Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene

Journal Article · Tue Sep 01 04:00:00 EDT 1992 · American Journal of Human Genetics; (United States)

OSTI ID:5017090

Goltsov, A A; Eisensmith, R C; Woo, S L.C. ^[1]; Konecki, D S; Lichter-Konecki, U

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1. Baylor College of Medicine, Houston, TX (United States)

The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by the presence of an AT-rich (70%) minisatellite region. This region contains various multiples of 30-bp tandem repeats and is located 3 kb downstream of the final exon of the gene. PCR-mediated amplification of this region from haplotyped PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine copies of this repeat. These variations permit more detailed analysis of mutant haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria families demonstrates Mendelian segregation of these VNTR alleles, as well as associations between theses alleles and certain PAH mutations. The R261Q mutation, associated with haplotype 1, is associated almost exclusively with an allele containing eight repeats; the R408W mutation, when occurring on a haplotype 1 background, may also be associated with the eight-repeat VNTR allele. Other PAH mutations associated with haplotype 1, R252W and P281L, do not appear to segregate with specific VNTR alleles. The IVS-10 mutation, when associated with haplotype 6, is associated exclusively with an allele containing seven repeats. The combined use of this VNTR system and the existing RFLP haplotype system will increase the performance of prenatal diagnostic tests based on haplotype analysis. In addition, this VNTR may prove useful in studies concerning the origins and distributions of PAH mutations in different human populations. 32 refs., 3 figs., 3 tabs.

• OSTI ID: 5017090
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 51:3; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
CARBOXYLIC ACIDS
DISEASES
ENZYMES
GENE MUTATIONS
HUMAN POPULATIONS
HYDROXYLASES
METABOLIC DISEASES
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHENYLALANINE
POPULATIONS
PROTEINS
SCREENING