Genetic variation and haplotype structures of innate immunity genes in eastern India.

This study reports results of an extensive and comprehensive study of genetic diversity in 12 genes of the innate immune system in a population of eastern India. Genomic variation was assayed in 171 individuals by resequencing approximately 75kb of DNA comprising these genes in each individual. Almost half of the 548 DNA variants discovered was novel. DNA sequence comparisons with human and chimpanzee reference sequences revealed evolutionary features indicative of natural selection operating among individuals, who are residents of an area with a high load of microbial and other pathogens. Significant differences in allele and haplotype frequencies of the study population were observed with the HapMap populations. Gene and haplotype diversities were observed to be high. The genetic positioning of the study population among the HapMap populations based on data of the innate immunity genes substantially differed from what has been observed for Indian populations based on data of other genes. The reported range of variation in SNP density in the human genome is one SNP per 1.19kb (chromosome 22) to one SNP per 2.18kb (chromosome 19). The SNP density in innate immunity genes observed in this study (>3SNPskb(-1)) exceeds the highest density observed for any autosomal chromosome in the human genome. The extensive genomic variation and the distinct haplotype structure of innate immunity genes observed among individuals have possibly resulted from the impact of natural selection.

Investigation on the genotoxic effects of long-term administration of sodium arsenite in bone marrow and testicular cells in vivo using the comet assay.

The main source of environmental arsenic exposure in most populations is drinking water in which inorganic forms of arsenic predominate. The single-cell gel electrophoresis technique (the comet assay) measures DNA damage, including double-strand and single-strand breaks, in somatic cells after a variety of genotoxic insults. We have used this method to measure damage to cellular DNA in the bone marrow and testicular cells of mice using the alkaline comet assay for the former and neutral comet assay for the latter. Swiss albino male mice were exposed to sodium arsenite in drinking water at concentrations of 10, 50,100, and 200 mg/l for a period of three months. Concurrently, negative and positive control sets were maintained. The negative control animals were given distilled water as drinking water for the same period of treatment while the animals in positive control sets were either given single or multiple injections of EMS (100 mg/kg body weight) according to the tissue sampled. Following long-term exposure, there was a significant dose-dependent reduction in the size and weight of testes. The comet parameters of DNA, such as tail length (microm), % of DNA in tail, and Olive tail moment (arbitrary units) were increased in both bone marrow and testicular cells due to arsenic-induced DNA strand breaks. A positive dose response relationship was noted. The magnitude of DNA strand break was more pronounced in the bone marrow cells than in the testicular cells. The minimum effective concentrations for inducing DNA damage in bone marrow cells and testicular cells were 10 mg/l and 50 mg/l, respectively. The results of the study indicate that arsenic in drinking water is genotoxic in mice and the comet assay can be used for examining DNA damage in testicular cells as a parameter for evaluating male reproductive toxicity.