Analysis of polymorphic markers located in the HEXA gene region associated with Tay-Sachs disease

Abstract

Tay-Sachs Disease (TSD) is a genetic disorder resulting from mutations in the HEXA gene. 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. A large number of SNP markers have been introduced for the HEXA gene in the databases. In the present study, the genotype and informative degree of rs2288258 and rs4777507genetic markers of HEXA gene region were investigated. This study has been conducted using Tetra-primer ARMS PCR and usual ARMS PCR in 148 healthy unrelated control individuals and 10 families in the Iranian population. The allele frequency, degree of heterozygosity and Hardy-Weinberg equilibrium (HWE) was estimated using the GENEPOP program. Also, the estimation of haplotype frequency and linkage disequilibrium for the unrelated individuals was performed using the PowerMmarker software. Based on the obtained results, the observed degree of heterozygosity for rs2288258 and rs4777507 were 18.24 and 27.70, respectively. The allele frequency of rs2288258 was 90.88% for allele A and 9.12% for allele G. Also, the allele frequency of rs4777507 was 84.8% and 15.2% for A and G allele respectively. The results showed two markers, rs2288258-rs4777507, were in linkage disequilibrium together. Consequently, A/A, A/G and G/G informative haplotypes in population level and A/A, A/G and G/A informative haplotypes in family level were identified by using a combination of these two markers. These haplotypes can serve as appropriate tools for linkage analysis and identification of heterozygous carriers and prenatal diagnosis of TSD in the Iranian families with affected children.