Rs1542705–67,992,843-1,050,239 represents a novel informative haplotype at the SMPD1 locus in the Iranian population

Abstract

Niemann-Pick disease (NPD) refers to a group of lysosomal storage diseases that cause abnormal metabolism of lipids. Direct sequencing and deletion analysis is used to detect mutations and sequence variations in the SMPD1 gene. However, due to technical difficulties, linkage analysis of polymorphic markers such as single nucleotide polymorphism (SNP) has been used in heterozygous carrier detection and prenatal diagnosis of the disease in families with an affected individual. The SNP markers usually show a population-based haplotype frequency and heterozygosity. A large number of SNP markers have been introduced for the SMPD1 gene. In the present study, rs1542705, rs67992843and rs1050239 genetic markers located in the SMPD1 gene region were genotyped using ARMS PCR technique in 188 unrelated control individuals and 11 family trios in the Iranian population. The allele frequency, degree of heterozygosity and Hardy-Weinberg equilibrium (HWE) were estimated using the GENEPOP program. The estimation of haplotype frequency and linkage disequilibrium for the unrelated individuals was estimated using the PowerMarker software. The observed degree of heterozygosity for rs1542705, rs6799843and rs1050239 were 39.36, 46.68 and 28.19, respectively. The result showed all markers were in linkage disequilibrium. Consequently, T-G-G, T-C-G, C-G-G, C-C-G, T-C-A, T-G-A, C-G-A informative haplotypes in population level were identified by using a combination of these three markers. Therefore, 1,542,705–6,799,843-1,050,239 represents a novel informative haplotype at the SMPD1 locus in the Iranian population, which could be suggested as appropriate markers for linkage analysis and identification of heterozygous carriers as well as prenatal diagnosis of NPD in the Iranian families with affected children.