New Delhi: India’s diversity has never really been up for debate, but a recent genome mapping revealed 44 million genetic variants that were missing from global databases. The sheer proportion left researchers stumped.
The findings came from the Genome India Project, funded by the Department of Biotechnology of India, which analysed the complete DNA of 9,768 healthy people from 83 groups from across India. Researchers found nearly 130 million genetic variants, of which one-third did not feature in global databases like the gnomAD, the 1000 Genomes Project, and GenomeAsia.
Over 20 research institutions participated in the study, hoping that the results would allow investigations into human ancestry, disease genetics, and the impact of inherited genetic variations on an individual’s response to drugs. Eventually, the Genome India project plans to scale up the genetic database to make sure global databases aren’t skewed toward populations of European descent.
Analabha Basu, a population geneticist at the BRIC-National Institute of Biomedical Genetics in Kalyani, West Bengal, and a corresponding author of the study, said that this is just a start.
“More work is needed to translate insights into clinical practice across health systems,” said Basu, adding that further studies can look at genetic mutations that may be clinically relevant.
Although the data is yet to have practical implications, the highlight of the study remains the diversity of variants. Bratati Kahali at the Centre for Brain Research, Bengaluru, told Nature India that even after removing very rare one-off variations and only counting those seen in at least a couple of people, more than 10 per cent of the findings were still completely new. “We expected novel variants, but the sheer proportion stumped us,” Kahali said.
However, investigations into genome data so far focus on DNA sequences that instruct the body to create certain proteins. This makes up only 2 per cent of the genome, while 98 per cent of the genome, which has several disease-related variants, remains largely unexplored. Sudhakaran Prabakaran at Northeastern University pointed out that if studies began looking into the rest of the genome, it could “transform GenomeIndia from a cataloguing exercise into a genuinely predictive tool for precision medicine”.
Also read: A growing list of scientists is questioning neo-Darwinism
What the DNA recounts
Among the millions of genes, DNA from some communities suggested that they may have undergone a long migration, followed by an isolated existence where endogamy was common practice. While the Finnish and the Ashkenazi Jewish are famous for markers of genetic isolations, the genes of some Indian tribes revealed five times more genetic homozygosity (where a person has received a similar version of a gene from each parent).
This is worrisome because when someone inherits two ‘defective’ genes, one from each parent, they can develop recessive genetic diseases. These include sickle cell disease, a blood disorder affecting hemoglobin, and cystic fibrosis, which affects the production of mucus and causes severe respiratory and digestive issues.
Researchers found that nearly 27 out of 29 tribal populations in India had at least one problematic disease-causing gene. In South India, for example, a tribal population’s HGD gene was mutated. This gene is responsible for the production of an enzyme that breaks down the amino acids phenylalanine and tyrosine. If the HGD malfunctions, it can lead to a disorder known as alkaptonuria, which leads to joint damage and dark urine, among other things. Due to this defective gene, nearly 12.5 per cent of that tribe’s population had developed alkaptonuria.
The study also found other such genetic mutations—where genes like the LPA and CD36 had stopped functioning the way they must—making it difficult for the body to digest, absorb, and break down fat, and leaving the individual’s heart at risk.
Based on the study, researchers also identified genes that affect how the body processes drugs like anti-coagulants, cancer, and psychiatric medications. However, molecular geneticist Meera Purushottam at the National Institute of Mental Health and Neurosciences in Bengaluru said that much more data and research are needed before such findings can be used clinically.
(Edited by Ratan Priya)