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PMID
24739399
TITLE
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.
2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
DATE PUBLISHED
2014 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/01/09
accepted 2014/04/14
aheadofprint 2014/05/12
entrez 2014/04/18 06:00
pubmed 2014/04/18 06:00
medline 2015/02/13 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Jagirdar K Jagirdar Kasturee K Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld, Australia.
Smit DJ Smit Darren J DJ
Ainger SA Ainger Stephen A SA
Lee KJ Lee Katie J KJ
Brown DL Brown Darren L DL
Chapman B Chapman Brett B
Zhen Zhao Z Zhen Zhao Zhen Z
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Stow JL Stow Jennifer L JL
Duffy DL Duffy David L DL
Sturm RA Sturm Richard A RA
INVESTIGATORS
JOURNAL
VOLUME: 27
ISSUE: 4
TITLE: Pigment cell & melanoma research
ISOABBREVIATION: Pigment Cell Melanoma Res
YEAR: 2014
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1755-148X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Pigment Cell Melanoma Res
COUNTRY: England
ISSNLINKING: 1755-1471
NLMUNIQUEID: 101318927
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
CA88363 NCI NIH HHS United States
R01 CA088363 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
albinism
melanin
melanocyte
pigmentation
tyrosinase
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alleles
Haplotypes
Humans
Male
Melanocytes enzymology
Models, Genetic enzymology
Monophenol Monooxygenase metabolism
Penetrance metabolism
Polymorphism, Genetic metabolism
Quantitative Trait Loci metabolism
Queensland metabolism
Skin Pigmentation genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 1.14.18.1 Monophenol Monooxygenase
OTHER ID's
OTHERID SOURCE
NIHMS590160 NLM
PMC4119297 NLM