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Title: Genetics of familial hip osteoarthritis :identification of genetic susceptibility factors
Author: Benson, Claire Elizabeth
ISNI:       0000 0001 3460 2868
Awarding Body: Queen's University of Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Osteoarthritis is already a major cause of disability worldwide and with an ageing population the associated socio-economic burden is expected to soar. Complex interactions between genetic and environmental factors are responsible for the initiation of osteoarthritis. There is a clear genetic contribution to hip' osteoarthritis but to date no major susceptibility gene has been identified. A large collection of affected sib pairs with hip osteoarthritis had already been recruited from Northern Ireland (416 participants) and Nottingham (115 participants) . Additional unaffected (n=42) family members were recruited. As part of a genome wide screen 160 microsatellite markers from chromosomes 9, 10, 11, 14, 19, 20, 21 and 22 were typed in each family member (n=531)and controls (n=49). Candidate genes were identified in areas suggesting positive linkage. Single nucleotide polymorphism (SNP) typing or sequencing were used to investigate these genes further. The three regions most suggestive of linkage were found in chromosomes 9 (at 74.4mB), 11 (at 11.7mB) and 19 (at 8mB). Ten of the candidate genes identified were typed with SNPs in one member of each family (n=206) and controls (n=49). The ten exons of the other gene, osteoclast stimulating factor 1 (OSTFl), were sequenced in both cases (n=40) and controls (n= 8). The only candidate gene with significantly positive results was the collagen type V, alpha 3 gene (COL5A3) on chromosome 19. One haplotype block was significantly more common in the control population (p=O.Ol). Further analyses of the COL5A3 gene and its neighbouring genes are currently underway. Identification of a major susceptibility gene will improve our understanding of the underlying pathogenesis and potentially identify new targets for drug therapy. The global impact of finding a major susceptibility gene for hip osteoarthritis should encourage us to continue with our search to elucidate the genetics of familial hip osteoarthritis
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available