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Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery
The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Gulf region, North Africa, and Central Asia (1–3), has resulted in an elevated burden of recessive disease(4). Here we generated a whole exome G...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019950/ https://www.ncbi.nlm.nih.gov/pubmed/27428751 http://dx.doi.org/10.1038/ng.3592 |
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author | Scott, Eric M. Halees, Anason Itan, Yuval Spencer, Emily G. He, Yupeng Azab, Mostafa Abdellateef Gabriel, Stacey B. Belkadi, Aziz Boisson, Bertrand Abel, Laurent Clark, Andrew G. Alkuraya, Fowzan S. Casanova, Jean-Laurent Gleeson, Joseph G. |
author_facet | Scott, Eric M. Halees, Anason Itan, Yuval Spencer, Emily G. He, Yupeng Azab, Mostafa Abdellateef Gabriel, Stacey B. Belkadi, Aziz Boisson, Bertrand Abel, Laurent Clark, Andrew G. Alkuraya, Fowzan S. Casanova, Jean-Laurent Gleeson, Joseph G. |
author_sort | Scott, Eric M. |
collection | PubMed |
description | The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Gulf region, North Africa, and Central Asia (1–3), has resulted in an elevated burden of recessive disease(4). Here we generated a whole exome GME variome from 1,111 unrelated subjects. We detected substantial diversity from sub-geographies, continental and subregional admixture, several ancient founder populations with little evidence of bottlenecks. Measured consanguinity was an order-of-magnitude above that of other sampled populations, and included an increased burden of runs of homozygosity (ROH), but no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved GME recessive conditions reduced the number of potential disease-causing variants by 4–7-fold. These results reveal the variegated GME genetic architecture and support future human genetic discoveries in Mendelian and population genetics. |
format | Online Article Text |
id | pubmed-5019950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-50199502017-01-18 Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery Scott, Eric M. Halees, Anason Itan, Yuval Spencer, Emily G. He, Yupeng Azab, Mostafa Abdellateef Gabriel, Stacey B. Belkadi, Aziz Boisson, Bertrand Abel, Laurent Clark, Andrew G. Alkuraya, Fowzan S. Casanova, Jean-Laurent Gleeson, Joseph G. Nat Genet Article The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Gulf region, North Africa, and Central Asia (1–3), has resulted in an elevated burden of recessive disease(4). Here we generated a whole exome GME variome from 1,111 unrelated subjects. We detected substantial diversity from sub-geographies, continental and subregional admixture, several ancient founder populations with little evidence of bottlenecks. Measured consanguinity was an order-of-magnitude above that of other sampled populations, and included an increased burden of runs of homozygosity (ROH), but no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved GME recessive conditions reduced the number of potential disease-causing variants by 4–7-fold. These results reveal the variegated GME genetic architecture and support future human genetic discoveries in Mendelian and population genetics. 2016-07-18 2016-09 /pmc/articles/PMC5019950/ /pubmed/27428751 http://dx.doi.org/10.1038/ng.3592 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Scott, Eric M. Halees, Anason Itan, Yuval Spencer, Emily G. He, Yupeng Azab, Mostafa Abdellateef Gabriel, Stacey B. Belkadi, Aziz Boisson, Bertrand Abel, Laurent Clark, Andrew G. Alkuraya, Fowzan S. Casanova, Jean-Laurent Gleeson, Joseph G. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title | Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title_full | Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title_fullStr | Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title_full_unstemmed | Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title_short | Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery |
title_sort | characterization of greater middle eastern genetic variation for enhanced disease gene discovery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019950/ https://www.ncbi.nlm.nih.gov/pubmed/27428751 http://dx.doi.org/10.1038/ng.3592 |
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