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Nat Commun. 2014 Sep 9;5:4835. doi: 10.1038/ncomms5835.

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

Author information

1
Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA.
2
Department of Internal Medicine, Genetics &Pediatrics, Yale School of Medicine, 300 Cedar Street, New Haven, Connecticut 06519, USA.
3
Department of Pathology and Cell Biology, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA.
4
1] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA [2] Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore-Long Island Jewish Health System, Glen Oaks, New York 11004, USA [3] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
5
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
6
1] Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA [2] Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
7
1] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA [2] Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore-Long Island Jewish Health System, Glen Oaks, New York 11004, USA.
8
1] Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA [2] Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
9
VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium.
10
VIB Center for the Biology of Disease, KU Leuven, Herestraat 49, bus 602, 3000 Leuven, Belgium.
11
VIB Vesalius Research Center, KU Leuven, Herestraat 49, bus 912, 3000 Leuven, Belgium.
12
VIB BioInformatics Training and Services facility, Rijvisschestraat 120, 9052 Gent, Belgium.
13
1] VIB Vesalius Research Center, KU Leuven, Herestraat 49, bus 912, 3000 Leuven, Belgium [2] Neurology Department, University Hospital Leuven, 3000 Leuven, Belgium.
14
Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
15
Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA.
16
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
17
1] Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA [2] Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
18
1] Department of Pathology and Cell Biology, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA [2] Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA.
19
1] Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA [2] Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore-Long Island Jewish Health System, Glen Oaks, New York 11004, USA [3] Departments of Psychiatry and Molecular Medicine, Hofstra University School of Medicine, Hempstead, New York 11550, USA.
20
1] Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA [2] Center for Computational Biology and Bioinformatics, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA.

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.

PMID:
25203624
PMCID:
PMC4164776
DOI:
10.1038/ncomms5835
[Indexed for MEDLINE]
Free PMC Article

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