Oral and Maxillofacial Surgery - Conference Papers

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Browsing Oral and Maxillofacial Surgery - Conference Papers by Subject "Genetic aetiology of clefts"

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    Association of Dickkopf-1 (DKK1) Mutations with Non-syndromic Orofacial Clefts in African Populations
    (Pan Arab Human Genetics Conference 2018, 2018-01-18) Adeyemo, W.L.; Lo, C.; James, O.; Busch, T.; Butali, A.
    Background and Purpose: Orofacial cleft (OFC) has both genetic and environmental. In studies with mice, when the TGFβ gene was knocked out, orofacial clefts resulted because the absence of the TGFβ gene led to upregulation of DKK1. However, the role of DKK1 in human orofacial clefts remains unclear. The purpose of this study was to identify certain loci in the DKK1 gene associated with non-syndromic OFCs in humans in order to further research about the genetic aetiology of clefts. Method: Two hundred and eighty-eight cleft lip and palate (CLP) samples and 192 cleft palate only (CPO) saliva samples were collected from Ghana, Ethiopia, and Nigeria and sequenced. Then, using the programs Primer 3, UCSC Genome Browser, and BLAT, primers were designed for the four DKK1 exons to be used for PCR. DNA was extracted from the collected saliva samples and underwent PCR to be amplified and used for sequencing. Using the computer program Consed, each individual’s nucleotide sequence acquired from Sanger Sequencing was compared to a reference sequence to identify variants. Once variants were identified, SIFT and Polyphen and HOPE were used to predict the degree of damage caused by the mutation. Results: One novel missense mutation was found on the fourth exon of DKK1 in an individual from the Ghana CLP population, and one known missense mutation (rs140471040) was found on the first exon of DKK1 in two individuals from the Ghana CLP population and four individuals from the Africa CPO population. The known missense mutation resulted in the amino acid change p. Met16Leu, and was predicted to be tolerated and benign. Conclusions: The novel variant found in one individual from the Ghana CLP population creates an association between DKK1 and non-syndromic orofacial clefts in humans, demonstrating the interactions between multiple signaling pathways in the aetiology of orofacial clefts. Keywords: DKK1; Orofacial clefts; Africans