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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
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.
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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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