A thesis submitted to the Faculty of Medicine, University of the
Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree
of Doctor of Philosophy. / Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal
recessive disorder of the melanin pigmentary system, characterised by
generalised hypopigmentation, with the accumulation of phacomelanin pigments
with increasing age. Southern African ty-pos OCA individuals occur with two
distinct phenotypes? with or without ephelides. These phenotypes are apparently
concordant within families, suggesting that there is more than one mutation at
the ty-pos OCA locus. Elucidation of the basic defcct{s) in ty-pos OCA would
be aided by a definitive localisation of the ty-pos OCA gene. Linkage studies
have been carried out in 41 families, using 52 markers, including 15 random
polymorphic serogenetic markers and 16 random polymorphic DNA markers, as
well as markers from two candidae, genes, TYR and CAS2, and 19 polymorphic
markers from 2 candidate chrome somal regions, on 11p and 15q. Pairwise 100
scores were calculated using the MLINK program of the LINKAGE package. A •
significant lad score was initially obtained in linkage analysis between ty-pos
OCA and two chromosome 15qll-q13 markers, in the Prader-Willi/Angelman
Syndrome (PWS/AS) region. Linkage analysis with 13 other markers on
chromosome 15, confirmed this localisation. A genetic linkage map of the
proximal region of the long arm of chromosome 15 was constructed and shows
that the most closely linked, flanking loci are the GABRB3 and D1SS24. Linkage
analysis has also shown no cross-overs between the D15S12 locus and ty-pos
OCA in southern African Negroids, suggesting that this locus is very close to, or
part of, the disease locus. Caucasoid "ty-pos" OCA individuals are characterised
by locus heterogeneity. Negroid ty-pos OCA families with and without ephelides
were analysed separately at the tyrosinase and D15S12 (PIRlO-l) loci. The
summated 100 scores at 9=0.01 were negative for the tyrosinase locus and
positive for the D15S12 locus, suggesting no evidence for locus heterogeneity in
this population. Allelic association was found between the polymorphic alleles
detected at the D15S12 (PIRIO-l) locus and ephelus status, which suggests th~t
there were multiple origins of the mutations at tne ty-pos OCA locus, The results
of this thesis show that the ty-pos OCA gene is located on chromosome ISq 11~
q12. The gene is postulated to be the human homologue, P, of the mouse pinkeyed
dilution gene, p; although definitive proof awaits the detection of mutations
in this gene in individuals with ty-pos OCA. / Andrew Chakane 2018
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/26133 |
| Date | January 1993 |
| Creators | Kedda, Mary-Anne |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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