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.

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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A 35‐year‐old, rare male pseudohermaphrodite with inguinal hernia, testis, fallopian tube and uterus, symptoms referrable to persistent Mullerian duct syndrome, is described. The patient has a 46,XY karyotype in 50% of metaphases, while the remaining metaphases show premature cnetromeric divisions and hypoploid counts.

Fragile sites, the heritable genomic weak points on the chromosomes which appear as nonstaining gaps of variable width (Sutherland 1979) have been the focus of attention ever since their similarity to the chromosomal breakpoints in disease were reported (Berger et al. 1985, Sutherland and Ledbetter 1989, Trent et al. 1989.As is evident, fragile site expression is affected by a number of specific tissue culture conditions (Fonatsch 1981, Hecht and Glover 1983, Yunis and Soreng 1984. Investigations into the basic mechanism of expression of fragile sites have provided the means for practical demonstration of these sites and at the same time provided some of the clues regarding their molecular structure.High affinity of Distamycin-A and related compounds for binding to d(A) clusters in B-DNA (Hahn 1975) provide a clue to the molecular structure of the fragile sites induced by these compounds. Binding is accompanied by subtle changes in DNA conformation and blocking of the DNA-dependent enzymes (Hahn 1975, Zimmer 1975. On the other hand, both common (Glover et al. 1984) and folate sensitive fragile sites have been proposed to represent stretches of Z-DNA consisting of alternating repeats of poly d(GC/CG) and poly d(AC/TG), which would form single strand lesions when replicating under conditions of limiting dCTP and dTTP.Essentially, the triradial is the most spectacular cytogenetic manifestation of a fragile site, breakage at the site followed by non-disjunction being the mechanism for its production (Noel et al. 1977). This breakage and unequal distribution of the distal fragments may occur repeatedly, giving rise to quadri-radial or even penta-radial figures (Fraccaro et al. 1972. The finding that micronuclei appear more often in individuals with fragile sites than in individuals without them is indicative of the fact that chromosome fragments resulting from breakage at such sites are eliminated by micronuclei formation (Beek et al. 1983).It has been suggested that fragile sites are single stranded gaps resulting from despiraliza tion of DNA due to failure of compact folding in metaphase chromosomes (Taylor and Hagerman 1983). Here, we present certain unique chromosomal features which represent different degrees of undercondensation involving different chromosomes in a case each of hairy cell leukemia and mental retardation. In view of the recent understanding of the role of histone and non-histone proteins, divalent cations and the structural basis of DNA in chromatin packaging, we have tried to explain these features vis-a-vis fragile sites. Material and methodsThe cases being presented in this report include a non-specific mentally retarded girl aged * Technical correspondence.