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- ItemOpen AccessPaternal 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
- ItemOpen AccessGenetics of lower third molar impaction and its association with height of an individual(Faculty of Dental Sciences Conference 2017, 2017-07-06) Adeyemo, W.L.; James, O.; Oladega, A.A.; Adamson, O.O.; Olorunsola, K.D.; Butali, A.Aim: To evaluate the relationship between height and presence of impaction of third molars. To also determine the role of genetics in third molar impaction by correlation with candidate genes reported to be associated with height, jaw growth and tooth agenesis. Material and methods: Cases consisted of subjects with third molar impaction; and controls were those without third molar impactions. Height of subjects was measured in metres; and saliva samples were also collected from all subjects. DNA was extracted from saliva samples. Taqman Genotyping using SNPs identified for jaw growth, height and tooth agenesis was employed. A total of 5 candidate genes were investigated using 11 SNPs. We conducted case-control analyses to determine association using PLINK. For this test, we used P < 0.05 to denote significant association. Results: There were 200 cases and 200 controls. The mean height of cases (1.68 0 ±.09 metres) was significantly lower than that of the controls (1.70 ± 0.09 metres) (P=0.04). No difference was found in allele frequency between cases and controls for 10 of the 11 SNPs. However, for rs6504591 the P-value was near significance (P= 0.07) with Odd Ratio of 2.131. Conclusions: Subjects with lower third molar impactions were significantly shorter than those who have fully erupted third molars. The rs6504591 G/T variation on human chromosome 17 (WNT9B gene) appears to increase for impaction albeit with limited power to detect significance. This suggests that with an increase in sample size and adequate power, we will be able to detect significance for this gene. Keywords: Third molars; impactions; height; genetics; WNT9B
- ItemOpen AccessAssociation 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
- ItemOpen AccessGenome-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
- ItemOpen AccessNeurosensory deficits of inferior alveolar nerve following impacted mandibular third molar extraction: comparison of a two stage versus one stage surgical technique(Unilag Press, 2019, 2019-08-21) James, O.; Oyeneyin, A.O.; Adeyemi, M.O.; Adeyemo, W.L.Background: Surgical extraction of impacted mandibular third molar (3M) may be associated with post-operative complications. Inferior alveolar nerve (IAN) neurosensory deficits in form of paraesthesia of lower lip and gingivae is a common complications which impacts negatively on the quality of life of the patients. Landi et al has proposed two stage surgical extraction as an alternative surgical procedure to reduce this complication. However, few published studies on staged partial coronectomy are only case reports and case series. Aim and Objectives: To compare neurosensory deficits of inferior alveolar nerve following impacted mandibular third molar extraction using either a two stage or one stage surgical technique. Material and methods: This randomized controlled study was conducted at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital (LUTH) Idi Araba, Lagos State, Nigeria between April 2016 and September 2018. Subjects with mesioangular or horizontal impacted 3M with intimate relationship with inferior alveolar canal who met the inclusion criteria were recruited for the study and informed consent obtained. Surgical extraction was done under local anaesthesia using buccal guttering technique. Subjects were divided into 2 groups (one-stage technique and two-stage technique). The subjects were evaluated for the presence of IAN neurosensory deficit and recovery, as well as the relationships of IAN neurosensory deficits with gender, age and type of impaction. Results: A total of 68 subjects who satisfied the inclusion criteria participated in the study with 34 subjects in each group. There were 33 (48.5%) males and 35 (51.5%) females. The age range of participants was 18-57years with a mean age of 28.07 ± 8.37. There was not statistically significant difference in the age and gender distribution between the 2 groups. Neurosensory deficit of IAN was observed in 6 subjects, comprising of 5 (14.7%) in group A and 1 (3.33%) in group B. This difference was not statistically significant (p=0.23). Temporary nerve deficit was observed in 5 cases while permanent nerve deficit was seen in one patient. Similarly, relationships between the incidence of IAN neurosensory deficit and age, gender, type; position; and class of impaction, and the relationship between the proximity of the root with IAN were found not to be related to the neurosensory deficit outcomes age, gender and type of impaction in both groups were not statistically significant. Conclusion: This study shows that two-stage surgical extraction technique of impacted 3M was associated with lower incidence of IAN injury when compared with conventional one stage technique. The difference was however, not statistically significant. Two-stage surgical technique may be a suitable alternative to one stage surgical extraction technique of impacted 3Ms at risk of IAN injury especially when cost of treatment is taken into consideration.