Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency

Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral v...

Full description

Bibliographic Details
Main Authors:	Kiezun, Adam, Pulit, Sara L., Francioli, Laurent C., van Dijk, Freerk, Swertz, Morris, Boomsma, Dorret I., van Duijn, Cornelia M., Slagboom, P. Eline, van Ommen, G. J. B., Wijmenga, Cisca, de Bakker, Paul I. W., Sunyaev, Shamil R.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585140/

id	pubmed-3585140
recordtype	oai_dc
spelling	pubmed-35851402013-03-06 Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency Kiezun, Adam Pulit, Sara L. Francioli, Laurent C. van Dijk, Freerk Swertz, Morris Boomsma, Dorret I. van Duijn, Cornelia M. Slagboom, P. Eline van Ommen, G. J. B. Wijmenga, Cisca de Bakker, Paul I. W. Sunyaev, Shamil R. Research Article Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral variation consists of deleterious alleles segregating at low population frequency due to incessant mutation. To date, studies characterizing selection against deleterious alleles have been based on allele frequency (testing for a relative excess of rare alleles) or ratio of polymorphism to divergence (testing for a relative increase in the number of polymorphic alleles). Here, starting from Maruyama's theoretical prediction (Maruyama T (1974), Am J Hum Genet USA 6:669–673) that a (slightly) deleterious allele is, on average, younger than a neutral allele segregating at the same frequency, we devised an approach to characterize selection based on allelic age. Unlike existing methods, it compares sets of neutral and deleterious sequence variants at the same allele frequency. When applied to human sequence data from the Genome of the Netherlands Project, our approach distinguishes low-frequency coding non-synonymous variants from synonymous and non-coding variants at the same allele frequency and discriminates between sets of variants independently predicted to be benign or damaging for protein structure and function. The results confirm the abundance of slightly deleterious coding variation in humans. Public Library of Science 2013-02-28 /pmc/articles/PMC3585140/ /pubmed/23468643 http://dx.doi.org/10.1371/journal.pgen.1003301 Text en © 2013 Kiezun et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kiezun, Adam Pulit, Sara L. Francioli, Laurent C. van Dijk, Freerk Swertz, Morris Boomsma, Dorret I. van Duijn, Cornelia M. Slagboom, P. Eline van Ommen, G. J. B. Wijmenga, Cisca de Bakker, Paul I. W. Sunyaev, Shamil R.
spellingShingle	Kiezun, Adam Pulit, Sara L. Francioli, Laurent C. van Dijk, Freerk Swertz, Morris Boomsma, Dorret I. van Duijn, Cornelia M. Slagboom, P. Eline van Ommen, G. J. B. Wijmenga, Cisca de Bakker, Paul I. W. Sunyaev, Shamil R. Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
author_facet	Kiezun, Adam Pulit, Sara L. Francioli, Laurent C. van Dijk, Freerk Swertz, Morris Boomsma, Dorret I. van Duijn, Cornelia M. Slagboom, P. Eline van Ommen, G. J. B. Wijmenga, Cisca de Bakker, Paul I. W. Sunyaev, Shamil R.
author_sort	Kiezun, Adam
title	Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
title_short	Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
title_full	Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
title_fullStr	Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
title_full_unstemmed	Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency
title_sort	deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency
description	Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral variation consists of deleterious alleles segregating at low population frequency due to incessant mutation. To date, studies characterizing selection against deleterious alleles have been based on allele frequency (testing for a relative excess of rare alleles) or ratio of polymorphism to divergence (testing for a relative increase in the number of polymorphic alleles). Here, starting from Maruyama's theoretical prediction (Maruyama T (1974), Am J Hum Genet USA 6:669–673) that a (slightly) deleterious allele is, on average, younger than a neutral allele segregating at the same frequency, we devised an approach to characterize selection based on allelic age. Unlike existing methods, it compares sets of neutral and deleterious sequence variants at the same allele frequency. When applied to human sequence data from the Genome of the Netherlands Project, our approach distinguishes low-frequency coding non-synonymous variants from synonymous and non-coding variants at the same allele frequency and discriminates between sets of variants independently predicted to be benign or damaging for protein structure and function. The results confirm the abundance of slightly deleterious coding variation in humans.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585140/
_version_	1611958464964198400

Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency

Similar Items