Host microsatellite alleles in malaria predisposition?

BACKGROUND: Malaria is a serious, sometimes fatal, disease caused by Plasmodium infection of human red blood cells. The host-parasite co-evolutionary processes are well understood by the association of coding variations such as G6PD, Duffy blood group receptor, HLA, and beta-globin gene variants with malaria resistance. The profound genetic diversity in host is attributed to polymorphic microsatellites loci. The microsatellite alleles in bacterial species are known to have aided their survival in fatal environmental conditions. The fascinating question is whether microsatellites are genomic cushion in the human genome to combat disease stress and has cause-effect relationships with infections. PRESENTATION OF THE HYPOTHESIS: It is hypothesized that repeat units or alleles of microsatellites TH01 and D5S818, located in close proximity to beta-globin gene and immune regulatory region in human play a role in malaria predisposition. Association of alleles at aforesaid microsatellites with malaria infection was analysed. To overrule the false association in unrecognized population stratification, structure analysis and AMOVA were performed among the sampled groups. TESTING OF HYPOTHESIS: Associations of microsatellite alleles with malaria infection were verified using recombination rate, Chi-square, and powerful likelihood tests. Further investigation of population genetic structure, and AMOVA was done to rule out the confounding effects of population stratification in interpretation of association studies. IMPLICATION OF THE HYPOTHESIS: Lower recombination rate (theta) between microsatellites and genes implicated in host fitness; positive association between alleles-13 (D5S818), 9 (TH01) and strong susceptibility to Plasmodium falciparum; and alleles-12 (D5S818) and 6 (TH01) rendering resistance to human host were evident. The interesting fact emerging from the study was that while predisposition to malaria was a prehistoric attribute, among TH01 alleles; evolution of resistant allele-6 was a recent phenomenon, which could conceivably be driven by infection related selective forces. The host's microsatellite allelic associations with malaria infection were valid in the light of low genetic variance between sampled groups and no population stratification.

Molecular insights into the origins of the Shompen, a declining population of the Nicobar archipelago.

The Shompen, one of the most isolated and poorly understood contemporary hunter-gatherer populations, inhabit Great Nicobar Island, the southernmost island of the Nicobar archipelago. Morphological imprints in the Shompen were interpreted to favour a mixed Indo-Chinese, Malay, Negrito and Dravidian origin. Analyses of the mitochondrial, Y-chromosomal and autosomal gene pool of contemporary Shompen have revealed low diversity, illustrating a founder effect in the island population. Mitochondrial sequence analyses revealed the presence of two haplogroups of R lineage: B5a, and a newly defined clade, R12. Y-chromosomal analyses demonstrated the occurrence of a single lineage found predominantly in Austro-Asiatic speakers across Asia. With the different types of genetic markers analysed, the Shompen exhibit varying levels of genetic relatedness with the Nicobarese, and Austro-Asiatic speakers of mainland India and Southeast Asia. These genetic analyses provide evidence that the Shompen, an offshoot of the Nicobarese, are descendants of Mesolithic hunter-gatherers of Southeast Asian origin, deriving from at least two source populations.