Caste endogamous marriages have led to rare genetic diseases developing over the years. This is indicated by new research. Perhaps it is high time to acknowledge that the rigid caste system practiced in India and other parts of South Asia must go.

HYDERABAD, JULY 20:  Not too long ago, when a person went in for a surgery in Indian hospitals, it was not uncommon to hear doctors ask him or her two questions — whether the patient was from the Vaishya community and if he/ she was allergic to Sulpha drugs.

While the second issue of allergy to drugs has been sorted out, the problem Vaishyas, a trading and business community, face when administered anaesthesia still persists. Numbering around three million, this community is predominantly based in the South and is known to have a troublesome response to muscle relaxants such as Succinylcholine and Mivacurium, which are injected prior to surgery as anaesthesia.

The reason for this response, according to scientists, is that the genes responsible for producing enzymes which metabolise these anaesthesia drugs are hardly produced in the people of this community. Therefore, they have to be administered a different set of drugs to facilitate surgery.

Thankfully, modern medicine has developed enough options to ensure that this genetic problem is not a major issue for the Vaishyas today.

The occurrence of such rare problems is attributed to the fact that very little genetic variation has taken place in these communities for centuries.

Terming them ‘recessive diseases’ (which are passed down families through generations), a study published on July 17 in Nature Genetics goes on to describe how the 1.5 billion people of South Asia are particularly vulnerable to such rare genetic diseases.

The study was led by co-senior authors Scientist Kumarasamy Thangaraj of the CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad and David Reich of Harvard Medical School and the Broad Institute, Boston and Cambridge, USA, in collaboration with colleagues from many other institutes.

In India, which is a mileu of hundreds of caste groups and communities that are close-knit and which have inward looking cultural practices and traditions, the prevalence or a pre-disposition to rare genetic diseases is significant.

South Asia is inhabited by about 5,000 anthropologically well-defined populations, many of which are endogamous (marrying within a population) communities with significant barriers to gene flow due to sociological, linguistic and cultural factors that restrict inter-population marriage.

Several diseases that are specific to these populations have been identified in the past. However, the genetic causes for the vast majority of population-specific disease are largely unknown and has been the subject of intense research.

Each person in the world carries several mutations, which if found in two copies, would lead to serious recessive diseases.

In South Asia, ‘founder events’, small numbers of ancestors carrying such mutations, gave rise to a large number of descendants. This, in combination with endogamy, causes these mutations to often be carried in two copies, leading to a higher rate of population specific diseases, explained Thangaraj.

The present study has been able to throw light on some of these trends. “We have analysed samples from more than 2,800 individuals from over 275 distinct South Asian populations, who belongs to various social and linguistic groups in India, Pakistan, Nepal, Sri Lanka, and Bangladesh, using about 600,000 genome-wide markers,” Thangaraj said.

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 100 generations.

The study analysed genetic data of the Gujjars, Baniyas, Rajus, Reddy’s and Kapus to identify gene mutations and the possible susceptibility to certain genetic diseases in India.

“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 Reich.

He further said this source of risk for recessive diseases is very different from that due to marriages among close relatives (consanguineous marriages), which is also a major cause of recessive disease in South Asia.

Explaining the significance of the study findings, Rakesh K Mishra, Director of CCMB, said it would lead to a paradigm shift, facilitating and accelerating predictive and personalised medicine.

A practical fall-out of these findings is the development of the approach called Dor Yeshorim, a community genetic testing programme among Orthodox Ashkenazi Jews, which screens students for common recessive disease causing mutations and enters the results into a confidential database. Matchmakers query the database, whether the potential couple is “incompatible” in the sense of both being carriers for a recessive mutation at the same gene, said Reich.

“This strategy has reduced the rate of many recessive diseases to near-zero among Orthodox Ashkenazi Jews, who use the service. A similar strategy could be effective in South Asians,” he felt.

  CSIR-Centre for Cellular and Molecular Biology (CCMB), development, health