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.
authors.affiliation: Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA.
authors.forename: Shai
authors.initials: S
authors.lastname: Carmi
authors.affiliation: Department of Internal Medicine, Genetics &Pediatrics, Yale School of Medicine, 300 Cedar Street, New Haven, Connecticut 06519, USA.
authors.forename: Ken Y
authors.initials: KY
authors.lastname: Hui
authors.affiliation: Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Kochav
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA.
authors.forename: James
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Computer Science, Columbia University, 500 W 120th Street, New York, New York 10027, USA.
authors.forename: Fillan
authors.initials: F
authors.lastname: Grady
authors.affiliation: 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.
authors.forename: Saurav
authors.initials: S
authors.lastname: Guha
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Kinnari
authors.initials: K
authors.lastname: Upadhyay
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Ben-Avraham
authors.affiliation: 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.
authors.forename: Semanti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Internal Medicine, Genetics &Pediatrics, Yale School of Medicine, 300 Cedar Street, New Haven, Connecticut 06519, USA.
authors.forename: B Monica
authors.initials: BM
authors.lastname: Bowen
authors.affiliation: 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.
authors.forename: Tinu
authors.initials: T
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Joseph
authors.initials: J
authors.lastname: Vijai
authors.affiliation: VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.affiliation: VIB Center for the Biology of Disease, KU Leuven, Herestraat 49, bus 602, 3000 Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.affiliation: VIB Vesalius Research Center, KU Leuven, Herestraat 49, bus 912, 3000 Leuven, Belgium.
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.affiliation: VIB BioInformatics Training and Services facility, Rijvisschestraat 120, 9052 Gent, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Plaisance
authors.affiliation: VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.affiliation: 1] VIB Vesalius Research Center, KU Leuven, Herestraat 49, bus 912, 3000 Leuven, Belgium [2] Neurology Department, University Hospital Leuven, 3000 Leuven, Belgium.
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: VIB BioInformatics Training and Services facility, Rijvisschestraat 120, 9052 Gent, Belgium.
authors.forename: Herwig
authors.initials: H
authors.lastname: Van Marck
authors.affiliation: 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.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.affiliation: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Darvasi
authors.affiliation: 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.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.affiliation: Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine, Genetics &Pediatrics, Yale School of Medicine, 300 Cedar Street, New Haven, Connecticut 06519, USA.
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
authors.affiliation: 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.
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.affiliation: 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.
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
authors.affiliation: 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.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: 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.
authors.forename: Itsik
authors.initials: I
authors.lastname: Pe'er
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D016678:Genome; D023281:Genomics; D064368:Healthy Volunteers; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*