Etiqueta: AmJHumGenet
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Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila
We characterized 100 conserved Alzheimer disease risk genes in Drosophila, uncovering dozens with previously unknown roles in brain structure, function, and stress resilience. These findings reveal pathways driving neurodegeneration and offer new insig…
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Logica: A likelihood framework for cross-ancestry local genetic correlation estimation using summary statistics
Logica estimates local cross-ancestry genetic correlation from genome-wide association study summary statistics via a bivariate linear mixed model that accounts for ancestry-specific linkage-disequilibrium structure. Across simulations and 13 traits fr…
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Bi-allelic variants in the ribosomal protein RPS6KC1 cause a complex neurodevelopmental disorder
Bi-allelic variants in RPS6KC1 cause a neurodevelopmental disorder with features overlapping with Coffin-Lowry syndrome. Functional studies reveal impaired ribosomal protein synthesis, disrupted lipid signaling, and reduced mTOR activity, highlighting …
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The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder
(The American Journal of Human Genetics 110, 963–978; June 1, 2023)
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Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans
Ploidy abnormalities affect over 1% of human embryos. Haploidy typically results from absent sperm DNA, while triploidy mainly arises from maternal meiosis II errors. Triploidy also shows a linear maternal age effect and can be characterized by genome-…
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A scalable framework for identifying allelic series from summary statistics
COAST-SS extends the coding-variant allelic series test to operate on summary statistics: per-variant effect sizes, standard errors, and local linkage disequilibrium (LD). COAST-SS controls the type I error, is robust to LD misspecification, and enable…
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The utility of ultra-deep RNA sequencing in Mendelian disorder diagnostics
RNA sequencing has emerged as a powerful tool for Mendelian disorder diagnostics, but the optimized sequencing depth has not been determined. Using Ultra-high-depth RNA sequencing (up to 1 billion reads), we improved detection of low-abundance genes an…
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COMPADRE: Combined pedigree-aware distant relatedness estimation for improved pedigree reconstruction
COMPADRE improves pedigree reconstruction through a novel combination of genome-wide IBD-sharing estimates with shared IBD segment data. COMPADRE achieves higher accuracy in comparison to existing tools, especially in pedigrees with many ungenotyped in…
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A scalable approach for genomic-first rare disorder detection in a healthcare-based population
Beyond commonly screened disorders, genomic-first ascertainment of genetic disorders remains underexplored. We developed a scalable framework for 2,701 additional rare genetic disorders, identifying pathogenic variants in 3.2% of a healthcare-based coh…
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Distinguishing syndromic and nonsyndromic cleft palate through analysis of protein-altering de novo variants in 818 trios
Cleft palate probands are globally enriched for protein-altering de novo variants, and gene-specific enrichment was found for seven cleft-related genes. Differences in individuals with syndromic versus nonsyndromic cleft palate were observed, although …