Hallgrimsson, BenediktJirik, FrankSchmidt, Eric J2017-12-182017-12-182012http://hdl.handle.net/1880/106026Bibliography: p. 166-179Some pages are in colour.Includes copy of animal protocol approvals and copyright permissions. Original copies with original Partial Copyright Licence.The "facial shape hypothesis" holds that cleft lip penetrance rates among A-strain lines differ owing to subtle genetic differences in midfacial primordia size, orientation, and rates of growth-summarily "facial shape"-that place more liable lines closer to, and less liable Jines further from, a threshold shape value that is set by physical constraints limiting the range of shape variation tolerated before the primordia fail to contact or consolidate adequately into a unified structure separating the nasal slits from the mouth. Fixation for an IAP allele of Wnt9b, which plays a regulatory role in midfacial development, is a key component of the genetic liability. Variation in genetic maternal effects modifies penetrance rates through an unknown function. I tested the hypothesis that maternal background influences the rate clefted primary palates in litters by differentially shifting the distributions of Wnt9b IAP epigenetic modification toward an expression threshold set by a common level of tolerance for low Wnt9b expression in the developing upper jaw. IAP methylation profiles between a reciprocal pair of hybrids with a two-fold difference in liability did not substantially differ. Nor did a morphometric analysis suggest that genetic maternal effects differences influenced embryonic facial shape. The data imply a role for maternal effects variation impacting palatogenesis via a mechanism outside epigenetic modification of the Wnt9b IAP but also independent of normal variations in midfacial shape with respect to a shape threshold. The significance of the alternative "two state" hypothesis, holding that penetrance rate differences among the A-strain are a function of the rate at which somatic differences arise between normal and cleft penetrant embryos, is considered.xv, 179 leaves : ill. ; 30 cm.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.doctoral thesis10.11575/PRISM/5025