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

Carmi S1, Hui KY2, Kochav E1, Liu X3, Xue J1, Grady F1, Guha S4, Upadhyay K5, Ben-Avraham D6, Mukherjee S7, Bowen BM2, Thomas T8, Vijai J8, Cruts M9,Froyen G10, Lambrechts D11, Plaisance S12, Van Broeckhoven C9, Van Damme P13, Van Marck H12, Barzilai N6, Darvasi A14, Offit K8, Bressman S15, Ozelius LJ16, Peter I16, Cho JH2, Ostrer H17, Atzmon G6, Clark LN18, Lencz T19, Pe'er I20.

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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.