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The first part of India’s ambitious programme to map the genetic diversity of its people is now complete, and its data are ready to be used. The Genome India Project (GIP) has catalogued entire gene sequences of 10,000 individuals from 83 population groups. This database will eventually be expanded significantly, but it is already a precious set of information with important implications in health and medicine, and some other areas as well.
The preliminary findings of GIP, in which 20 Indian academic and research institutions, and more than 100 scientists, were involved, have just been published in the journal Nature Genetics. The analysis of the data is still ongoing, and the full results are planned to be published next year.
The genome database will open up the possibility of personalised medicine, and faster and efficient diagnostics. It will also reveal information about the evolutionary history and migrations of population groups within India, and how they have adapted themselves to local climate and environment.
Getting the genome
Most importantly, the genome database would help improve human health. The genome sequences have been prepared after obtaining blood samples from individuals.
The full genome of an individual means getting the exact order in which four nucleotide molecules in the human DNA are arranged in an approximately three-billion-long sequence. These four nucleotide molecules — adenine, thymine, cytosine, and guanine, or simply A, T, C and G — along with a phosphate molecule and a sugar molecule, form the long double-helix DNA strands which is essentially the genetic blueprint of the individual.
More than 99.9% of the nucleotide sequence is the same in all human beings. It is the 0.1% difference that makes a person unique, not just in outer appearance — height, or facial features — but also in behavioural tendencies. This means that in every individual, about three to four million nucleotide molecules are uniquely placed in the sequence, and this is what gives rise to the diversity.
People within a closed and isolated population group are likely to have fewer variations in their nucleotide sequences. Whereas, a heterogeneous population will show greater genetic diversity.
Most genetic variations — the out-of-place, or unique, instances of A, T, C or G nucleotides in the full gene sequence — are benign. They do not result in any noticeable difference in the individual. Only a small fraction, 1-2%, are critical, their placement in the sequence affecting appearance, traits or health. It is these critical parts of the sequence that are of maximum interest to scientists.
The GIP database
Through a project like GIP, scientists collect and store what is known as germline sequence — the nucleotide sequence that a person was conceived and born with. Over time, the genetic sequence of a person changes, with every cycle of cell division introducing a few more variations, called mutations.
Germline sequences are obtained from white blood cells that are relatively better at preserving the original sequence during cell division. Among other things, the unique parts of this germline sequence could offer clues about an individual’s predisposition towards certain diseases or disorders. It can indicate, for example, not just why a particular person might have developed a certain disorder, but also why some lines of treatment might not be very effective in this case. This could lead to the evolution of personalised medicine, where a patient is not administered a general treatment but gets a tailor-made solution for the disease or disorder.
Sometimes population groups as a whole might be predisposed to certain diseases because all the individuals in the group share the same pattern in the consequential part of the sequence. For example, the widespread prevalence of diabetes in the Indian population is likely linked to the genetic makeup of the population. This kind of information can be handy in developing population-specific drugs.
Mapping the genetic diversity of the entire population, which is what the GIP seeks to do, can help develop health policies and targeted interventions, particularly for rare diseases found only in the Indian population.
Population evolution
The GIP can also contribute to a better understanding of population history and evolution. The germline sequences are what an individual receives from the parents. There is a way to establish ancestry and parentage by studying the sequences. Genetic variations that are more widespread in the population are likely to have emerged much earlier, while those that are found in just a few individuals are quite likely to be new developments. DNA from fossils and isolated tribes, which have undergone relatively fewer changes over generations, fill up important pieces of the overall puzzle.
By comparing the genomes of a large number of people, over several generations and belonging to different ethnic, geographical, and linguistic groups, scientists can gather a lot of information about the history and evolution of populations. For instance, scientists can get evidence for how populations moved from one place to another, socialised and intermingled with other groups through marriages, and adapted to local conditions. This kind of information helps a great deal in resolving the identity issue — who we are, and where we come from — which is an eternal curiosity of human beings.
The GIP, conceptualised and launched in 2020 under the leadership of Prof Vijayalakshmi Ravindranath, founding director of Centre for Brain Research, Bengaluru, is the Indian equivalent of the Human Genome Project which has tried to map the entire human genome at the global scale. That project, however, did not have enough samples from the Indian region to provide good information about the Indian population. The large number, and the diversity, of Indian population groups demanded a similar exercise focused on this region.
