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Indian Today/ 21/ 09/ 09
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The great Indian gene findings
Raj Chengappa
Who were the first Indians? Were they the chocolate-hued Dravidian southerners or the darkskinned tribals that inhabit East India and the Andaman islands? Was the relatively fair IndoEuropean population of the North the original settler? Or did the Mongoloid-featured
Tibetan-Burmans beat the rest to it? When and how did the pioneers reach India? What routes
did they take?
The answers to these questions have always been the subject of contentious debate and till
recently well nigh impossible to conclude. After all today there are more than a billion
Indians consisting of 4,693 communities, 4,500 endogamous groups, 325 functioning
languages and 25 scripts. Not to mention the four main castes and the hundreds of sub-castes
that throw up even more controversial questions such as: Are the Brahmins from a different
genetic pool than that of the Shudras?
Now an unprecedented surge in genetic research across the country is overturning long-held
theories and coming out with some fascinating revelations of how Indians became, well,
Indians. Equally significant and directly relevant to the quality of life, for the first time, major
genetic studies are underway at a clutch of top national laboratories, which when complete
will help us know if any of us run a higher risk of being afflicted with life-threatening
diseases such as cancer, diabetes, malaria, cardio-vascular blocks, neurological disorders and
asthma. And possibly help in ushering a revolution in healthcare.
Blame gene
Recent studies show that some Indians exhibit genetic variations that make them
susceptible to specific diseases.
Malaria: East and Central India populations were found to have a gene that makes them
susceptible to 4,693 cerebral malaria.
Cancer: Initial studies have found certain populations in the extremes to have higher risk
of cancer.
Immune response: Indians showed varying immune response to certain drugs holding the
key for future treatment.
Heart diseases: North Indian vegetarians were more susceptible to heart diseases.
Among the more striking results is the finding that Indians are the global melting pot of
human diversity containing every possible known genotype. That it is now clear that India
was the first stop made by early settlers after the first known human populations migrated out
of Africa. That the tremendous genetic diversity originated in the sub-continent itself rather
than as a result of the so-called 'Aryan invasion' that historians have theorised about. That
some regions in Northern India are more susceptible to heart diseases while some populations
in Rajasthan and Jammu have a genetic immunity that puts them at lower risk of HIV
infections.
The trigger for Indian researchers has been the most spectacular scientific achievement since
man walked on the moon: deciphering the book of human life. In 2001, the international
Human Genome Project (HGP) came out with a raw translation of the 3 billion strands of
DNA-deoxyribonucleic acid-the basic building blocks of all life. To understand the
complexity of the effort, if the genome sequence obtained for a single human being were to
be published in typed form as books these would stack up as tall as Delhi's Qutab Minar.
What the HGP did show was that the human genetic code or genome is 99.9 per cent identical
in all people. It was in line with the theory that we all had a common ancestry with the
earliest humans who lived in Africa and possibly to a single woman, the "mitochrondial Eve."
The 0.1 difference in DNA sequencing is responsible for our individual differences whether
in hair or eye colour or our susceptibility to diseases.
The project revealed that humans have around 25,000 genes-the basic physical and functional
units of heredity. Since then scientists have been able to decode the role played in 50 per cent
of the known genes. The unravelling of the human genetic structure is helping researchers
worldwide find the most fundamental answers to our origins and in enhancing healthcare.
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In India, genetic research got a major boost in 2003 when the Council of Scientific and
Industrial Research (CSIR), with funding from the government, launched the Indian Genome
Variation (IGV) consortium consisting of seven major laboratories: the Institute of Genomics
and Integrative Biology (IGIB), Delhi, Centre for Cellular and Molecular Biology (CCMB),
Hyderabad, Indian Statistical Institute (ISI), Kolkata, Central Drug Research Institute
(CDRI), Lucknow, Institute of Microbial Technology (IMTECH), Chandigarh, Industrial
Toxicological Research Centre (ITRC), Lucknow and Indian Institute of Chemical Biology
(IICB), Kolkata.
The team first collected blood samples of 2,000 people from 55 populations representing the
four major linguistic groups: Austro-Asiatic, Tibeto-Burman, Indo-European and Dravidian
before splicing their genes and looking for tell-tale variations. In doing so the project
established the first large-scale database of genomic diversity in the Indian population.
Samir Brahmachari, a geneticist of repute and CSIR's director-general says, "India is among
the first country to do a diseases-specific, drug-response mapping on large populations which
gives us risk analysis and benefits." Apart from reinforcing what Brahmachari calls the
"genetic mosaic" of India, the study also showed that the risk of susceptibility to a disease
was more specific to a geographical region rather than to caste, creed or linguistic affinities.
Reviewing the consortium's work, Evelyne Heyer, geneticist at the French Natural History
Museum, said, "This study forms a valuable first step in building our knowledge of the
genetic diversity in India."
While the consortium released its preliminary findings last year, since then individual
laboratories have come out with a host of important findings. At the CDRI, geneticist Saman
Habib focused on the more lethal form of cerebral malaria caused by the Plasmodium
falciparum. Studies were conducted on people who lived in the regions where malaria was
endemic. Analysing the samples and also from control groups, Habib found a "clear
indication of variety of genes affecting the susceptibility of the individual towards this deadly
form of malaria including the severity of the attack". One pointer: Health officials would be
well-advised to double their efforts in regions with such susceptibility.
At the IGIB, Shantanu Sengupta is coming out with surprising findings about cardiovascular
diseases and genetic factors. Contrary to popular notions, vegetarians in India have a high
susceptibility to heart diseases. That is now found to be due to a deficiency of Vitamin B12.
But there was a significant variation of this phenomenon between North and South India.
Shompen tribals of the Andaman And Nicobar Islands.
The study found that Northern Indians who were also vegetarian had a much higher degree of
susceptibility to heart problems than their southern brethren because of a genetic variation
that made them vulnerable. The deficiency in Vitamin B12 and the genetic variation
increased the level of an amino acids associated as a risk factor for cardiovascular disease.
In a laboratory not far from Sengupta, Balaram Ghosh, Head of the Genomics and Molecular
Medicine Unit, IGIB is proving just how useful the emerging field known as
pharmacogenomics could be. Researching on the cause of asthma in India, his team, after
examining over 700 patients, found that many genetic variations that are known to make
people susceptible to asthma among European populations were not seen among Indians.
They were also able to identify a novel gene that is associated with asthma among Indian
patients. These would help them identify high-risk individuals and also advise them on
preventive steps.
Carrying the process forward, the team studied the absorptive ability of populations to the
drug salbutamol used to treat asthma. In some people it was found to be not as effective as in
others. Understanding the process would help in administering the right amount of doses of
the drug and getting away from "the one-size-fits-all" approach.
Somewhat similar work is being done on Diabetes Type II by his colleague Dwaipayan
Bharadwaj who is looking for genetic markers that could help doctors identify those
susceptible to it long before they come in for treatment. Again here, after examining over
7,000 patients suffering from this type of diabetes, Bharadwaj's study shows that while
Indians did have some main gene markers that Europeans had, large amount of them were
absent too.
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The hope is that if they could home in on genetic markers for Diabetes Type II they could
warn those Indians at risk early to enable them to take preventive measures and improve their
quality of life. Such is the promise of pharmacogenomics that Brahmachari says: "We should
soon be able to do rapid tests to determine a patient's genotype and then guide treatment with
the most effective drugs apart from reducing adverse reactions."
There is also the growing clamour to resort to gene therapy or the potential of using genes
themselves to treat disease or enhance particular traits much like the research into stem cells.
While genetics holds up the promise of revolutionising health care, there is need to be
cautious about its use.
Genetic profiling would reveal some of the innermost secrets that could, for instance, be used
by employers to weed out candidates found to be susceptible to certain ailments or diseases.
"We deliberately didn't release details of the communities in our studies because of the social
ramifications involved," says Mitali Mukerji, IGV consortium co-ordinator. So before you go
out and get your genes sequenced-it costs around Rs 2.5 lakh abroad-know the benefits and
the cost.
Experts speak
Gene analysis at a Delhi laboratory
"India is the first country to do a disease-specific drug-response mapping on large
populations. It will give us a risk analysis and also the benefits."
Samir Brahmachari
Director-General, CSIR
"The tribals of India, especially those living in The Andamans, hold the clue to not just
who were the earliest Indians but also the origin of man itself."
Lalji Singh
Former Director, CCMB
"South Asia played a pivotal role in the out-of-Africa colonisation and dispersal of modern
humans."
Partha P. Majumder
Head of Human Genetics Unit, ISI
"There is a clear indication of a variety of genes affecting the susceptibility of the
individual towards lethal cerebral malaria."
Saman Habib
Scientist, CDRI
"The best way to understand the Indian gene pool is to compare it to a large banyan tree
which has a trunk with branches than twigs and leaves."
Ramaswamy Pitchappan
Professor Emeritus, Madurai Kamaraj University