Use this URL to cite or link to this record in EThOS:
Title: Linkage and association studies in melanocytic naevi and cutaneous malignant melanoma
Author: Everett, Kate Victoria
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Previous studies have demonstrated that total naevus count (TNC) is a strong risk factor for cutaneous malignant melanoma CMM, both sporadic and familial. Both traits are known to have a genetic component, and host and environmental risk factors are also similar. Several genes for CMM have been identified but the genetic basis of TNC has not been elucidated. AIM: The primary aim of this study was to conduct a genome wide linkage search to locate genes associated with TNC, and hence potentially CMM. The second aim was to perform association analyses between markers in the linked regions and TNC. A longer term objective was to sequence any candidate genes identified in these regions. Finally, a specific family with 4 confirmed cases of CMM was used to examine whether any specific regions of the genome were linked to CMM. STUDY SET: For the genome screen, a total of 364 individuals were genotyped. All of these were in sibships of at least 3 and came from a total of 76 families. For the CMM investigation, a 3-generation family of 25 individuals was used. DNA was available for 17 members of this family. RESULTS: The strongest evidence for linkage in the genome screen was found with markers on chromosome 11pl5, with a maximum LOD score of 3.044. This locus was estimated to explain approximately 30% of the genetic variance in naevus count. Other loci with LOD scores greater than 1 were found on chromosomes 1, 5, 14 and the X chromosome. Strong evidence of associations between TNC and genotypes of 3 markers on chromosome lip 15 were also found. RRAS2 was investigated as a candidate gene but no variants associated with TNC were found. CONCLUSION: The results provide evidence of a gene, or genes, associated with the naevus phenotype on chromosome 11. However, this region does not account for all the variation in naevus count indicating that other loci are important. l1p15 needs to be further investigated for potential candidate genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available