University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2017 Facial Shape Variation in Humans Larson, Jacinda R. Larson, J. R. (2017). Facial Shape Variation in Humans (Unpublished doctoral thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/26141 http://hdl.handle.net/11023/4208 doctoral thesis University 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. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY Facial Shape Variation in Humans by Jacinda R. Larson A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN MEDICAL SCIENCES CALGARY, ALBERTA October, 2017 © Jacinda R. Larson 2017 Abstract The human face is a highly variable feature. Facial shape variation is seen between and within multiple populations. However, the source of this variation is mostly unknown. Furthermore, phenotypic variation is observed within syndromes that display a unique craniofacial phenotype. Because of this inherent variation, facial shape has a large clinical important and diagnostic significance. To explore facial shape variation, I have conducted several studies that examine the role of morphological integration in producing coordinated shape changes in the face. In these studies, I hypothesized that the size of the face and skull are correlated with facial shape; and that dysmorphic patients will display different morphological relationships between parts of the face, when compared to controls. These hypotheses were tested in several groups; namely healthy controls, patients with non-syndromic cleft lip and/or palate, and patients with ectodermal dysplasia. While these conditions have different etiologies, genetics, inheritance, mechanism of development, and resultant facial shape, using both of these patient groups has allowed me to explore these hypotheses in starkly different phenotypic groups. My studies have shown that the allometric factors of facial shape variation are complex and overlapping. Size represents a relatively small proportion of facial shape variation in humans. Furthermore, different classifications of cleft phenotypes are crucial when deciphering covariance structure in cleft individuals. Collectively, these studies have furthered the knowledge of complex craniofacial phenotypes, and have extended the knowledge on how allometry affects human facial shapes. Keywords: phenotypic variation, birth defects, cleft lip, cleft palate, ectodermal dysplasia, geometric morphometrics, Tanzania, Tanzanians, bantu, covariation, covariance ii Acknowledgements Drs. Benedikt Hallgrimsson, Heather Jamniczky, Robertson Harrop, and Campbell Rolian; thank you for the academic and scholarly guidance and assistance over the years. Thank you to Dr. Mange Manyama for his camaraderie and friendship, and for his leadership in organizing our field work seasons in Mwanza, Tanzania. Thank you to Dr. Charles Roseman for teaching me how to write code using R software. I appreciate your patience and kindness through my many struggles with learning R. Thank you to the Cleft Palate Clinic at the Alberta Children’s Hospital for facilitating my research data collection. Thank you to Edimer Pharmaceuticals for facilitating my research data collection in Houston, Texas. Thank you to my lab colleagues Drs. Hayley Britz, Rebecca Green and Chris Percival; and J. David Aponte. You have all made me a better scientist. Finally, thank you to all of the study participants. I would not have been able to complete my research without your participation. Thank you to my parents Claire Jack and Leander Larson for always encouraging me to keep going; I would have given up without your support. Thank you to my late Gramma, Ada Emard, for always insisting that I was allowed to be “bossy”; and for teaching me that women can accomplish anything that men can – but that it doesn’t hurt to look like a lady while doing so. Thank you to my rock, Leanne. You came at a time that I needed you the most. Thank you to the Alberta Children’s Hospital Research Institute, and to Alberta Innovates Health Solutions, for the generous funding to complete my research. iii Dedication "And to all the little girls who are watching this, never doubt that you are valuable and powerful and deserving of every chance and opportunity in the world to pursue and achieve your own dreams." -Hillary Rodham Clinton iv Table of Contents Abstract ............................................................................................................................... ii Acknowledgements ............................................................................................................ iii Dedication .......................................................................................................................... iv Table of Contents .................................................................................................................v List of Tables ................................................................................................................... viii List of Figures and Illustrations ......................................................................................... ix List of Symbols, Abbreviations and Nomenclature ......................................................... xiii CHAPTER 1: INTRODUCTION ........................................................................................1 Introduction ......................................................................................................................1 1.1.1 Thematic Overview ............................................................................................1 1.1.2 Craniofacial Development .................................................................................3 1.1.3 Allometry and Variation ....................................................................................8 1.1.4 Congenital Craniofacial Anomalies and Syndromic Phenotypes ....................10 1.1.5 Synthesis of Background Information .............................................................11 Organization of the Dissertation ....................................................................................12 1.2.1 General Information .........................................................................................12 1.2.2 Chapter Two .....................................................................................................12 1.2.3 Chapter Three ...................................................................................................13 1.2.4 Chapter Four ....................................................................................................14 1.2.5 Chapter Five .....................................................................................................15 CHAPTER 2: BODY SIZE AND ALLOMETRIC VARIATION IN FACIAL SHAPE IN CHILDREN ..............................................................................................................16 Abstract ..........................................................................................................................16 Introduction ....................................................................................................................17 Materials and Methods ...................................................................................................19 2.1.1 Sample Collection. ...........................................................................................19 2.1.2 Three-dimensional Imaging and automated 3D Landmarking. .......................21 2.1.3 Morphometric Analysis ...................................................................................23 v Results ............................................................................................................................26 2.1.4 Distribution of variation across PCs ................................................................26 2.1.5 Analysis of allometric variance components ...................................................30 2.1.6 Variation due to Sex and Population ...............................................................34 2.1.7 Comparison of linear and polynomial regressions ...........................................37 2.1.8 Comparisons of the allometric trajectories associated with different measures of size and age ......................................................................................................38 Discussion ......................................................................................................................44 Acknowledgements ........................................................................................................49 CHAPTER 3: VARIATION IN NON-SYNDROMIC CLEFT LIP AND/OR PALATE PATIENTS ................................................................................................................50 Abstract ..........................................................................................................................50 Introduction ....................................................................................................................51