Morphometrics and the Middle-Out Approach to Complex Traits
Benedikt Hallgrímsson is Professor of Cell Biology and Anatomy at the University of Calgary’s Alberta Children’s Hospital Research Institute and the McCaig Institute for Bone and Joint Health. He is a biological anthropologist and evolutionary biologist who combines developmental genetics and bioinformatics with 3D imaging and morphometrics to address the developmental basis as well as evolutionary significance of phenotypic variation and variability. His work has focused on the mammalian craniofacial complex, craniofacial dysmorphology in humans, and skeletal biology and disease, and has employed both experimental and comparative approaches.
The Rohlf Medal will be presented to Professor Hallgrímsson at this lecture.
Abstract: How development translates genetic into phenotypic variation is one of the hardest questions in biology. This issue is central to understanding how selection acting on phenotypic variation produces evolutionary change. It is also a key challenge that must be overcome to enable precision medicine for structural birth defects. My collaborators and I blend morphometrics and advanced imaging with developmental biology and genetics to create and analyze large sets of 3D image data from animal models and humans to study how genes relate to variation in facial shape. This allows us to identify patterns of variation that correspond to particular developmental mechanisms or genetic pathways. We then manipulate those mechanisms experimentally in animal models in order to determine how they generate variation in the facial form including birth defects. Finally, we apply our understanding of facial genetics and development to determine how disruption of growth, either by nutrition or syndromes influences facial shape. This approach is innovative because, rather than focusing on individual genes, we focus on pathways or processes that correspond to the effects of many genes on the development of the face. In this way, we break down the complexity of the genetics of complex traits such as facial shape. This results in explanations of variation that have significant implications for how organismal form evolves. Our hope is that such “middle-out” explanations will eventually also help inform individualized treatment for patients.