Chromosomal regions harboring genes for the work to femur failure in mice.
The work to failure is defined as the maximum energy bone can absorb before breaking, and therefore is a direct test of the risk of fracture. To determine the genetic loci influencing work to failure, we have performed a high density genome-wide scan in 633 (MRL x SJL) F(2) female mice. Five loci ( P<0.005) with significant effects on work to failure were found on chromosomes 2, 7, 8, 9, and X, which collectively explained around 20% variance of work to femur failure in F(2) mice. Of those, only the QTL on chromosome 9 was concordant with bone mineral density (BMD) QTLs. Eight significant interactions ( P<0.01) between marker loci were identified, which accounted for an equivalent amount of F(2) variance (23%) to combined single QTL effects. Our results demonstrate that most of the genetic loci regulating work to failure are different from those for BMD in the 7-week-old female mice. If this is also true in humans, this finding will challenge the predictive value of BMD for the risk of fracture.
Li
Xinmin
X
Molecular Genetics Division, Musculoskeletal Disease Center, JL Pettis VA Medical Center, 11201 Benton Street (151), Loma Linda, CA 92357, USA.
Masinde
Godfred
G
Gu
Weikuan
W
Wergedal
Jon
J
Hamilton-Ulland
Melanie
M
Xu
Shizhong
S
Mohan
Subburaman
S
Baylink
David J
DJ
D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005264:Femoral Fractures / Q000235:genetics*; D005269:Femur / Q000378:metabolism*; D005819:Genetic Markers; D016678:Genome; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D019655:Quantitative Trait, Heritable
D005819:Genetic Markers