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.
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U2 - 10.1073/pnas.2536718100
DO - 10.1073/pnas.2536718100
M3 - Article
C2 - 14660790
AN - SCOPUS:0346103664
SN - 0027-8424
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
IS - 26
ER -