Evaluation of resequencing on number of tag SNPs of 13 atherosclerosis-related genes in Thai population

Abstract

In the candidate gene approach, information about the distribution of single nucleotide polymorphisms (SNPs) is a crucial requirement for choosing efficient markers necessary for a case-control association study. To obtain such information, we discovered SNPs in 13 genes related to atherosclerosis by resequencing exon-flanking regions of 32 healthy Thai individuals. In total, 194 polymorphisms were identified, 184 of them SNPs, four insertions, and the rest deletions. Fifty-nine of the SNPs were characterized as novel polymorphisms, and these accounted for 30% of the identified SNPs. Comparing allele frequency distributions of the Thai population with other Asian populations shows similar patterns. In contrast, a low correlation pattern (r = 0.521) was found when comparing with either Caucasian or African populations. However, some rare alleles (rs11574541 and rs10874913) are found in the Thai population but not in other Asian populations. Most of the novel SNPs found were located outside the haplotype blocks generated by known SNPs in the Thai population. Only 5.77% of the novel SNPs lies in these defined haplotype blocks. The selection of haplotype-tagging SNPs shows that 8 of 13 genes benefited from the ethnicspecific genotype information. That is, when at least one novel SNP was present, the tagging SNPs chosen were altered. Functional prediction of 16 nonsynonymous SNPs (nsSNPs) by three different algorithm tools demonstrated that five nsSNPs possibly alter their corresponding protein functions. These results provide necessary information for conducting further genetic association studies involving the Thai population and demonstrate that resequencing of candidate genes provides more complete information for full genetic studies.

Thailand mutation and variation database (ThaiMUT)

“…SNP discovery of a given genomic region is also important. Knowing the extent of population sequence variation diversity will be tremendously useful for the design of genetic association study (Tocharoentanaphol, et al, 2008).…”

Resequencing DCDC5 in the Flanking Region of an LD‐SNP Derived from a Kidney‐Yang Deficiency Syndrome Family

“…Most functionally important SNPs are located within genes and other critical gene regulatory regions, such as the promoters, 5′ and 3′ untranslated regions, and predicted splice sites [20–23]. Therefore, SNPs can alter gene  expression and phenotypes through a variety of mechanisms.…”

“…Therefore, SNPs can alter gene  expression and phenotypes through a variety of mechanisms. Thus far, only a few SNPs have been identified as LD SNPs representing strong candidate biomarkers for certain diseases [8, 10, 22, 23]. However, given the extreme complexity of genomic structure, resequencing and relevant methods that can identify the specific variants in a sequence of interest compared with a known genomic sequence is a monumental task [22].…”

Genomic medicine and developing countries: creating a room of their own

“…The Thai SNP Discovery Project is a collaboration between Mahidol University's Faculty of Medicine, Ramathibodi Hospital and Oracle Co. Ltd (Thailand), the National Center for Genetic Engineering and Biotechnology (BIOTEC, Thailand) and Centre National de Genotypage (CNG, France) 41,42 .…”