GENETIC ARCHITECTURE OF THE HUMAN CRANIOFACIAL COMPLEX

Wright State University, Dayton OH

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The ultimate objective of the proposed pilot study is to discover genes that influence craniofacial morphology. This will be accomplished through a series of analyses aimed at elucidating fundamental aspects of the genetic architecture of the human craniofacial complex. Understanding the nature of genetic influences on the regions of the cranium is of critical importance to a wide variety of clinicians. As it becomes increasingly possible to incorporate gene therapy and tissue engineering when approaching repair of craniofacial dysmorphology (congenital or acquired), studies that elucidate the genetic underpinnings of continuous phenotypes typifying normal variation in craniofacial morphology are of critical importance. Recent work in humans has revealed that many endocranial traits are significantly heritable, and traits located in different developmental components of the cranium appear to be under differential genetic control. Examination of genetic contributions to normal variation in the craniofacial complex will be addressed through the accomplishment of three specific aims: 1) Collect quantitative measures of craniofacial morphology in order to characterize variation in biomedically-relevant phenotypes. 2) Explore fundamental aspects of the genetic architecture of craniofacial morphology. 3) Identify chromosomal regions (Quantitative Trait Loci; QTL) harboring genes that influence variation in craniofacial measures. Twenty-eight craniometric points will be marked on lateral cephalographs of participants of the Fels Longitudinal Study. Over 10,000 radiographs are available of 1,541 participants from 193 families. A maximum likelihood variance decomposition method for pedigree data using the algorithm implemented in the software program SOLAR is the analytic platform for the analyses. Heritability of each trait will be estimated, and genetic and environmental correlations matrices will be examined for all traits. Finally, linkage analysis will identify quantitative trait loci (QTL) harboring genes influencing variation in adult craniofacial morphology. The proposed study of the genetic architecture of the craniofacial complex will provide information critical in characterizing the genetic underpinnings to normal craniofacial development and morphology.