Molecular profiling of the CFTR gene in black and coloured South African cystic fibrosis patients

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dc.contributor.author De Carvalho, Candice Lee
dc.date.accessioned 2008-09-23T08:23:23Z
dc.date.available 2008-09-23T08:23:23Z
dc.date.issued 2008-09-23T08:23:23Z
dc.identifier.uri http://hdl.handle.net/10539/5689
dc.description.abstract ABSTRACT INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. The gene mutation profile is extremely heterogeneous and mutations show a variable distribution among population groups. In SA the 3120+1G->A splice site mutation has been found predominantly in Black and Coloured patients. It occurs in Black CF patients at an estimated frequency of 46%. The CF carrier frequency is estimated at 1/34 in Black and 1/55 in Coloured populations, and based on these rates, it is clear that a significant number of Black and Coloured patients remain undiagnosed. Point mutations account for the majority of the mutations that have been found in the CFTR gene. Copy number mutations are, however, increasingly being detected in CF patients through the use of gene dosage-dependant assays. These mutations have been found to occur in the CFTR gene in various African American families and exon rearrangements are thought to account for 1.3% of all CF chromosomes across all populations. AIMS: To use haplotypes to analyse the origin(s) of the 3120+1G->A mutation and the likely frequencies of the remaining unknown mutations. To increase mutation detection in the SA Black and Coloured groups by searching for CFTR gene exons for copy number mutations. METHODS: In patients with at least one copy of the 3120+1G>A mutation haplotype studies will be used to elucidate the origin(s) of this mutation in SA Black and Coloured CF patients, by analyzing pyrosequencing SNP genotype data. In patients with at least one unknown mutation, haplotype studies will reveal the likely relative frequencies of the unknown mutations in these populations. In Black and Coloured CF patients with at least one unknown mutation, a multiplex ligation dependant probe amplification (MLPA) CF kit will be used for the detection of exon copy number mutations. RESULTS: The results of the haplotype data show that there is a G-G-C-G-T-A haplotype, for markers MetD-KM19-J44-T854T-Tub18-J32, associated with the 3120+1G->A mutation in both Black and Coloured patients. Unknown mutation-associated haplotypes indicate that there are two relatively common unknown mutations in each of these populations. MLPA results show that one patient is a carrier of an exon 2 deletion. CONCLUSION: A single origin for the 3120+1G>A mutation in Black and Coloured CF patients is supported by the data. Exon copy number changes in the CFTR gene are not a major mutational mechanism leading to CF in SA Black and Coloured patients. en
dc.language.iso en en
dc.subject cystic fibrosis en
dc.subject molecular profiling en
dc.subject CFTR gene en
dc.subject South Africa en
dc.title Molecular profiling of the CFTR gene in black and coloured South African cystic fibrosis patients en
dc.type Thesis en


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