The Time and Place of European Gene Flow into Ashkenazi Jews

Slides:

Advertisements

Similar presentations

The Ashkenazi Genome Project

Advertisements

M168 M89 M91 M96 M60 M304 M170 M130 M201 M52 NEXT.

IBD sharing: Theory and applications in the Ashkenazi Jewish population Shai Carmi Pe’er lab, Columbia University Mt. Sinai, NY March 2014.

Genetic Patterns of Ashkenazi Jews Victoria Olson.

Patterns of population structure and admixture among human populations Katarzyna Bryc OEB 275br February 19, 2013.

MALD Mapping by Admixture Linkage Disequilibrium.

Methods and challenges in the analysis of admixed human genomes Simon Gravel Stanford University.

Human Migrations Saeed Hassanpour Spring Introduction Population Genetics Co-evolution of genes with language and cultural. Human evolution: genetics,

Imputation-based local ancestry inference in admixed populations Ion Mandoiu Computer Science and Engineering Department University of Connecticut Joint.

Out-of-Africa Theory: The Origin Of Modern Humans

Sequencing an Ashkenazi Jewish Reference Cohort for Medical Genetics and Implications for Ashkenazi History Shai Carmi Department of Computer Science Columbia.

Sequencing 128 Ashkenazi Genomes: Implications for Medical Genetics and History Shai Carmi Department of Computer Science Columbia University Itsik Pe’er’s.

Differential relatedness of African Americans to populations within West Africa Katarzyna Bryc 1**, Amy Williams 1**, Nick Patterson 2, Solomon Musani.

The Ashkenazi Genome Project Shai Carmi Pe’er lab, Columbia University and The Ashkenazi Genome Consortium (TAGC) Boston September 2013.

The Ashkenazi Genome Project Shai Carmi Pe’er lab, Columbia University and The Ashkenazi Genome Consortium (TAGC) Personal Genomes & Medical Genomics Cold.

Hidenki Innan and Yuseob Kim Pattern of Polymorphism After Strong Artificial Selection in a Domestication Event Hidenki Innan and Yuseob Kim A Summary.

Sharing of long genomic segments: Theory and results in Ashkenazi Jews Bar-Ilan University July 26, 2012 Shai Carmi Itsik Pe’er’s lab Department of Computer.

The Ashkenazi Genome Project

Length Distributions of Identity by Descent Reveal Fine-Scale Demographic History Pier Francesco Palamara, Todd Lencz, Ariel Darvasi, Itsik Pe’er The American.

MStruct: A New Admixture Model for Inference of Population Structure in Light of Both Genetic Admixing and Allele Mutations Suyash Shringarpure and Eric.

Evolution as Genetic Change in Populations. Learning Objectives  Explain how natural selection affects single-gene and polygenic traits.  Describe genetic.

Recombination based population genomics Jaume Bertranpetit Marta Melé Francesc Calafell Asif Javed Laxmi Parida.

Directional selection When individuals at one end of the curve have a higher fitness than individuals in the middle or at the other end.

Imputation-based local ancestry inference in admixed populations

Separation of the largest eigenvalues in eigenanalysis of genotype data from discrete populations Katarzyna Bryc Postdoctoral Fellow, Reich Lab, Harvard.

The distribution of the IBD sharing and applications Tel Aviv University July 23, 2012 Shai Carmi Itsik Pe’er’s lab Department of Computer Science Columbia.

Biostatistics-Lecture 19 Linkage Disequilibrium and SNP detection

Inferring the Demographic History of the Ashkenazi Jewish population Shai Carmi Pe’er lab, Columbia University Leicester, UK April 2014.

Evolutionary Genome Biology Gabor T. Marth, D.Sc. Department of Biology, Boston College

Sequencing of the South Asian Genome Lamri Amel Postdoctoral fellow 1.

PGC Worldwide Lab Call Details DATE: Friday, April 12 th, 2013 PRESENTER: Alkes Price, Harvard University TITLE: “GWAS in multiple ancestries: heritability,

Understanding human admixture, and association mapping in admixed populations. Simon Myers.

What causes geographic populations to become differentiated?

POPULATION GENOMICS, ADMIXTURE AND EPIDEMIOLOGY AT HIGH RESOLUTION

OUTLINE 22 Forces that disrupt HW equilibrium

Common variation, GWAS & PLINK

Karim A. Sharif, Ph.D. August 27, 2016

Do we really need theory?

Recent Admixture in an Indian Population of African Ancestry

Signatures of Selection

Fig. 1. Genetic affinity and population structure of Xinjiang’s Uyghur (XJU). (A) Distribution map of XJU samples. The abbreviated name of each region.

Fig. 2. —The 26 models implemented in this study

Marker heritability Biases, confounding factors, current methods, and best practices Luke Evans, Matthew Keller.

What Is Genetic Drift? Genetic drift definition: A random change in the frequency of alleles in a gene pool, usually due to small population size.

Genetic Drift: Chance Change A common misconception about evolution is that the features of organisms have evolved due to random chance alone Random cause.

Welcome Back! 3/01/17 What is one trait that all species share?

Imputation-based local ancestry inference in admixed populations

Genome-wide Association Studies

Fast Principal-Component Analysis Reveals Convergent Evolution of ADH1B in Europe and East Asia Kevin J. Galinsky, Gaurav Bhatia, Po-Ru Loh, Stoyan Georgiev,

Mechanisms of Evolution

Vineet Bafna/Pavel Pevzner

Alicia R. Martin, Christopher R. Gignoux, Raymond K

Gene Discovery for Complex Traits: Lessons from Africa

Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations Marc Haber, Massimo Mezzavilla, Anders Bergström, Javier.

The Genetic Legacy of the Indian Ocean Slave Trade: Recent Admixture and Post- admixture Selection in the Makranis of Pakistan Romuald Laso-Jadart, Christine.

Brian K. Maples, Simon Gravel, Eimear E. Kenny, Carlos D. Bustamante

Ida Moltke, Matteo Fumagalli, Thorfinn S. Korneliussen, Jacob E

Volume 27, Issue 14, Pages e8 (July 2017)

Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations Marc Haber, Massimo Mezzavilla, Anders Bergström, Javier.

Volume 24, Issue 21, Pages (November 2014)

EVOLUTIONARY MECHANISMS

Detection of human adaptation during the past 2000 years

Shuhua Xu, Wei Huang, Ji Qian, Li Jin

Pier Francesco Palamara, Todd Lencz, Ariel Darvasi, Itsik Pe’er

Natural Selection Microevolution.

Evolution of Populations

Abraham's Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry Gil Atzmon,

Recent Admixture in an Indian Population of African Ancestry

Fig. 2 Genetic structure of the three species.

Giulio Genovese, Robert E. Handsaker, Heng Li, Eimear E

Presentation transcript:

The Time and Place of European Gene Flow into Ashkenazi Jews Shai Carmi The Hebrew University of Jerusalem 2016 Joint work with Itsik Pe’er, James Xue (Columbia University)

Ashkenazi History: Known Ca. 1000: Small communities in Northern France, Rhineland Migration east Expansion Migration to US and Israel

Ashkenazi History: Genetics Origin? Middle-Eastern/European Relation to other Jews? Close to Sephardi Jews Founder event? Effective size: hundreds Time: ≈25-35 generations ago European gene flow: How much? ≈50-60% When? Where?

The Geographic Origin of Polish Jews “Most of these theories … are myths or speculation … based on some vague or misunderstood references. … It will probably be impossible to say definitely where the ... Jews in Poland … came from.” B. Weinryb, The Jews of Poland, 1972

The Geographic Origin of Polish Jews “Most of these theories … are myths or speculation … based on some vague or misunderstood references. … It will probably be impossible to say definitely where the ... Jews in Poland … came from.” B. Weinryb, The Jews of Poland, 1972

Simple Approach: Problem ME EU An Ashkenazi genome ME x x x x x x x x EU x x x x x o o o PC2 x x o o o x x x x x x x x x x x x AJ PC1 Kopelman et al., BMC Genet, 2009 Atzmon et al., AJHG, 2010 Behar et al., Nature, 2010 Bray et al., PNAS, 2010 Guha et al., Genome Biol, 2012 Behar et al., Hum Biol, 2014 Carmi et al., Nat Commun, 2014 O’connor et al., Mol Biol Evol, 2015 Turkic origin hypothesis

Our Approach: Local Ancestry Inference ME EU An Ashkenazi genome ME x x x x x x x x EU x x x x x o o o ME EU PC2 x x o o o x x x x x x x x x x x x AJ EU PC1 x x x x ME x x x x x x x x x x x o o x x x x x x o o o o x x x x x o o o o o x PC2 x x o PC2 x x x x x x x x x x x x x x x x x x x x x x x x x Use RFMix (Maples et al., AJHG, 2013) Per-SNP accuracy ≈70-80% PC1 PC1 Johnson et al., PLoS Genet, 2011 Moreno-Estrada et al., PLoS Genet, 2013

Localization of AJ admixture Sources Used Naïve Bayes approach Likelihood of source X: Product of allele frequencies of all SNPs in EU/ME segments Most likely source is Southern-EU (mostly Italy) Simulations suggest that Southern-EU is ≈34% of AJ ancestry or ≈2/3 of EU ancestry Minor sources? Real data

Localization of the Minor Source IBD sharing between AJ and other populations Sharing with Eastern-EU is highest

Comments on Localization We ran other methods to find localization Alder, f4 stats, TreeMix were not robust in simulations Globetrotter (Hellenthal et al., Science, 2014) worked better Also identified Southern-EU as the predominant source Middle-Eastern most likely source was the Levant

Time of Admixture Multiple methods: The mean EU segment lengths The distribution of total EU ancestry The decay of admixture LD (Alder, Globetrotter) Inferred admixture time: ≈25-40 generations ago What if there were multiple events?

Admixture vs Bottleneck EU EU ME ME 25-35 gen ago EU Time Ancestry of IBD segments ≈ Ancestry at the bottleneck IBD Genome

Admixture vs Bottleneck EU ME EU Replacing ≈20% Higher Eastern-EU ancestry ME EU IBD 42% Genome 53%

A Very Speculative Historical Model Time (generations ago) Ancestral Middle-Eastern population Southern EU admixture Replacing ≈35-60% ≈25-50 Eastern EU admixture Bottleneck Replacing ≈15-25% ≈25-35 ≈10-20 Population size

Thank you for your attention! Acknowledgements Columbia University: Itsik Pe’er James Xue (now @ Harvard) AJ genotypes: Todd Lencz (LIJMC) Ariel Darvasi (HUJI) Discussion: Ashkenazi Genome Consortium members Manuscript available on Thank you for your attention!

Local Ancestry Inference LAMP-LD on simulate admixed individuals (Baran et al., 2012) Admixture FST Accuracy (6 generations) CEU:YRI 7.2% 99% CHB:TSI 5.4% 94.7% FIN:TSI 0.6% Same as random CEU:TSI 0.15% For EU/ME, FST≈1-2% RFMix (Maples et al., 2013) Simulated EU/ME admixed genomes, 30 generations Accuracy was 70-80%

Geographic Inference Advertised PCA method does not work Used “Naïve Bayes” to classify the source of each chr Likelihood of source X: product of allele freq of all SNPs in EU/ME segments Does it work even for low LAI accuracy?