Numerous loci of large effect have been shown to underlie phenotypic variation between species. However, loci with subtle effects are presumably more frequently involved in microevolutionary processes, but have rarely been discovered. We explore the genetic basis of shape variation in the first upper molar of hybrid mice between Mus musculus musculus and M. m. domesticus. We performed the first genome-wide association study for molar shape and used 3D surface morphometrics to quantify subtle variation between individuals. We show that many loci of small effect underlie phenotypic variation, and identify five genomic regions associated with tooth shape; one region contained the microphthalmia-associated transcription factor Mitf gene that has previously been associated with tooth malformations. Using a panel of five mutant laboratory strains, we show the effect of the Mitf gene on tooth shape. This is the first report of a gene causing subtle but consistent variation in tooth shape resembling variation in nature.
Use of a natural hybrid zone for genome-wide association mapping of craniofacial traits in the house mousehttp://www.datadryad.org/resource/doi:10.5061/dryad.bt848.
- Ronan Ledevin
- Sophie Pantalacci
- Sabrina Renaud
- Eirikur Steingrimsson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: The mice used for the association mapping were previously used in another study; details on animal experiment and ethics can be found in the original publication Turner et. al. 2012 Evolution.The mutant mice used for the validation of the gene Mitf were raised at the University of Iceland, BioMedical Center, under permit number 2013-03-01 from the Committee on Experimental Animals (Tilraunadýranefnd).
- Craig T Miller, University of California, Berkeley, United States
© 2017, Pallares et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.