Genome India project: The Department of Biotechnology recently announced its new platform and framework for sharing its 10,000 human genome dataset. The sequences of healthy individuals — from 99 ethnic populations of the country — has helped create a baseline map of India’s genetic diversity. The researchers in the second phase plan to sequence genomes of those with specific diseases. First, what is genome sequencing? The human genome is essentially an instruction manual we inherit from our parents that decides how our body develops and functions. This genetic information determines everything from a person’s height, to the colour of their hair and eyes, to the diseases they may inherit, or the ones they are pre-disposed to. It is a tome written with just four letters A,C,G, and T - the four bases that come together to create the unique genetic makeup of everyone. There are around 3 billion pairs of bases in the complete human genome. To sequence the genome, researchers first extract the information from the blood. Handling the entire genome, however, is extremely difficult. So, the researchers cut it up into smaller pieces and tag them. A sequencer is then used to decode these smaller chunks of the genetic material. Once done, it is put together using the tags to create a whole genome — in the same way one would assemble say an Ikea furniture by numbers. What is the Genome India project? India is a country that is varied not only in geography, languages that are spoken, food, and culture, it is also diverse in genetic make-up. There are over 4,600 distinct populations. The Genome India project was first approved in 2020 with the aim of capturing this diversity at the genomic level. 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, data sharing platform, and a framework — the department of biotechnology aims to expand the programme further and sequence up to 1 million genomes. How does creating the database help? One, 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. Two, 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. Three, 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 own genome dataset. Four, it may also help identify rare disease and develop gene therapies that can treat them. Five, 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. Use of these anaesthetics can result in them remain under for hours or even death. What is the second phase of the project? The second phase of the project would involve sequencing the genomes of those with specific disease. This will enable researchers compare the diseased genomes with the healthy ones, helping in identifying genes that are responsible for or pre-dispose a person to certain diseases. They may be able to study the genetic changes when someone gets a disease, take for example cancer. The team is currently in discussion with experts to identify the diseases for which genomes should be sequenced and the number of genomes for each disease required to produce meaningful results. The diseases that would most likely be included in the list would be different types of cancers, chronic conditions such as diabetes, and various neurological or neurodegenerative diseases. Rare diseases that are found in Indian populations are also likely to be included in the list of diseases to be studied for the next phase of Genome India project. How will the data be shared? For now, the data will be available to Indian researchers through managed access. “This is the first time that we have created a resource such as this and we have to be very careful how we share this highly sensitive data. The data will be made available only through managed access — meaning it would be available only to research institutes that partner with us for the study,” said Dr Suchita Ninawe, senior scientist from department of biotechnology. Scientists wishing to utilise the data would have to respond to a call for proposals and collaborate with the department. The research will be funded by the government. To maintain the anonymity of the data, it would also be double blinded. “After the samples from different regions are collected and sequenced by one of the partner institutes, it would be encoded before being uploaded to the central database. When the data is shared further with those wishing to study it, it would be encoded once again. This is to ensure that there is no way for the anonymity to be breached,” said Dr Ninawe. Are there other such projects across 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 by 2018. There has also been a European effort to sequence 1+ Million Genomes across 24 countries.
