A new study concludes that all Ashkenazi Jews can trace their ancestry to a “bottleneck” of just 350 individuals, dating back to between 600 and 800 years ago.
The study, published in the Nature Communications journal Tuesday, was authored by Shai Carmi, a computer science professor at Columbia University, and more than 20 medical researchers from Yale, Columbia, Yeshiva University’s Albert Einstein College of Medicine, Memorial Sloan-Kettering Cancer Center, Hebrew University of Jerusalem and other institutions.
Researchers analyzed the genomes of 128 Ashkenazi Jews and compared them to those of non-Jewish Europeans in order to determine which genetic markers are unique to Ashkenazi Jews. They found that the Ashkenazi Jews’ genetic similarities were so acute that one of the study’s researchers, Columbia professor Itsik Pe’er, told the Live Science website that among Ashkenazi Jews, “everyone is a 30th cousin.”
The findings will enable researchers to catalog nearly all of the genetic variations from the founding population, the study’s authors said. Such thorough genetic cataloging could help clinicians interpret individual genetic mutations, improve disease mapping and provide insight into the histories of Middle Eastern and European populations, the study said.
The catalog of complete Ashkenazi Jewish genomes should help identify the disease-causing mutations that the progenitors of Ashkenazi Jewry they passed on. Until now, data has only been available for a small subset of common Ashkenazi DNA markers – about one in every 3,000 letters of DNA. The findings are also expected to help with disease research in other ethnic groups.
“Our study is the first full DNA sequence dataset available for Ashkenazi Jewish genomes,” said Itzik Pe’er, an Israeli computer scientist at Columbia University, who led the study. “With this comprehensive catalog of mutations present in the Ashkenazi Jewish 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.”
Ashkenazi Jews are known to have origins in the Levant, which Israel is smack dab in the middle of. But exactly who “European” Ashkenazi Jews are has long been debated. An analysis of the gene database shows that the original Ashkenazi Jews were about half European and half Middle Eastern. They lived in the medieval era, about 600 to 800 years ago, according to the analysis – and numbered just 350 or so people.
“Our analysis shows that Ashkenazi Jewish medieval founders were ethnically admixed, with origins in Europe and in the Middle East, roughly in equal parts,” said Shai Carmi, a post-doctoral scientist who works with Pe’er and conducted the analysis. “[The] 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.”
The analysis also suggested that today’s Europeans are descended primarily from migrants from the Middle East after the last ice age, about 20,000 years ago, not from the first humans to arrive to the continent about 40,000 years ago. The researchers are now looking into where the Middle Eastern and European Jews first met and who their closest descendants are today.
Because the Ashkenazi community started out so small, and remained genetically isolated, it developed a higher load of disease-causing mutations. Even today, Ashkenazi Jews are known to be at higher risk for many diseases, including breast and ovarian cancer and Tay-Sach’s disease. But many potentially disease-causing Ashkenazi mutations remain unknown.
To address this problem, Pe’er and a team of researchers at the Ashkenazi Genome Consortium (TAGC) did high-depth sequencing of the Ashkenazi genomes. Finding that the genomes had almost 50 percent more mutations than did European samples on average, they compiled a comprehensive catalog of genetic mutations found among Ashkenazi Jews.
The catalog is already proving useful for carrier testing, the genetic analyses prospective parents undergo to see what diseases they risk passing onto future children. They are also working to sequence some 500 more Ashkenazi genomes to further strengthen the catalog.
“TAGC advances the goal of bringing personal genomics to the clinic, as it tells the physician whether a mutation in a patient’s genome is shared by healthy individuals, and can alleviate concerns that it is causing disease,” said Lencz. “Without our work, a patient’s genome sequence is much harder to interpret, and more prone to create false alarms. We have eliminated two thirds of these false alarms.”
By revealing genetic information unique to Ashkenazi Jews, the catalog should also allow the pinpointing of genes behind more of the diseases that plague the population. The researchers are already studying specific Ashkenazi diseases to this end, including schizophrenia, Parkinson’s disease, Crohn’s disease, and cancer, as well as other traits, such as longevity. The researchers expect many of these medical insights to be relevant to the general population as well.
JTA contributed to this report.