Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

PLoS One

article

David C. Katz¹  J. David Aponte¹  Wei Liu¹  Rebecca M. Green¹  Jessica M. Mayeux²  K. Michael Pollard²  Daniel Pomp³  Steven C. Munger⁴  Stephen A. Murray⁴  Charles C. Roseman⁵  Christopher J. Percival⁶  James Cheverud⁷  Ralph S. Marcucio⁸  Benedikt Hallgrímsson¹ 

[1] Department of Cell Biology & Anatomy, Alberta Children’s Hospital Research Institute and McCaig Bone and Joint Institute, Cumming School of Medicine, University of Calgary;Department of Molecular Medicine, The Scripps Research Institute;Department of Genetics, University of North Carolina School of Medicine;The Jackson Laboratory;Department of Evolution, University of Illinois Urbana Champaign;Department of Anthropology, Stony Brook University;Department of Biology, Loyola University Chicago;Department of Orthopaedic Surgery, School of Medicine, University of California San Francisco

DOI  :  10.1371/journal.pone.0233377

学科分类：急救医学

来源: Public Library of Science

【 摘 要 】

The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL’s peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.

【 授权许可】

CC BY