The patterning of genetic variation in the Collaborative Cross and mutant mice

HALLGRIMSSON B; PAVLICEV M.; MITTEROECKER P.; GONZALEZ P; YOUNG N.; ROLIAN C; JAMNICZKY H; PARDO-MANUEL VILLENA F; MARCUCIO R; SPRITZ R

Calgary

Congreso; 83rdAnnual Meeting of the American Association of Physical Anthropologists; 2014

The genetic basis for variation in the shape of the skull is a key topic of interest in hominid evolution. How genetic variants influence skull shape via developmental processes has important implications for how the hominid skull may have been shaped by natural selection, constraints and drift. We have investigated the developmental and genetic basis for variation in the shape of the skull using a growing database of mouse mutations of diverse origin (N>2000 individuals). In addition, we have also analyzed the parental and F1 generations of mice from the collaborative cross (N=1250). We demonstrate a surprising level of concordance between the structure of the additive genetic variation in the collaborative cross and that seen in the mutant database. Further, analysis of the non-additive genetic variation in the collaborative cross shows a similar concordance in the structure of variation across F1 crosses between the parental strains. In particular, the directionality of dominance deviations in the F1 crosses deviates significantly from random. The mean direction of deviation is a coordinated morphological pattern that involves facial width, neurocranial size and basicranial length.This result reflects the extent to which developmental processes produce highly integrated variation in the skull. This is surprising in light of the genetic complexity of craniofacial development which may involve, to some degree, up to 5% of the genome. The complexity of epistatic interactions produced by these processes has important implications both for the genetics of craniofacial variation a and for the evolvability of this complex structure.