Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

Greater Middle East Variome Consortium

Research output: Contribution to journalLetter

74 Citations (Scopus)

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 Asia1-3, has resulted in an elevated burden of recessive disease4. 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.

Original languageEnglish
Pages (from-to)1071-1079
Number of pages9
JournalNature Genetics
Volume48
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016
Externally publishedYes

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Genetic Association Studies
Middle East
Population
Consanguinity
Human Migration
Exome
Indian Ocean
Northern Africa
Medical Genetics
Population Genetics
Databases

ASJC Scopus subject areas

  • Genetics

Cite this

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery. / Greater Middle East Variome Consortium.

In: Nature Genetics, Vol. 48, No. 9, 01.09.2016, p. 1071-1079.

Research output: Contribution to journalLetter

Greater Middle East Variome Consortium. / Characterization of greater middle eastern genetic variation for enhanced disease gene discovery. In: Nature Genetics. 2016 ; Vol. 48, No. 9. pp. 1071-1079.
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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 Asia1-3, has resulted in an elevated burden of recessive disease4. 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.",
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AU - Azab, Mostafa Abdellateef

AU - Gabriel, Stacey B.

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AU - Aslanger, Ayca

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AU - Aytekin, Caner

AU - Azam, Matloob

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N2 - 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 Asia1-3, has resulted in an elevated burden of recessive disease4. 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.

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