The International Complex Trait Consortium

Quantitative Trait Loci for murine cerebroventricular size

Corinna C. Zygourakis, Glenn D. Rosen

Charles A. Dana Research Institute, Division of Behavioral Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston MA 02215
Harvard Medical School, Boston, MA 02115

Hydrocephalus can lead to serious cognitive and motor deficiencies in humans and animals. In this study, we map quantitative trait loci modulating cerebroventricular size in mice. We hypothesize that genes underlying hydrocephalus might also modulate normal variation in ventricular size. Using digital images of mouse brain sections and stereological techniques, we estimated the volume of the entire brain as well as the volume of the lateral and 3rd ventricles combined in 228 AXB and BXA recombinant inbred mice and their parent strains. Ventricle size, expressed as percent of entire brain volume, is a heritable trait (h2=0.30). and linkage analysis found a significant quantitative locus (QTL) for this phenotype on chromosome 4. Suggestive QTLs on chromosomes 8 and 13 were also identified. These linkages are further supported by their close proximity to the Nfia, hy-3, and Foxc1 genes respectively, previously shown to modulate hydrocephalus (and other abnormalities) in mice. Epistatic interactions, primarily between loci on chromosomes 4 and 7, also affected ventricular size. The results presented here suggest that ventricular size is a polygenic trait modulated by epistatic gene interactions.