Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1989 May;44(5):652–659.

Haplotype distribution of the human phenylalanine hydroxylase locus in Scotland and Switzerland.

S E Sullivan 1, S D Moore 1, J M Connor 1, M King 1, F Cockburn 1, B Steinmann 1, R Gitzelmann 1, S P Daiger 1, S L Woo 1
PMCID: PMC1715636  PMID: 2565077

Abstract

RFLP haplotypes at the phenylalanine hydroxylase (PAH) locus were determined in 45 nuclear Caucasian families from Switzerland and Scotland. The RFLPs at the PAH locus are highly informative, and prenatal diagnosis is possible in 85% of the families studied. The data were combined with the profiles previously observed in the Danish population, in order to study the variation in RFLP haplotype distribution among European populations. A total of 22 different haplotypes were observed in Denmark, Switzerland, and Scotland. Fifteen and 19 haplotypes are associated with the normal (non-PKU) and with the mutant chromosomes, respectively. The haplotype distribution and the allele frequency of normal chromosomes remain constant between Denmark, Switzerland, and Scotland. However, both the haplotype distribution and allele frequencies of mutant chromosomes show significant variation between the three countries. Our results suggest there may be additional mutations in the PAH gene that cause PKU.

Full text

PDF
658

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aulehla-Scholz C., Vorgerd M., Sautter E., Leupold D., Mahlmann R., Ullrich K., Olek K., Horst J. Phenylketonuria: distribution of DNA diagnostic patterns in German families. Hum Genet. 1988 Apr;78(4):353–355. doi: 10.1007/BF00291734. [DOI] [PubMed] [Google Scholar]
  2. Chakraborty R., Lidsky A. S., Daiger S. P., Güttler F., Sullivan S., Dilella A. G., Woo S. L. Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria. Hum Genet. 1987 May;76(1):40–46. doi: 10.1007/BF00283048. [DOI] [PubMed] [Google Scholar]
  3. Daiger S. P., Lidsky A. S., Chakraborty R., Koch R., Güttler F., Woo S. L. Polymorphic DNA haplotypes at the phenylalanine hydroxylase locus in prenatal diagnosis of phenylketonuria. Lancet. 1986 Feb 1;1(8475):229–232. doi: 10.1016/s0140-6736(86)90771-3. [DOI] [PubMed] [Google Scholar]
  4. DiLella A. G., Kwok S. C., Ledley F. D., Marvit J., Woo S. L. Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. Biochemistry. 1986 Feb 25;25(4):743–749. doi: 10.1021/bi00352a001. [DOI] [PubMed] [Google Scholar]
  5. DiLella A. G., Marvit J., Brayton K., Woo S. L. An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. 1987 May 28-Jun 3Nature. 327(6120):333–336. doi: 10.1038/327333a0. [DOI] [PubMed] [Google Scholar]
  6. DiLella A. G., Marvit J., Lidsky A. S., Güttler F., Woo S. L. Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria. 1986 Aug 28-Sep 3Nature. 322(6082):799–803. doi: 10.1038/322799a0. [DOI] [PubMed] [Google Scholar]
  7. Kwok S. C., Ledley F. D., DiLella A. G., Robson K. J., Woo S. L. Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry. 1985 Jan 29;24(3):556–561. doi: 10.1021/bi00324a002. [DOI] [PubMed] [Google Scholar]
  8. Ledley F. D., Grenett H. E., DiLella A. G., Kwok S. C., Woo S. L. Gene transfer and expression of human phenylalanine hydroxylase. Science. 1985 Apr 5;228(4695):77–79. doi: 10.1126/science.3856322. [DOI] [PubMed] [Google Scholar]
  9. Lichter-Konecki U., Schlotter M., Konecki D. S., Labeit S., Woo S. L., Trefz F. K. Linkage disequilibrium between mutation and RFLP haplotype at the phenylalanine hydroxylase locus in the German population. Hum Genet. 1988 Apr;78(4):347–352. doi: 10.1007/BF00291733. [DOI] [PubMed] [Google Scholar]
  10. Lidksy A. S., Robson K. J., Thirumalachary C., Barker P. E., Ruddle F. H., Woo S. L. The PKU locus in man is on chromosome 12. Am J Hum Genet. 1984 May;36(3):527–533. [PMC free article] [PubMed] [Google Scholar]
  11. Lidsky A. S., Law M. L., Morse H. G., Kao F. T., Rabin M., Ruddle F. H., Woo S. L. Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6221–6225. doi: 10.1073/pnas.82.18.6221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lidsky A. S., Ledley F. D., DiLella A. G., Kwok S. C., Daiger S. P., Robson K. J., Woo S. L. Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria. Am J Hum Genet. 1985 Jul;37(4):619–634. [PMC free article] [PubMed] [Google Scholar]
  13. Morton N. E., Wu D. Alternative bioassays of kinship between loci. Am J Hum Genet. 1988 Jan;42(1):173–177. [PMC free article] [PubMed] [Google Scholar]
  14. Orkin S. H., Kazazian H. H., Jr The mutation and polymorphism of the human beta-globin gene and its surrounding DNA. Annu Rev Genet. 1984;18:131–171. doi: 10.1146/annurev.ge.18.120184.001023. [DOI] [PubMed] [Google Scholar]
  15. Riess O., Michel A., Speer A., Meiske W., Cobet G., Coutelle C. Linkage disequilibrium between RFLP haplotype 2 and the affected PAH allele in PKU families from the Berlin area of the German Democratic Republic. Hum Genet. 1988 Apr;78(4):343–346. doi: 10.1007/BF00291732. [DOI] [PubMed] [Google Scholar]
  16. Scriver C. R., Clow C. L. Phenylketonuria and other phenylalanine hydroxylation mutants in man. Annu Rev Genet. 1980;14:179–202. doi: 10.1146/annurev.ge.14.120180.001143. [DOI] [PubMed] [Google Scholar]
  17. Speer A., Dahl H. H., Riess O., Cobet G., Hanke R., Cotton R. G., Coutelle C. Typing of families with classical phenylketonuria using three alleles of the Hindiii linked restriction fragment polymorphism, detectable with a phenylalanine hydroxylase cDNA probe. Family typing for PKU by linked HindIII RFLP. Clin Genet. 1986 Jun;29(6):491–495. [PubMed] [Google Scholar]
  18. Woo S. L. Collation of RFLP haplotypes at the human phenylalanine hydroxylase (PAH) locus. Am J Hum Genet. 1988 Nov;43(5):781–783. [PMC free article] [PubMed] [Google Scholar]
  19. 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]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES