1. J Bone Miner Res. 2008 Jun;23(6):850-9. doi: 10.1359/jbmr.080221.
Sex-specific genetic loci for femoral neck bone mass and strength identified in
inbred COP and DA rats.
Alam I(1), Sun Q, Liu L, Koller DL, Carr LG, Econs MJ, Foroud T, Turner CH.
Author information:
(1)Department of Biomedical Engineering, Indiana University School of Medicine,
Indianapolis, Indiana 46202, USA.
INTRODUCTION: Hip fracture is the most devastating osteoporotic fracture type
with significant morbidity and mortality. Several studies in humans identified
chromosomal regions linked to hip size and bone mass. Animal models, particularly
the inbred rat, serve as complementary approaches for studying the genetic
influence on hip fragility. The purpose of this study is to identify
sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck
density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti
(DA) rats.
MATERIALS AND METHODS: A total of 828 (405 males and 423 females) F(2) progeny
derived from the inbred COP and DA strains of rats were phenotyped for femoral
neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip),
neck width, ultimate force, and energy to break. A whole genome screen was
performed using 93 microsatellite markers with an average intermarker distance of
20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the
COP x DA F(2) data and compared with published Rat Genome Database (RGD) maps.
These maps were used for genome-wide linkage analyses to detect sex-independent
and sex-specific QTLs.
RESULTS: Significant evidence of linkage (p < 0.01) for sex-independent QTLs were
detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2)
femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties
on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for
total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on
Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for
ultimate force. The effect size of the individual QTL varied between 1% and 4%.
CONCLUSIONS: We detected evidence that sex-independent and sex-specific QTLs
contribute to hip fragility in the inbred rat. Several QTLs regions identified in
this study are homologous to human chromosomal regions previously linked to QTLs
contributing to femoral neck and related phenotypes.
PMCID: PMC2677085
PMID: 18282130 [PubMed - indexed for MEDLINE]
PUBMED: 18282130
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