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.