title: Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients in Japan indicate that three polymorphic sequences in the tyrosinase gene promoter could be powerful markers for indirect gene diagnosis.
abstract: Since 1989, a large number of mutations of the tyrosinase gene, which result in oculocutaneous albinism (OCA), have been reported. However, approximately 15% of patients with tyrosinase-related OCA (OCA1) heterozygously carried an uncharacterized mutation, which presumably existed outside of the ordinarily examined area of the tyrosinase gene. In such cases, polymorphic sequence(s) of the tyrosinase gene might be useful to identify the OCA1 allele. In this study, we examined four polymorphic sequences of the tyrosinase gene in 16 patients with OCA1, their relatives, and 108 normally pigmented Japanese individuals. The results showed a complex dinucleotide repeat in the promoter region at -800 to -900 of seven different lengths, and a polythymidine sequence in the 3' end of intron 2 of three different lengths. Polymerase chain reaction-restriction fragment length polymorphism analysis of two polymorphic sequences at -301 (C/T) and -199 (C/A) in the promoter region allows us to classify the tyrosinase gene into three groups. Using these polymorphic sequences, we could identify the OCA1 allele in more than 80% of cases in which the parents' genomic DNA was available. Three polymorphic sequences in the tyrosinase gene promoter are particularly useful for this purpose.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Tanita
authors.forename: Jun
authors.initials: J
authors.lastname: Matsunaga
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyamura
authors.forename: Miwako
authors.initials: M
authors.lastname: Dakeishi
authors.forename: Eriko
authors.initials: E
authors.lastname: Nakamura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hachiro
authors.initials: H
authors.lastname: Tagami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomita
mesh_terms: D016115:Albinism, Oculocutaneous / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D000483:Alleles; D004247:DNA / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D014442:Monophenol Monooxygenase / Q000097:blood / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D004247:DNA; D014442:Monophenol Monooxygenase