Human Alpha-L-Iduronidase (Idua) Gene: Apparent Recombination in Intron 2 by Haplotype Analysis in a Taiwanese Population

Abstract

The polymorphic DNA haplotype of the alpha-L-iduronidase ( IDUA) gene in a Taiwanese population was investigated. Genomic DNA extracted from 85 volunteers was used to amplify fragments containing the polymorphic sites A8, A20 and Q33H from exon 1 and a variable number of tandem repeats (VNTR ) region in intron 2. Additionally, sites R105Q and L118 in exon 3, A314 from exon 7, A361T and T388 from exon 8, T410 and V454I from exon 9, and R 489 from exon 10 were amplified. The polymerase chain reaction-amplified products were analyzed by restriction fragment length polymorphism (RFLP) analysis, allele specific oligonucleotide (ASO) hybridization, or gel electrophoresis. Of the examined polymorphisms, the intron 2 VNTR was not in Hardy-Weinberg equilibrium. Conversely, all 11 single base change polymorphisms were in Handy-Weinberg equilibrium. Linkage disequilibrium analysis of the haplotype data revealed strong nonrandom association between A8 and A20 in exon 1 as well as among R105Q, A314, A361T, T388, T 410, V454I, and R 489 in exons 3 to 10. In contrast, little linkage disequilibrium between two clusters of linked polymorphisms on either side of the VNTR was observed. The results suggest apparent recombination in intron 2 of the IDUA gene, with little or no recombination in exon 1 or exons 3 to 10.