Single nucleotide polymorphisms, putatively neutral DNA markers and population genetic parameters in Indian Plasmodium vivax isolates

SUMMARYWith a view to developing putatively neutral markers based on Single Nucleotide Polymorphisms (SNPs) in the human malaria parasite, Plasmodium vivax, we utilized the published whole genome sequence information of P. falciparum and P. vivax to find a ~200 kb conserved syntenic region between these two species. We have selected 27 non-coding DNA fragments (in introns and intergenic regions) of variable length (300–750 bp) in P. vivax in this syntenic region. PCR of P. vivax isolates of a population sample from India could successfully amplify 17 fragments. Subsequently, DNA sequencing and sequence analysis confirmed the polymorphic status of only 11 fragments. Altogether, 18 SNPs were detected and 2 different measures of nucleotide diversity showed variable patterns across different fragments; in general, introns were less variable than the intergenic regions. All 11 polymorphic fragments were found to be evolving according to a neutral equilibrium model and thus could be utilized as putatively neutral markers for population genetic studies in P. vivax. Different molecular population genetics parameters were also estimated, providing initial insight into the population genetics of Indian P. vivax.

Rat model of familial combined hyperlipidemia as a result of comparative mapping

Total genome scan was carried out in 266 F2 intercrosses from the Prague hypertriglyceridemic (HTG) rat that shares several clinical characteristics with human metabolic syndrome. Two loci for plasma triglycerides (TG) were localized on chromosome 2 (Chr 2) (LOD 4.4, 3.2). The first locus overlapped with the rat syntenic region of the human locus for the metabolic syndrome and for small, dense LDL, while the second overlapped with the syntenic region of another locus for small, dense LDL in humans by the comparative mapping approach. Loci for TG on rat Chr 13 (LOD 3.3) and Chr 1 (LOD 2.7) overlapped with the syntenic region of loci for human familial combined hyperlipidemia (FCHL) in Finnish and Dutch populations, respectively. The concordances of loci for TG localized in this study with previously reported loci for FCHL and its related phenotypes are underlying the generalized importance of these loci in dyslipidemia. These data suggest the close relationship between dyslipidemia in HTG rats and human FCHL, establishing a novel animal model for exploration of pathophysiology and therapy based on genomic determinants.