The Centre for Genomic Applications (TCGA), Delhi, has generated genetic information on over 4,000 genetic markers from over 1,000 biomedically important and pharmacogenetically relevant genes in reference populations encompassing diversity of populations from across the country.
TCGA is a joint venture between between the IGIB, a CSIR organization which is supported by the Department of Science and Technology (DST) and IMM-The Chatterjee Group. The latter is headed by Indian-born entrepreneur Dr Purnendu Chatterjee, who has also been the founding shareholder of Haldia Petrochemicals in West Bengal.
This collaborative project also involved the efforts of scientists and researchers drawn from six laboratories from the Council of Scientific and Industrial Research (CSIR), along with the Kolkata-based Indian Statistical Institute, and anthropologists from several institutes,
This project is, till date, the largest scientific endeavour in the country after the Indian Council of Agricultural Research's (ICAR) efforts that led to the green revolution in the 1970s. This is the first large scale comprehensive study of the structure of the Indian population. The ultimate goal is to create a DNA variation database of the people of India and make it available to researchers for understanding human biology with respect to disease predisposition, adverse drug reaction, population migration
The six CSIR institutions involved in this collaborative research are Centre for Cellular and Molecular Biology (CCMB), Hyderabad; Central Drug Research Institute (CDRI), Lucknow; Institute of Genomics and Integrative Biology (IGIB), Delhi; Indian Institute of Chemical Biology (IICB), Calcutta; Indian Institute of Toxicology Research (IITR), Lucknow, formerly known as Industrial Toxicology Research Centre (ITRC) and Institute of Microbial Technology (IMT), Chandigarh.
Revealing this at a press conference in New Delhi yesterday, union minister for science and technology, and earth sciences Kapil Sibal said that it would help in the construction of 'specific drug response / disease predisposition maps' to aid policy level decision making for drug dosage interventions and disease risk management, especially for complex as well as infectious diseases.
Prof Samir K Brahmachari, director general, CSIR, and the leader of this endeavour, said that this monumental study had resulted in a clear genetic profile of our population groups, explicitly indicating the strong association between genetic and linguistic profiles in India and that there were significant genetic differences in the frequencies of disease-associated genetic markers. This marks the second step after the Human Genome Project of the early part of this century.
The background to this project
The Human Genome Project (HGP) was an international scientific research project with a primary goal to determine the sequence of chemical base pairs which make up DNA and to identify the approximately 25,000 genes of the human genome from both a physical and functional standpoint.
The project began in 1990 initially headed by James D. Watson at the US National Institutes of Health. A working draft of the genome was released in 2000 and a complete one in 2003, with further analysis still being published. A parallel project was conducted by the private company Celera Genomics.
Post the human genome sequencing era, there is an increased expectation in the masses to get improved and faster diagnosis related to genetic defects leading to occurrence of diseases. It is hoped that harnessing the enormous amount of variability now available in different population would accelerate identification of predictive and predisposition markers for common and complex diseases genes as well as individual responsiveness to medications and different environments. The most challenging task now is to identify informative markers from a milieu of variation data which are likely to be informative in such studies.
The Indian Genome Variation database (IGVdb) is a consortium activity established in 2003 deemed it pertinent to understand the inherent genetic variability of the subpopulations as a first step towards identifying susceptible biomarkers for any disease or understanding drug response in different subpopulations. This consortium, therefore, aims at providing information on variations in the subpopulations representing the entire country. These variations would be useful for investigators for specific candidate gene studies conducted in any part of the country.
For example, this study has led to the discovery of a known protective genetic marker against HIV-1 being virtually absent in India, implying the absence of natural or genetic protection against HIV-AIDS in our country, Prof Brahmachari disclosed.
The overall results of this study would help in (a) predicting of both diseases and the effectiveness of specific drugs used for their treatment, and (b) designing future scientific studies to understand genetic roots of major diseases in India. These results have also provided the first set of insights into the processes of human adaptation to different types of environment in India. The first phase of these results on 55 population groups involving several hundred markers has been released in the April 2008 issue of Journal of Genetics (J Genet, 87, 3-20 April 2008).
Findings of the Indian Genome Variation Consortia
Earlier, in 2002 the International HapMap Consortium had initiated a programme to build the next generation map of human genome at the total cost of $100 million. To capture the extent of genomic diversity, the above study covered 45 Chinese, 45 Japanese, 90 Caucasian, and 90 African individuals.
Fully realising that 45 samples would not represent the total diversity of India, the Indian Genome Variation Consortia was launched independently to study a large number of samples (over 2000 samples drawn from 55 populations) on smaller number of highly informative markers, cost-effectively at one-twentieth cost of the HapMap Consortium. In addition, 58,000 SNPs (50K Affymetrix array) were analysed in about 600 individuals representing 26 populations from four major clusters, as a part of this study.
The study reveals that the genetic landscape of Indian populations captures the genetic diversity of the world - that Indian population groups form a continuum of genetic spectrum bridging the two distinct HapMap populations, the Caucasians and the Oriental Asians. The research also revealed the existence of population groups unique to India, mainly derived from Austro-Asiatic and Dravidian speaking populations.
These findings have major implications in designing drug-discovery studies and selecting suitable populations for testing drug efficacy. For instance, a pilot pharmacogenomic study on response to salbutamol (a Beta-2-adrenergic agonist used to treat asthma) identified genetic markers in a receptor gene which could classify individuals as poor and good responders – a finding that would help in better management of the disease.
A large number of projects are being funded for research in the 11th Five-year Plan that are aimed at utilising this basal data for predictive marker discovery and pharmacogenomics. Additional data is available in The Indian Genome Variation database (http://igvdb.res.in). The paper consisting the study is available at www.ias.ac.in/jgenet/Forthcoming.html