doi:10.1038/nindia.2017.85 Published online 17 July 2017

South Asian genomics data throws up 'extreme' surprises

Study could help pinpoint many disease-associated genes from across the region

Kate Telma

A genome-level scrutiny of South Asian populations has revealed that 81 different groups of people descended from a 'founder event' more extreme than that of other known limited-ancestry descendants, such as the Ashkenazi Jews and the Finns1.

Researchers compared genomes of nearly 3000 people from 260 distinct groups from 15 years of DNA samples banked at the CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad. Many of these people come from isolated groups, which are at risk for population-specific genetic disorders. Understanding their genomes could provide a way to assess and decrease disease burden in the region, the researchers say.

81 unique groups in South Asia descended from a founder event more extreme than those in Ashkenazi Jews and Finns.
© K. Thangaraj
South Asia is anthropologically diverse with more than 5,000 well-defined groups. Many of these are isolated, and arose from a small handful of ancestors. “Marriage is very restricted. Therefore, the disease pattern is restricted only to that population,” said Kumarasamy Thangaraj, a senior scientist at CCMB and co-author of the study. “Whatever happens in that population is going to remain in the population.”

By comparing members of the same group, the researchers calculated an ‘identity by descent’ (IBD) score to measure how much identical DNA people share. Though people may be unable to trace their ancestry beyond four generations, IBD scores can show close degrees of relatedness that stretch decades back.

Even when communities haven’t practiced consanguinity for several generations, scientists and clinicians observe higher levels of population-specific recessive genetic disorders in communities that arose from an extreme founder event, or a limited number of ancestors. Affected individuals are more likely to be homozygous for recessive conditions, carrying the same mutation from both parents.

“It felt nice that what we were seeing [in the clinic], they have been able to prove with proper data,” said Ashwin Dalal, who heads the diagnostics division at the Centre for DNA Fingerprinting and Diagnostics in Hyderabad. Though not involved with this study, Dalal led early work on pseudorheumatoid dysplasia, a rare progressive skeletal disease found in certain populations in India2. The present South Asia population study used this disease as an example of the prevalence of homozygous recessive mutations in communities that do not practice consanguinity.

“They are showing it in a more scientific way — even with no consanguinity, we are getting homozygous mutations, and there must have been some common ancestor way back,” Dalal told Nature India.

Of the groups studied, 81 groups arose from a founder event more extreme than that of Finns or Ashkenazi Jews. 14 of these groups have populations of more than a million, providing substantial opportunity to test for and decrease instances of disease in the future.

“It’s important to look and identify the mutations that cause the disease. It needs to be treated very cautiously, one can counsel the couples who are going to marry. That way in future [these data] will be very, very useful to avoid health issues,” said Thangaraj, adding that such counseling is not standard practice now.

The Ashkenazi Jewish community, for example, created Dor Yeshorim, a community genetic screening programme whose database is credited for nearly eliminating once-common disorders such as Tay-Sachs. But the types of recessive genetic disorders prevalent in South Asia — and the genes responsible — are only beginning to be studied. While companies are developing carrier screenings, current genetic counselling typically occurs only after a first child is born with a genetic disorder, and parents want to ensure a healthy second child. With an estimated 40 to 50 geneticists trained in counselling for a population of more than one billion, these consultations are in short supply.

“It’s not something like Ashkenazi Jews, where only a few diseases are common and you can screen for them. Mostly we still can’t predict what diseases will be common in which communities,” Dalal said.


1. Nakatsuka, N. et al. The promise of discovering population-specific disease-associated genes in South Asia. Nat. Genet. (2017) doi: 10.1038/ng.3917
2. Dalal A, et al. Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia. Am. J. Med. Genet. Part A. (2012). doi: 10.1002/ajmg.a.35620