The time and place of European admixture in Ashkenazi Jewish history

The Ashkenazi Jewish (AJ) population is important in genetics due to its high rate of Mendelian disorders. AJ appeared in Europe in the 10th century, and their ancestry is thought to comprise European (EU) and Middle-Eastern (ME) components. However, both the time and place of admixture are subject to debate. Here, we attempt to characterize the AJ admixture history using a careful application of new and existing methods on a large AJ sample. Our main approach was based on local ancestry inference, in which we first classified each AJ genomic segment as EU or ME, and then compared allele frequencies along the EU segments to those of different EU populations. The contribution of each EU source was also estimated using GLOBETROTTER and haplotype sharing. The time of admixture was inferred based on multiple statistics, including ME segment lengths, the total EU ancestry per chromosome, and the correlation of ancestries along the chromosome. The major source of EU ancestry in AJ was found to be Southern Europe (≈60–80% of EU ancestry), with the rest being likely Eastern European. The inferred admixture time was ≈30 generations ago, but multiple lines of evidence suggest that it represents an average over two or more events, pre- and post-dating the founder event experienced by AJ in late medieval times. The time of the pre-bottleneck admixture event, which was likely Southern European, was estimated to ≈25–50 generations ago.

[1]  Swapan Mallick,et al.  Ancient Admixture in Human History , 2012, Genetics.

[2]  Cory Y. McLean,et al.  Reducing Pervasive False-Positive Identical-by-Descent Segments Detected by Large-Scale Pedigree Analysis , 2013, Molecular biology and evolution.

[3]  J. Marchini,et al.  Multiway Admixture Deconvolution Using Phased or Unphased Ancestral Panels , 2013, Genetic epidemiology.

[4]  R. Nielsen,et al.  Understanding Admixture Fractions , 2014, bioRxiv.

[5]  Noah A. Rosenberg,et al.  A General Mechanistic Model for Admixture Histories of Hybrid Populations , 2011, Genetics.

[6]  S. Rasmussen,et al.  Genome-wide Ancestry Patterns in Rapanui Suggest Pre-European Admixture with Native Americans , 2014, Current Biology.

[7]  Kenneth Offit,et al.  Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins , 2014, Nature Communications.

[8]  Saharon Rosset,et al.  The genome-wide structure of the Jewish people , 2010, Nature.

[9]  H. Ostrer,et al.  Contrasting patterns of Y chromosome variation in Ashkenazi Jewish and host non-Jewish European populations , 2004, Human Genetics.

[10]  Christopher R. Gignoux,et al.  Reconstructing Native American Migrations from Whole-Genome and Whole-Exome Data , 2013, PLoS genetics.

[11]  A. Motulsky.  Jewish diseases and origins , 1995, Nature Genetics.

[12]  Eran Halperin,et al.  Inference of locus-specific ancestry in closely related populations , 2009, Bioinform..

[13]  B. Weinryb.  The Jews of Poland: A Social and Economic History of the Jewish Community in Poland from 1100 to 1800 , 1972 .

[14]  C. Tyler-Smith,et al.  Genome-Wide Diversity in the Levant Reveals Recent Structuring by Culture , 2013, PLoS genetics.

[15]  O. Delaneau,et al.  Supplementary Information for ‘ Improved whole chromosome phasing for disease and population genetic studies ’ , 2012 .

[16]  John Wakeley,et al.  A renewal theory approach to IBD sharing. , 2014, Theoretical population biology.

[17]  A. Clark,et al.  Population genetic structure of the people of Qatar. , 2010, American journal of human genetics.

[18]  Alexander Gusev,et al.  Whole population, genome-wide mapping of hidden relatedness. , 2009, Genome research.

[19]  M. Stoneking,et al.  Dating the age of admixture via wavelet transform analysis of genome-wide data , 2011, Genome Biology.

[20]  H. Ostrer,et al.  The History of African Gene Flow into Southern Europeans, Levantines, and Jews , 2011, PLoS genetics.

[21]  M. Slatkin.  A population-genetic test of founder effects and implications for Ashkenazi Jewish diseases. , 2004, American journal of human genetics.

[22]  E. Elhaik.  The Missing Link of Jewish European Ancestry: Contrasting the Rhineland and the Khazarian Hypotheses , 2012, Genome biology and evolution.

[23]  Christopher R. Gignoux,et al.  Gene flow from North Africa contributes to differential human genetic diversity in southern Europe , 2013, Proceedings of the National Academy of Sciences.

[24]  Itsik Pe'er,et al.  Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry. , 2010, American journal of human genetics.

[25]  Joseph K. Pickrell,et al.  Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium , 2012, Genetics.

[26]  David H. Alexander,et al.  Fast model-based estimation of ancestry in unrelated individuals. , 2009, Genome research.

[27]  N. Risch,et al.  Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection. , 2003, American journal of human genetics.

[28]  M. Feldman,et al.  Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation , 2008 .

[29]  Sergio Baranzini,et al.  Detection of identity by descent using next-generation whole genome sequencing data , 2012, BMC Bioinformatics.

[30]  Annette Lee,et al.  Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder , 2013, Nature Communications.

[31]  D. Reich,et al.  Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations , 2009, PLoS genetics.

[32]  S. Gravel.  Population Genetics Models of Local Ancestry , 2012, Genetics.

[33]  Ryan D. Hernandez,et al.  Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data , 2009, PLoS genetics.

[34]  John Wakeley,et al.  Gene Genealogies Within a Fixed Pedigree, and the Robustness of Kingman’s Coalescent , 2012, Genetics.

[35]  R. Kaplan,et al.  Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL) , 2016, G3: Genes, Genomes, Genetics.

[36]  A. Clark,et al.  Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations , 2016, Genome research.

[37]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[38]  L. Excoffier,et al.  Robust Demographic Inference from Genomic and SNP Data , 2013, PLoS genetics.

[39]  Vladimir Vacic,et al.  The Variance of Identity-by-Descent Sharing in the Wright–Fisher Model , 2012, Genetics.

[40]  D. Falush,et al.  A Genetic Atlas of Human Admixture History , 2014, Science.

[41]  David Comas,et al.  North African Jewish and non-Jewish populations form distinctive, orthogonal clusters , 2012, Proceedings of the National Academy of Sciences.

[42]  M. Feldman,et al.  Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations , 2009, BMC Genetics.

[43]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[44]  D. Reich,et al.  Population Structure and Eigenanalysis , 2006, PLoS genetics.

[45]  Kenny Q. Ye,et al.  An integrated map of genetic variation from 1,092 human genomes , 2012, Nature.

[46]  Ariella L. Gladstein,et al.  No Evidence from Genome-Wide Data of a Khazar Origin for the Ashkenazi Jews , 2013, Human biology.

[47]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[48]  H. Ostrer,et al.  The impact of Converso Jews on the genomes of modern Latin Americans , 2011, Human Genetics.

[49]  R. Nielsen,et al.  Inference of Historical Changes in Migration Rate From the Lengths of Migrant Tracts , 2009, Genetics.

[50]  C. Bustamante,et al.  RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference. , 2013, American journal of human genetics.

[51]  J. M. Luck,et al.  Statistics of the Occupation Time of Renewal Processes , 2000, cond-mat/0010428.

[52]  R. Nielsen,et al.  The Lengths of Admixture Tracts , 2014, Genetics.

[53]  Nicholas A. Johnson,et al.  Ancestral Components of Admixed Genomes in a Mexican Cohort , 2011, PLoS genetics.

[54]  I. Pe’er,et al.  Length distributions of identity by descent reveal fine-scale demographic history. , 2012, American journal of human genetics.

[55]  A. Salas,et al.  A Genome-Wide Study of Modern-Day Tuscans: Revisiting Herodotus's Theory on the Origin of the Etruscans , 2014, PloS one.

[56]  D. Gurwitz,et al.  The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event. , 2006, American journal of human genetics.

[57]  Joseph K. Pickrell,et al.  Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data , 2012, PLoS genetics.

[58]  Alexander Gusev,et al.  The architecture of long-range haplotypes shared within and across populations. , 2012, Molecular biology and evolution.

[59]  Aging correlation functions for blinking nanocrystals, and other on-off stochastic processes. , 2004, The Journal of chemical physics.

[60]  Y. Bartal.  The Jews of Eastern Europe, 1772-1881 , 2005 .

[61]  M. Pirinen,et al.  The fine-scale genetic structure of the British population , 2015, Nature.

[62]  E. Xing,et al.  Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions , 2015, bioRxiv.

[63]  Mark George Thomas,et al.  Pitfalls of the Geographic Population Structure (GPS) Approach Applied to Human Genetic History: A Case Study of Ashkenazi Jews , 2016, Genome biology and evolution.

[64]  Itsik Pe'er,et al.  Inference of historical migration rates via haplotype sharing , 2013, Bioinform..

[65]  The Jews: A Study in Race and Environment , 1911 .

[66]  W. Scott.  The Jews: A Study of Race and Environment , 1911, Bristol Medico-Chirurgical Journal (1883).

[67]  D. Falush,et al.  Inference of Population Structure using Dense Haplotype Data , 2012, PLoS genetics.

[68]  Itsik Pe'er,et al.  Implications for health and disease in the genetic signature of the Ashkenazi Jewish population , 2012, Genome Biology.

[69]  S. Carmi,et al.  A non-zero variance of Tajima’s estimator for two sequences even for infinitely many unlinked loci , 2016, bioRxiv.

[70]  S. Warren,et al.  Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population , 2010, Proceedings of the National Academy of Sciences.

[71]  Pedro C. Avila,et al.  Fast and accurate inference of local ancestry in Latino populations , 2012, Bioinform..

[72]  Jake K. Byrnes,et al.  Reconstructing the Population Genetic History of the Caribbean , 2013, PLoS genetics.

[73]  N. Rosenberg,et al.  Autosomal Admixture Levels Are Informative About Sex Bias in Admixed Populations , 2014, Genetics.

[74]  P. Stam,et al.  The distribution of the fraction of the genome identical by descent in finite random mating populations , 1980 .