How Patterns of Craniofacial Variation Are Driven by Genetic Variation
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2023-04-19
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Abstract
Craniofacial shape is extraordinarily diverse and highly heritable in humans. We often feel an intuition from facial presentation that allows us to guess the ethnicity, sex, and even syndromic conditions of people we see every day. These aspects of facial shape likely have a strong genetic basis, although it has proven difficult to elucidate exactly which genes contribute to this variation that we intuitively understand. This dissertation aims to better understand why it can be so difficult to unravel the genetic underpinnings of facial shape variation. It starts with an interactive atlas of syndromic facial shape that allows a user to visualize the range of craniofacial phenotypes observed in over 80 congenital syndromes across ages, sexes, and severities. I then delve into how well syndromes can be classified from measurements of facial shape using machine learning. The challenges in classifying syndromes then directly led me to compare non- syndromic and syndromic facial shape to test how morphologically and genetically unique craniofacial phenotypes can be. Finally, I turned to mice to compare the craniofacial variation associated with groups of genes to the craniofacial variation produced in mouse mutants of large effect. These studies in humans and mice have shown substantial overlap in morphology between non-syndromic and syndromic facial variation, suggesting that facial variation operates in a limited scope of dimensionality. Importantly, that variation has a quantifiable genomic basis that suggests that many developmental pathways jointly contribute to the patterns of craniofacial variation that we observe.
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Aponte, J. D. (2023). How patterns of craniofacial variation are driven by genetic variation (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.