Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery.

TitleCharacterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery.
Publication TypeJournal Article
Year of Publication2016
AuthorsScott, EM, Halees, A, Itan, Y, Spencer, EG, He, Y, Azab, MAbdellatee, Gabriel, SB, Belkadi, A, Boisson, B, Abel, L, Clark, AG, Alkuraya, FS, Casanova, J-L, Gleeson, JG
Corporate AuthorsGreater Middle East Variome Consortium
JournalNat Genet
Volume48
Issue9
Pagination1071-6
Date Published2016 Sep
ISSN1546-1718
Abstract

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia, has resulted in an elevated burden of recessive disease. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized 'genetic purging'. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics.

DOI10.1038/ng.3592
Alternate JournalNat. Genet.
PubMed ID27428751
PubMed Central IDPMC5019950
Grant ListUL1 TR000043 / TR / NCATS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U01 AI088685 / AI / NIAID NIH HHS / United States
R01 AI095983 / AI / NIAID NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
R01 NS048453 / NS / NINDS NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
UL1 RR024143 / RR / NCRR NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R37 AI095983 / AI / NIAID NIH HHS / United States
P01 HD070494 / HD / NICHD NIH HHS / United States
R01 AI088364 / AI / NIAID NIH HHS / United States
P01 AI061093 / AI / NIAID NIH HHS / United States
U01 AI109697 / AI / NIAID NIH HHS / United States
R21 AI107508 / AI / NIAID NIH HHS / United States