Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits.
Pigment Cell Melanoma Res
; 27(4): 552-64, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24739399
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Haplotipos
/
Pigmentación de la Piel
/
Monofenol Monooxigenasa
/
Sitios de Carácter Cuantitativo
/
Alelos
/
Melanocitos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
/
Male
País/Región como asunto:
Oceania
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Australia