Data from: Mapping of craniofacial traits in outbred mice identifies major developmental genes involved in shape determination

The vertebrate cranium is a prime example of the high evolvability of
complex traits. While evidence of genes and developmental pathways
underlying craniofacial shape determination is accumulating, we are still
far from understanding how such variation at the genetic level is
translated into craniofacial shape variation. Here we used 3D geometric
morphometrics to map genes involved in shape determination in a population
of outbred mice (Carworth Farms White, or CFW). We defined shape traits
via principal component analysis of 3D skull and mandible measurements. We
mapped genetic loci associated with shape traits at ~80,000 candidate
single nucleotide polymorphisms in ~700 male mice. We found that
craniofacial shape and size are highly heritable, polygenic traits.
Despite the polygenic nature of the traits, we identified 17 loci that
explain variation in skull shape, and 8 loci associated with variation in
mandible shape. Together, the associated variants account for 11.4% of
skull and 4.4% of mandible shape variation, however, the total additive
genetic variance associated with phenotypic variation was estimated in
~45%. Candidate genes within the associated loci have known roles in
craniofacial development; this includes 6 transcription factors and
several regulators of bone developmental pathways. One gene, Mn1, has an
unusually large effect on shape variation in our study. A knockout of this
gene was previously shown to affect negatively the development of
membranous bones of the cranial skeleton, and evolutionary analysis shows
that the gene has arisen at the base of the bony vertebrates
(Eutelostomi), where the ossified head first appeared. Therefore, Mn1
emerges as a key gene for both skull formation and within-population shape
variation. Our study shows that it is possible to identify important
developmental genes through genome-wide mapping of high-dimensional shape
features in an outbred population.