AbstractIntroduction: There is now substantial evidence that unaffected parents of NSOFC individuals have been shown to manifest distinctive dento-craniofacial phenotypes / cleft microforms compared to unaffected controls. Identification of the cleft microforms in the sub-phenotypes of clefting will improve the recurrence risk estimation and provide more informative and genetically homogenous groups for gene mapping.
Aim: To assess facial morphology, the prevalence of upper lip sub-epithelial orbicularis oris (MOO) defects and lower lip whorls, and to determine tooth size and arch width dimensions in unaffected parents of children with non-syndromic orofacial clefts (NSOFC) as a cleft-related subclinical phenotype and their association with specific candidate genes.
Methods: Using a case-control study design with 156 participants of Celtic background (81 parents, 75 controls), 2D photographs of the face and lower lip (Nikon D70, www.europe-nikon.com), an ultrasound scan of the upper lip (M-Turbo/HFL38X/13-6MHz linear transducer, SonoSite, Bothell, WA), impressions for study models of the upper and lower dental arches were taken, and a saliva sample was collected for collection of human DNA, (Oragene DNA, OG_500 DNA Genotek, Inc. Canada) and analysed using high-density genome-wide human arrays (Cytoscan 750K _array, Affymetrix). Facial dataxxxiiwere analysed using the discriminant analysis test in MorphoJ (http://www.flywings.org.uk/MorphoJ_page.htm), lip data using a Fisher exact test (p<0.0625 Bonferroni correction) and dental data using a Man-Whitney test (p<0.0625 Bonferroni correction) (SPSS version 22). Also, a genotype-phenotype analysis was conducted with the Odds Ratio calculated for 144 SNPs across 20 candidate loci.
Results: There was a significant facial difference between the two groups (p<0.0001, T-square). The frequency of OOM defects was greater in the parents (11.1%) than in controls (4.1%), which was non-significant (p>0.05). There was no significant difference in the prevalence of lip whorls between the parents and controls (p>0.05). However, statistically, significant differences in tooth dimensions were found between the parents and controls (p<0.05).The mesiodistal dimension of the crown of the lower left second premolar showed a statistically significant (p<0.05) association with SNP rs6657063 in the ARHGAP29 gene when the parental-control group factor was included in the analysis.The symmetrical PC5 of the facial morphology showed an association with SNP (rs7972295) in the ADAMTS 20 gene for the father-male control group data.
Conclusion: Non-cleft parents have distinctive facial morphological features and different dental width measurements, but only tooth 35 width - gene association was recorded when the parental - control factor included in the analysis.
|Date of Award||2016|
|Supervisor||Peter Mossey (Supervisor) & Grant McIntyre (Supervisor)|
Subclinical Phenotypes and Genotypes in Parents of Children with Non-Syndromic Cleft of Lip and/or Palate
Al-Talabani, S. Z. J. (Author). 2016
Student thesis: Doctoral Thesis › Doctor of Philosophy