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 Ϫ800 to Ϫ900 of seven different lengths, and a polythymidine sequence in the 3Ј end of intron 2 of three different lengths. Polymerase chain reaction-restriction fragment length polymorphism analysis of two polymorphic sequences at Ϫ301 (C/T) and Ϫ199 (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.

Mutational spectrum of theTYRandSLC45A2genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase

“…During this study, the missense substitution c.230G>A (p.Arg77Gln) was identified in exon 1 of TYR in five different families (1–3, 5 and 13). This mutation has also been been reported in Japanese, Korean, Chinese and German populations . The affected individuals of the five families have white hair, light‐coloured eyes and very pale skin, and at the time of the study were aged between 3 and 42 years.…”

Tyrosinase gene analysis in Japanese patients with oculocutaneous albinism

“…R278X is an exceptional and frequent mutation in several races and in the different places [12][13][14][15]. According to haplotype analysis, R278X had at least two different origins, which was thought to have occurred a long time in the past [16]. Our study is unique because we have found the R278X mutation in our patients from Hokkaido, whose inhabitants had moved from various districts of Japan in the 19th century.…”

Investigating the relationship between precocious puberty and obesity: a cross-sectional study in Shanghai, China

“…This cross-sectional study was conducted in June 2014 by multistage and stratified cluster random sampling. Nineteen districts of Shanghai were stratified into central urban area, suburb and outer suburb according to the 2005 Shanghai census report 12 and seven districts were randomly chosen, including Jing’an, Changning, Zhabei, Jiading, Jinshan, Pudong and Chongming. From these, 26 general primary schools were randomly sampled from school lists and students in grades 1–5 were recruited ( figure 1 ).…”