Mapping the DNA sequence of Ashkenazi Jews

Ashkenazi Jews have played an important role in the study of human genetics, with notable successes in gene mapping as well as prenatal and cancer screening.

Ultra-Orthodox Jews are taught in school. (photo credit: REUTERS)
Ultra-Orthodox Jews are taught in school.
(photo credit: REUTERS)
Genomic research of Ashkenazi Jews will soon become more effective and personalized, thanks to the creation of a data resource at Columbia University in Manhattan. The team, which includes experts from 11 labs in Israel and New York City, focused on Ashkenazim because of their demographic history of genetic isolation and the resulting abundance of population-specific mutations and high prevalence of rare genetic disorders.
The study, headed by Columbia computer science professor Itsik Pe’er, was published recently in the journal Nature Communications.
Ashkenazi Jews have played an important role in the study of human genetics, with notable successes in gene mapping as well as prenatal and cancer screening.
“Our study is the first full DNA sequence dataset available for Ashkenazi genomes,” said Pe’er. “With this comprehensive catalog of mutations present in the Ashkenazi population, we will be able to more effectively map disease genes onto the genome and thus gain a better understanding of common disorders. We see this study serving as a vehicle for personalized medicine and a model for researchers working with other populations.”
To help in his hunt for disease genes, Pe’er founded the Ashkenazi Genome Consortium (TAGC) three years ago.
One of the board members is Prof. Ariel Darvasi, vice-dean of the Faculty of Life Sciences at the Hebrew University of Jerusalem who has spent many years studying “Jewish genes” for chronic diseases. The TAGC researchers performed highdepth sequencing of 128 complete genomes of healthy Jews of Ashkenazi origin. They compared their data to European samples and found that Ashkenazi genomes had significantly more mutations that had not yet been mapped.
Pe’er and his team analyzed the raw data and created a comprehensive catalog of mutations present in the Ashkenazi population.
The TAGC database is already proving useful for clinical genomics, identifying specific new mutations for carrier screening, as it informs the physician whether a mutation in a patient’s genome is shared by healthy individuals and can alleviate concerns that it is causing disease. The study will also make it easier to discover disease-causing mutations, since some genetic factors are observable in Ashkenazim but essentially absent elsewhere. Moreover, the demography of the Ashkenazi population – the largest isolated population in the US – enables large-scale recruitment of study patients and hence more genetic discoveries than in other wellknown isolated populations like the Amish and Hutterites locally or the Icelanders overseas. The researchers expect that medical insights from studies of specific populations will also be relevant to general populations as well.
The Columbia team said they also shed light on the long-debated origin of Ashkenazim and Europeans. The genetic data indicates that the Ashkenazi population was founded in the late medieval period by only a few hundred individuals, whose descendants spread out geographically quite rapidly while remaining mostly isolated genetically.
“Our analysis shows that Ashkenazi Jewish medieval founders were ethnically admixed, with origins in Europe and in the Middle East, roughly in equal parts,” says Dr.
Shai Carmi, a post-doctoral scientist who works with Pe’er and who conducted the analysis. “TAGC data are more comprehensive than what was previously available, and we believe the data settle the dispute regarding European and Middle Eastern ancestry in Ashkenazi Jews. Our data provide evidence for today’s European population being genetically descended primarily from late Middle Eastern migrations that took place after the last Ice Age, rather than from the first humans to arrive to the continent, more than 40,000 years ago.”
Pe’er said the data is being made available to the entire research community.
“We’ve released it to public-access databases and fully expect the creativity of the scientific world to come up with additional uses for the data. What’s especially gratifying is the idea that our work will pave the way for personalized genomics in other populations as well.”
They will next study specific diseases in the Ashkenazi population such as schizophrenia, Parkinson’s, Crohn’s, diabetes and cancer, as well as other inherited traits such as longevity.
A Hebrew University researcher is part of an international team of astronomers that used new measuring techniques to describe our galaxy’s place in the universe. The researchers, including Prof. Yehuda Hoffman from the university’s Racah Institute of Physics, mapped our local supercluster of galaxies in new research that appeared on the cover of Nature.
Superclusters – among the largest structures in the known universe – are comprised of galaxy groups containing dozens of galaxies and galaxy clusters containing hundreds of galaxies. These groups and clusters intersect, creating superclusters with poorly defined boundaries. A galaxy between two such structures will be caught in a gravitational tug-ofwar, with the balance of the gravitational forces determining the galaxy’s motion.
By mapping the velocities of galaxies throughout our local universe, the researchers found that the galactic supercluster containing the Milky Way galaxy is 500 million light-years in diameter.
They also found that it contains the mass of a hundred quadrillion suns in 100,000 galaxies. This is the first time the supercluster has been carefully mapped using these new techniques.
Led by University of Hawaii at Manoa astronomer R. Brent Tully, the team named the supercluster “Laniakea,” which means “immense heaven” in Hawaiian. The name honors Polynesian navigators who used knowledge of the heavens to voyage across the immensity of the Pacific Ocean.