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

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
Article number	4835
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5835
State	Published - 2014
Externally published	Yes

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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10.1038/ncomms5835

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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

@article{1c359a2070fa410a8cf586fe1a11dcb9,

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

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.",

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

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{\textquoteright}er); NSF research grants 08929882 and 0845677 (I.Pe{\textquoteright}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{\textquoteright}s Foundation (I.Peter); Edwin and Caroline Levy and Joseph and Carol Reich (S.B.); the Parkinson{\textquoteright}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: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

doi = "10.1038/ncomms5835",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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

TY - JOUR

T1 - Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

AU - Carmi, Shai

AU - Hui, Ken Y.

AU - Kochav, Ethan

AU - Liu, Xinmin

AU - Xue, James

AU - Grady, Fillan

AU - Guha, Saurav

AU - Upadhyay, Kinnari

AU - Ben-Avraham, Dan

AU - Mukherjee, Semanti

AU - Bowen, B. Monica

AU - Thomas, Tinu

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

N1 - 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.

PY - 2014

Y1 - 2014

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84917712273&partnerID=8YFLogxK

U2 - 10.1038/ncomms5835

DO - 10.1038/ncomms5835

M3 - Review article

C2 - 25203624

AN - SCOPUS:84917712273

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4835

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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