DNA sequence variation and haplotype structure of the ICAM1 and TNF genes in 12 ethnic groups of India reveal patterns of importance in designing association studies

We have examined the patterns of DNA sequence variation in and around the genes coding for ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India. We aimed to (a) quantify the nature and extent of the variation, and (b) analyse the observed patterns of variation in relation to population history and ethnic background. At the ICAM1 and TNF loci, respectively, the total numbers of SNPs that were detected were 28 and 12. Many of these SNPs are not shared across ethnic groups and are unreported in the dbSNP or TSC databases, including two fairly common non-synonymous SNPs at positions 13487 and 13542 in the ICAM1 gene. Conversely, the TNF-376A SNP that is reported to be associated with susceptibility to malaria was not found in our study populations, even though some of the populations inhabit malaria endemic areas. Wide between-population variation in the frequencies of shared SNPs and coefficients of linkage disequilibrium have been observed. These findings have profound implications in case-control association studies

Single nucleotide polymorphisms in two genes among the Jarawa, a primitive tribe of the Andaman and Nicobar Islands

Discovery and validation of single nucleotide poly-morphisms (SNPs) in the human genome is an active area of interest, because of their usefulness in evolutionary and disease-association studies. We have resequenced 70 chromosomes from the Jarawa, a Negrito tribal group inhabiting the Andaman and Nicobar archipelago, for a ≈ 10kb genomic region spanning two genes, ICAM1 and TNF-α. We have discovered three new SNPs in the TNF-α gene. There is low sequence variability among the Jarawa, possibly due to founder effect and genetic drift

Use of Fluorescent Amplified Fragment Length Polymorphism for Molecular Epidemiology of Leptospirosis in India

Nineteen isolates of leptospires recovered from patients during three epidemics that occurred at different places and different times in the Andaman Islands and eight isolates from sporadic cases were characterized using serological and molecular genetic techniques. Group sera and monoclonal antibodies were used for antigenic characterization, whereas fluorescent amplified fragment length polymorphism (FAFLP) was used for genotyping. Of the 27 isolates, 19 were identified as belonging to serogroup Grippotyphosa, 3 belonged to serogroup Australis, 2 belonged to serogroup Icterohaemorrhagiae, and 1 each belonged to serogroups Hebdomadis, Canicola, and Sejroe. Analysis of FAFLP data grouped these 27 isolates into two main clusters of genotypes. One of the clusters, populated by 19 isolates, included 16 outbreak isolates. Seven of these 19 isolates belonged to serovar Ratnapura, 10 belonged to serovar Valbuzzi, and 1 each belonged to serovar Grippotyphosa and serovar Saxkoebing. Of the 27 patients from whom isolates were obtained, 9 had severe illness, and 6 of these 9 patients had pulmonary involvement, 1 had pulmonary and hepatorenal involvement, and the remaining 2 had hepatorenal involvement alone. Two patients out of the nine severe cases died subsequently. The isolates from sporadic cases showed great genetic diversity and were also diverse antigenically. Perhaps the strains belonging to a dominant genotype (the outbreak-associated cluster) possessed epidemic potential and higher virulence with a greater predilection to cause pulmonary complications than strains belonging to other genetic backgrounds

Genetic Affinities of the Andaman Islanders, a Vanishing Human Population

AbstractBackground: The Andaman Islands in the Bay of Bengal are inhabited by hunter-gatherers of unknown origin, now on the verge of extinction. The Andamanese and other Asian small-statured peoples, traditionally known as “Negritos,” resemble African pygmies. However, it is generally believed that they descend from the early Australo-Melanesian settlers of Southeast Asia and that their resemblance to some Africans is due to adaptation to a similar environment, rather than shared origins.Results: We analyzed mitochondrial DNA (mtDNA) sequences and RFLP polymorphisms, and Y chromosome biallelic markers and microsatellites, in present-day Andamanese of the Onge, Jarawa, and Great Andamanese tribes, and of inhabitants of the neighboring Nicobar Islands. We also analyzed mtDNA sequences from Andamanese hair samples collected by an ethnographer during 1906–1908. Living Andamanese exhibit low genetic variability that is consistent with their small population size and reproductive isolation.Conclusions: Our data indicate that the Andamanese have closer affinities to Asian than to African populations and suggest that they are the descendants of the early Palaeolithic colonizers of Southeast Asia. In contrast, the Nicobarese have genetic affinities to groups widely distributed throughout Asia today, presumably descended from Neolithic agriculturalists