Faculty Collaboration Database

Linkage mapping of femoral material properties in a reciprocal intercross of HcB-8 and HcB-23 recombinant mouse strains. Bone 2010 May;46(5):1251-9

Date

01/28/2010

Pubmed ID

20102754

Pubmed Central ID

PMC2854180

DOI

10.1016/j.bone.2010.01.375

Scopus ID

2-s2.0-77951254488 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Skeletal fragility is an important health problem with a large genetic component. We performed a 603 animal F2 reciprocal intercross of the recombinant congenic strains HcB-8 and HcB-23 to genetically map quantitative trait loci (QTLs) for tissue-level femoral biomechanical performance. These included elastic and post-yield strain, Young's modulus, elastic and maximum stress, and toughness and were calculated from 3-point bend testing of femora by the application of standard beam equations. We mapped these with R/qtl and QTL Cartographer and established significance levels empirically by permutation testing. Significant QTLs for at least one trait are present on chromosomes 1, 6, and 10 in the full F2 population, with additional QTLs evident in subpopulations defined by sex and cross direction. On chromosome 10, we find a QTL for post-yield strain and toughness, phenotypes that have not been mapped previously. Notably, the HcB-8 allele at this QTL increases post-yield strain and toughness, but decreases bone mineral density (BMD), while the material property QTLs on chromosomes 1, 6, and at a second chromosome 10 QTL are independent of BMD. We find significant sex x QTL and cross direction x QTL interactions. A robust, pleiotropic chromosome 4 QTL that we previously reported at the whole-bone level showed no evidence of linkage at the tissue-level, supporting our interpretation that modeling capacity is its primary phenotype. Our data demonstrate an inverse relationship between femoral perimeter and Young's modulus, with R(2)=0.27, supporting the view that geometric and material bone properties are subject to an integrated set of regulatory mechanisms. Mapping QTLs for tissue-level biomechanical performance advances understanding of the genetic basis of bone quality.

Author List

Saless N, Lopez Franco GE, Litscher S, Kattappuram RS, Houlihan MJ, Vanderby R, Demant P, Blank RD

MESH terms used to index this publication - Major topics in bold

Animals
Biomechanical Phenomena
Bone Density
Chromosome Mapping
Crosses, Genetic
Female
Femur
Genotype
Male
Mice
Phenotype
Quantitative Trait Loci