title: Development Shapes a Consistent Inbreeding Effect in Mouse Crania of Different Line Crosses.
abstract: Development translates genetic variation into a multivariate pattern of phenotypic variation, distributing it among traits in a nonuniform manner. As developmental processes are largely shared within species, this suggests that heritable phenotypic variation will be patterned similarly, in spite of the different segregating alleles. To investigate developmental effect on the variational pattern in the shape of the mouse skull across genetically differentiated lines, we employed the full set of reciprocal crosses (a.k.a. diallel) between eight inbred mouse strains of the Collaborative Cross Project. We used geometric morphometrics and multivariate analysis to capture cranial size and shape changes in 8 parentals and their 54 F1 crosses. The high heterozygosity generated in the F1 crosses allowed us to compare the multivariate deviations of the F1 phenotypes from the expected midparental phenotypes in different haplotype combinations. In contrast to body weight, we found a high degree of nonadditive deviation in craniofacial shape. Whereas the phenotypic and genetic divergence of parental strains manifested in high dimensionality of additive effects, the nonadditive deviations exhibited lesser dimensionality and in particular a strikingly coherent direction in shape space. We interpret this finding as evidence for a strong structuring effect of a relatively small set of developmental processes on the mapping of genetic to phenotypic variation.
authors.affiliation: Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Pavličev
authors.affiliation: Department of Theoretical Biology, University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mitteroecker
authors.affiliation: Instituto de Genetica Veterinaria, University of La Plata, La Plata, Argentina.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Gonzalez
authors.affiliation: Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Campbell
authors.initials: C
authors.lastname: Rolian
authors.affiliation: Department of Cell Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta.|McCaig Bone and Joint Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Jamniczky
authors.affiliation: Department of Genetics, University of North Carolina, Durham, North Carolina.
authors.forename: Fernando Pardo-Manuel
authors.initials: FP
authors.lastname: Villena
authors.affiliation: Department of Orthopedic Surgery, University of California San Francisco, California.
authors.forename: Ralph
authors.initials: R
authors.lastname: Marcucio
authors.affiliation: Department of Pediatrics and Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Denver, Colorado.
authors.forename: Richard
authors.initials: R
authors.lastname: Spritz
authors.affiliation: Department of Cell Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta.|McCaig Bone and Joint Institute, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Alberta, Canada.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrimsson
mesh_terms: D000818:Animals; D049628:Body Size / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D007178:Inbreeding; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012886:Skull / Q000254:growth & development*