DNA Haplotypes Determination for Members of Families with Phenylketonuria (PKU)

Abstract

Phenylalanine hydroxylase deficiency causes phenylketonuria (PKU) in humans. PKU is a recessive genetic disease that affects 1 in 10000 births among the Caucasian population. Its gene locus is highly polymorphic in its DNA sequence among different individuals and patients with PKU. DNA polymorphisms at the PAH gene locus are used to obtain haplotypes through restriction enzyme analysis. So far forty-six distinct RFLP haplotypes have been discovered in the human population. In theory, 384 distinct RFLP haplotypes can exist. This project is to develop a program to assist the geneticists by obtaining haplotypes for each member of the PKU family. It uses information obtained from digestion of the DNA samples from the family members with the restriction enzymes. The restriction enzymes employed for this purpose are Pvuii, Bglii, EcoRI, Mspi, Xmni, Hindiii, and EcoRV. The program "PKU" generates all possible haplotypes for each member of the PKU family. The generated haplotypes may include haplotypes from the forty-six defined haplotypes list or from the 338 other haplotypes that may fit the description from the restriction enzyme analysis. The program then carries out an elimination phase during which the "extra" haplotypes that had been generated for the family members but whose presence was not supported by the data from the other family members are eliminated from the individuals' haplotype lists. The remaining haplotypes are then used to determine a sibling's carrier status of the PKU disease, i.e., whether or not a sibling is a carrier of the PKU disease.