1. A genome-wide spectrum of tandem repeat expansions in 338,963 humans
- Author
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Cui, Ya, Ye, Wenbin, Li, Jason Sheng, Li, Jingyi Jessica, Vilain, Eric, Sallam, Tamer, and Li, Wei
- Subjects
Biological Sciences ,Genetics ,Human Genome ,Neurodegenerative ,Good Health and Well Being ,Humans ,Genome ,Human ,Tandem Repeat Sequences ,Whole Genome Sequencing ,Databases ,Genetic ,DNA Repeat Expansion ,Genome-Wide Association Study ,GWAS ,TR-gnomAD ,ancestries ,expansion ,genome aggregation ,human genetics ,missing heritability ,rare diseases ,tandem repeat ,whole genome sequencing ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
The Genome Aggregation Database (gnomAD), widely recognized as the gold-standard reference map of human genetic variation, has largely overlooked tandem repeat (TR) expansions, despite the fact that TRs constitute ∼6% of our genome and are linked to over 50 human diseases. Here, we introduce the TR-gnomAD (https://wlcb.oit.uci.edu/TRgnomAD), a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries (39.5% non-European samples). TR-gnomAD offers critical insights into ancestry-specific disease prevalence using disparities in TR unit number frequencies among ancestries. Moreover, TR-gnomAD is able to differentiate between common, presumably benign TR expansions, which are prevalent in TR-gnomAD, from those potentially pathogenic TR expansions, which are found more frequently in disease groups than within TR-gnomAD. Together, TR-gnomAD is an invaluable resource for researchers and physicians to interpret TR expansions in individuals with genetic diseases.
- Published
- 2024