Analysis of genetic variation of rs11658369 marker in AIPL1 gene as an informative marker for molecular diagnosis of Leber Congenital Amaurosis (LCA) in Isfahan population

Abstract

Leber Congenital Amaurosis (LCA) is the most severe form of inherited retinopathy in humans. LCA is genetically heterogeneous and inherited in an autosomal recessive manner. Aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) gene mutations have been identified to cause the most clinically severe forms of the disease. Direct sequencing is usually used to detect point mutations and other sequence variations in the gene, which is expensive and time consuming. Alternatively, 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 in the AIPL1 gene region in the electronic databases. In the present study, the characteristics of rs11658369 as an informative marker located in intron 2 of AIPL1 gene region was investigated. Genotyping was carried out by tetra-primer ARMS PCR technique in 154 unrelated healthy individuals from Isfahan, Iran, using newly designed primers. Estimation of allelic frequency, heterozygosity rate, and presence of Hardy Weinberg Equilibrium (HWE) was performed using GenePop website and the amount of polymorphism information content (PIC) was computed by Power Marker software for the marker. The results indicated 23.2% minor allele frequency (MAF), 38.56% heterozygosity rate and 29.29% PIC for rs11658369 marker in the Isfahan population. Moreover, analysis of Hardy-Weinberg Equilibrium showed the presence of equilibrium for this marker in the mentioned population. In total, according to the results of this study (MAF>0.2 and PIC>0.25), rs11658369 can be considered as a highly informative SNP marker for molecular diagnosis of AIPL1 related LCA by indirect genetic analysis in the Isfahan population as a representative sample of the Iranian population. © 2014, Iranian Neurogenetics Society. All rights reserved.