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Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits
Author(s) -
Jagirdar Kasturee,
Smit Darren J.,
Ainger Stephen A.,
Lee Katie J.,
Brown Darren L.,
Chapman Brett,
Zhen Zhao Zhen,
Montgomery Grant W.,
Martin Nicholas G.,
Stow Jennifer L.,
Duffy David L.,
Sturm Richard A.
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12253
Subject(s) - haplotype , tyrosinase , biology , locus (genetics) , genetics , allele , genotype , penetrance , microbiology and biotechnology , gene , enzyme , phenotype , biochemistry
Summary 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, DOPA oxidase activity, glycosylation and temperature sensitivity of protein and DOPA oxidase 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 DOPA oxidase. 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.