Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Shai Carmi, Ken Y. Hui, Ethan Kochav, Xinmin Liu, James Xue, Fillan Grady, Saurav Guha, Kinnari Upadhyay, Dan Ben-Avraham, Semanti Mukherjee, B. Monica Bowen, Tinu Thomas, Joseph Vijai, Marc Cruts, Guy Froyen, Diether Lambrechts, Stéphane Plaisance, Christine Van Broeckhoven, Philip Van Damme, Herwig Van MarckNir Barzilai, Ariel Darvasi, Kenneth Offit, Susan Bressman, Laurie J. Ozelius, Inga Peter, Judy H. Cho, Harry Ostrer, Gil Atzmon, Lorraine N. Clark, Todd Lencz, Itsik Pe'Er

Research output: Contribution to journalReview articlepeer-review


The Ashkenazi Jewish (AJ) population is a genetic isolate close to European and Middle Eastern groups, with genetic diversity patterns conducive to disease mapping. Here we report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Our panel improves imputation accuracy for AJ SNP arrays by 28%, and covers at least one haplotype in ∼67% of any AJ genome with long, identical-by-descent segments. Reconstruction of recent AJ history from such segments confirms a recent bottleneck of merely ∼350 individuals. Modelling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. We date the split between the two ancestral populations to ∼12-25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.

Original languageEnglish
Article number4835
JournalNature Communications
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
We thank Shlomo Hershkop for technical assistance and Barry Moore and Omicia Inc. for providing a disease gene catalogue. We thank Adam Auton and Alon Keinan for commenting on the manuscript. We acknowledge financial support from the Human Frontier Science Program (S.C.); NIH research grants AG042188 (G.A.), DK62429, DK062422, DK092235 (J.H.C.), NS050487, NS060113 (L.N.C.), AG021654, AG027734 (N.B.), MH089964, MH095458, MH084098 (T.L.), GM007205, DK098927 (K.Y.H.), and CA121852 (computational infrastructure, I.Pe’er); NSF research grants 08929882 and 0845677 (I.Pe’er); Rachel and Lewis Rudin Foundation (H.O.); North Shore–LIJ Health System Foundation (T.L.); Brain & Behaviour Foundation (T.L.); US-Israel Binational Science Foundation (T.L., A.D.); New York Crohn’s Foundation (I.Peter); Edwin and Caroline Levy and Joseph and Carol Reich (S.B.); the Parkinson’s Disease Foundation (L.N.C.); the Sharon Levine Corzine Cancer Research Fund (K.O.); and the Andrew Sabin Family Research Fund (K.O.).

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • General
  • Physics and Astronomy (all)


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