番茄社区

The well-known genetic isolation of Old Order Amish, Ashkenazi Jews, and Finns that has given rise to rare recessive diseases in those populations likely may be just a drop in the bucket compared with South Asia, researchers suggested.

In one of the first studies to look beyond consanguineous marriages there, researchers found that 81 out of 263 unique groups studied that are isolated by caste, language, religion, and geography "descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events."

Notably, 14 of those groups have populations of more than 1 million people, according to David Reich, DPhil, of Harvard, and colleagues mostly in India, .

"However, the groups with smaller census sizes are also important: outside of South Asia, groups with small census sizes and extremely strong founder events, such as the Amish, Hutterites, and people of the Saguenay-Lac Saint-Jean region have led to the discovery of dozens of novel disease-causing variants," they wrote.

Reich and colleagues said the findings point to a big opportunity to improve health in South Asia (India, Pakistan, Bangladesh, Nepal, Bhutan, and Sri Lanka). Whereas many know to avoid marriage to close relatives, entire cultural groups are at risk of recessive diseases.

"As an example of the promise of founder-event mapping of disease-associated genes in South Asia, we highlight the case of the Vysya, who have a census size of more than 3 million and an estimated IBD [identity by descent] score approximately 1.2-fold higher than that of Finns. The Vysya have an approximately 100-fold higher rate of butyrylcholinesterase deficiency than other groups, and Vysya ancestry is a known counterindication for the use of muscle relaxants, such as succinylcholine or mivacurium, that are given before surgery."

Many other recessive diseases are likely implicated too, as examples are known anecdotally in South Asia.

A "fruitful" way forward would be to take the same approach as taken in the 1950s for the Old Order Amish in the U.S. that mapped many dozens of recessive diseases. "That research program was crucial to founding modern medical genetics and provided extraordinary health benefits," Reich's group wrote. "Our results suggest that the potential for disease gene mapping in South Asia would be orders of magnitude greater."

That's especially true for these South Indian communities that often practice arranged marriages. A community genetic testing program among religious Ashkenazi Jews that feeds into a confidential database for matchmakers has almost eliminated recessive diseases such as Tay-Sachs in these communities. "A similar approach should work as well in South Asian communities," Reich's group wrote. "Given the potential for saving lives, this or similar types of research could be a valuable investment for future generations."