Widespread purifying selection at polymorphic sites in human protein-coding loci

Austin L. Hughes, Bernice Packer, Robert Welch, Andrew W. Bergen, Stephen J. Chanock, Meredith Yeager

Research output: Contribution to journalArticle

Abstract

Estimation of gene diversity (heterozygosity) at 1,442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.

Original languageEnglish (US)
Pages (from-to)15754-15757
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number26
DOIs
StatePublished - Dec 23 2003
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Genes
Proteins
Amino Acids
Genetic Selection
Sample Size
Population
Alleles
Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Widespread purifying selection at polymorphic sites in human protein-coding loci. / Hughes, Austin L.; Packer, Bernice; Welch, Robert; Bergen, Andrew W.; Chanock, Stephen J.; Yeager, Meredith.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 26, 23.12.2003, p. 15754-15757.

Research output: Contribution to journalArticle

Hughes, Austin L. ; Packer, Bernice ; Welch, Robert ; Bergen, Andrew W. ; Chanock, Stephen J. ; Yeager, Meredith. / Widespread purifying selection at polymorphic sites in human protein-coding loci. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 26. pp. 15754-15757.
@article{03f1e06fd1ab413b97b458b4b763bf32,
title = "Widespread purifying selection at polymorphic sites in human protein-coding loci",
abstract = "Estimation of gene diversity (heterozygosity) at 1,442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.",
author = "Hughes, {Austin L.} and Bernice Packer and Robert Welch and Bergen, {Andrew W.} and Chanock, {Stephen J.} and Meredith Yeager",
year = "2003",
month = "12",
day = "23",
doi = "10.1073/pnas.2536718100",
language = "English (US)",
volume = "100",
pages = "15754--15757",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "26",

}

TY - JOUR

T1 - Widespread purifying selection at polymorphic sites in human protein-coding loci

AU - Hughes, Austin L.

AU - Packer, Bernice

AU - Welch, Robert

AU - Bergen, Andrew W.

AU - Chanock, Stephen J.

AU - Yeager, Meredith

PY - 2003/12/23

Y1 - 2003/12/23

N2 - Estimation of gene diversity (heterozygosity) at 1,442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.

AB - Estimation of gene diversity (heterozygosity) at 1,442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.

UR - http://www.scopus.com/inward/record.url?scp=0346103664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346103664&partnerID=8YFLogxK

U2 - 10.1073/pnas.2536718100

DO - 10.1073/pnas.2536718100

M3 - Article

C2 - 14660790

AN - SCOPUS:0346103664

VL - 100

SP - 15754

EP - 15757

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 26

ER -