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September 21, 1999
What is the bet on the DNA chip?Y Bala Murali Krishna in New Delhi
The 'DNA chip' is all set to rival the importance of the silicon microchip in the development of technology.
The DNA chip diagnoses the genetic make up of humans and is expected to open up amazing new possibilities in the field of pharmaco-genetics.
Scientists have pleaded for a multi-centric approach and higher investment in human genomic research by national laboratories and industrial research and development because the DNA chip technology is likely to change the way molecular biology research is done.
They say the computational genomic will provide several new molecular targets for new drug discovery and can play an important role in developing computational methods to replace or reduce drug trials for toxicity test.
The DNA microarray or DNA chips are fabricated by high-speed robotics on glass or nylon substrates for which probes with known identity are used to determine complementary binding, allowing massive parallel gene expression and gene discovery studies.
An experiment with a single gene chip can provide researchers with information on thousands of genes simultaneously.
Ultimately, multicolour fluorescent detection system and advance scanners will be required to analyse such array and the DNA chip technology is already underway in this direction.
Human genomic studies promise to transform biology and medicine, taking us from curative and preventive medicine to an era of predictive medicine, according to Professor Samir K Brahmachari, director, Centre for Biochemical Technology here.
The Human Genome Initiative is a worldwide research effort with the goal to understand the hereditary instructions that make each of us unique.
The objective is to find the location of the 100,000 and odd human genes and to read the entire genetic scripts, all three billion bits of information, by 2005.
The research is in its incipient stage in India that has poor resources but is in advanced stage in Europe where billions of dollars have been pumped into it.
It is likely to provide in-depth understanding and possible treatment for over 6,000 genetic disorders as well as genetic alterations that increase the risks of developing some common diseases.
The human genome research is further expected to unravel the variability in response to pathogenic organisms and the basis of neoplastic proliferation and human behaviour, thus paving way to an era of predictive medicine.
Professor Brahmachari says recombinant DNA research of the two decades focussed on understanding single gene function at a time and expression of human or foreign genes in microorganisms.
Genomic study is a new way of looking at gene function in its natural context and a complete genome sequence provides a holistic view of the organism. It is likely to deliver a new generation diagnosis and therapeutics for health care.
The widespread use of DNA sequencing technology and polymerase chain reaction have helped increase our understanding of the molecular basis of many genetic disorders and multi-factorial diseases, he said.
The human genome project is moving three to four years ahead of time and it is hoped that most of the 88,000 human genes will be completely sequenced along with large regions of non-coding sequence by next year.
It is expected that by the 2003, the complete human genome with three billion nucleotides will be sequenced, he says.
At the dawn of the new millennium, the first draft of the human genome sequence will be available, posing the biggest challenge in the biological science in unravelling the functional role of sequenced data.
This vast amount of information will open up opportunities for discovering relationship between gene and phenotypic variability in human beings besides helping us to unravel rules of the biological world.
It is expected that the biotechnology of tomorrow will be dominated by the knowledge derived from genomic research. But it will need determining all the variations of sequences in the genome for all of the population.
Identification of 'single nucleotide polymorphism' at 100 KB or closer in the human genome and subsequently establishing association of specific SNP with specific disease will enable us to discover the molecular basis of many polygenic diseases like cancer, hypertension, asthma, epilepsy, schizophrenia and bipolar disorders, he says.
This will further enable us to identify new molecular targets for many diseases for which no drugs are available at present, Professor Brahmachari says.
Understanding the molecular basis of 6,000 known genetic disorders will allow us to develop future tools for gene therapy.
The detection of nucleotide variation by conventional sequencing will be replaced by the DNA chip where array of oligonucleotides are fixed on silicon or glass surface.
It provides a medium for matching known and unknown DNA samples based on base pairing rules and automating the process of identifying the unknowns, Professor Brahmachari says.
The DNA sequence data provided by genome projects have spawned the new field of functional genomic studies, yielding exciting insights into pathways to which specific genes belong besides providing clues to their roles in health and diseases.
It is estimated that there are about 70,000 to 100,000 genes in the human genome. To turn this genetic blueprint into a functioning organism, each of these genes must be expressed in specific temporal and spatial contexts, he says.
Software and database systems to design arrays, track materials, collect, analyse, and interpret data from gene expression studies are still in their infancy, he adds.
Such systems have to catalogue the expression behaviour of thousands of genes in a single experiment using DNA chip and subsequently make comparisons across tissues, developmental and pathological states or cellular perturbations.
Time is not far off when data from thousands of gene expression experiments will be available for analysis that has the potential to balance out artefacts from many individual studies, thus leading to more subtle findings and robust results, he says.
However, it requires more investments as knowledge of genome sequences of pathogenic organisms benefit discovery of highly specific drugs infectious diseases like tuberculosis, stomach ulcer and malaria without any side effects.
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