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

Eric M. Scott, Anason Halees, Yuval Itan, Emily G. Spencer, Yupeng He, Mostafa Abdellateef Azab, Stacey B. Gabriel, Aziz Belkadi, Bertrand Boisson, Laurent Abel, Andrew G. Clark, Sohair Abdel Rahim, Fowzan S. Alkuraya, Jean Laurent Casanova, Joseph G. Gleeson, Mohammed Abdou, Avinash Abhytankar, Parisa Adimi, Jamil Ahmad, Mustafa AkcakusGuside Aksu, Sami Al Hajjar, Suliman Al Juamaah, Saleh Al Muhsen, Nouriya Al Sannaa, Salem Al Tameni, Jumana Al-Aama, Nasir Al-Allawi, Raidah Al-Baradie, Lihadh Al-Gazali, Amal Al-Hashem, Waleed Al-Herz, Deema Al-Jeaid, Asma Al-Tawari, Abdullah Alangari, Alexandre Alcais, Tariq S. AlFawaz, Zobaida Alsum, Aomar Ammar-Khodja, Sepideh Amouian, Cigdem Arikan, Omid Aryani, Ayca Aslanger, Cigdem Aydogmus, Caner Aytekin, Matloob Azam, Boglarka Bansagi, Mohamed Rhida Barbouche, Laila Bastaki, Katta M. Girisha, Greater Middle East Variome Consortium

Research output: Contribution to journalLetterpeer-review

215 Citations (Scopus)


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
Issue number9
Publication statusPublished - 01-09-2016

All Science Journal Classification (ASJC) codes

  • Genetics


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