A genome is the total DNA in each cell of an organism. The genome contains the genetic blue-print which dictates the form and functions of that organism. Even though the human body consists of 60,000 billion cells, the DNA contained in each of these cells is constant. The human body is the most complicated living system on earth. It contains 46 chromosomes in 23 pairs. It is presently predicted that the human body contains more than a hundred thousand genes. According to present estimates, the human genome consists of 3.2 billion base pairs.
Taking advantage of the modern biotechnology, advancements in molecular biology and genetic techniques, scientists all over the world systematically sequenced 3.2 billion bases of human genome and announced the working draft on 26th June, 2000. This has opened up a new era of molecular medicine and is expected to give a big boost to all aspects of genetic research in the world.
Rapid and more specific gene-based diagnostic tests will make possible treatment of countless maladies not merely based on symptoms but detecting the cause of pathogenesis as well. Medical researchers also will be able to devise novel therapeutic regimens based on new classes of drugs, immunotherapy techniques, avoidance of environmental conditions that may trigger disease and possible augmentation or even replacement of defective genes through gene therapy.
The international Human Genome Project (HGP) plans to come out by the year 2005 with the sequence of the entire genome involving reading and assembling of the mind-boggling 3.2 billion bases that constitute 80,000-100,000 human genes. India is preparing to position itself in the forefront of utilization of this global research.
The HGP was first conceived somewhere around 1985 (in an editorial by a Nobel laureate Renato Dulbecco, published in the March, 1986 issue of Science). It was suggested that the problems of cancer might be most expeditiously solved if the human genome were completely sequenced.
Some current and potential applications of genome research include molecular medicine, microbial genomics, risk assessment, bioarchaeology, anthropology, evolution and human migration, DNA forensics, agriculture, livestock breeding and bio-processing among others.
Today, we have a draft of 3.2 billion nucleotide sequences of the human genome. It contains an estimated 90 per cent of all the genes and 90 per cent of those that causes disease. The challenge of the new millennium is to unravel the function and the meaning of the sequences. It is an encrypted data set which has to be deciphered.
The complexity is that the human genome has anywhere between 35,000 to 100,000 genes; most probably about 60,000 genes, which make up only about three to five per cent of the genome. So one has to remember that there are sentences buried among junk words and characters. Those sentences have to be deciphered. Each sentence will become a gene. With these 60,000 or 100,000 sentences is written the story of life.
The problem of deciphering the code is to be handled in multiple ways. First, it is a huge database and needs computational handling. So computational analysis to understand the hidden sentences among the huge numbers of junk characters have to be done. Then patterns will have to be found out of these junk characters which must have some meaning because many of these are repetitive sequences or non-coding sequences which are highly conserved among eukaryotic genomes. The second exercise will involve comparing the human genome sequence with those of mouse and Drosophila to find out what is common in them.
The study of DNA variation in the population is very important. It will not only tell us what we are, but also where we came from.
The genome project opens up a new vista. It takes us from the era of drug-based curative medicine and vaccine-based preventive medicine to the era of predictive medicine. The most imaginative of the HGP programme seen by the scientists is visualising the day when the physician will be able to send patients' DNA to the laboratory for screening to detect any genetic mutation that might jeopardise patients' health when all of us may have a "Genome Credit Card" with all our genetic liabilities listed or printed on it. By inserting the card into the computer, the doctor would be able to put together the prognosis, diagnosis and treatment course.
The challenges that lie ahead for scientists during the post-genome era are to appropriately expand and develop methodologies for identification of functions of human genome sequences, determination of effects of sequence variation in ethnic populations on common diseases and for development of preventive and therapeutic measures based on DNA sequence information and variation.
The Department of Bio-Technology (DBT) with the help of an Advisory Committee initiated a programme in the area of human genetics and genome analysis and related technology development in India and constituted a Task Force. The main objective is to develop basic capabilities, strengthen existing institutions which have good expertise in this area and other institutions with expertise in related areas to initiate work in molecular genetics to take up some application-oriented projects to reduce the burden of genetic disorders in the country. The following three major areas have been identified human genome - India's initiative, human genome diversity and minton and gene therapy and bioethics.
The focus of the Indian effort would be on utilisation of the information on human genome for diagnosis, prevention and therapy of genetic disorders. It will aim at identifying, mapping and characterizing the new genes related to genetic disorders prevalent in India and also to carry out studies on regulation of gene function, genotypephenotype correlation and functional significance of repetitive DNA in human genome. The focus of human genome diversity will be towards understanding the history and prehistory of the people of India - how the population of India related to one another; how they relate to populations in other parts of the world; the level of diversity within and between communities, especially tribal communities, to develop the new science of genetic epidemiology, that is the relationship between genomic variation and disease.
The fourteen genetic diagnosis-cum-counselling units established by DBT have been providing molecular diagnosis and counselling for the common genetic disorders such as beta-thalassemia, Duchenne Muscular Dystrophy (DMD), haemoglobino-pathies and neurogenetic disorders prevalent in the country, to the affected families. A total of more than 11,000 affected families got benefited from these genetic units for prenatal diagnosis and counselling for major genetic disorders in select areas was also screened for these disorders.
The Department has developed specific guidelines to initiate gene therapy projects in the country. In addition to the Bioinformatics Network, the Department under the Jai Vigyan Mission has also implemented four mirror sites of genome sequence information . The effort will accelerate research in areas of computational genomics, comparative genomics and functional genomics, which are all focused towards discovering the functions of genomic segments, which will ultimately lead to novel DNA-based diagnostics and therapeutics.
The department has also set up a National Bioethics Committee to take up the issues related to the Universal Declaration on Human Genome and Human Rights, liaison with the International Bioethics Committees of UNESCO and prepare bioethics policy and consider or monitor programmes on gene therapy research in the country. The future strategy of the department includes taking up programmes on functional genomics, pharmacogenetics, custom-made drug designing, develop molecular diagnosis methods for various infections, genetic disorders and microbial genomics with focus on identifying virulence gene and target for drug development.
(The author is with Department of Biotechnology) (Source: PIB Features)