Ancestry adjustment improves genome-wide estimates of regional intolerance.
Genetics
; 221(2)2022 05 31.
Article
en En
| MEDLINE
| ID: mdl-35385101
Genomic regions subject to purifying selection are more likely to carry disease-causing mutations than regions not under selection. Cross species conservation is often used to identify such regions but with limited resolution to detect selection on short evolutionary timescales such as that occurring in only one species. In contrast, genetic intolerance looks for depletion of variation relative to expectation within a species, allowing species-specific features to be identified. When estimating the intolerance of noncoding sequence, methods strongly leverage variant frequency distributions. As the expected distributions depend on ancestry, if not properly controlled for, ancestral population source may obfuscate signals of selection. We demonstrate that properly incorporating ancestry in intolerance estimation greatly improved variant classification. We provide a genome-wide intolerance map that is conditional on ancestry and likely to be particularly valuable for variant prioritization.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Genómica
Límite:
Humans
Idioma:
En
Revista:
Genetics
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos