Categoría: The American Journal of Human Genetics
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Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly
Seven individuals from five families harboring monoallelic PSMB8 variants presented with immunodeficiency and systemic inflammation. Mutant PSMB8 proteins are inefficiently incorporated into immunoproteasome complexes, impairing assembly and triggering…
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MARRVEL-MCP: An agentic interface for Mendelian disease discovery via tool-augmented context engineering
Everton et al. develop MARRVEL-MCP, a natural-language interface that enables large language models to use 44 genomic tools for rare disease variant interpretation. With tool access, small models (3B–20B) matched or outperformed larger models without t…
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Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly
Seven individuals from five families harboring monoallelic PSMB8 variants presented with immunodeficiency and systemic inflammation. Mutant PSMB8 proteins are inefficiently incorporated into immunoproteasome complexes, impairing assembly and triggering…
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MARRVEL-MCP: An agentic interface for Mendelian disease discovery via tool-augmented context engineering
Everton et al. develop MARRVEL-MCP, a natural-language interface that enables large language models to use 44 genomic tools for rare disease variant interpretation. With tool access, small models (3B–20B) matched or outperformed larger models without t…
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A phenome-wide association study of CNVs genotyped from genome sequencing read depth in the UK Biobank
We developed an accurate and highly scalable method for genotyping copy-number variants from sequencing data using read depth. Applying this to the UK Biobank, we performed phenome-wide association studies of >13,000 traits, identifying 501 CNVs associ…
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A phenome-wide association study of CNVs genotyped from genome sequencing read depth in the UK Biobank
We developed an accurate and highly scalable method for genotyping copy-number variants from sequencing data using read depth. Applying this to the UK Biobank, we performed phenome-wide association studies of >13,000 traits, identifying 501 CNVs associ…
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Genetics of skeletal proportions across two different populations
(The American Journal of Human Genetics 113, 794–808; April 2, 2026)
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Genetics of skeletal proportions across two different populations
(The American Journal of Human Genetics 113, 794–808; April 2, 2026)
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A next-generation episignature for Kabuki syndrome enables fine mapping of the impact of KMT2D variants to inform precision medicine
A next-generation KMT2D episignature, defined using the largest Kabuki syndrome type 1 cohort to date, can be used to map pathogenic variants using array or long-read platforms, to improve missense variant interpretation, and to demonstrate the diagnos…
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A next-generation episignature for Kabuki syndrome enables fine mapping of the impact of KMT2D variants to inform precision medicine
A next-generation KMT2D episignature, defined using the largest Kabuki syndrome type 1 cohort to date, can be used to map pathogenic variants using array or long-read platforms, to improve missense variant interpretation, and to demonstrate the diagnos…