Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population.
The aim of this study was to examine the genetic effects on cortical bone geometry. Genotypes from 487 mice were compared with geometric traits obtained from microCT. We found 14 genetic markers that associate with geometric traits, showing the complexity of genetic control over bone geometry.


BACKGROUND
Previous studies have shown that genetic background affects bone characteristics, particularly bone mineral density, in both mouse and human populations. Much less is known, however, about the effects of polymorphic genes on bone size, shape, and mechanical integrity. In this study, we investigated the genetic determinants of geometric properties of cortical bone in mice.


METHODS
This study used a genetically heterogeneous mouse population, which is denoted UM-HET3 stock and is derived as the progeny of (BALB/cJ X C57BL/6J) F1 females and (C3H/HeJ X DBA/2J) F1 males. The experimental group consisted of 487 female UM-HET3 mice. Genotypic data from 99 polymorphic genetic loci was obtained from the mice at 4 weeks of age. At 18 months of age, the mice were humanely killed, and the right femurs were scanned with microcomputed tomography to assess geometric properties of cortical bone. A permutation-based test was used to detect significant associations between genetic markers and geometric traits. This test generates experiment-wise p values, which account for the effect of testing multiple hypotheses. An experiment-wise p < or = 0.05 was considered statistically significant.


RESULTS
Fourteen genetic markers were found to significantly associate with one or more geometric traits. Two markers (D3Mit62 and D4Mit155) were associated with traits describing bone size; 2 (D12Mit167 and D14Mit170) were linked with traits describing bone shape; and 10 (D1Nds2, D5Mit95, D6Mit216, D7Mit91, D8Mit51, D9Mit110, D11Mit83, D15Mit100, D15Mit171, and D17Mit46) were associated with both size and shape.


CONCLUSIONS
Our results indicate that the genetic control of cortical bone geometry is complex and that femoral size and shape may be influenced by different, although overlapping, groups of polymorphic loci.
Volkman
Suzanne K
SK
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Galecki
Andrzej T
AT
Burke
David T
DT
Paczas
Michael R
MR
Moalli
Maria R
MR
Miller
Richard A
RA
Goldstein
Steven A
SA
D000818:Animals; D015519:Bone Density; D005260:Female; D005269:Femur / Q000033:anatomy & histology* / Q000378:metabolism*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D008297:Male; D051379:Mice / Q000033:anatomy & histology* / Q000235:genetics*; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic / Q000235:genetics; D040641:Quantitative Trait Loci