Originally published as Genetics Published Articles Ahead of Print on June 18, 2005.

Genetics, Vol. 171, 239-249, September 2005, Copyright © 2005
doi:10.1534/genetics.104.040162

Functional Mapping of Quantitative Trait Loci That Interact With the hg Mutation to Regulate Growth Trajectories in Mice

Rongling Wu*,1, Chang-Xing Ma*, Wei Hou*, Pablo Corva{dagger} and Juan F. Medrano{dagger}

* Department of Statistics, University of Florida, Gainesville, Florida 326111 and {dagger} Department of Animal Science, University of California, Davis, California 95616

1 Corresponding author: Department of Statistics, 533 McCarty Hall C, University of Florida, Gainesville, FL 32611.
E-mail: rwu{at}stat.ufl.edu

The high growth (hg) mutation increases body size in mice by 30–50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals.