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 Marck & 12 others Nir 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 journalArticle

68 Citations (Scopus)

Abstract

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 (US)
Article number4835
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

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sequencing
genome
Genomics
Genes
Genome
Population
Ancient History
histories
biological diversity
descent
admixtures
Gene Frequency
Haplotypes
Single Nucleotide Polymorphism
Joints
History

ASJC Scopus subject areas

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

Cite this

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. / Carmi, Shai; Hui, Ken Y.; Kochav, Ethan; Liu, Xinmin; Xue, James; Grady, Fillan; Guha, Saurav; Upadhyay, Kinnari; Ben-Avraham, Dan; Mukherjee, Semanti; Bowen, B. Monica; Thomas, Tinu; Vijai, Joseph; Cruts, Marc; Froyen, Guy; Lambrechts, Diether; Plaisance, Stéphane; Van Broeckhoven, Christine; Van Damme, Philip; Van Marck, Herwig; Barzilai, Nir; Darvasi, Ariel; Offit, Kenneth; Bressman, Susan; Ozelius, Laurie J.; Peter, Inga; Cho, Judy H.; Ostrer, Harry; Atzmon, Gil; Clark, Lorraine N.; Lencz, Todd; Pe'Er, Itsik.

In: Nature Communications, Vol. 5, 4835, 2014.

Research output: Contribution to journalArticle

Carmi, S, Hui, KY, Kochav, E, Liu, X, Xue, J, Grady, F, Guha, S, Upadhyay, K, Ben-Avraham, D, Mukherjee, S, Bowen, BM, Thomas, T, Vijai, J, Cruts, M, Froyen, G, Lambrechts, D, Plaisance, S, Van Broeckhoven, C, Van Damme, P, Van Marck, H, Barzilai, N, Darvasi, A, Offit, K, Bressman, S, Ozelius, LJ, Peter, I, Cho, JH, Ostrer, H, Atzmon, G, Clark, LN, Lencz, T & Pe'Er, I 2014, 'Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins', Nature Communications, vol. 5, 4835. https://doi.org/10.1038/ncomms5835
Carmi, Shai ; Hui, Ken Y. ; Kochav, Ethan ; Liu, Xinmin ; Xue, James ; Grady, Fillan ; Guha, Saurav ; Upadhyay, Kinnari ; Ben-Avraham, Dan ; Mukherjee, Semanti ; Bowen, B. Monica ; Thomas, Tinu ; Vijai, Joseph ; Cruts, Marc ; Froyen, Guy ; Lambrechts, Diether ; Plaisance, Stéphane ; Van Broeckhoven, Christine ; Van Damme, Philip ; Van Marck, Herwig ; Barzilai, Nir ; Darvasi, Ariel ; Offit, Kenneth ; Bressman, Susan ; Ozelius, Laurie J. ; Peter, Inga ; Cho, Judy H. ; Ostrer, Harry ; Atzmon, Gil ; Clark, Lorraine N. ; Lencz, Todd ; Pe'Er, Itsik. / Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. In: Nature Communications. 2014 ; Vol. 5.
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