Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Am J Hum Genet. 2011 Apr 8;88(4):458-68. doi: 10.1016/j.ajhg.2011.03.008. Epub 2011 Mar 31.

A genome-wide comparison of the functional properties of rare and common genetic variants in humans.

Author information

  • 1Center for Human Genome Variation, Duke University School of Medicine, Durham, NC 27708, USA.

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.

Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PMID:
21457907
[PubMed - indexed for MEDLINE]
PMCID:
PMC3071924
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Write to the Help Desk