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dc.contributor.advisorVan der Merwe, N. C.
dc.contributor.advisorVisser, B.
dc.contributor.authorCombrink, H. M. V. E.
dc.date.accessioned2016-11-17T09:08:35Z
dc.date.available2016-11-17T09:08:35Z
dc.date.issued2016-01
dc.identifier.urihttp://hdl.handle.net/11660/4563
dc.description.abstractEnglish: The lifetime risk for developing breast cancer within the Indian population of South Africa is one in 17. Disease causing mutations in BRCA1/2 increase the risk of developing this disease by up to 80%. The main objective of this study was to screen this unique population for mutations in BRCA1/2. This was achieved by optimising High Resolution Melting Analysis (HRMA) as the screening technique for the smaller exons while the Protein Truncation Test (PTT) was used to screen exon 11 for BRCA1/2 respectively. In order to optimise HRMA, a full BRCA1/2 screen was performed on 24 patients from four different South African ethnic groups using Single-Stranded Conformation Polymorphism/ Heteroduplex Analysis (SSCP/HA). These results were compared to a HRMA screen performed on the same patients. No differences were observed between the sensitivity of the three techniques and the turnaround time (TAT) was considerably less for HRMA. The entire cohort used in this study came from 50 unrelated South African Indian patients. A full BRCA1/2 screen was performed on these patients. A total of nine different pathogenic mutations were detected. Four of the disease causing mutations (BRCA1 c.1360_1361delAG, p.Ser454Terfs; c.3593T>A, p.Leu1198Ter and BRCA2 c.5279C>G, p.Ser1760Ter; 5563C>G, p.Ser1855Ter) were detected using PTT, whereas the other five mutations (BRCA1 185delAG, p.Leu22_Glu23LeuValfs; c.191G>A, p.Cys64Tyr; c.5365_5366delGCinsA, p.Ala1789_Ile1790LeuTrpfs and BRCA2 c.9435_9436delGT, Val3145_Phe3146=fs; c.8754+1G>A, IVS21+1G>A) were detected using HRMA. Three unrelated patients were carriers of the splice site mutation found within BRCA2 exon 21. The research that was conducted, contributed to the knowledge pool for predictive testing in the clinical setting of South Africa and gave insight into possible diagnostic tests that could be designed for this population.en_ZA
dc.description.abstractAfrikaans: Die risiko onder die Indiër bevolking van Suid-Afrika om borskanker te ontwikkel was een in 17. Siekteveroorsakende mutasies in BRCA1/2 het die risiko om hierdie siekte te ontwikkel met tot 80% verhoog. Die hoofdoelwit van hierdie studie was om sifting van BRCA1/2 in hierdie unieke bevolkingsgroep te doen. Dit is bereik deur High Resolution Melting Analysis (HRMA) as die siftingsmetode vir kleiner eksons te optimiseer, terwyl Protein Truncation Test (PTT) gebruik is om ekson 11 vir BRCA1/2 te sif. Om HRMA te optimiseer is volle BRCA1/2 sifting uitgevoer op 24 pasiënte vanuit 4 verskillende Suid-Afrikaanse etniese groepe deur middel van Single-Stranded Conformation Polymorphism/ Heteroduplex Analysis (SSCP/HA). Hierdie resultate is met HRMA vergelyk wat op dieselfde pasiënte uitgevoer is. Geen verskille is opgemerk tussen die sensitiwiteit van die drie tegnieke nie en die omkeertyd was aansienlik korter vir HRMA. Die hele studiegroep het bestaan uit 50 onverwante Suid-Afrikaanse Indiër pasiënte. Volle BRCA1/2 sifting is uitgevoer op hierdie pasiënte. ‘n Totaal van nege verskillende patogeniese mutasies is ontdek. Vier van die siekteveroorsakende mutasies (BRCA1 c.1360_1361delAG, p.Ser454Terfs; c.3593T>A, p.Leu1198Ter en BRCA2 c.5279C>G, p.Ser1760Ter; 5563C>G, p.Ser1855Ter) is ontdek deur middel van PTT, terwyl die ander vyf mutasies (BRCA1 185delAG, p.Leu22_Glu23LeuValfs; c.191G>A, p.Cys64Tyr; c.5365_5366delGCinsA, p.Ala1789_Ile1790LeuTrpfs en BRCA2 c.9435_9436delGT, Val3145_Phe3146=fs; c.8754+1G>A, IVS21+1G>A) ontdek is deur middel van HRMA. Drie onverwante pasiënte was draers van die mutasie wat in BRCA2 ekson 21 ontdek is. Die navorsing wat gedoen is het bygedra tot die kennis vir voorspellingstoetsing in die kliniese omgewing van Suid-Afrika en het insig gelewer van die moontlike diagnostiese toetse wat ontwerp kan word vir hierdie bevolkingsgroep.af
dc.description.sponsorshipStruwig-Germeshuysen Kankernavorsingstrusten_ZA
dc.language.isoenen_ZA
dc.publisherUniversity of the Free Stateen_ZA
dc.subjectIndian populationen_ZA
dc.subjectBRCA1/2en_ZA
dc.subjectOptimisingen_ZA
dc.subjectHRMAen_ZA
dc.subjectScreeningen_ZA
dc.subjectBreast -- Canceren_ZA
dc.subjectBreast -- Cancer -- Genetic aspectsen_ZA
dc.subjectRadiology, Medicalen_ZA
dc.subjectDissertation (M.Med.Sc. (Human Genetics))--University of the Free State, 2016en_ZA
dc.titleMolecular screening of the South African Indian population for BRCA1 and BRCA2 using high resolution melting analysisen_ZA
dc.typeDissertationen_ZA
dc.rights.holderUniversity of the Free Stateen_ZA


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