A genome-wide comparison of the functional properties of rare and common genetic variants in humans.
Am J Hum Genet
; 88(4): 458-68, 2011 Apr 08.
Article
en En
| MEDLINE
| ID: mdl-21457907
ABSTRACT
One of the longest running debates in evolutionary biology concerns the kind of genetic variation that is primarily responsible for phenotypic variation in species. Here, we address this question for humans specifically from the perspective of population allele frequency of variants across the complete genome, including both coding and noncoding regions. We establish simple criteria to assess the likelihood that variants are functional based on their genomic locations and then use whole-genome sequence data from 29 subjects of European origin to assess the relationship between the functional properties of variants and their population allele frequencies. We find that for all criteria used to assess the likelihood that a variant is functional, the rarer variants are significantly more likely to be functional than the more common variants. Strikingly, these patterns disappear when we focus on only those variants in which the major alleles are derived. These analyses indicate that the majority of the genetic variation in terms of phenotypic consequence may result from a mutation-selection balance, as opposed to balancing selection, and have direct relevance to the study of human disease.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos