Endogamy linked to persistence of harmful genetic variants

August 7, 2023

General Studies Paper 3

Context

A new study has found higher frequency of homozygous genotypes in South-Asian populations, most likely as a result of caste, endogamy, and consanguineous sexual unions. Such a frequency could lead to higher risk of genetic disorders.

The study

In 2009, a study in Nature Genetics by the group of Kumarasamy Thangaraj, at the Centre for Cellular and Molecular Biology, Hyderabad, reported a fascinating finding on why a small group of Indians were prone to cardiac failure at relatively young ages.
They found that the DNA of such individuals lacked 25 base-pairs in a gene crucial for the rhythmic beating of the heart (a 25-base-pair deletion).
Intriguingly, this deletion was unique to the Indian population and, barring a few groups in Southeast Asia, was not found elsewhere.
They estimated that this deletion arose around 30,000 years ago, shortly after people began settling in the subcontinent, and affects roughly 4% of the Indian population today.
Another recent study found stark genetic differences between people from different regions of the subcontinent.
While this is to be expected between different countries in the region, it was actually evident even at the level of smaller geographies within India.
Unbiased computational approaches showed little mixing between individuals from different communities.
It is a no-brainer that endogamous practices (including caste-based, region-based, and consanguineous marriages) in the subcontinent are responsible for such conserved genetic patterns at the community level.
In an ideal scenario, there would have been random mating in a population, leading to greater genetic diversity and lower frequency of variants, which are linked to disorders.

A worrying trend

The study also highlighted a worrying trend in the Indian population.
Compared with a relatively outbred population, like that of Taiwan, the South Asian cohort – and within it, the South-Indian and Pakistani subgroups – showed a higher frequency of homozygous genotypes.
Humans typically have two copies of each gene. When an individual has two copies of the same variant, it is called a homozygous genotype.
Most genetic variants linked to major disorders are recessive in nature and exert their effect only when present in two copies.
Having different variants – being heterozygous – is usually protective.
The South Indian and Pakistani subgroups were estimated to have a high degree of inbreeding, while the Bengali subgroup showed significantly lower inbreeding.

Map of the Indian genome

It has been some 20 years since scientists published the human genome sequence.
In this time, several studies have shown important ethnic differences in the genome. Thanks to this, scientists have sequenced populations from Africa and China – but a detailed map of the Indian genome has been missing.
This is important because of India’s incredible diversity as well as for economic, matrimonial, and geographical reasons.
The study has not just highlighted this but also indicated how our cultural aspects might need mending for the sake of population health.
This is obviously fraught with sensitivities owing to deep-rooted customs and biases, but we must move away from the idea of genetic puritanism because it will be the simplest way to prevent major hereditary disorders.

Way forward

Genetics was once practised with the sole aim of ensuring the lineage of European royal families. Since then, we have come a long way to mapping the human genome and identifying genes linked to haemophilia, skin colour, and cardiac failure.
We need to develop the competence and infrastructure to undertake a study of this magnitude within the country and as a multi-centre collaboration.
Conducting such studies within the country would also help safeguard the many vulnerable communities within the country who might be exploited.
As an ambitious nation, we should devote efforts to harness the power of such studies for our well-being.