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Sex-specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats.

Authors: Alam, I  Sun, Q  Liu, L  Koller, DL  Carr, LG  Econs, MJ  Foroud, T  Turner, CH 
Citation: Alam I, etal., J Bone Miner Res. 2008 Feb 18;.
Pubmed: (View Article at PubMed) PMID:18282130
DOI: Full-text: DOI:10.1359/jbmr.080221

Microabstract 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. A total of 828 (405 males and 423 females) F2 progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric bone mineral density (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 F2 data and compared with published Rat Genome Database (RGD) maps. These maps were then employed for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. 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. Female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1 and 4%. 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.


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CRRD Object Information
CRRD ID: 2293456
Created: 2008-05-29
Species: All species
Last Modified: 2008-05-29
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.