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

Autor: Jagirdar K; Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld, Australia., Smit DJ, Ainger SA, Lee KJ, Brown DL, Chapman B, Zhen Zhao Z, Montgomery GW, Martin NG, Stow JL, Duffy DL, Sturm RA
Jazyk: angličtina
Zdroj: Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2014 Jul; Vol. 27 (4), pp. 552-64. Date of Electronic Publication: 2014 May 12.
DOI: 10.1111/pcmr.12253
Abstrakt: 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.
(© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje