A new genomic analysis reveals how populations in South Asia—including people living in Bangladesh, India, Nepal, Pakistan, and Sri Lanka—are particularly vulnerable to rare genetic diseases.
Several diseases specific to South Asian populations have previously been identified, but the genetic causes of the vast majority have remained largely mysterious. A multi-institutional study, led by researchers at HMS and the CSIR-Centre for Cellular and Molecular Biology in Hyderabad, India, reveals that so-called founder effects, in which a small number of ancestors give rise to many descendants, significantly contributed to the high rates of population-specific, recessive diseases in the region. The work appeared online July 17 in Nature Genetics.
“Our work highlights an opportunity to identify mutations that are responsible for population-specific disease and to test for and decrease the burden of recessive genetic diseases in South Asia,” says David Reich, an HMS professor of genetics and co-senior author of the study.
The researchers analyzed genome-wide data from more than 2,800 people within upwards of 260 South Asian subgroups. They found that nearly one-third of these subgroups derived from distinctive founder events.
Such founder events tend to limit genetic diversity. Geographic, linguistic, or cultural barriers, such as restrictions on marriage between groups, increase the likelihood that mates share much of the same ancestry. This can lead to the perpetuation and proliferation of certain rare, recessive diseases.
“Everybody carries a small number of mutations that could cause severe disease, but each person usually only has one copy. Two copies are needed to get sick,” says the study’s first author, Nathan Nakatsuka, a graduate student in Reich’s lab. “If parents share a common ancestry, there is a greater risk that they will carry the same recessive mutation, so their offspring are at much greater risk of inheriting the two copies needed to manifest disease.”
The prevalence of these genetic variants increases disease risk—and makes them easier to detect.
Fourteen of the groups identified are made up of more than 1 million people, according to census data. Discoveries stemming from rare disease research in these populations could affect large swaths of people in South Asia.
Studying these variants may highlight the mechanisms causing disease, which could lead to new treatments.
Image: Clemensmarabu/Wikimedia Commons