Browsing by Author "Ramsay, Michele"

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    Computational selection and prioritization of candidate genes for Fetal Alcohol Syndrome
    (BioMed Central Ltd, 2007) Lombard, Zane; Tiffin, Nicki; Hofmann, Oliver; Bajic, Vladimir; Hide, Winston; Ramsay, Michele
    BACKGROUND:Fetal alcohol syndrome (FAS) is a serious global health problem and is observed at high frequencies in certain South African communities. Although in utero alcohol exposure is the primary trigger, there is evidence for genetic- and other susceptibility factors in FAS development. No genome-wide association or linkage studies have been performed for FAS, making computational selection and -prioritization of candidate disease genes an attractive approach. RESULTS: 10174 Candidate genes were initially selected from the whole genome using a previously described method, which selects candidate genes according to their expression in disease-affected tissues. Hereafter candidates were prioritized for experimental investigation by investigating criteria pertinent to FAS and binary filtering. 29 Criteria were assessed by mining various database sources to populate criteria-specific gene lists. Candidate genes were then prioritized for experimental investigation using a binary system that assessed the criteria gene lists against the candidate list, and candidate genes were scored accordingly. A group of 87 genes was prioritized as candidates and for future experimental validation. The validity of the binary prioritization method was assessed by investigating the protein-protein interactions, functional enrichment and common promoter element binding sites of the top-ranked genes. CONCLUSION: This analysis highlighted a list of strong candidate genes from the TGF-beta, MAPK and Hedgehog signalling pathways, which are all integral to fetal development and potential targets for alcohol's teratogenic effect. We conclude that this novel bioinformatics approach effectively prioritizes credible candidate genes for further experimental analysis.
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    Diagnosing cystic fibrosis in South Africa
    (2006) Westwood, Tony; Henderson, Bertram; Ramsay, Michele
    Cystic fibrosis (CF) occurs in all South Africa’s population groups. While well described in the white and coloured populations, its presence in black African populations is less well known. Recent evidence from the group of CF patients in the Western Cape suggests an incidence of 1 in 3 000 and 1 in 10 300 live births in the white and coloured populations respectively.1 In black South African populations, carrier frequency estimates have been used to project an incidence of 1 in 4 624 live births.2 Further evidence of the presence of CF in these populations is presented in this issue of the Journal. 3 While considering or being aware of the diagnosis is the first step in identifying CF, diagnosing the disease presents challenges at clinical and laboratory levels in South Africa. In simple terms, the diagnosis of CF requires a patient to have suggestive clinical features as well as 2 positive sweat tests and/or 2 identified disease-causing CF transmembrane conductance regulator (CFTR) gene mutations.