Linkage mapping of principal components for femoral biomechanical performance in a reciprocal HCB-8 × HCB-23 intercross

Abstract

Studies of bone genetics have addressed an array of related phenotypes, including various measures of biomechanical performance, bone size, bone, shape, and bone mineral density. These phenotypes are not independent, resulting in redundancy of the information they provide. Principal component (PC) analysis transforms multiple phenotype data to a new set of orthogonal “synthetic” phenotypes. We performed PC analysis on 17 femoral biomechanical, anatomic, and body size phenotypes in a reciprocal intercross of HcB-8 and HcB-23, accounting for 80% of the variance in 4 PCs. Three of the 4 PCs were mapped in the cross. The linkage analysis revealed a quantitative trait locus (QTL) with LOD = 4.7 for PC2 at 16 cM on chromosome 19 that was not detected using the directly measured phenotypes. The chromosome 19 QTL falls within a ~ 10 megabase interval, with Osf1 as a positional candidate gene. PC QTLs were also found on chromosomes 1, 2, 4, 6, and 10 that coincided with those identified for directly measured or calculated material property phenotypes. The novel chromosome 19 QTL illustrates the power advantage that attends use of PC phenotypes for linkage mapping. Constraint of the chromosome 19 candidate interval illustrates an important advantage of experimental crosses between recombinant congenic mouse strains.