Genetic studies have shown that the Ashkenazi Jewish (AJ) population (numbering about 10 million individuals worldwide) had undergone a severe founder event in medieval times, followed by an extremely rapid expansion. This demographic history makes the AJ population attractive for disease mapping studies, since deleterious variants may have arisen in frequency in AJ and are thus easier to detect.
The Ashkenazi Genome Consortium (TAGC), of which our lab is a member, was founded a few years ago to realize the potential of Ashkenazi genetics. We have so far completed the sequencing and analysis of over 700 high-coverage complete genomes of healthy AJ individuals (a “reference panel”). Our analysis has established the utility of our reference panel for a number of medical genetics applications, such as carrier screening, clinical genomics, and imputation of missing variants [1-3]. We are in the process of sequencing hundreds of additional genomes.
We have also studied the population genetics of AJ, by itself and in comparison to other populations [1,4,5]. Our studies established that the Ashkenazi ancestry draws from an approximately equal mixture of European and Middle-Eastern ancestries, and that the effective population size at the founder event was only ≈300-400 individuals. We also dated the founder event to around 700 years ago. The admixture in Europe likely happened in two stages, before and after the founder event, with a major contribution from Southern Europeans. We are currently interested in decoding sex-specific demographic events in the Ashkenazi history using a combination of autosomal and uniparental genetic markers.
In parallel, the lab is collaborating on multiple medical studies of specific diseases and traits (Crohn’s disease , gut microbiome composition , age-related macular degeneration, and anthropometric and metabolic traits ; see also [8-10]). A long-term goal of the lab is to develop efficient methods that leverage the unique AJ demographic history for accurate inference of Ashkenazi genomes that were only sparsely sequenced. A particular application of interest is pre-implantation genetic testing, in which genetic material is extracted and sparsely sequenced from single embryonic cells.
 Carmi et al., Nature Communications, 2014 (link)
 Baskovich et al., Genetics in Medicine, 2016 (link)
 Lencz et al., Human Genetics, 2018 (link)
 Xue et al, PLoS Genetics, 2017 (link)
 Granot-Hershkovitz et al., bioRxiv, 2017 (link)
 Hui et al., Science Translational Medicine, 2018 (link)
 Rothchild et al., Nature, 2018 (link)
 Quint et al., European Journal of Medical Genetics, 2016 (link)
 Jaron et al., Clinical Genetics, 2016 (link)
 Vijai et al., Cancer Discovery, 2016 (link)