An Investigation into Genes Underlying Normal Variation in Facial Morphology in Admixed Populations
Open Access
- Author:
- Liberton, Denise Kristen
- Graduate Program:
- Anthropology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- December 19, 2011
- Committee Members:
- Mark Shriver, Dissertation Advisor/Co-Advisor
Joan Therese Richtsmeier, Committee Member
David Andrew Puts, Committee Member
Nina G Jablonski, Committee Member
David John Vandenbergh, Committee Member - Keywords:
- facial variation
genetic ancestry
natural selection
population genetics - Abstract:
- The human face is highly variable within and across populations and is likely under strong genetic control. Despite this, most research on craniofacial genetics has focused on genes underlying dysmorphologies, leaving normal-range facial variation understudied. My dissertation research focuses on normal facial variation in admixed populations of West African and European genetic ancestry sampled in the United States, Brazil, and the Cape Verde Islands. First, morphometric analyses using a dense mesh of quasi-landmarks were performed on a set of three-dimensional facial photographs captured using the 3dMD imaging system. Facial variation was explored in terms of Principal Components (PCs) and these facial PCs were then tested for an association with West African genetic ancestry. Genetic ancestry was estimated in ADMIXMAP using a set of Ancestry Informative Markers (AIMs) and a three-population model with Europeans, West Africans, and Native Americans as parental populations. A subset of the facial PCs representing various facial traits was found to be associated with West African genetic ancestry. Next, a list of 199 craniofacial candidate genes known to affect craniofacial dysmorphology was made and refined to those of interest for these particular admixed populations by searching for evidence of natural selection. The areas within and around the genes were explored for the presence of AIMs and this set subset of candidate genes were screened for evidence of directional selection in HapMap populations through the use of three population genetics statistics: Tajima’s D, the log of the Ratio of the Heterozygosities, and Locus-Specific Branch Length. The final list included 50 selection-nominated candidate genes (SNCGs) that had evidence for signatures of selection in either West African or European populations. These SNCGs were then tested for an association with the facial PCs associated with genetic ancestry using an admixture mapping approach in the Cape Verdean sample. Of the 50 genes tested, there was strong evidence of an association with five candidate genes: RAI1, ASPH, FBN1, SKI, and SATB2. Additionally, a genome-wide scan was performed on the facial PCs and three SNPs remained significant after a correction for multiple testing. Future work will focus on replicating these results in the subjects from the United States and Brazil to determine a final set of genes associated with normal-range variation in facial morphology.