the CRC patients into high- and low-risk groups based on the signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that in the low-risk group (p = 3.31 × 10−11). Moreover, the patients in the high-risk groups had shorter recurrence-free survival (RFS) (p = 6.5 × 10−3) and disease-free survival (DFS) (p = 4.27 × 10−4), as well as higher tumor recurrence rate. Additionally, we found that the oncogenic pathways were enriched in the high-risk group, whereas the ferroptosis pathway that probably repressed CRC development was enriched in the low-risk group. In summary, our signature may provide a theoretical foundation for not only accurate judgment for prognosis but also evaluation for recurrence and metastasis in CRC patients.
      Citation: Genes
      PubDate: 2022-06-19
      DOI: 10.3390/genes13061094
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1095: Genome-Wide Association Studies Reveal

    • Authors: Yingying Yang, Shaoyun Dong, Han Miao, Xiaoping Liu, Zhuonan Dai, Xiangsheng Li, Xingfang Gu, Shengping Zhang
      First page: 1095
      Abstract: The stem diameter, an important agronomic trait, affects cucumber growth and yield. However, no genes responsible for cucumber stem diameter have been identified yet. In this study, the stem diameter of 88 cucumber core germplasms were measured in spring 2020, autumn 2020 and autumn 2021, and a genome-wide association study (GWAS) was carried out based on the gene sequence and stem diameter of core germplasms. A total of eight loci (gSD1.1, gSD2.1, gSD3.1, gSD3.2, gSD4.1, gSD5.1, gSD5.2, and gSD6.1) significantly associated with cucumber stem diameter were detected. Of these, five loci (gSD1.1, gSD2.1, gSD3.1, gSD5.2, and gSD6.1) were repeatedly detected in two or more seasons and were considered as robust and reliable loci. Based on the linkage disequilibrium sequences of the associated SNP loci, 37 genes were selected. By further investigating the five loci via analyzing Arabidopsis homologous genes and gene haplotypes, five genes (CsaV3_1G028310, CsaV3_2G006960, CsaV3_3G009560, CsaV3_5G031320, and CsaV3_6G031260) showed variations in amino acid sequence between thick stem lines and thin stem lines. Expression pattern analyses of these genes also showed a significant difference between thick stem and thin stem lines. This study laid the foundation for gene cloning and molecular mechanism study of cucumber stem development.
      Citation: Genes
      PubDate: 2022-06-19
      DOI: 10.3390/genes13061095
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1096: Comparative Transcriptome Analysis of
           Organ-Specific Adaptive Responses to Hypoxia Provides Insights to Human

    • Authors: Kuo-Sheng Hung, Shiow-Yi Chen, Pang-Hung Hsu, Bo-An Lin, Chin-Hua Hu, Cing-Han Yang, Tun-Wen Pai, Wen-Shyong Tzou, Hsin-Yu Chung
      First page: 1096
      Abstract: The common carp is a hypoxia-tolerant fish, and the understanding of its ability to live in low-oxygen environments has been applied to human health issues such as cancer and neuron degeneration. Here, we investigated differential gene expression changes during hypoxia in five common carp organs including the brain, the gill, the head kidney, the liver, and the intestine. Based on RNA sequencing, gene expression changes under hypoxic conditions were detected in over 1800 genes in common carp. The analysis of these genes further revealed that all five organs had high expression-specific properties. According to the results of the GO and KEGG, the pathways involved in the adaptation to hypoxia provided information on responses specific to each organ in low oxygen, such as glucose metabolism and energy usage, cholesterol synthesis, cell cycle, circadian rhythm, and dopamine activation. DisGeNET analysis showed that some human diseases such as cancer, diabetes, epilepsy, metabolism diseases, and social ability disorders were related to hypoxia-regulated genes. Our results suggested that common carp undergo various gene regulations in different organs under hypoxic conditions, and integrative bioinformatics may provide some potential targets for advancing disease research.
      Citation: Genes
      PubDate: 2022-06-19
      DOI: 10.3390/genes13061096
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1097: Integrated Analysis of Tissue-Specific Gene
           Expression in Diabetes by Tensor Decomposition Can Identify Possible
           Associated Diseases

    • Authors: Y-H. Taguchi, Turki Turki
      First page: 1097
      Abstract: In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still being developed and the existing methods have scope for improvement. The previously proposed tensor decomposition-based unsupervised feature extraction method was improved by introducing standard deviation optimization. The improved method was applied to perform an integrated analysis of three tissue-specific gene expression profiles (namely, adipose, muscle, and liver) for diabetes mellitus, and the results showed that it can detect diseases that are associated with diabetes (e.g., neurodegenerative diseases) but that cannot be predicted by individual tissue expression analyses using state-of-the-art methods. Although the selected genes differed from those identified by the individual tissue analyses, the selected genes are known to be expressed in all three tissues. Thus, compared with individual tissue analyses, an integrated analysis can provide more in-depth data and identify additional factors, namely, the association with other diseases.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061097
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1098: Identifying Rare Genetic Variants of Immune
           Mediators as Risk Factors for Autism Spectrum Disorder

    • Authors: Chunquan Cai, Zhaoqing Yin, Aiping Liu, Hui Wang, Shujuan Zeng, Zhangxing Wang, Huixian Qiu, Shijun Li, Jiaxiu Zhou, Mingbang Wang
      First page: 1098
      Abstract: Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2–12 years old) and 107 healthy controls without ASD (20–78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061098
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1099: Psychosis in Parkinson’s Disease: A
           Lesson from Genetics

    • Authors: Efthalia Angelopoulou, Anastasia Bougea, Sokratis G. Papageorgiou, Chiara Villa
      First page: 1099
      Abstract: Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe psychosis consisting of visual hallucinations (and rarely, auditory and tactile or gustatory) and paranoid delusions. PDP is associated with increased caregiver stress, poorer quality of life for patients and carers, reduced survival and risk of institutionalization with a significant burden on the healthcare system. Although several risk factors for PDP development have been identified, such as aging, sleep disturbances, long history of PD, cognitive impairment, depression and visual disorders, the pathophysiology of psychosis in PD is complex and still insufficiently clarified. Additionally, several drugs used to treat PD can aggravate or even precipitate PDP. Herein, we reviewed and critically analyzed recent studies exploring the genetic architecture of psychosis in PD in order to further understand the pathophysiology of PDP, the risk factors as well as the most suitable therapeutic strategies.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061099
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1100: The Sweetpotato Voltage-Gated K+ Channel
           β Subunit, KIbB1, Positively Regulates Low-K+ and High-Salinity
           Tolerance by Maintaining Ion Homeostasis

    • Authors: Hong Zhu, Xue Yang, Qiyan Li, Jiayu Guo, Tao Ma, Shuyan Liu, Shunyu Lin, Yuanyuan Zhou, Chunmei Zhao, Jingshan Wang, Jiongming Sui
      First page: 1100
      Abstract: Voltage-gated K+ channel β subunits act as a structural component of Kin channels in different species. The β subunits are not essential to the channel activity but confer different properties through binding the T1 domain or the C-terminal of α subunits. Here, we studied the physiological function of a novel gene, KIbB1, encoding a voltage-gated K+ channel β subunit in sweetpotato. The transcriptional level of this gene was significantly higher in the low-K+-tolerant line than that in the low-K+-sensitive line under K+ deficiency conditions. In Arabidopsis, KIbB1 positively regulated low-K+ tolerance through regulating K+ uptake and translocation. Under high-salinity stress, the growth conditions of transgenic lines were obviously better than wild typr (WT). Enzymatic and non-enzymatic reactive oxygen species (ROS) scavenging were activated in transgenic plants. Accordingly, the malondialdehyde (MDA) content and the accumulation of ROS such as H2O2 and O2− were lower in transgenic lines under salt stress. It was also found that the overexpression of KIbB1 enhanced K+ uptake, but the translocation from root to shoot was not affected under salt stress. This demonstrates that KIbB1 acted as a positive regulator in high-salinity stress resistance through regulating Na+ and K+ uptake to maintain K+/Na+ homeostasis. These results collectively suggest that the mechanisms of KIbB1 in regulating K+ were somewhat different between low-K+ and high-salinity conditions.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061100
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1101: Synthetic Lethality Targeting Polθ

    • Authors: Małgorzata Drzewiecka, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Tomasz Skorski, Tomasz Śliwiński
      First page: 1101
      Abstract: Research studies regarding synthetic lethality (SL) in human cells are primarily motivated by the potential of this phenomenon to be an effective, but at the same time, safe to the patient’s anti-cancer chemotherapy. Among the factors that are targets for the induction of the synthetic lethality effect, those involved in DNA repair seem to be the most relevant. Specifically, when mutation in one of the canonical DNA double-strand break (DSB) repair pathways occurs, which is a frequent event in cancer cells, the alternative pathways may be a promising target for the elimination of abnormal cells. Currently, inhibiting RAD52 and/or PARP1 in the tumor cells that are deficient in the canonical repair pathways has been the potential target for inducing the effect of synthetic lethality. Unfortunately, the development of resistance to commonly used PARP1 inhibitors (PARPi) represents the greatest obstacle to working out a successful treatment protocol. DNA polymerase theta (Polθ), encoded by the POLQ gene, plays a key role in an alternative DSB repair pathway—theta-mediated end joining (TMEJ). Thus, it is a promising target in the treatment of tumors harboring deficiencies in homologous recombination repair (HRR), where its inhibition can induce SL. In this review, the authors discuss the current state of knowledge on Polθ as a potential target for synthetic lethality-based anticancer therapies.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061101
      Issue No: Vol. 13, No. 6 (2022)
  • Genes, Vol. 13, Pages 1102: Gene Conversion Explains Elevated Diversity in
           the Immunity Modulating APL1 Gene of the Malaria Vector Anopheles funestus

    • Authors: Jack Hearn, Jacob M. Riveron, Helen Irving, Gareth D. Weedall, Charles S. Wondji
      First page: 1102
      Abstract: Leucine-rich repeat proteins and antimicrobial peptides are the key components of the innate immune response to Plasmodium and other microbial pathogens in Anopheles mosquitoes. The APL1 gene of the malaria vector Anopheles funestus has exceptional levels of non-synonymous polymorphism across the range of An. funestus, with an average πn of 0.027 versus a genome-wide average of 0.002, and πn is consistently high in populations across Africa. Elevated APL1 diversity was consistent between the independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide resistance was observed. Although lacking the diversity of APL1, two further mosquito innate-immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. The cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, a result discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogues, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. In conclusion, we hypothesize that higher gene expression of APL1 than its paralogues is correlated with a more open chromatin formation, which enhances gene conversion and elevated diversity at this locus.
      Citation: Genes
      PubDate: 2022-06-20
      DOI: 10.3390/genes13061102
      Issue No: Vol. 13, No. 6 (2022)
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