Genetics, Gene Therapy & Genetic Disease
Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity, and sex are the primary predictors of COVID-19 severityThe TMPRSS2 rs75603675 genotype (OR = 0.586), dyslipidemia (OR = 2.289), sex (OR = 0.586), and the Charlson Comorbidity Index (OR = 1.126) were identified as the main predictors of COVID-19 severity in 817 patients who attended Hospital Universitario de La Princesa during March and April 2020.
Distinct landscapes of deleterious variants in DNA damage repair system in ethnic human populationsDeleterious variants in the DNA damage repair system can cause genome instability and increase cancer risk. The highly ethnic-specific DDR deleterious variation from this study suggests its potential relationship with different disease susceptibility in ethnic human populations.
miR-486 is essential for muscle function and suppresses a dystrophic transcriptomeThe authors identify miR-486 as essential for normal muscle function and a driver of dystrophic transcriptomic pathways using mir-486 knockout mice and multiple sequencing platforms.
Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in miceThis longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea.
The expression of essential selenoproteins during development requires SECIS-binding protein 2–likeThis work reveals that the Sbp2 paralogue, Secisbp2-like, is required for selective selenoprotein synthesis when the function of Sbp2 is compromised.
MMD-associated RNF213 SNPs encode dominant-negative alleles that globally impair ubiquitylationMMD-associated SNPs of RNF213 encode dominant-negative alleles that globally impair ubiquitylation by RNF213-UBE2D2.
Cis-regulatory hubs: a new 3D model of complex disease genetics with an application to schizophreniaGenes and their regulatory elements are organized in neurons within 3D networks which model functional structures and explain schizophrenia genetic etiology.
Recruitment of Scc2/4 to double-strand breaks depends on γH2A and DNA end resectionDSB recruitment of the cohesin loader Scc2/4 relies on Tel1 and γH2A, but contrary to cohesin not on Mec1; binding emanates from the break site and depends on as well as coincides with end resection.
Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for reninUsing cellular models of the ADTKD–SEC61A1 causing mutations V67G and T185A, this study reveals specific aberrations of protein transport and calcium homeostasis as a potential pathogenic mechanism.
Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila musclesRbfox1 is required for the development of both fibrillar and tubular muscle fibers in adult Drosophila and interacts with Bruno1 to define fiber type–specific patterns of alternative splicing.