Publisher: Oxford University Press   (Total: 412 journals)

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Showing 1 - 200 of 412 Journals sorted alphabetically
ACS Symposium Series     Full-text available via subscription   (Followers: 3, SJR: 0.189, CiteScore: 0)
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Adaptation     Hybrid Journal   (Followers: 9, SJR: 0.143, CiteScore: 0)
Advances in Nutrition     Hybrid Journal   (Followers: 61, SJR: 2.196, CiteScore: 5)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 8, SJR: 1.434, CiteScore: 1)
Aesthetic Surgery J. Open Forum     Open Access   (Followers: 1)
African Affairs     Hybrid Journal   (Followers: 74, SJR: 1.869, CiteScore: 2)
Age and Ageing     Hybrid Journal   (Followers: 97, SJR: 1.989, CiteScore: 4)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 24, SJR: 1.376, CiteScore: 3)
American Entomologist     Hybrid Journal   (Followers: 8)
American Historical Review     Hybrid Journal   (Followers: 223, SJR: 0.467, CiteScore: 1)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 54, SJR: 2.113, CiteScore: 3)
American J. of Clinical Nutrition     Hybrid Journal   (Followers: 232, SJR: 3.438, CiteScore: 6)
American J. of Epidemiology     Hybrid Journal   (Followers: 236, SJR: 2.713, CiteScore: 3)
American J. of Health-System Pharmacy     Full-text available via subscription   (Followers: 65, SJR: 0.595, CiteScore: 1)
American J. of Hypertension     Hybrid Journal   (Followers: 29, SJR: 1.322, CiteScore: 3)
American J. of Jurisprudence     Hybrid Journal   (Followers: 19, SJR: 0.281, CiteScore: 1)
American J. of Legal History     Full-text available via subscription   (Followers: 11, SJR: 0.116, CiteScore: 0)
American Law and Economics Review     Hybrid Journal   (Followers: 31, SJR: 1.053, CiteScore: 1)
American Literary History     Hybrid Journal   (Followers: 19, SJR: 0.391, CiteScore: 0)
Analysis     Hybrid Journal   (Followers: 27, SJR: 1.038, CiteScore: 1)
Animal Frontiers     Hybrid Journal   (Followers: 2)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 15, SJR: 1.423, CiteScore: 3)
Annals of Botany     Hybrid Journal   (Followers: 39, SJR: 1.721, CiteScore: 4)
Annals of Oncology     Hybrid Journal   (Followers: 60, SJR: 5.599, CiteScore: 9)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 11, SJR: 0.722, CiteScore: 1)
Annals of Work Exposures and Health     Hybrid Journal   (Followers: 11, SJR: 0.728, CiteScore: 2)
Antibody Therapeutics     Open Access   (Followers: 1)
AoB Plants     Open Access   (Followers: 4, SJR: 1.28, CiteScore: 3)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 18, SJR: 0.858, CiteScore: 2)
Applied Linguistics     Hybrid Journal   (Followers: 68, SJR: 2.987, CiteScore: 3)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 1.241, CiteScore: 1)
Arbitration Intl.     Full-text available via subscription   (Followers: 20)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 14)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 33, SJR: 0.731, CiteScore: 2)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 48, SJR: 0.146, CiteScore: 0)
Behavioral Ecology     Hybrid Journal   (Followers: 59, SJR: 1.871, CiteScore: 3)
Bioinformatics     Hybrid Journal   (Followers: 402, SJR: 6.14, CiteScore: 8)
Biology Methods and Protocols     Open Access   (Followers: 1)
Biology of Reproduction     Full-text available via subscription   (Followers: 11, SJR: 1.446, CiteScore: 3)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 3.485, CiteScore: 2)
BioScience     Hybrid Journal   (Followers: 30, SJR: 2.754, CiteScore: 4)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 3, SJR: 0.146, CiteScore: 0)
Biostatistics     Hybrid Journal   (Followers: 17, SJR: 1.553, CiteScore: 2)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 243, SJR: 2.115, CiteScore: 3)
BJA Education     Hybrid Journal   (Followers: 70)
Brain     Hybrid Journal   (Followers: 78, SJR: 5.858, CiteScore: 7)
Brain Communications     Open Access   (Followers: 4)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 54, SJR: 2.505, CiteScore: 5)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 3, SJR: 2.15, CiteScore: 3)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 43, SJR: 2.161, CiteScore: 2)
British J. of Aesthetics     Hybrid Journal   (Followers: 24, SJR: 0.508, CiteScore: 1)
British J. of Criminology     Hybrid Journal   (Followers: 620, SJR: 1.828, CiteScore: 3)
British J. of Social Work     Hybrid Journal   (Followers: 102, SJR: 1.019, CiteScore: 2)
British Medical Bulletin     Hybrid Journal   (Followers: 6, SJR: 1.355, CiteScore: 3)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 37)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.376, CiteScore: 1)
Cambridge J. of Economics     Hybrid Journal   (Followers: 77, SJR: 0.764, CiteScore: 2)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 13, SJR: 2.438, CiteScore: 4)
Cambridge Quarterly     Hybrid Journal   (Followers: 11, SJR: 0.104, CiteScore: 0)
Capital Markets Law J.     Hybrid Journal   (Followers: 4, SJR: 0.222, CiteScore: 0)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.135, CiteScore: 5)
Cardiovascular Research     Hybrid Journal   (Followers: 17, SJR: 3.002, CiteScore: 5)
Cerebral Cortex     Hybrid Journal   (Followers: 56, SJR: 3.892, CiteScore: 6)
CESifo Economic Studies     Hybrid Journal   (Followers: 24, SJR: 0.483, CiteScore: 1)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.42, CiteScore: 3)
Children and Schools     Hybrid Journal   (Followers: 8, SJR: 0.246, CiteScore: 0)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 7, SJR: 0.412, CiteScore: 0)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 24, SJR: 0.329, CiteScore: 0)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 11, SJR: 1.392, CiteScore: 2)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 10, SJR: 0.183, CiteScore: 0)
Classical Receptions J.     Hybrid Journal   (Followers: 30, SJR: 0.123, CiteScore: 0)
Clean Energy     Open Access   (Followers: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 83, SJR: 5.051, CiteScore: 5)
Communication Theory     Hybrid Journal   (Followers: 29, SJR: 2.424, CiteScore: 3)
Communication, Culture & Critique     Hybrid Journal   (Followers: 29, SJR: 0.222, CiteScore: 1)
Community Development J.     Hybrid Journal   (Followers: 29, SJR: 0.268, CiteScore: 1)
Computer J.     Hybrid Journal   (Followers: 9, SJR: 0.319, CiteScore: 1)
Conservation Physiology     Open Access   (Followers: 3, SJR: 1.818, CiteScore: 3)
Contemporary Women's Writing     Hybrid Journal   (Followers: 12, SJR: 0.121, CiteScore: 0)
Contributions to Political Economy     Hybrid Journal   (Followers: 8, SJR: 0.906, CiteScore: 1)
Critical Values     Full-text available via subscription  
Current Developments in Nutrition     Open Access   (Followers: 5)
Current Legal Problems     Hybrid Journal   (Followers: 29)
Current Zoology     Full-text available via subscription   (Followers: 6, SJR: 1.164, CiteScore: 2)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 10, SJR: 1.791, CiteScore: 3)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 16, SJR: 0.259, CiteScore: 1)
Diplomatic History     Hybrid Journal   (Followers: 25, SJR: 0.45, CiteScore: 1)
DNA Research     Open Access   (Followers: 6, SJR: 2.866, CiteScore: 6)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 5)
Early Music     Hybrid Journal   (Followers: 17, SJR: 0.139, CiteScore: 0)
Econometrics J.     Hybrid Journal   (Followers: 34, SJR: 2.926, CiteScore: 1)
Economic J.     Hybrid Journal   (Followers: 125, SJR: 5.161, CiteScore: 3)
Economic Policy     Hybrid Journal   (Followers: 51, SJR: 3.584, CiteScore: 3)
ELT J.     Hybrid Journal   (Followers: 27, SJR: 0.942, CiteScore: 1)
English Historical Review     Hybrid Journal   (Followers: 62, SJR: 0.612, CiteScore: 1)
English: J. of the English Association     Hybrid Journal   (Followers: 23, SJR: 0.1, CiteScore: 0)
Environmental Entomology     Full-text available via subscription   (Followers: 13, SJR: 0.818, CiteScore: 2)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental History     Hybrid Journal   (Followers: 28, SJR: 0.408, CiteScore: 1)
EP-Europace     Hybrid Journal   (Followers: 3, SJR: 2.748, CiteScore: 4)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 4.505, CiteScore: 8)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 24, SJR: 0.113, CiteScore: 0)
European Heart J.     Hybrid Journal   (Followers: 71, SJR: 9.315, CiteScore: 9)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 10, SJR: 3.625, CiteScore: 3)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 2)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. : Case Reports     Open Access   (Followers: 1)
European Heart J. Supplements     Hybrid Journal   (Followers: 7, SJR: 0.223, CiteScore: 0)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 9, SJR: 1.681, CiteScore: 2)
European J. of Intl. Law     Hybrid Journal   (Followers: 246, SJR: 0.694, CiteScore: 1)
European J. of Orthodontics     Hybrid Journal   (Followers: 5, SJR: 1.279, CiteScore: 2)
European J. of Public Health     Hybrid Journal   (Followers: 23, SJR: 1.36, CiteScore: 2)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 12, SJR: 1.172, CiteScore: 2)
European Review of Economic History     Hybrid Journal   (Followers: 31, SJR: 0.702, CiteScore: 1)
European Sociological Review     Hybrid Journal   (Followers: 48, SJR: 2.728, CiteScore: 3)
Evolution, Medicine, and Public Health     Open Access   (Followers: 12)
Family Practice     Hybrid Journal   (Followers: 17, SJR: 1.018, CiteScore: 2)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 19, SJR: 1.492, CiteScore: 4)
Fems Microbiology Letters     Hybrid Journal   (Followers: 29, SJR: 0.79, CiteScore: 2)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 38, SJR: 7.063, CiteScore: 13)
Fems Yeast Research     Hybrid Journal   (Followers: 14, SJR: 1.308, CiteScore: 3)
Food Quality and Safety     Open Access   (Followers: 1)
Foreign Policy Analysis     Hybrid Journal   (Followers: 26, SJR: 1.425, CiteScore: 1)
Forest Science     Hybrid Journal   (Followers: 8, SJR: 0.89, CiteScore: 2)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 16, SJR: 1.133, CiteScore: 3)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.104, CiteScore: 0)
French History     Hybrid Journal   (Followers: 36, SJR: 0.118, CiteScore: 0)
French Studies     Hybrid Journal   (Followers: 21, SJR: 0.148, CiteScore: 0)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.152, CiteScore: 0)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 17, SJR: 2.578, CiteScore: 4)
Geophysical J. Intl.     Hybrid Journal   (Followers: 39, SJR: 1.506, CiteScore: 3)
German History     Hybrid Journal   (Followers: 28, SJR: 0.161, CiteScore: 0)
GigaScience     Open Access   (Followers: 6, SJR: 5.022, CiteScore: 7)
Global Summitry     Hybrid Journal   (Followers: 1)
Glycobiology     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Health and Social Work     Hybrid Journal   (Followers: 70, SJR: 0.388, CiteScore: 1)
Health Education Research     Hybrid Journal   (Followers: 20, SJR: 0.854, CiteScore: 2)
Health Policy and Planning     Hybrid Journal   (Followers: 26, SJR: 1.512, CiteScore: 2)
Health Promotion Intl.     Hybrid Journal   (Followers: 27, SJR: 0.812, CiteScore: 2)
History Workshop J.     Hybrid Journal   (Followers: 33, SJR: 1.278, CiteScore: 1)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 30, SJR: 0.105, CiteScore: 0)
Human Communication Research     Hybrid Journal   (Followers: 16, SJR: 2.146, CiteScore: 3)
Human Molecular Genetics     Hybrid Journal   (Followers: 11, SJR: 3.555, CiteScore: 5)
Human Reproduction     Hybrid Journal   (Followers: 76, SJR: 2.643, CiteScore: 5)
Human Reproduction Open     Open Access   (Followers: 2)
Human Reproduction Update     Hybrid Journal   (Followers: 18, SJR: 5.317, CiteScore: 10)
Human Rights Law Review     Hybrid Journal   (Followers: 69, SJR: 0.756, CiteScore: 1)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 59, SJR: 1.591, CiteScore: 3)
ICSID Review : Foreign Investment Law J.     Hybrid Journal   (Followers: 11)
ILAR J.     Hybrid Journal   (Followers: 3, SJR: 1.732, CiteScore: 4)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.679, CiteScore: 1)
IMA J. of Management Mathematics     Hybrid Journal   (SJR: 0.538, CiteScore: 1)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.496, CiteScore: 1)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 1.987, CiteScore: 2)
Industrial and Corporate Change     Hybrid Journal   (Followers: 12, SJR: 1.792, CiteScore: 2)
Industrial Law J.     Hybrid Journal   (Followers: 30, SJR: 0.249, CiteScore: 1)
Inflammatory Bowel Diseases     Hybrid Journal   (Followers: 45, SJR: 2.511, CiteScore: 4)
Information and Inference     Free  
Innovation in Aging     Open Access   (Followers: 1)
Insect Systematics and Diversity     Hybrid Journal  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 10, SJR: 1.319, CiteScore: 2)
Integrative Biology     Full-text available via subscription   (Followers: 5, SJR: 1.36, CiteScore: 3)
Integrative Organismal Biology     Open Access  
Interacting with Computers     Hybrid Journal   (Followers: 10, SJR: 0.292, CiteScore: 1)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 6, SJR: 0.762, CiteScore: 1)
Intl. Affairs     Hybrid Journal   (Followers: 73, SJR: 1.505, CiteScore: 3)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 22)
Intl. Health     Hybrid Journal   (Followers: 7, SJR: 0.851, CiteScore: 2)
Intl. Immunology     Hybrid Journal   (Followers: 4, SJR: 2.167, CiteScore: 4)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 40, SJR: 1.348, CiteScore: 2)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 59, SJR: 0.601, CiteScore: 1)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 297, SJR: 3.969, CiteScore: 5)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 5, SJR: 0.202, CiteScore: 1)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 20, SJR: 0.223, CiteScore: 1)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 9, SJR: 0.285, CiteScore: 1)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.403, CiteScore: 1)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.808, CiteScore: 4)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 11, SJR: 1.545, CiteScore: 1)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 39, SJR: 0.389, CiteScore: 1)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 14, SJR: 0.724, CiteScore: 2)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.168, CiteScore: 1)
Intl. Political Sociology     Hybrid Journal   (Followers: 42, SJR: 1.465, CiteScore: 3)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 26, SJR: 0.401, CiteScore: 1)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 9, SJR: 0.983, CiteScore: 1)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 55, SJR: 2.581, CiteScore: 2)
Intl. Studies Review     Hybrid Journal   (Followers: 24, SJR: 1.201, CiteScore: 1)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 2, SJR: 0.15, CiteScore: 0)
ITNOW     Hybrid Journal   (Followers: 1, SJR: 0.103, CiteScore: 0)
J. of African Economies     Hybrid Journal   (Followers: 18, SJR: 0.533, CiteScore: 1)
J. of American History     Hybrid Journal   (Followers: 56, SJR: 0.297, CiteScore: 1)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 15, SJR: 1.065, CiteScore: 2)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 18, SJR: 2.419, CiteScore: 4)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 2)
J. of Biochemistry     Hybrid Journal   (Followers: 46, SJR: 1.226, CiteScore: 2)
J. of Breast Imaging     Full-text available via subscription   (Followers: 2)

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Similar Journals
Journal Cover
Human Molecular Genetics
Journal Prestige (SJR): 3.555
Citation Impact (citeScore): 5
Number of Followers: 11  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0964-6906 - ISSN (Online) 1460-2083
Published by Oxford University Press Homepage  [412 journals]
  • Pharmacological read-through of R294X Mecp2 in a novel mouse model of Rett
    • Authors: Merritt J; Collins B, Erickson K, et al.
      Pages: 2461 - 2470
      Abstract: AbstractRett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in Methyl-CpG-binding Protein 2 (MECP2). More than 35% of affected individuals have nonsense mutations in MECP2. For these individuals, nonsense suppression has been suggested as a possible therapeutic approach. To assess the viability of this strategy, we created and characterized a mouse model with the common p.R294X mutation introduced into the endogenous Mecp2 locus (Mecp2R294X). Mecp2R294X mice exhibit phenotypic abnormalities similar to those seen in complete null mouse models; however, these occur at a later time point consistent with the reduced phenotypic severity seen in affected individuals containing this specific mutation. The delayed onset of severe phenotypes is likely due to the presence of truncated MeCP2 in Mecp2R294X mice. Supplying the MECP2 transgene in Mecp2R294X mice rescued phenotypic abnormalities including early death and demonstrated that the presence of truncated MeCP2 in these mice does not interfere with wild-type MeCP2. In vitro treatment of a cell line derived from Mecp2R294X mice with the nonsense suppression agent G418 resulted in full-length MeCP2 protein production, demonstrating feasibility of this therapeutic approach. Intraperitoneal administration of G418 in Mecp2R294X mice was sufficient to elicit full-length MeCP2 protein expression in peripheral tissues. Finally, intracranial ventricular injection of G418 in Mecp2R294X mice induced expression of full-length MeCP2 protein in the mouse brain. These experiments demonstrate that translational read-through drugs are able to suppress the Mecp2 p.R294X mutation in vivo and provide a proof of concept for future preclinical studies of nonsense suppression agents in RTT.
      PubDate: Fri, 29 May 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa102
      Issue No: Vol. 29, No. 15 (2020)
  • C1orf194 deficiency leads to incomplete early embryonic lethality and
           dominant intermediate Charcot–Marie–Tooth disease in a knockout mouse
    • Authors: Huang C; Shen Z, Huang J, et al.
      Pages: 2471 - 2480
      Abstract: AbstractCharcot–Marie–Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5–15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt–Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.
      PubDate: Sat, 27 Jun 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa129
      Issue No: Vol. 29, No. 15 (2020)
  • Serum biomarkers associated with baseline clinical severity in young
           steroid-naïve Duchenne muscular dystrophy boys
    • Authors: Dang U; Ziemba M, Clemens P, et al.
      Pages: 2481 - 2495
      Abstract: AbstractDuchenne muscular dystrophy (DMD) is caused by loss of dystrophin in muscle, and while all patients share the primary gene and biochemical defect, there is considerable patient–patient variability in clinical symptoms. We sought to develop multivariate models of serum protein biomarkers that explained observed variation, using functional outcome measures as proxies for severity. Serum samples from 39 steroid-naïve DMD boys 4 to <7 years enrolled into a clinical trial of vamorolone were studied (NCT02760264). Four assessments of gross motor function were carried out for each participant over a 6-week interval, and their mean was used as response for biomarker models. Weighted correlation network analysis was used for unsupervised clustering of 1305 proteins quantified using SOMAscan® aptamer profiling to define highly representative and connected proteins. Multivariate models of biomarkers were obtained for time to stand performance (strength phenotype; 17 proteins) and 6 min walk performance (endurance phenotype; 17 proteins) including some shared proteins. Identified proteins were tested with associations of mRNA expression with histological severity of muscle from dystrophinopathy patients (n = 28) and normal controls (n = 6). Strong associations predictive of both clinical and histological severity were found for ERBB4 (reductions in both blood and muscle with increasing severity), SOD1 (reductions in muscle and increases in blood with increasing severity) and CNTF (decreased levels in blood and muscle with increasing severity). We show that performance of DMD boys was effectively modeled with serum proteins, proximal strength associated with growth and remodeling pathways and muscle endurance centered on TGFβ and fibrosis pathways in muscle.
      PubDate: Sat, 27 Jun 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa132
      Issue No: Vol. 29, No. 15 (2020)
  • Longitudinal increases in somatic mosaicism of the expanded CTG repeat in
           myotonic dystrophy type 1 are associated with variation in age-at-onset
    • Authors: Morales F; Vásquez M, Corrales E, et al.
      Pages: 2496 - 2507
      Abstract: AbstractIn myotonic dystrophy type 1 (DM1), somatic mosaicism of the (CTG)n repeat expansion is age-dependent, tissue-specific and expansion-biased. These features contribute toward variation in disease severity and confound genotype-to-phenotype analyses. To investigate how the (CTG)n repeat expansion changes over time, we collected three longitudinal blood DNA samples separated by 8–15 years and used small pool and single-molecule PCR in 43 DM1 patients. We used the lower boundary of the allele length distribution as the best estimate for the inherited progenitor allele length (ePAL), which is itself the best predictor of disease severity. Although in most patients the lower boundary of the allele length distribution was conserved over time, in many this estimate also increased with age, suggesting samples for research studies and clinical trials should be obtained as early as possible. As expected, the modal allele length increased over time, driven primarily by ePAL, age-at-sampling and the time interval. As expected, small expansions <100 repeats did not expand as rapidly as larger alleles. However, the rate of expansion of very large alleles was not obviously proportionally higher. This may, at least in part, be a result of the allele length-dependent increase in large contractions that we also observed. We also determined that individual-specific variation in the increase of modal allele length over time not accounted for by ePAL, age-at-sampling and time was inversely associated with individual-specific variation in age-at-onset not accounted for by ePAL, further highlighting somatic expansion as a therapeutic target in DM1.
      PubDate: Tue, 30 Jun 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa123
      Issue No: Vol. 29, No. 15 (2020)
  • Correction of cilia structure and function alleviates multi-organ
           pathology in Bardet–Biedl syndrome mice
    • Authors: Husson H; Bukanov N, Moreno S, et al.
      Pages: 2508 - 2522
      Abstract: AbstractBardet–Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy affecting multiple organs. The development of potential disease-modifying therapy for BBS will require concurrent targeting of multi-systemic manifestations. Here, we show for the first time that monosialodihexosylganglioside accumulates in Bbs2−/− cilia, indicating impairment of glycosphingolipid (GSL) metabolism in BBS. Consequently, we tested whether BBS pathology in Bbs2−/− mice can be reversed by targeting the underlying ciliary defect via reduction of GSL metabolism. Inhibition of GSL synthesis with the glucosylceramide synthase inhibitor Genz-667161 decreases the obesity, liver disease, retinal degeneration and olfaction defect in Bbs2−/− mice. These effects are secondary to preservation of ciliary structure and signaling, and stimulation of cellular differentiation. In conclusion, reduction of GSL metabolism resolves the multi-organ pathology of Bbs2−/− mice by directly preserving ciliary structure and function towards a normal phenotype. Since this approach does not rely on the correction of the underlying genetic mutation, it might translate successfully as a treatment for other ciliopathies.
      PubDate: Fri, 03 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa138
      Issue No: Vol. 29, No. 15 (2020)
  • Skewed allelic expression on X chromosome associated with aberrant
           expression of XIST on systemic lupus erythematosus lymphocytes
    • Authors: Zhang Y; Li X, Gibson A, et al.
      Pages: 2523 - 2534
      Abstract: AbstractA common feature of autoimmune diseases, including systemic lupus erythematosus (SLE), is an increased prevalence in women. However, the molecular basis for sex disparity in SLE remains poorly understood. To examine the role of X-linked transcription in SLE adaptive immune cells, we performed RNA-seq in T cell and B cell subsets from either healthy donors or patients with SLE. Analyses of allelic expression (AE) profiles identified a pattern of increased allelic imbalance across the entire X chromosome in SLE lymphocytes. X-linked genes exhibiting AE in SLE had an extensive overlap with genes known to escape X chromosome inactivation (XCI). XIST RNA was overexpressed in SLE patients. Differential XIST expression correlated with AE profiles more positively at X-linked genes than the genome-wide background. Analysis of three independent RNA-seq data verified the XIST-associated skewed AE on X chromosome in SLE. Integrative analyses of DNA methylation profiles showed an increased variability of DNA methylation levels at these AE-related X-linked genes. In cultured lymphoblastic cells, knockdown of XIST specifically altered allelic imbalance patterns between X chromosomes. Our study provides genetic evidence that upregulation of XIST accompanied with more skewed allelic expression on X chromosome is associated with the pathogenesis of SLE and may provide mechanistic insights into the increased incidence of SLE in females.
      PubDate: Mon, 06 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa131
      Issue No: Vol. 29, No. 15 (2020)
  • Targeted chromatin conformation analysis identifies novel distal neural
           enhancers of ZEB2 in pluripotent stem cell differentiation
    • Authors: Birkhoff J; Brouwer R, Kolovos P, et al.
      Pages: 2535 - 2550
      Abstract: AbstractThe transcription factor zinc finger E-box binding protein 2 (ZEB2) controls embryonic and adult cell fate decisions and cellular maturation in many stem/progenitor cell types. Defects in these processes in specific cell types underlie several aspects of Mowat–Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of a ±3.5 Mb-long gene-desert, lacking any protein-coding gene. Using temporal targeted chromatin capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 promoter and this gene desert during neural differentiation of human-induced pluripotent stem cells, including at early neuroprogenitor cell (NPC)/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500 kb upstream of the ZEB2 transcription start site. Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis Regulatory Elements located in ZEB2’s gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of multiple cell types and the molecular characterization of newly identified MOWS patients that lack mutations in ZEB2 protein-coding exons.
      PubDate: Mon, 06 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa141
      Issue No: Vol. 29, No. 15 (2020)
  • Patterns of CAG repeat instability in the central nervous system and
           periphery in Huntington’s disease and in spinocerebellar ataxia type 1
    • Authors: Mouro Pinto R; Arning L, Giordano J, et al.
      Pages: 2551 - 2567
      Abstract: AbstractThe expanded HTT CAG repeat causing Huntington’s disease (HD) exhibits somatic expansion proposed to drive the rate of disease onset by eliciting a pathological process that ultimately claims vulnerable cells. To gain insight into somatic expansion in humans, we performed comprehensive quantitative analyses of CAG expansion in ~50 central nervous system (CNS) and peripheral postmortem tissues from seven adult-onset and one juvenile-onset HD individual. We also assessed ATXN1 CAG repeat expansion in brain regions of an individual with a neurologically and pathologically distinct repeat expansion disorder, spinocerebellar ataxia type 1 (SCA1). Our findings reveal similar profiles of tissue instability in all HD individuals, which, notably, were also apparent in the SCA1 individual. CAG expansion was observed in all tissues, but to different degrees, with multiple cortical regions and neostriatum tending to have the greatest instability in the CNS, and liver in the periphery. These patterns indicate different propensities for CAG expansion contributed by disease locus-independent trans-factors and demonstrate that expansion per se is not sufficient to cause cell type or disease-specific pathology. Rather, pathology may reflect distinct toxic processes triggered by different repeat lengths across cell types and diseases. We also find that the HTT CAG length-dependent expansion propensity of an individual is reflected in all tissues and in cerebrospinal fluid. Our data indicate that peripheral cells may be a useful source to measure CAG expansion in biomarker assays for therapeutic efforts, prompting efforts to dissect underlying mechanisms of expansion that may differ between the brain and periphery.
      PubDate: Tue, 07 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa139
      Issue No: Vol. 29, No. 15 (2020)
  • A synonymous UPF3B variant causing a speech disorder implicates NMD as a
           regulator of neurodevelopmental disorder gene networks
    • Authors: Domingo D; Nawaz U, Corbett M, et al.
      Pages: 2568 - 2578
      Abstract: AbstractLoss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individual show altered UPF3B RNA splicing. The resulting mRNA species encodes a frame-shifted protein with a premature termination codon (PTC) predicted to elicit degradation via nonsense-mediated mRNA decay (NMD). UPF3B mRNA was reduced in the cell line, and no UPF3B protein was produced, confirming a loss-of-function allele. UPF3B is itself involved in the NMD mechanism which degrades both PTC-bearing mutant transcripts and also many physiological transcripts. RNAseq analysis showed that ~1.6% of mRNAs exhibited altered expression. These mRNA changes overlapped and correlated with those we identified in additional cell lines obtained from individuals harbouring other UPF3B mutations, permitting us to interrogate pathogenic mechanisms of UPF3B-associated NDDs. We identified 102 genes consistently deregulated across all UPF3B mutant cell lines. Of the 51 upregulated genes, 75% contained an NMD-targeting feature, thus identifying high-confidence direct NMD targets. Intriguingly, 22 of the dysregulated genes encoded known NDD genes, suggesting UPF3B-dependent NMD regulates gene networks critical for cognition and behaviour. Indeed, we show that 78.5% of all NDD genes encode a transcript predicted to be targeted by NMD. These data describe the first synonymous UPF3B mutation in a patient with prominent speech and language disabilities and identify plausible mechanisms of pathology downstream of UPF3B mutations involving the deregulation of NDD-gene networks.
      PubDate: Thu, 16 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa151
      Issue No: Vol. 29, No. 15 (2020)
  • Transcriptomic and epigenomic dynamics associated with development of
           human iPSC-derived GABAergic interneurons
    • Authors: Inglis G; Zhou Y, Patterson D, et al.
      Pages: 2579 - 2595
      Abstract: AbstractGABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN function may provide new insight into the pathways underlying proper GIN activity while also indicating potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. In this study, we examined the temporal changes in gene expression and chromatin accessibility during GIN development by performing transcriptomic and epigenomic analyses on human induced pluripotent stem cell-derived neurons at 22, 50 and 78 days (D) post-differentiation. We observed 13 221 differentially accessible regions (DARs) of chromatin that associate with temporal changes in gene expression at D78 and D50, relative to D22. We also classified families of transcription factors that are increasingly enriched at DARs during differentiation, indicating regulatory networks that likely drive GIN development. Collectively, these data provide a resource for examining the molecular networks regulating GIN functionality.
      PubDate: Thu, 16 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa150
      Issue No: Vol. 29, No. 15 (2020)
  • Ubiquilin-2 differentially regulates polyglutamine disease proteins
    • Authors: Gerson J; Safren N, Fischer S, et al.
      Pages: 2596 - 2610
      Abstract: AbstractDivergent protein context helps explain why polyglutamine expansion diseases differ clinically and pathologically. This heterogeneity may also extend to how polyglutamine disease proteins are handled by cellular pathways of proteostasis. Studies suggest, for example, that the ubiquitin-proteasome shuttle protein Ubiquilin-2 (UBQLN2) selectively interacts with specific polyglutamine disease proteins. Here we employ cellular models, primary neurons and mouse models to investigate the potential differential regulation by UBQLN2 of two polyglutamine disease proteins, huntingtin (HTT) and ataxin-3 (ATXN3). In cells, overexpressed UBQLN2 selectively lowered levels of full-length pathogenic HTT but not of HTT exon 1 fragment or full-length ATXN3. Consistent with these results, UBQLN2 specifically reduced accumulation of aggregated mutant HTT but not mutant ATXN3 in mouse models of Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3), respectively. Normally a cytoplasmic protein, UBQLN2 translocated to the nuclei of neurons in HD mice but not in SCA3 mice. Remarkably, instead of reducing the accumulation of nuclear mutant ATXN3, UBQLN2 induced an accumulation of cytoplasmic ATXN3 aggregates in neurons of SCA3 mice. Together these results reveal a selective action of UBQLN2 toward polyglutamine disease proteins, indicating that polyglutamine expansion alone is insufficient to promote UBQLN2-mediated clearance of this class of disease proteins. Additional factors, including nuclear translocation of UBQLN2, may facilitate its action to clear intranuclear, aggregated disease proteins like HTT.
      PubDate: Sat, 18 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa152
      Issue No: Vol. 29, No. 15 (2020)
  • Epigenetic hallmarks of age-related macular degeneration are recapitulated
           in a photosensitive mouse model
    • Authors: Luu J; Kallestad L, Hoang T, et al.
      Pages: 2611 - 2624
      Abstract: AbstractAge-related macular degeneration (AMD) is a chronic, multifactorial disorder and a leading cause of blindness in the elderly. Characterized by progressive photoreceptor degeneration in the central retina, disease progression involves epigenetic changes in chromatin accessibility resulting from environmental exposures and chronic stress. Here, we report that a photosensitive mouse model of acute stress-induced photoreceptor degeneration recapitulates the epigenetic hallmarks of human AMD. Global epigenomic profiling was accomplished by employing an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq), which revealed an association between decreased chromatin accessibility and stress-induced photoreceptor cell death in our mouse model. The epigenomic changes induced by light damage include reduced euchromatin and increased heterochromatin abundance, resulting in transcriptional and translational dysregulation that ultimately drives photoreceptor apoptosis and an inflammatory reactive gliosis in the retina. Of particular interest, pharmacological inhibition of histone deacetylase 11 (HDAC11) and suppressor of variegation 3–9 homolog 2 (SUV39H2), key histone-modifying enzymes involved in promoting reduced chromatin accessibility, ameliorated light damage in our mouse model, supporting a causal link between decreased chromatin accessibility and photoreceptor degeneration, thereby elucidating a potential new therapeutic strategy to combat AMD.
      PubDate: Tue, 21 Jul 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa158
      Issue No: Vol. 29, No. 15 (2020)
  • Protein QTL analysis of IGF-I and its binding proteins provides insights
           into growth biology
    • Authors: Bartell E; Fujimoto M, Khoury J, et al.
      Pages: 2625 - 2636
      Abstract: AbstractThe growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGF binding protein-3 (IGFBP-3), pregnancy-associated plasma protein A (PAPP-A2), IGF-II and IGFBP-5 in 838 children (3–18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated single nucleotide polymorphisms near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger causal relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.
      PubDate: Mon, 01 Jun 2020 00:00:00 GMT
      DOI: 10.1093/hmg/ddaa103
      Issue No: Vol. 29, No. 15 (2020)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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