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; 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

doi:10.1038/ncomms5835

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 journal › Review article › peer-review

120 Scopus citations

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 language	English (US)
Article number	4835
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5835
State	Published - 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Carmi, S., Hui, K. Y., Kochav, E., Liu, X., Xue, J., Grady, F., Guha, S., Upadhyay, K., Ben-Avraham, D., Mukherjee, S., Bowen, B. M., Thomas, T., Vijai, J., Cruts, M., Froyen, G., Lambrechts, D., Plaisance, S., Van Broeckhoven, C., Van Damme, P., ... Pe'Er, I. (2014). Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins. Nature communications, 5, Article 4835. https://doi.org/10.1038/ncomms5835

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

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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.",

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AU - Carmi, Shai

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AU - Kochav, Ethan

AU - Liu, Xinmin

AU - Xue, James

AU - Grady, Fillan

AU - Guha, Saurav

AU - Upadhyay, Kinnari

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AU - Vijai, Joseph

AU - Cruts, Marc

AU - Froyen, Guy

AU - Lambrechts, Diether

AU - Plaisance, Stéphane

AU - Van Broeckhoven, Christine

AU - Van Damme, Philip

AU - Van Marck, Herwig

AU - Barzilai, Nir

AU - Darvasi, Ariel

AU - Offit, Kenneth

AU - Bressman, Susan

AU - Ozelius, Laurie J.

AU - Peter, Inga

AU - Cho, Judy H.

AU - Ostrer, Harry

AU - Atzmon, Gil

AU - Clark, Lorraine N.

AU - Lencz, Todd

AU - Pe'Er, Itsik

PY - 2014

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N2 - 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.

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

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