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Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome

MOTIVATION: Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. However, the factors that affect SNP density are poorly understood. The goal of this study was to estimate the relative effects of mutability and selection on SNP density in transcribed region...

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Autores principales: Gorlov, Ivan P, Gorlova, Olga Y, Amos, Christopher I
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442617/
https://www.ncbi.nlm.nih.gov/pubmed/18559102
http://dx.doi.org/10.1186/1471-2164-9-292
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author Gorlov, Ivan P
Gorlova, Olga Y
Amos, Christopher I
author_facet Gorlov, Ivan P
Gorlova, Olga Y
Amos, Christopher I
author_sort Gorlov, Ivan P
collection PubMed
description MOTIVATION: Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. However, the factors that affect SNP density are poorly understood. The goal of this study was to estimate the relative effects of mutability and selection on SNP density in transcribed regions of human genes. It is important for prediction of the regions that harbor functional polymorphisms. RESULTS: We used frequency-validated SNPs resulting from single-nucleotide substitutions. SNPs were subdivided into five functional categories: (i) 5' untranslated region (UTR) SNPs, (ii) 3' UTR SNPs, (iii) synonymous SNPs, (iv) SNPs producing conservative missense mutations, and (v) SNPs producing radical missense mutations. Each of these categories was further subdivided into nine mutational categories on the basis of the single-nucleotide substitution type. Thus, 45 functional/mutational categories were analyzed. The relative mutation rate in each mutational category was estimated on the basis of published data. The proportion of segregating sites (PSSs) for each functional/mutational category was estimated by dividing the observed number of SNPs by the number of potential sites in the genome for a given functional/mutational category. By analyzing each functional group separately, we found significant positive correlations between PSSs and relative mutation rates (Spearman's correlation coefficient, at least r = 0.96, df = 9, P < 0.001). We adjusted the PSSs for the mutation rate and found that the functional category had a significant effect on SNP density (F = 5.9, df = 4, P = 0.001), suggesting that selection affects SNP density in transcribed regions of the genome. We used analyses of variance and covariance to estimate the relative effects of selection (functional category) and mutability (relative mutation rate) on the PSSs and found that approximately 87% of variation in PSS was due to variation in the mutation rate and approximately 13% was due to selection, suggesting that the probability that a site located in a transcribed region of a gene is polymorphic mostly depends on the mutability of the site.
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spelling pubmed-24426172008-07-02 Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome Gorlov, Ivan P Gorlova, Olga Y Amos, Christopher I BMC Genomics Research Article MOTIVATION: Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. However, the factors that affect SNP density are poorly understood. The goal of this study was to estimate the relative effects of mutability and selection on SNP density in transcribed regions of human genes. It is important for prediction of the regions that harbor functional polymorphisms. RESULTS: We used frequency-validated SNPs resulting from single-nucleotide substitutions. SNPs were subdivided into five functional categories: (i) 5' untranslated region (UTR) SNPs, (ii) 3' UTR SNPs, (iii) synonymous SNPs, (iv) SNPs producing conservative missense mutations, and (v) SNPs producing radical missense mutations. Each of these categories was further subdivided into nine mutational categories on the basis of the single-nucleotide substitution type. Thus, 45 functional/mutational categories were analyzed. The relative mutation rate in each mutational category was estimated on the basis of published data. The proportion of segregating sites (PSSs) for each functional/mutational category was estimated by dividing the observed number of SNPs by the number of potential sites in the genome for a given functional/mutational category. By analyzing each functional group separately, we found significant positive correlations between PSSs and relative mutation rates (Spearman's correlation coefficient, at least r = 0.96, df = 9, P < 0.001). We adjusted the PSSs for the mutation rate and found that the functional category had a significant effect on SNP density (F = 5.9, df = 4, P = 0.001), suggesting that selection affects SNP density in transcribed regions of the genome. We used analyses of variance and covariance to estimate the relative effects of selection (functional category) and mutability (relative mutation rate) on the PSSs and found that approximately 87% of variation in PSS was due to variation in the mutation rate and approximately 13% was due to selection, suggesting that the probability that a site located in a transcribed region of a gene is polymorphic mostly depends on the mutability of the site. BioMed Central 2008-06-17 /pmc/articles/PMC2442617/ /pubmed/18559102 http://dx.doi.org/10.1186/1471-2164-9-292 Text en Copyright © 2008 Gorlov et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gorlov, Ivan P
Gorlova, Olga Y
Amos, Christopher I
Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title_full Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title_fullStr Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title_full_unstemmed Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title_short Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
title_sort relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442617/
https://www.ncbi.nlm.nih.gov/pubmed/18559102
http://dx.doi.org/10.1186/1471-2164-9-292
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