Frequencies of chromosomal abnormalities, sister chromatid exchanges, and replicative index were assessed following peripheral lymphocyte culture in 129 individuals from Bhopal, India. Of these, 83 persons (40 male and 43 female) had been exposed directly to the methyl isocyanate (MIC) gas after the accident at the Union Carbide plant on December 2 and 3, 1984. The remaining 46 samples were taken from age-matched unexposed persons in the same city. Chromosome aberrations were recorded at first cycle metaphase (M1) and sister chromatid exchanges, at second cycle metaphase (M2), following standard schedule. The frequency of chromosomal aberrations was, in general, higher in individuals from the exposed populations, with the females showing a higher incidence. Nondisjunction of chromosomes or laggard was rare. The frequencies of sister chromatid exchanges and depression in mitotic and replicative indices could not be related to exposure or sex. The persistence of chromosomal abnormalities in the form of replicating minutes and exchange configurations, even 1114 days after exposure to the gas, may indicate a residual effect on T-cell precursors.

A chromosomal survey using standard lymphocyte cultures employing different media and G-banding techniques was initiated in 1984. This study became particularly important following the tragic gaseous exposure of the population in Bhopal at midnight on 2 December 1984. We have been able to formulate a chromosomal profile for each person whom we have studied; during 1986-1988, 154 persons were examined twice. Among seemingly normal individuals, as many as 20% might possess some chromosomal abnormality; of these, 50% may develop, at a later date, some kind of pathological complication (such as tumours, recurrent abortion or transmission of defects to their offspring). The people exposed to methyl isocyanate have repeatedly shown Robertsonian translocations, mostly in acrocentric chromosomes 13 and 21. Other types of translocations have been studied among all exposed (53) and normal (101) persons; the involvement of chromosomes 5, 9, 11, 14 and 16 is statistically significant (P = less than 0.001). One of the major clinical symptoms is dyspnoea; we have estimated that almost all seriously dyspnoeic patients have developed at least two categories of chromosomal aberrations, one of which is Robertsonian translocation, in at least 10% metaphases. Our chromosomal survey will be of significance because we are able to identify people with chromosomal aberrations that might be correlated with future pathological consequences of the accident. The "chromosomal load" that can be sustained with an apparently normal phenotype can also be measured.

Frequencies of chromosomal abnormalities, sister chromatid exchanges, and replicative index were assessed following peripheral lymphocyte culture in 129 individuals from Bhopal, India. Ofthese, 83 persons (40 male and 43 female) had been exposed directly to the methyl isocyanate (MIC) gas after the accident at the Union Carbide plant on December 2 and 3,1984. The remaining 46 samples were taken from age-matched unexposed persons in the same city. Chromosome aberrations were recorded at first cycle metaphase (Ml) and sister chromatid exchanges, at second cycle metaphase (M2), following standard schedule. The frequency of chromosomal aberrations was, in general, higher in individuals from the exposed populations, with the females showing a higher incidence. Nondisjunction of chromosomes or laggard was rare. The frequencies of sister chromatid exchanges and depression in mitotic and replicative indices could not be related to exposure or sex. The persistence ofchromosomal abnormalities in the form of replicating minutes and exchange configurations, even 1114 days after exposure to the gas, may indicate a residual effect on T-cell precursors.

The human genome sequence has given us the view of the internal genetic scaffold around which human life is molded. We have inherited this heritage from our ancestors and through it we are connected to all life on earth. The sequencing of the human genome, amongst others, has led to the newer areas of healthcare and medicine. The human population is heterogeneous and consists of populations of immense ethnic diversity. There are considerable allelic differences between human populations as well as individuals within each ethnic group as a result of molecular heterogeneity of the genome. This, in turn, is responsible for differential allelic expression of genes endowing them with polymorphic characters. The molecular diversity within genes is responsible amongst others, of disease resistance or susceptibility or for that matter drug response. The objective of this article is to understand the nuances of the genetic repertoire and correlate it with disease gene identification, genes that have been or can be used as drug targets, identify candidate genes for drug development and recent trends in drug discovery. As regular clinical trials for drugs does not take into account the ethnic variations, it sometimes results in the differential response with respect to the efficacy and/or adverse reaction of the drug. Therefore the diverse ethnic populations of the world pose a challenge to the pharma industry. The concept of the personal medicine seems to be the answer to this problem. But it is a Herculean task requiring immense innovation in technology, is time consuming and is not a financially viable proposition at this point of time. An alternate approach would be to divide the populations in genetic cohorts and design drugs according to their genetic profile and haplotype. In addition, the ethical and legal bindings have also to be taken into consideration.

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