Every person carries several genetic mutations which if occurred in two copies leads to serious recessive diseases. But, the 1.5 billion people of South Asia were more vulnerable to rare genetic population specific diseases than elsewhere in the world because of the endogamous marriages or marrying with the same ethnicity, community, caste, etc.
A new study led by co-senior authors Kumarasamy Thangaraj of CSIR-Centre for Cellular and Molecular Biology (CCMB) and David Reich of Broad Institute MIT & Harvard, Cambridge, USA, in collaboration with other institutes, has identified that about a third of populations here have had such strong defective genes passed on through generations. “We have analysed samples from more than 2,800 individuals from over 275 distinct South Asian populations belonging to various social and linguistic groups from India, Pakistan, Nepal, Sri Lanka, and Bangladesh using about 600,000 genome-wide markers”, said Mr. Thangaraj flanked by CCMB Director R.K. Mishra at a press conference on Tuesday.
It was found that 81 out of 263 unique South Asian groups, including 14 groups with estimated census sizes of over a million, have a genetic mutation base with recessive diseases much more than the one that occurred in both Finns and Ashkenazi Jews in the West. This source of risk for genetic recessive diseases was different from that due to marriages among close relatives (consanguineous marriages), also a major cause of recessive disease here, said the study published in online edition of ‘Nature Genetics,’ on July 17.
The authors highlighted the case of the Vysya community, with a census size of more than three million and endogamous for centuries where the occurrence of a defective gene causing ailments was about 1.2-fold stronger than in the Finnish population. Vysyas have an approximately 100-fold higher rate of ‘butyrylcholinesterase’ deficiency than other groups, and is a known counter-indication for the use of muscle relaxants such as ‘succinylcholine’ or ‘mivacurium’ given prior to surgery.
The authors had analysed six patients from Hyderabad and Bangalore with a progressive ‘Pseudorheumatoid Dysplasia’ (PPD), a disease known to be caused by mutations. Five were from non-consanguineous marriages and they passed on the genetic mutation to their offspring who died within 10 years as “none could identify the genetic reasons or diagnose the ailments”.
“Our study is an opportunity for discovering population-specific disease causing genes in communities known to pass on such recessive diseases. Mapping mutations of these would help in developing strategies for diagnosis, modifying clinical course and reduce disease burden,” explained Mr. Thangaraj.
Hoping the study would lead to actionable medical research, he cited the example of ‘Dor Yeshorim’, a community genetic testing program among Orthodox Ashkenazi Jews which screens students for common recessive disease causing mutations, creates a confidential database for prospective couples to check and this has helped reduce rate of many recessive diseases to near-zero so a similar strategy could be effective here too. CCMB Director Mr. Mishra said the study will be enable a paradigm shift towards facilitating and accelerating predictive and personalized medicine.
