Mutations in the PAH gene: A Tool for population genetics study

Phenylketonuria (PKU), an inborn error of metabolism, is caused by mutations in the phenylalanine hydroxylase (PAH) gene. In the Serbian population, 19 different PAH mutations have been identified. We used PAH mutations as molecular markers for population genetics study. The low homozygosity value of the PAH gene (0.10) indicates that PKU in Serbia is heterogeneous, reflecting numerous migrations throughout Southeast Europe. The strategy for molecular diagnostics of PKU was designed accordingly. To elucidate the origin of the most common (L48S) PKU mutation in Serbia, we performed haplotype analysis by PCR-RFLP. Our results suggest that the L48S mutation was imported into Serbia from populations with different genetic backgrounds. Fenilketonurija je urodjena metabolicka bolest prouzrokovana mutacijama u genu za fenilalanin hidroksilazu (PAH). U srpskoj populaciji je identifikovano 19 razlicitih PAH mutacija. PAH mutacije koriscene su kao molekularni markeri za populaciono-geneticko istrazivanje. Niska vrednost homozigotnosti PAH gena (0,10) ukazuje na heterogenost fenilketonurije u Srbiji i odrazava brojne migracije u regionu jugoistocne Evrope. U skladu sa tim, osmisljena je strategija molekularne dijagnostike fenilketonurije za Srbiju. U cilju rasvetljavanja porekla najcesce mutacije koja uzrokuje fenilketonuriju u Srbiji, L48S, uradjena je haplotipska analiza PCR-RFLP metodom. Nasi rezultati sugerisu da je L48S mutacija poreklom iz vise populacija sa razlicitim genetickim karakteristikama. .