Recently, the Department of Biotechnology (DBT) has made the genome data of 10,000 individuals publicly accessible, under the Genome India Project (GIP). The sequences of healthy individuals — from 99 ethnic populations of the country — have helped create a baseline map of India’s genetic diversity. This dataset is made available to researchers as a “digital public good.” The data can be utilised to develop new diagnostics and targeted therapies, identify new rare diseases, and cure existing ones. This initiative also addresses the underrepresentation of Indian genomes in global databases, promoting inclusivity in genomic research.
Key Takeaways:
1. The GIP was approved by the government in 2020 to create a comprehensive catalogue of genetic variations found in the Indian population. A map of genetic diversity is essential for understanding the history of our evolution, discovering the genetic basis for various diseases, and creating therapies of the future. This cannot be done using data available in existing international databases, as Indian genomes are likely to be different from that of other populations.
2. Researchers from 20 different scientific institutions have come together to sequence the first 10,000 genomes under the project. With everything in place — a successful collaboration, a data storage facility, a data sharing platform, and a framework — the Department of Biotechnology aims to expand the programme further and sequence up to 1 million genomes.
3. The second phase of the project would involve sequencing the genomes of those with specific diseases. This will enable researchers to compare the diseased genomes with the healthy ones, helping in identifying genes that are responsible for or pre-dispose a person to certain diseases.
Significance of creating this database
1. This map can help identify genetic basis or genetic risk factors for various diseases. These can then be used as targets for developing therapies and diagnostic tests. Newer therapies for several diseases work by modifying, deleting, or adding certain genes — something that would not be possible without having a genetic map and an understanding of which genes lead to the disease.
2. An Indian dataset helps identify new variants. The researchers have identified 135 million genetic variations in the 10,000 genomes so far, 7 million of which are not found in the global databases.
3. Population-level sequencing can also tell scientists and clinicians the frequency at which certain genetic variations that are known to cause disease appear and hence how common a disease might be. Take for example, the MYBPC3 mutation known to lead to cardiac arrest at a young age is found in 4.5% of the Indian population but is rare globally. Or, another mutation called LAMB3 that causes a lethal skin condition is found in nearly 4% of the population near Madurai but it is not seen in global databases. This is the reason India requires its genome dataset.
4. It may also help identify rare disease and develop gene therapies that can treat them.
5. It can also help in identifying resistance-indicating variants, for example, genes that might make certain medicines or anaesthetics ineffective in certain populations. An example from India is a sect of the Vaishya community from South India who have the gene missing for properly processing common anaesthetics. The use of these anesthetics can result in prolonged unconsciousness or even death.
What is a genome, how is it sequenced?
There are around 3 billion pairs of bases in the complete human genome. This contains all the information needed to create your physical form and maintain it throughout life. From your height, colour of the eyes, the genetic diseases you get or those you are at a higher risk for, everything is determined by your genetic makeup.
To sequence the genome, researchers first extract the information from the blood. With a complete sequence of 3 billion pairs being extremely hard to handle, scientists cut it up into small pieces and tag them — like you would when you disassemble furniture. The A, C, G, T codes of these smaller chunks are written down by a DNA sequencer and then the complete sequence is put together.
Other similar projects around the world
The first Human Genome Project — which was an international consortium funded by the US National Institutes of Health among others — published the world’s first complete human genome in 2003.
Since then, the 1,000 genome project — again through international collaboration — published 1,092 sequences in 2012.
A UK government project sequenced 100,000 genomes in 2018. There has also been a European effort to sequence 1+ Million Genomes across 24 countries.
Genome Editing Technology
1. Genome editing is a technique that allows scientists to ‘cut’ DNA strands and edit genes. The technology enables a simple but remarkably efficient way to ‘edit’ the genetic codes of living organisms, thus opening up the possibility of ‘correcting’ genetic information to cure diseases, prevent physical deformities, or to even produce cosmetic enhancements.
2. Advanced research has allowed scientists to develop highly effective clustered regularly interspaced palindromic repeat (CRISPR) -associated proteins-based systems. This system allows for targeted intervention at the genome sequence.
3. Its mechanism is often compared to the ‘cut-copy-paste’, or ‘find-replace’ functionalities in common computer programmes. A bad stretch in the DNA sequence, which is the cause of disease or disorder, is located, cut, and removed — and then replaced with a ‘correct’ sequence. The tools used to achieve this are not mechanical, but biochemical — specific protein and RNA molecules (Cas9).
4. A vast number of diseases and disorders are genetic in nature — that is, they are caused by unwanted changes or mutations in genes. These include common blood disorders like sickle cell anaemia, eye diseases including colour blindness, several types of cancer, diabetes, HIV, and liver and heart diseases. Many of these are hereditary as well. This technology and genome sequencing have opened up the possibility of finding a permanent cure to many of these diseases.