Centre for Brain Research, IISc



The human genome is made of 3.2 billion DNA base pairs and between any two humans, the amount of genetic variation is about 0.1 percent. Therefore, one base pair out of every 1000 will differ between any two individuals. These genetic variations differentiate one individual from the other and play an important role in inherited traits, susceptibility to diseases, response to drugs and help track migration and evolution patterns. India’s population of 1.3 billion people comprises of >4,600 well defined ethnic groups could have numerous distinct genetic variations. It is postulated that the Indian population originated from a few founding groups, which gave rise to multiple groups, that we see today. The antiquity of the population groups, the variability of demographic history coupled with combination of unique cultural practices, like endogamy has contributed to the genetic diversity of the current day Indian population. These ethnic groups, though share some genetic similarities, also harbor distinct variations and often many disease-causing mutations are amplified within some of these group. Thus, research from other populations of the world cannot be used for Indians, as the genetic variations seen therein may be less frequent or even absent.

GenomeIndia project aims to catalogue these genetic variations for the Indian population through whole genome sequencing of representative population groups across the country. The data thus generated will be an all-encompassing national resource that will serve the needs of both scientific and medical community.

Therefore, we need to identify the genetic variations that lead to various traits in Indians, and the catalogue of genetic variations generated from this project will serve as a baseline for that. Large scale genomic data from the representative groups will also shed light on some of the unanswered questions of origin and migration of Indian population.

The current proposal aims to carryout whole genome sequencing of 10,000 Indians in the first phase representing the genetic diversity of the population. The precise objectives are:
1.Create an exhaustive catalog of genetic variations (common, low frequency, rare, SNPs and structural).
2.Construct a reference genome for the Indian population.
3.Design genome wide arrays for undertaking diagnostics and basic or clinical research at an affordable cost.
4.Create a biobank for DNA and plasma samples collected from these individuals for future use in research.
This large-scale project will be the first of its kind in the country that aims to bring together researchers from varied disciplines across the country to build a national genetic resource. An interactive web portal for sharing the genetic resources and querying the data will be developed. Also, the previously genotyped Indian samples from various studies could be better imputed with the reference panel created from this project, and thus researchers will have more accurate genome wide level genetic variation information without investing in genotyping (or sequencing) once again. In the second phase of the project, some of the samples will come from large prospective population-based cohorts with a wealth of deep phenotype information over time giving us the ability to better understand the genotype-phenotype associations. The findings from this project will improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses – including cancer, heart diseases, stroke, diabetes, eye disorders, and forms of dementia. Finally, this will provide a resource for designing, and interpreting large scale collaborative genomic studies in India for understanding the underlying diseases and devising better diagnosis and treatment strategies.