Etiqueta: AmJHumGenet
-
Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline PALB2 sequence variants
(The American Journal of Human Genetics 112, 2266–2280; October 2, 2025)
-
Bi-allelic variants in OLA1 cause a neurodevelopmental disorder with joint hypermobility
Our study identifies the first human knockouts of OLA1 presenting with a hypermobility-neurodevelopmental syndrome supported by functional data derived from patient cells and C. elegans models. The work highlights OLA1 as a key regulator of microtubule…
-
BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy
We identify bi-allelic BLOC1S1 variants in 11 individuals with severe neurodevelopmental disease, including leukodystrophy, epilepsy, spasticity, and optic atrophy. Functional analyses demonstrate impaired lysosomal transport, defective autophagy, and …
-
Adaptive admixture at ACKR1, the Duffy blood group locus, may have shaped Plasmodium vivax prevalence in Oman
Genomic analyses of Omani blood donors reveal a high frequency of the FyES allele at the Duffy locus, accompanied by elevated African ancestry. These alleles were likely introduced via early African admixture and rose in frequency through positive sele…
-
Genome-wide detection of human 5′ UTR variants that impact protein translation
Chaldebas et al. develop 5ULTRA, a computational method for prioritizing 5′ UTR variants that could alter protein translation. By integrating 17 features of 5′ UTR biology into a machine-learning model, 5ULTRA identifies and prioritizes pathogenic germ…
-
The Electronic Medical Records and Genomics study: Design and analytic framework for assessing the impact of genome-informed risk assessments
The eMERGE Network implemented genome-informed risk assessment integrating polygenic, monogenic, clinical, and family history data for 11 diseases, returning results to 23,840 participants. This large prospective study evaluates whether genomic risk di…
-
Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants
Standard eQTL mapping and GWAS interpretation assume that each variant acts on one gene. However, neighboring genes can exhibit “allelic proxitropy,” where regulatory effects are shared. To identify these effects, we map QTLs on expression principal co…
-
Return of genome-informed risk-assessment results for common conditions to 23,840 adults and children: An eMERGE network study
The eMERGE Network’s multisite study of nearly 24,000 adults and children demonstrates the feasibility of returning genome-informed risk assessments for 11 diseases. Integrating polygenic risk scores with traditional factors increases high-risk identif…
-
Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes
We show that bi-allelic variants in the minor spliceosome snRNAs RNU6ATAC and RNU4ATAC cause early-onset autoimmune diabetes with immune dysregulation. We define a shared mechanism involving U12 intron retention and impaired B cell development, expandi…
-
Genetics of skeletal proportions across two different populations
Bartell et al. identify variation at hundreds of genetic loci that are associated with the sitting height ratio, a measurement of body proportion. Many are distinct from genetic associations with height. Additionally, a small number of these genetic si…