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

Nat Genet. 2016 Sep;48(9):1071-6. doi: 10.1038/ng.3592. Epub 2016 Jul 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Cohort Studies
  • Consanguinity
  • Disease / genetics*
  • European Continental Ancestry Group / genetics*
  • Exome / genetics
  • Genes, Recessive
  • Genetic Markers / genetics*
  • Genetic Variation / genetics*
  • Genetics, Population*
  • Genome, Human
  • Genome-Wide Association Study
  • Homozygote
  • Human Migration
  • Humans
  • Middle East

Substances

  • Genetic Markers