Etiqueta: AmJHumGenet
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This month in The Journal
The current biotechnology industry is characterized by intense competition. Although this competition can drive innovation and increased investment, too much competition can prevent collaboration and potentially foster a culture in which data and metho…
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Bi-allelic loss-of-function variants in JKAMP cause a neurodevelopmental syndrome associated with dysregulation of GPR37 trafficking
Bi-allelic loss-of-function variants in JKAMP cause a neurodevelopmental syndrome. A zebrafish jkamp knockout recapitulates key disease features. Functional studies show that JKAMP deficiency impairs folding and trafficking of the brain-enriched orphan…
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Variant interpretation training for the genomics era: Learning outcomes to inform professional competencies and education
Clear professional competencies and career pathways in variant interpretation (VI) are lacking. We co-developed learning outcomes in VI and describe how these can inform education and competencies across professions and can assist credentialing and car…
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AncientProxy: A catalog of ancient proxies for modern genetic variants
Ancient DNA enables direct observation of alleles through time. However, the utility of available ancient human genotypes is limited by a focus on ∼1.23 million variants. Here, we address this limitation by generating a catalog of ancient genotyped pro…
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Dominant and recessive ATOH1 variants cause distinct neurodevelopmental disorders with hearing loss
This study reveals that dominant and recessive variants in ATOH1, a key transcription factor for hindbrain and mechanosensory development, cause distinct syndromes. Dominant C-terminal truncating variants induce a recognizable hindbrain malformation, m…
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MDGA2 homozygous loss-of-function variants cause developmental and epileptic encephalopathy
Morsy, Kim, and Jang et al. identify homozygous loss-of-function variants in MDGA2 in individuals with autosomal-recessive developmental and epileptic encephalopathy (DEE). Functional data demonstrate impaired MDGA2 trafficking and disrupted MDGA2-depe…
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Competition in human genetic technologies: The current US legal landscape
Here, we offer a perspective on the US legal landscape regarding the promotion of competition, with specific attention given to the human genetics and genomics industry. We highlight current policy on mergers, non-competition agreements, and exclusive …
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A gene-specific variance-control approach corrects polygenicity-driven inflation observed in transcriptome-wide association studies
We show that transcriptome-wide association studies (TWAS) and related methods (xWAS) using genetic predictors suffer from inflated false-positive rates for highly polygenic complex traits, increasing linearly with sample size and heritability. We prop…
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Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders
This manuscript firmly establishes ASTN1 as a recessive neurodevelopmental disease gene, broadens the phenotypic spectrum of ASTN1-related neurodevelopmental disorders, provides further evidence for the contribution of splicing aberration to neurodevel…
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Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications
(The American Journal of Human Genetics 112, 2493–2508; October 2, 2025)