Estimation haplotype frequency of BglII/EcoRI/VNTR markers at the PAH gene region in Iranian population

Abstract

Deficiency in phenylalanine hydroxylase (PAH) is the main molecular characteristic of phenylketonuria (PKU). So far over 500 different mutations in the PAH gene have been identified as associated with the disease. Mutation analysis of the PAH gene is a time-consuming and cost-effective procedure. Therefore, molecular markers which are highly linked to the PAH gene, have been used in carrier detection and prenatal diagnosis in PKU families. These markers show a population dependent based haplotype frequency. In the present study, the haplotype frequency of three markers including BglII, EcoRI and VNTR, at the PAH gene region were investigated in Iranian population. Nine different alleles for VNTR marker with 3, 5, 6, 7, 8, 9, 10, 11 and 13 core repeats were detected. Alleles 4 and 13 were found specific to the Iranian population. The haplotype frequency was calculated using FBAT, PHASE and Arlequin (haplotype frequency estimation computer programs). Among the 36 possible estimated haplotypes identified for 2 alleles (+ and -) for BglII and EcoRI; and nine alleles for VNTR, ten haplotypes showed relatively high frequency (e" 5%), based on the above programs. Therefore, a combination of BglII-EcoRI-VNTR could be suggested as an informative haplotype in performing carrier and prenatal diagnosis of the PAH gene mutations in Iranian population. © Kamla-Raj 2009.