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Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.

ABSTRACT: We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild-type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild-type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R and 192S-402Q with a double-variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.

SUBMITTER: Jagirdar K

PROVIDER: S-EPMC4119297 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.

Jagirdar Kasturee K Smit Darren J DJ Ainger Stephen A SA Lee Katie J KJ Brown Darren L DL Chapman Brett B Zhen Zhao Zhen Z Montgomery Grant W GW Martin Nicholas G NG Stow Jennifer L JL Duffy David L DL Sturm Richard A RA

Pigment cell & melanoma research 20140512 4

We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild-type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displa ...[more]

PMID: 24739399

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Dataset Information

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.

Publications

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.

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