CSIR-IIGB Human genome mapped

India has successfully mapped the human genome. This will help develop effective drug development in the country, an achievement that puts the country among an elite league of six countries that have achieved the feat so far. The feat has helped India join a select club of countries -the US, UK, Canada, Korea and China. The Council of Scientific & Industrial Research (CSIR)’s, India’s leading research organization, New Delhibased Institute of Genomics and Integrative Biology (IGIB) have succeeded in completely sequencing the genome of an individual has cracked the Human genome code without any international support. The DNA mapping of a 52-year-old man from Jharkhand has found marked genetic variations that suggest vulnerability to cardiovascular disorders,colorectal cancer and schizophrenia. ‘’The findings will definitely be a hypothesis for future genetic studies. If more Indians show similar variations, it could establish a clearer pattern,’’ said Sridhar Sivasubbu, who led the project along with Vinod Scaria. It has been ascertained that 2,000 new variations are studied. The genome has 3.1 billion base pairs and the team at IGIB generated over 51 Gigabases of data using next generation sequencing technology. Gene mapping promises predictive healthcare by identifying specific vulnerabilities of a population to certain diseases and developing new methods of prevention and targeted treatment. Genetic sequencing will help in early diagnosis and management of diseases, including cancer. Persons with genetic profiling will get an indication of diseases to come. It is significant because the ability to assemble the genome shows our capability to study the variations in genes and, thus, will revolutionise future disease predictions and treatment methodologies. Earlier, CSIR scientists at the IGIB had sequenced the genome of a zebrafish, having about 1.8 billion base pairs as against that of human genome that comprised around 3.1 billion base pairs. The zebrafish genome was considered as a significant step as it was the popular organism for modelling human diseases. India was the first country to sequence the wild type strain of the zebrafish, an exercise that gave scientists the confidence to take up the challenge of mapping the complete human genome.

Benefits:
1. Virtually all health conditions have a genetic component. You are 5-10 times more prone to diabetes, if you have a diabetic patient at home. Knowledge of your genetic endowment empowers you to better predict your risk to a common disease.

2. It is a great development as genomics has the potential to bring down the cost of healthcare by offering specific drugs by identifying the gene mutation, and can also predict the onset of a disease. Companies can make more accurate drugs for specific populations.

3. Currently, scientists at Reliance Life Sciences are working on decoding the oral cancer genome by analysing the single nucleotide polymorphisms (SNPs). SNPs are variations at a single site in a DNA and 10 million such
variations are there in a human genome. The research is to understand the genetic constitution favouring the development of oral cancer in tobacco chewers, lung cancer in tobacco smokers, heart attack in people with high blood pressure and vitiligo — a chronic skin disorder that causes discoloration in patches of skin.

4. Such diagnostic tools may be expensive in the current context, but going forward genomics-based disease detection and therapy based on personalised medicine will bring down the overall healthcare cost. Biocon conducts cutting-edge research
on the structure of complex proteins to develop innovative drugs.

5. A number of companies, such as Myriad Genetics started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, disorders of hemostasis, cystic fibrosis, liver diseases and many others. Also, the etiologies for cancers, Alzheimer’s disease and other areas of clinical interest are considered likely to benefit from genome information and possibly may lead in the long term to significant advances in their management.

Role of Private sector:
Genomic research in the publicprivate sector is also shaping up in the country. The Centre for Genomic Applications (TCGA) in Delhi is the first such partnership that maintains a multipurpose national facility that provides gene-based research services. Today, it has over 200 clients, mostly universities and research institutes across the country. A collaboration between IGBT and Institute of Molecular Medicine promoted by Kolkata-based Chatterjee Group, TCGA excels in the area of gene sequencing, genotyping, gene expression and proteomics or the large-scale study of the structures and functions of proteins. Biocon conducts cutting-edge research on the structure of complex proteins to develop inno--vative drugs.

The first ever study of human genomes of Asia conducted by Human Genome Organisation (HUGO) Pan-Asian SNP Consortium also says that some of the Indian population showed evidence of shared ancestry with European population and this is consistent with the expansion of Indo-European speaking population. This HUGO's Pan-Asian initiative is a consortium of 90 geneticists and 40 institutions from 10 Asian nations, namely China, India, Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan and Thailand. It collected samples from 1,928 unrelated individuals represe-nting 73 groups of people from 10 countries and 10 linguistic lineages from member countries as well as from two non-Asian population groups of Africo- American and Caucasian ancestry. Human, animal, and plant life forms all share the same DNA genetic code made up of the four amino acids A, T, G, and C. At the molecular level all life is the same.

1. Human genome is a list of instructions, encoded in DNA needed to make a human;
2. The four letters in the DNA alphabet — A, C, G & T — are used to carry instructions to make an organism;
3. It is like reading the meaning of a “word”;
4. Each set of 3 letters corresponds to a single amino acid, the building blocks;
5. Human DNA is 98 per cent identical to chimpanzees;
6. 20 different amino acids in various combinations make proteins;
7. Human genome is made up of 3 billion bases of DNA, split into 24 chromosomes;
8. Human body is made up of 100 trillion cells, each has at least one nucleus, which houses chromosomes;
9. Most human cells contain 46 chromosomes;
10. Human genome contains 20,000-25,000 genes
11. Information in a human genome will fill 200 telephone directories of 500-page each; and
12. Will take a century to recite, at a rate of one letter per second for 24 hours a day.

International Human Genome Project: The international human genome project, comprising scientists from US, Britain, France, Germany, Japan and China, was successfully completed in 2003 after 13 years and an investment of $3.5 billion. The first available assembly of the genome was completed in 2000 by the UCSC Genome Bioinformatics Group, composed of Jim Kent (then a UCSC graduate student of molecular, cell and developmental biology), Patrick Gavin, Terrence Furey and David Kulp.

Biotech Regulations:
With the Bt. Brinjal controversy, India needs better regulations in coming times. The biotech revolution in India needs an efficient regulatory system. The present system is the outgrowth of ad hoc regulatory mechanisms built up piecemeal, since 1989, to deal with issues as and when they would arise. India’s biotechnology regulatory system has experienced a number of changes since the Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically
Engineered Organisms or Cells 1989 (Rules, 1989) were first notified under the E n v i r o n - m e n t (Protection) Act, 1986, including the elaboration of aseries of guidance documents published by the Department of Biotechnology (DBT) in 1990, 1998 and 1999. The entities involved are the Recombinant DNA Advisory commi-ttee (RDAC), Review Committee on Genetic Manipulation (RCGM), Institutional Biosafety Committees (IBSC), Genetic Engineering Approval Committee (GEAC), Drugs Controller-General of India (DCGI), the Health Ministry Screening Committee (HMSC), among others. The National Institutes of Health (NIH) established the Recombinant DNA Advisory Committee (RAC) on October 7, 1974 in response to public concerns regarding the safety of manipulating genetic material through the use of recombinant DNA techniques. Although the RAC’s membership and responsibilities have evolved over time with scientific understanding and developments in this technology, it continues to serve the NIH, as well as the scientific and lay publics, as a critically important forum for open, public deliberation on the panoply of scientific, ethical, and legal issues raised by recombinant DNA technology and its basic and clinical research applications.

Main functions of RCGM :
1. To bring out manuals of guidelines specifying producers for regulatory process on GMOs in research, use and applications including in industry with a view to ensure environmental safety;

2. To review all on going r-DNA projects involving high risk category and controlled field experiments;
3. To lay down producers for restriction or prohibition, production, sale, import & use of GMOs both for research and applications;
4. To permit experiments with category III risks and above with appropriate containment.
5. To authorize imports of GMOs/ transgenes/ transgenic seeds for research purposes.

The main functions of GEAC :
1. To permit the use of GMOs and products thereof for commercial applications.
2. To adopt producers for restriction or prohibition, production, sale, import & use of GMOs both for research and applications under EPA.
3. To approve for conduct of large scale field trials, evaluation of large scale field trial data and final approval for release of transgenic crop in to the environment.

4. To authorize large scale production and release of GMOs and products thereof into the environment.
5. To authorize agencies or persons to have powers to take punitive actions under the EPA.

Institutional Biosafety Committees (IBCs) are the cornerstone of institutional oversight of recombinant DNA research. The following information and resources are provided to help IBCs perform this critical role, as well as to inform others about the roles and responsibilities of these important committees.Under the Drug and Cosmetics Act, the regulation of manufacture, sale and distribution of Drugs is primarily the concern of the State authorities while the Central Authorities are
responsible for approval of New Drugs, Clinical Trials in the country, laying down the standards for Drugs, control over the quality of imported Drugs, coordination of the activities of State Drug Control Organisations and providing expert advice with a view to bring about the uniformity in the enforcement of the Drugs and Cosmetics Act. Drug Controller General of India is responsible for approval of licenses of specified categories of Drugs such as blood and blood products, I. V. Fluids, Vaccine and Sera.

The Health Ministry’s Screening Committee (HMSC) is a high level committee constituted by the Ministry of Health and Family Welfare (MOHFW), Govt. of India, to consider and approve international research proposals in biomedical sciences for collaboration with foreign institutions and/or assistance from foreign funding agencies. Indian Council of Medical Research (ICMR) acts as the technical arm and is the Secretariat for this Committee. HMSC is also responsible to monitor the progress of such projects and assess the suitability of research results for inclusion in various national health programmes and policies.

The Mashelkar-led Task Force on recombinant pharma, set up to look into this problem, made a number of recommendations in 2006, including setting up of a single National Biotechnology Regulatory Agency (NBRA), for providing a single window mechanism for giving various regulatory approvals, including those concerning bio-safety issues. This was also the recommendation of the M. S. Swaminathan led Task Force on agro-biotechnology.

The Department of Biotechnology (DBT)’s National Biotechnology Development Strategy (NBDS), approved in 2007, envisages the NBRA as an “independent, autonomous and professionally-led body to provide a single-window mechanism for biosafety clearance of genetically modified products and processes”. The DBT published an establishment plan for the NBRA (May 2008) and a draft NBRA Bill (July 2008). The Bill is pending and may be approved at the earliest, so that our regulatory system can be cleaned up. This can give a further boost to India’s biotech sector which crossed the $2.5 billion mark during 2007–08 with a CAGR over the past five years of over 30 per cent.