Genetics Confirm Oral Traditions Of Druze In Israel

The Druze harbor a remarkable diversity of mitochondrial DNA types or lineages that appear to have separated from each other many thousands of years ago, according to a new study by multinational team, led by researchers at the Technion-Israel Institute of Technology Rappaport School of Medicine.

But instead of dispersing throughout the world after their separation, the full range of lineages can still be found within the small, tightly knit Druze population.

Technion researcher Karl Skorecki noted that the findings are consistent with Druze oral tradition suggesting the adherents came from diverse ancestral lineages "stretching back tens of thousands of years." The Druze represent a "genetic sanctuary" or "living relic" that provides a glimpse of the genetic diversity of the Near East in antiquity, the researchers write in the May 7th issue of the journal PLoS ONE.

But there is a modern twist to their story: the diversity of Druze mitochondrial DNA, which is the part of the genome that is passed on strictly through the maternal line, offers a unique opportunity for researchers to study whether people in different mitochondrial DNA lineages are predisposed to different kinds of diseases.

Skorecki points to metabolic syndrome, the combination of insulin resistance, high cholesterol, abdominal obesity and other factors, as one such disease. Mitochondria are the energy factories within cells, so one might expect that differences in mitochondrial DNA might be linked to different predispositions to energy-related diseases such as metabolic syndrome, he explained.

With the Druze, "you can look at 150 kinds of mitochondrial DNA within one group with a similar environment, and be able to see the specific contribution of these variations" to disease, Skorecki said.

Dan Mishmar, a genetics researcher at Ben-Gurion University who was not involved with the study, said there is another "great advantage" to studying the link between disease and mitochondrial DNA variation in a group like the Druze. Although the Druze have great variety in their mitochondrial genome, the rest of their genome inherited from both paternal and maternal lines has grown less diverse as a result of thousands of years of intermarriage.

That means that researchers searching for genetic mutations linked to disease would have an easier time discerning whether these mutations are limited to the mitochondrial genome, which could help researchers design specific, targeted therapies, Mishmar explained.

The findings also guide the approach to screen for genetic disease among the Druze. Instead of scanning for disease-linked genes associated with an entire population--as is the case with Ashkenazi Jews, for example-it may make sense to screen within smaller groups. "Since they are comprised of so many distinct lineages, genetic disease may vary from clan to clan and village to village," Skorecki explained.

The researchers, including Druze co-authors Fuad Basis of the Rambam Medical Center and former Technion student Yarin Hadid, took genetic samples from 311 Druze households in 20 villages in Israel. They soon discovered an unusually high frequency of a mitochondrial DNA haplogroup-a distinct collection of genetic markers - called haplogroup X - among the Druze. Haplogroup X is found at low frequencies throughout the world, and is not confined to a specific geographical region as are most other mitochondrial DNA haplogroups.

Even more unusual, the Druze villages contained a striking range of variations on the X haplogroup. Together, the high frequency and high diversity of the X haplogroup "suggest that this population provides a glimpse into the past genetic landscape of the Near East, at a time when the X haplogroup was more prevalent," the researchers note.

How did the Druze become a genetic sanctuary in the Near East? The religious minority has lived for centuries in remote, mountainous regions, and unlike other monotheistic religions, the group has not sought converts since shortly after the "Dawa" or "revelation" of the religion in 1017 C.E. These factors, along with other cultural and political practices, may have kept the Druze a people apart for thousands of years, according to Skorecki and colleagues.

Skorecki is best-known for his 1997 discovery of genetic evidence indicating that the majority of modern-day Jewish priests (Kohanim) are descendants of a single common male ancestor, consistent with the Biblical high priest, Aaron. He also led an international team of researchers who, in 2006, found that some 3.5 million or 40 percent of Ashkenazi Jews are descended from just four "founding mothers," who lived in Europe 1,000 years ago.

Researchers from the Rambam Health Care Campus, Haifa, Israel, Washington University in St. Louis, Missouri, the University of Arizona in Tucson, Arizona and the Weizmann Institute of Science in Rehovot, Israel also contributed to the PLoS ONE study.