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 about one in 10,000 among Caucasians, so that 2% of the population are carriers of the PKU trait. We have recently reported the cloning of human phenylalanine hydroxylase cDNA and that 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 has been 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 has recently been confirmed by gene mapping, the PKU locus in man is determined to be on chromosome 12.
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- Berg K., Saugstad L. F. A linkage study of phenylketonuria. Clin Genet. 1974;6(2):147–152. doi: 10.1111/j.1399-0004.1974.tb00644.x. [DOI] [PubMed] [Google Scholar]
- HSIA D. Y., STEINBERG A. G. Studies on linkage between phenylketonuria and the blood groups. Am J Hum Genet. 1960 Sep;12:277–286. [PMC free article] [PubMed] [Google Scholar]
- Kamarýt J., Mrskos A., Podhradská O., Kolcová V., Cabalska B., Duczyńska N., Borzymowska J. PKU locus: genetic linkage with human amylase (Amy) loci and assignment to linkage group I. Hum Genet. 1978 Aug 31;43(2):205–210. doi: 10.1007/BF00293596. [DOI] [PubMed] [Google Scholar]
- Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PENROSE L. S. Data for the study of linkage in man; phenylketonuria and the ABO and MN loci. Ann Eugen. 1951 Dec;16(3):241–248. doi: 10.1111/j.1469-1809.1951.tb02477.x. [DOI] [PubMed] [Google Scholar]
- Paul T. D., Brandt I. K., Elsas L. J., Jackson C. E., Nance C. S., Nance W. E. Linkage analysis using heterozygote detection in phenylketonuria. Clin Genet. 1979 Oct;16(4):217–232. doi: 10.1111/j.1399-0004.1979.tb00994.x. [DOI] [PubMed] [Google Scholar]
- Ryan J., Barker P. E., Shimizu K., Wigler M., Ruddle F. H. Chromosomal assignment of a family of human oncogenes. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4460–4463. doi: 10.1073/pnas.80.14.4460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woo S. L., Lidsky A. S., Güttler F., Chandra T., Robson K. J. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature. 1983 Nov 10;306(5939):151–155. doi: 10.1038/306151a0. [DOI] [PubMed] [Google Scholar]