|dc.contributor.advisor||Rees, Jonathan L.||
|dc.contributor.advisor||Jackson, Ian J.||
|dc.contributor.author||Wong, Terence Hawkin||
|dc.description.abstract||Variation in pigmentation of hair and skin is one of the most striking forms of human
diversity. Human pigmentation and sun sensitivity is a complex trait. The
melanocortin 1 receptor gene (MC1R) (OMIM 15555) has been shown to be a key
determinant of hair and skin colour. Recently a number of other genes have been
implicated in human pigmentation.
This thesis presents the relationship between human pigmentary phenotypes and
genetic variation at MC1R and 34 other candidate loci from 159 individuals. The
relationship between experimentally induced cutaneous erythemal and facultative
pigmentary response to UVB radiation and MC1R and other pigmentation genotypes
was investigated in a subset of 98 individuals. Some of this work involved the
development of novel methods of assaying phenotype.
I present a detailed description of human pigmentation and facultative pigmentation
with respect to a number of key variables (e.g. sex, site, freckling, skin type) and
seek to explain the variation in pigmentation in relation to these factors.
The effect of MC1R on hair colour is large, but MC1R explains a smaller amount of
the variation for skin colour.
I found that a number of loci including MC1R, oculocutaneous albinism type 2
OCA2 (OMIM 611409), KIT oncogene ligand KITLG (OMIM 184745) and the
Hermansky-Pudlak syndrome 3 HPS3 (OMIM 606118) are determinants of
pigmentary phenotype. Some of these findings are in keeping with previous work
and some are novel.
I present data showing novel SNPs in genes Hermansky-Pudlak syndrome 3 (HPS3)
and KIT ligand (KITLG) to be associated with human skin and hair colour variation.
Association of HPS3 to eye colour was also found and has to be confirmed in another
population. The possible putative mechanisms for the novel association finding in
HPS3 are discussed. I am in the process of confirming these positive significant
findings in collaboration with another laboratory in Denmark. Further experiments
are proposed to confirm other associations and phenotypes.||en
|dc.contributor.sponsor||Medical Research Council (MRC)||en
|dc.publisher||The University of Edinburgh||en
|dc.title||Pigmentation and the cutaneous response to ultraviolet radiation||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en