Bengaluru: The Council of Scientific and Industrial Research (CSIR) has launched an ambitious project, IndiGen, to sequence whole genomes of diverse ethnic Indian population to develop public health technology applications.
The CSIR last month announced sequencing of 1,008 Indian genomes as part of the project. It aims to complete sequencing of at least 10,000 Indian genomes over the next three years.
A genome is an organism’s complete set of DNA. It includes all genes, which house the DNA, and chromosomes. The genome contains all the data that is needed to describe the organism completely — acting essentially as a blueprint. The genome can be understood through the process described as sequencing.
Whole-genome sequencing is the decoding of the entire DNA present in the human cell. This data can be analysed to understand the function of various genes, identify genetic mutations and explore how the mutations impact gene functions.
Genetic mutations underlie many diseases, including congenital conditions like thalassemia and diseases like cancer. Thus, deciphering a person’s DNA can reveal information about that person’s health.
This apart, analysing DNA data of human population can reveal population-level predispositions to diseases. Take the case of a specific Vysya community in Andhra Pradesh, which is believed to possess a genetic mutation that renders them susceptible to a category of anaesthetics.
Studying DNA data from patients who suffer a specific disease can also help trace the origin of that disease. The UK has been running a 100,000 programme — creating a database of over 85,000 patients suffering from rare diseases/cancer to discover the mutations that underlie those diseases.
The UK is, however, not the only country investing in population genomics. The US, Japan, China, Australia, Saudi Arabia, Estonia, France, Dubai and Turkey have all embarked on genomic programmes to better understand the healthcare needs of their citizens.
The IndiGen project is India’s first step in collating such a national database for its citizens.
Advantages of genome sequencing
Around 70 million Indians suffer from rare genetic diseases. It is estimated that about 64 out of 1,000 live births in India carry a congenital birth defect. Yet the molecular basis of a number of diseases remains unknown.
Further, India has a unique genetic history underpinned by centuries of endogamy (marrying within the same community) practised in various communities.
The resultant South Asian genetic population is comprised of more than 5,000 genetic sub-groups. While diseases may appear rare in the entire Indian population, specific sub-groups may show a higher frequency of disease incidence.
Specific sub-groups, which practise endogamy, will also have a conserved mutation that has spread through that population as exemplified by the Vysya community case.
Another study had demonstrated some sub-groups containing a mutation that caused a predisposition to glaucoma.Thus, a comprehensive Indian genome project essentially will study disease prevalence within these individual ethnic populations.
The analysis of a significant sample set representative of a particular sub-population can provide data on the predisposition of various diseases present in that sub-group. Using this information, individuals belonging to that sub-group can make informed decisions to get screened for particular mutations. Those found to contain genetic mutations can make necessary lifestyle changes or seek medical assistance to lead healthier lives.
Some congenital diseases result when a child inherits two defective genes from a parent. For this category of diseases, pre-emptive action such as screening of partners before marriage or PGD (preimplantation genetic diagnosis) to pick healthy embryos can ensure the birth of healthy children.
Dor Yeshorim, a US-based not-for-profit organisation, runs a programme within specific Jewish communities to inform prospective couples of their genetic compatibility.
Over the past few years, this continued programme has led to the eradication of Tay-Sachs disease from at least one US-based Jewish community.
The analysis of genomic data, combined with medical information, from victims of rare diseases can reveal the mutations that underpin the disease. This data can be used to create improved diagnostics and therapeutics for targeting the disease. Newer tools like gene-editing can also be explored for treating genetic diseases.
Data assessments can massively impact healthcare in India — either by helping couples raise healthy children or by creating avenues for better medical interventions for preventing or treating diseases.
The major challenge of a project of this scale is adequate and representative sampling of the population. The more the number of samples, the better the accuracy.
The genome projects of other countries target about 1,00,000 genomes. India’s target of 10,000 genomes in comparison is a good start but needs substantial expansion.
There also needs to be clarity on the sampling approach — does the sample identify a representative set for each subpopulation or for each rare disease? An exercise of a massive scale as this has to be led by a specific predetermined objective.
The second challenge is of consent — a publicly-funded project of this nature may likely start off as a research project based in academic labs, but the creation of diagnostic or therapeutic tools would be facilitated by sharing the data with commercial ventures.
While taking volunteer/patient samples, it is important to take consent for the use of any data in creating commercial products, may it be diagnostics or therapeutics. If commercially viable products are created based on contributed data, financial or benefit-sharing agreements need to be addressed beforehand to prevent any unnecessary litigation later on.
The database for this project not only contains genetic information, but also medical and sensitive personal information, and contributors should have a say in how much information gets shared with additional partners.
A third question that needs to be sorted is about how much information to share with the donors. Dor Yeshorim believes that burdening people with mutation information can lead them to unnecessarily make lifestyle changes. Thus, clinically actionable information should only be shared where robust scientific proof exists, linking the mutation to a disease.
To implement this, clinicians and genetic counsellors need to be trained to determine best medical intervention in the context of the particular patient. Hence, capacity building to gather, analyse, interpret and communicate the genomic data will determine the success of this project.
In conclusion, the IndiGen project embraces scientific technology for the advancement of Indian healthcare, ushering India towards the new gold standard of precision medicine. Policies that can enable the project to work optimally need to be framed to ensure its smooth and sustained functioning.
Shambhavi Naik is a fellow at the Takshashila Institution’s Technology and Policy Programme.