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Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics
This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652078/ https://www.ncbi.nlm.nih.gov/pubmed/19282984 http://dx.doi.org/10.1371/journal.pgen.1000415 |
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author | Nalls, Michael A. Simon-Sanchez, Javier Gibbs, J. Raphael Paisan-Ruiz, Coro Bras, Jose Tomas Tanaka, Toshiko Matarin, Mar Scholz, Sonja Weitz, Charles Harris, Tamara B. Ferrucci, Luigi Hardy, John Singleton, Andrew B. |
author_facet | Nalls, Michael A. Simon-Sanchez, Javier Gibbs, J. Raphael Paisan-Ruiz, Coro Bras, Jose Tomas Tanaka, Toshiko Matarin, Mar Scholz, Sonja Weitz, Charles Harris, Tamara B. Ferrucci, Luigi Hardy, John Singleton, Andrew B. |
author_sort | Nalls, Michael A. |
collection | PubMed |
description | This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so. |
format | Text |
id | pubmed-2652078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26520782009-03-13 Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics Nalls, Michael A. Simon-Sanchez, Javier Gibbs, J. Raphael Paisan-Ruiz, Coro Bras, Jose Tomas Tanaka, Toshiko Matarin, Mar Scholz, Sonja Weitz, Charles Harris, Tamara B. Ferrucci, Luigi Hardy, John Singleton, Andrew B. PLoS Genet Research Article This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so. Public Library of Science 2009-03-13 /pmc/articles/PMC2652078/ /pubmed/19282984 http://dx.doi.org/10.1371/journal.pgen.1000415 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Nalls, Michael A. Simon-Sanchez, Javier Gibbs, J. Raphael Paisan-Ruiz, Coro Bras, Jose Tomas Tanaka, Toshiko Matarin, Mar Scholz, Sonja Weitz, Charles Harris, Tamara B. Ferrucci, Luigi Hardy, John Singleton, Andrew B. Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title | Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title_full | Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title_fullStr | Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title_full_unstemmed | Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title_short | Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics |
title_sort | measures of autozygosity in decline: globalization, urbanization, and its implications for medical genetics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652078/ https://www.ncbi.nlm.nih.gov/pubmed/19282984 http://dx.doi.org/10.1371/journal.pgen.1000415 |
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