Allele frequencies of six miniSTR loci of three ethnic populations in Singapore.

MiniSTR loci has demonstrated to be an effective approach to recover genetic information from degraded sample, due to the improved PCR efficiency of their reduced PCR product sizes. This study investigated the allele frequency of six miniSTR loci, D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045, in three Singapore populations. All loci showed a moderate degree of polymorphism with observed heterozygosity >0.6 for all three populations. The allele frequencies, forensic parameters and heterozygosity comparison with other CODIS STR in similar populations are presented.

Y-chromosome STR haplotype diversity in three ethnic populations in Singapore.

In this study, 12 Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438 and DYS439) were genotyped in the three major ethnic populations in Singapore, namely the Chinese, Malay and Indian. Allele frequency distribution, locus diversity, haplotype diversity and discrimination capacity were estimated. Analysis of molecular variance between the three ethnic populations indicated that 87.71% of the haplotypic variation is found within population and 12.29% is between populations (Fixation Index FST=0.123, p=0.000). Population pairwise comparisons showed significant Phist values between all population pairs, with the lowest (RST=0.05) for Chinese-Malay and the highest (RST=0.19) for Chinese-Indian.

A two-stage approach identifies a Q344X mutation in the rhodopsin gene of a Chinese Singaporean family with autosomal dominant retinitis pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a group of hereditary retinal diseases in which photoreceptor cells degenerate. It is both clinically and genetically heterogenous. Using a two-stage approach by combining linkage analysis with mutation detection, we have rapidly identified the gene locus and the mutation site of a Chinese Singaporean family with autosomal dominant RP. MATERIALS AND METHODS: Three Chinese Singaporean families were tested. One family showed autosomal dominant inheritance pattern, while the other two could be recessive or sporadic. Twelve di-nucleotide markers tightly linked to 6 genes known to be responsible for either autosomal dominant or recessive RP were selected for linkage analysis. Cosegregation of marker and disease inheritance pattern permits identification of the target candidate gene. RFLP (restriction fragment length polymorphism) markers were added to confirm the linkage result prior to the detailed mutation detection study. RESULTS: With this two-stage strategy, the autosomal dominant RP family showed the rhodopsin locus segregating concordantly with the disease. Mutation screening later identified a nonsense mutation 5261C>T in the last exon of rhodopsin gene. It predicted a Q344X changes at the C-terminus of the gene product, truncating it by 5 amino acids. CONCLUSION: This systematic approach facilitates molecular diagnosis of a genetically heterogenous disease like RP. This is the first report of an RP mutation in Singapore. This 5261C>T mutation has been reported in the Caucasian, but not the Chinese population. The relatively milder phenotype in this family showed similarity to the reported US family, indicating the correlation of mutation site to severity of disease regardless of ethnicity.

Allele frequencies of 15 STR loci of three main ethnic populations in Singapore using an in-house marker panel.

Allele frequency data for 15 Short Tandem Repeat (STR) loci was studied for the three main ethnic groups residing in Singapore, namely Chinese, Malay and Indian. An in-house STR marker panel was employed, consisting all 13 tetranucleaotide STR listed in CODIS (Combined DNA Index System, USA) and two pentanucleaotide STR, Penta D and Penta E. This represents a comprehensive report for allele distribution in the Singapore population for these 15 microsatellite markers commonly used in forensic science.

Association of intronic single-nucleotide polymorphisms in the EMILIN1 gene with essential hypertension in a Chinese population.

Studies in mice suggest that the elastin microfibril interfacer-1 gene (EMILIN1), the gene encoding elastin microfibril interfacer-1 protein, contributes to the pathogenesis of essential hypertension (EH) in humans. EMILIN1 in part maintains elastic fibres in vessel walls, and hence peripheral arterial compliance. In a case-control study, we assessed 942 non-obese non-diabetic Chinese, comprising 467 patients with EH and 475 normotensive control subjects (166 without, and 309 with, family history of hypertension in first-degree relatives (FHH)). Hypertension in first-degree relatives occurred in 88%, 65% and 0% of cases, all controls and controls without FHH, respectively. We scanned for single-nucleotide polymorphisms (SNPs) and genotyped them in the EMILIN1 gene using high-resolution melt-curve analysis. No exonic variants were detected. We assessed the association of SNPs and their haplotypes with EH. Three SNPs in introns 1 and 5 (rs2289360, rs2011616 and rs7424556) were in strong pair-wise linkage disequilibrium (r(2)>0.89). All three SNPs were significantly associated with hypertension. Genotypic frequencies at the three SNPs differed significantly between cases and only those controls without FHH. Healthy controls with FHH should be excluded to increase the odds of detecting association. All the G alleles of rs2289360 (odds ratio = 1.69, P = 0.010), rs2011616 (odds ratio = 1.52, P = 0.038) and rs7424556 (odds ratio = 1.59, P = 0.023) were high-risk alleles in the recessive genetic model. We observed significant overall haplotypic association with EH (empirical P = 0.0072); GGG is a risk haplotype (P = 0.043). The overall results support EMILIN1 as a candidate gene for human EH.