Oral and Maxillofacial Surgery - Conference Papers

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Browsing Oral and Maxillofacial Surgery - Conference Papers by Author "Busch, T."

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    Open Access
    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
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    Open Access
    Genome-wide analysis refines the genetic architecture of orofacial clefts and identifies novel risk loci in the african population.
    (Unilag Press, 2018, 2018-08-28) Adeyemo, W.L.; James, O.; Ogunlewe, M.O.; Oseni, G.O.; Jain, D.; Mossey, P.A.; Busch, T.; Gowans, L.J.J.; Eshete, M.A.; Laurie, C.A.; Olaitan, P.B.; Aregbesola, B.S.; Bello, S.A.; Abdur-Rahman, L.; Marazita, M.L.; Murray, J.C.; Adeyemo, A.A.; Butali, A.
    BACKGROUND: Orofacial clefts (OFCs) are the most common birth defects in the head and neck region, affecting one out of every 700 live births worldwide. These defects lead to significant financial, educational, medical, psychological, and cultural problems. OBJECTIVE: To conduct genome wide association study (GWAS) for OFC in Africa. METHODS: A total of 3,353 participants were genotyped on the pre-release consortium version of Illumina Multi Ethnic Genotyping Array (MEGA). Imputation was done into the 1000 Genomes Phase 3 reference imputation panel using IMPUTE2. The final dataset that passed quality control consisted of 3,178 participants enrolled from Ethiopia (30%), Ghana (43%), and Nigeria (27%). They included 814 cases of CLP, 205 cases of isolated CP, and 2,159 related and unrelated controls. Over 45million SNPs were imputed including the 2.2million SNPs in the Multi Ethnic Genotyping Array. Of these SNPs, only 16 million passed our quality control filter and were included in the final analyses. Given the known differences in the developmental and genetic basis of CL/P versus isolated CP, we conducted two separate GWAS (one for each phenotype). RESULTS: The GWAS for CL/P showed that the most significant hits are on chromosomes 8 and 3. The chromosome 8 locus (leading SNP, rs72728755, p = 1.52 × 10–6) is in the 8q.24 region that has been previously reported to be associated with CL/P in Europeans. The GWAS for isolated CP revealed one genome-wide significant locus on chromosome 2 (leading SNP rs140938806, p = 2.76 × 10–9). CONCLUSIONS: Our study has refined the genetic architecture of OFC in Africa, identified new loci and demonstrated genetic heterogeneity for the two cleft sub-phenotypes. This will lead to additional insights into craniofacial development and biology. Keywords: Orofacial clefts; GWAS, Africa
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    Open Access
    Paternal uniparental disomy on chromosome 22 and a de-novo deletion on chromosome 18 in individuals with orofacial clefts.
    (Unilag Press, 2017, 2017-08-15) Adeyemo, W.L.; James, O.; Ogunlewe, M.O.; Oseni, G.O.; Jain, D.; Mossey, P.A.; Busch, T.; Gowans, L.J.J.; Eshete, M.A.; Laurie, C.A.; Olaitan, P.B.; Aregbesola, B.S.; Bello, S.A.; Abdur-Rahman, L.; Marazita, M.L.; Murray, J.C.; Adeyemo, A.A.; Butali, A.
    Background: Orofacial clefts are the commonest malformations of the head and neck region. Genetics, genomics and environmental factors have been implicated in the aetiology of these traits. Objective: Although paternal and maternal uniparental disomy (UPD) in clefts are very rare, they have been reported on chromosomes 6, 7, 10, 12,15 16 and 21. However, none has been reported on chromosome 22. To identify variation associated with non-syndromic clefts in sub-Saharan African population, we recently genotyped samples from affected cases, cases families and unrelated controls. The aim of study is to report cases of sex aneuploidies, trisomies, chromosomal anomalies, large deletions and duplications detected in our analysis. Methods: The recruitment of eligible individuals and families has been published (Butali et al., 2011; Gowans et al., 2016). Ethical approval was obtained from the Institutional Review Boards at the Kwame Nkrumah University of Science and Technology, Lagos University Teaching Hospital Idi-Araba, Lago, Obafemi Awolowo University Teaching Hospital Ile-Ife and the Addis Ababa University. We used the multi-ethnic genotyping array (MEGA) to identify genetic variation associated with non-syndromic clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. Results: During data cleaning, we identified the first case of paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de-novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with Klinefelter syndrome, Turner syndrome and Triple X syndrome. Conclusion: Observations from our study support the need for genetic testing in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is very important in genetic counselling for families that are at risk. Therefore, clinicians should be mindful of the fact that not all isolated clefts are complex traits. Clinicians should also endeavor to share this information with families during routine clinical visits and evaluations. Keywords: Disomy; Paternal; Uniparental; Orofacial Clefts; Deletion