September 1, 2010

Jewish genomes reveals diversity, history

Through genomic analysis, Emory geneticists have shown that the Ashkenazi Jewish population is genetically more diverse than people of European descent. In addition, analyses of disease-related genes in the Ashkenazi Jewish population indicate that a minority of these traits shows signs of positive selection, suggesting that most have arisen through random genetic drift.

The results were published online Aug. 26 in the early edition of the Proceedings of the National Academy of Sciences.

The work comes from a collaboration between Emory human genetics chairman Stephen Warren and Ann Pulver, a psychiatrist at Johns Hopkins who recruited the participants for a study of schizophrenia genetics.

Warren’s laboratory used DNA microarray technology to read close to one million single nucleotide polymorphisms (SNPs) across the genomes of 471 Ashkenazi Jews (Jews whose ancestry can be traced to Central and Eastern Europe).

Isolation contradicted

“Our study represents the largest cohort of Ashkenazi Jews examined to date with such a high density of genetic markers,” says postdoc Steven Bray.

SNPs are common alternative spellings of a specific “letter” in the genome. A measure of genetic diversity in a population is heterozygosity, or how many of the SNPs inherited from the mother and father are different.

“We were surprised to find evidence that Ashkenazi Jews have higher heterozygosity than Europeans, contradicting the widely-held presumption that they have been a largely isolated group,” Bray says.

He and his colleagues found evidence for interbreeding or “admixture” between Middle Eastern and European populations, estimating that between 35 and 55 percent of the modern Ashkenazi genome comes from European descent.

Data on cancer susceptibility

The genomic analysis also provided information about selection pressures on mutations prevalent in the Ashkenazi Jewish population, such as those leading to conditions like Tay-Sachs disease or mutations in cancer susceptibility genes like BRCA1.

Some scientists have proposed that disease-related mutations have persisted in the Ashkenazi Jewish population because of a hidden positive effect, similar to the interaction between sickle-cell anemia and malaria.

“Only six of the 21 disease genes that we examined showed evidence of selection,” Bray says. “This supports the argument that most of the Ashkenazi-prevalent diseases are not generally being selected for, but instead are likely a result of a genetic bottleneck effect, followed by random drift.”

Bray and colleagues went on to look for other regions of the Ashkenazi Jewish genome that display signs of selection, in comparison to European genomes, and discovered differences in genes affecting lactose and alcohol metabolism.

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