Marriage within groups causes rare genetic diseases among South Asians

A new study led by co-senior authors Dr Kumarasamy Thangaraj of CSIR-Centre for Cellular and Molecular Biology (CCMB) here  and Dr. David Reich of Harvard Medical School and the Broad Institute) Boston and Cambridge, (USA), in collaboration with colleagues from many other institutes, has identified that about a third of populations in South Asia have had strong founder events or  population bottlenecks, which are responsible for a high rate of population-specific disease in South Asia.

“We have analyzed samples from more than 2,800 individuals from over 275 distinct South Asian populations who belongs to various social and linguistic groups from India, Pakistan, Nepal, Sri Lanka, and Bangladesh using about 600,000 genome-wide markers”, said Dr. Thangaraj. The authors devised an algorithm to quantify the measure of the founder events in each group based on Identity-by-Descent (IBD) segments, large stretches of DNA shared from a common founder in the last approximately one hundred generations.


“We found that 81 out of 263 unique South Asian groups, including 14 groups with estimated census sizes of over a million, have a strong founder event than the one that occurred in both Finns and Ashkenazi Jews in the West – these are founder groups known to have large numbers of recessive diseases”, said Dr. Reich. He further said that this source of risk for recessive diseases is very different from that due to marriages among close relatives (consanguineous) which is also a major cause of recessive disease in South Asia.

As an example of founder event disease gene mapping in South Asia, the authors highlighted the case of the Vysya, who have a census size of more than 3 million and a founder event that they estimated to be about 1.2-fold stronger than that in the Finnish population. The Vysya have an approximately 100-fold higher rate of butyrylcholinesterase deficiency than other groups, and Vysya ancestry is a known counter-indication for the use of muscle relaxants such as succinylcholine or mivacurium that are given prior to surgery. This disease is likely to occur at a higher rate due to the founder event in the history of the Vysya.

“Our study provides opportunity for discovering population-specific disease causing genes in communities known to have strong founder events. Mapping of mutations that are responsible for population-specific disease would help in developing strategies for diagnosis, counseling, management and modifying the clinical course of these disorders and to reduce the disease burden among South Asians.”, said Dr. Thangaraj.