THE PKU LOCUS IN MAN IS ON CHROMOSOME-12

  • 1 January 1984
    • journal article
    • research article
    • Vol. 36  (3) , 527-533
Abstract
Classical phenylketonuria (PKU) is a typical example of inborn errors in metabolism and is characterized by a complete lack of the hepatic enzyme phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine. The genetic disorder causes impairment of postnatal brain development, resulting in severe mental retardation in untreated children. The disease is transmitted as an autosomal recessive trait and has a collective prevalence of .apprx. 1/10,000 among Caucasians, so that 2% of the population are carriers of the PKU trait. The cloning of human phenylalanine hydroxylase c[complementary]DNA was reported recently. The human chromosomal phenylalanine hydroxylase gene is encoded by a unique DNA sequence. Using the human phenylalanine hydroxylase cDNA clone to analyze a clonal human/mouse hybrid cell panel by Southern hybridization, the phenylalanine hydroxylase gene was assigned to human chromosome 12. Since the hypothesis that classical PKU is caused by structural mutations in the phenylalanine hydroxylase gene itself rather than through some transregulatory mechanisms was recently confirmed by gene mapping, the PKU locus in man is determined to be on chromosome 12.