Characterization of greater middle eastern genetic variation for enhanced disease gene discovery
Makaleler > Tam Makale · 2016
Yazarlar: 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 Akcakus, Güzide 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, Tawfeg Ben-Omran, Parayil Sankaran Bindu, Lizbeth Blancas, Stéphanie Boisson-Dupuis, Damien Bonnet, Omar Boudghene Stambouli, Aziz Bousfiha, Lobna Boussafara, Jeannette Boutros, Jacinta Bustamante, Huseyin Caksen, Yildiz Camcioglu, Emilie Catherinot, Fatma C. Celik, Michael Ciancanelli, Funda E. Cipe, Gary Clark, Aurélie Cobat, Sinan Comu, Angela Condie, Antonio Condino-Neto, Mukesh Desai, William Dobyns, Figen Dogu, Mohamed Domaia, Meltem Dorum, Odul Egritas, Safa El Azbaoui, Jamila El Baghdadi, Mona El Ruby, Ashraf El-Harouni, Reem A. Elfeky, Gehad Elghazali, Eissa Faqeih, Elif Fenerci, Claire Fieschi, Cipe Funda, Iman Gamal, Umit Gelik, Fetah Genel, Alper Gezdirici, Katta M. Girisha, Amy Goldstein, Padraic Grattan-Smith, Neerja Gupta, Jin Hahn, Nevin Hatipoglu, Raoul Hennekam, Massoud Houshmand, Philippe Ichai, Aydan Ikinciogullari, Necil KÜTÜKÇÜLER, Neslihan KARACA
NATURE GENETICS, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Scopus, 2016, cilt 48, ss 1071-1079
DOI: 10.1038/ng.3592
Özet
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.