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New SNP Array Study Sheds Light on Genetic History of Middle Eastern Druze Populations

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NEW YORK (GenomeWeb) – A joint Israeli and American research team has been able to for the first time characterize the relationship between various Druze populations living in the Middle East.

Using Affymetrix SNP 6.0 microarrays, the researchers genotyped 40 family trios from communities in the Upper Galilee and Golan Heights regions and compared the resulting data to information collected from other Druze communities located in Lebanon and Israel.

While identity-by-descent, or IBD, analysis confirmed a 15-fold reduction in genetic diversity that occurred between 22 and 47 generations ago — roughly about the time the highly endogamous religious community emerged — the researchers also found that all four of the Druze communities surveyed were genetically distinct, raising questions about the demographic history of the group.

The findings were published in a new European Journal of Human Genetics paper.

Numbering about 1.5 million worldwide, the Druze form a religious and social community and reside mainly in isolated communities in Israel, Lebanon, and Syria. The group developed in the 11th century as an offshoot of Islam, blending in beliefs from Abrahamic religions and other philosophies. The Druze also exhibit a high rate of consanguinity, as their religion prohibits marriage to non-Druze, and there has been limited conversion to the faith, according to the paper.

These various characteristics piqued the interest of the research team, which includes investigators from Chaim Sheba Medical Center in Tel-Hashomer, Israel; Tel Aviv University; Bar-Ilan University in Zefat, Israel; Columbia University; Albert Einstein College of Medicine; and Golan for Development, a nonprofit based in the Druze town of Madjal Shams in the Golan Heights.

"We decided to focus on this population for several reasons," said Eitan Friedman, director of the oncogenetics unit at Chaim Sheba Medical Center and corresponding author on the paper.

Friedman told BioArray News that the Druze are a "little studied population, there is a paucity of genetic data on diseases in that population, and previous attempts did not use the trio setup." And while the Middle East is in general considered a hot bed of consanguinity by geneticists, Friedman related that Druze populations are even more endogamous than other populations in the regions, with associated increases in the rates of genetic diseases.

Friedman noted that there are several specific diseases that are more prevalent in Druze, such as Thalassemia, than in non-Druze populations. Druze individuals also have a higher rate of Behcet's disease, a rare disorder that causes inflammation in the blood vessels, Friedman said.

Indeed, according to the paper, the Druze rate of Behcet's disease is between 55 and 185 per 100,000 people, whereas the rate among non-Druze populations is less than 1 per 100,000 people.

While the ultimate goal of Friedman and colleagues' research has been to generate a map of the healthy Druze population, so that any subsequent study that targets Druze populations will not need to genotype healthy controls, the current EJHG study also provided insights into the demographic evolution of the different Druze populations, including findings that question the traditional view of how the group developed.

According to the paper, the Druze religion was formed as an Islamic reform movement during the reign of Hakim, sixth caliph of the Fatimid Dynasty of Egypt, who ruled between 966 and 1020 AD. Since that time, Druze have strictly prohibited marriage to non-Druze. This practice, combined with the group's residence in remote, mountainous areas, made them an attractive group to research.

As noted in the paper, the Druze live in three major regions: Upper Galilee, the Golan Heights, and Mount Carmel. While previous studies had demonstrated kinship between Druze and other Middle Eastern populations, the new paper is the first to dig into the relationship between the different Druze communities themselves.

Friedman and colleagues first selected and genotyped 40 Druze trios from Upper Galilee and Golan Heights representative of different ancestries. Initial analyses showed Druze began to split from other Middle Eastern populations between 47 and 66 generations ago, or about 500 AD, roughly the time that Islam was established.

By phasing the trio data, they were able to detect a large number of IBD segments within the populations, revealing the more recent bottleneck, around the time that the Druze religion emerged a thousand years ago. At the same time, comparison of the Upper Galilee and Golan Heights data with published genotypes of individuals from Mount Carmel and in Lebanon showed that all four communities were genetically distinct, with different levels of IBD sharing and heterozygosity.

In the paper, the authors proposed three different scenarios to explain these findings. The first supposed that the Druze arose as a single founder group that split into various communities followed by homogenization by gene flow. The second suggested that each community descended from a unique population that accepted the Druze religion. And the third married the two scenarios, envisioning a single founder group splintering and then admixing with local populations.

"This is actually one of the most interesting issues," said Friedman. "It is a finding that is inconsistent with the way the Druze sect has evolved according to tradition and that implies that thaere was some joining into the sect despite the strict rules of not facilitating becoming a Druze unless you were born as a Druze," he said.

Based on the data obtained, the researchers were unable to determine if a single Druze founder population had existed, and were unable to say which of the four communities genotyped were closer to such a reconstructed population. Instead, they stated that with more data and improved modeling, answers to questions about the origins of the Druze population will be clarified.

Moreover, the investigators believe that the consanguineous nature of the Druze, and its perceived importance in medical genetics, should make the trio-based data set that they generated "indispensable in mapping and investigating medically-relevant haplotypes," according to the paper.

Friedman said that the researchers are currently planning a follow up study using whole-exome sequencing of the trios in combination with additional SNP array analyses. He also said that the investigators will perform whole-exome sequencing of Druze women with breast cancer to define the genetic basis of the disease in that population.

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