RGD Reference Report - Sex-specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats. - Rat Genome Database

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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;.
RGD ID: 2293456
Pubmed: PMID:18282130   (View Abstract at PubMed)
PMCID: PMC2677085   (View Article at PubMed Central)
DOI: DOI:10.1359/jbmr.080221   (Journal Full-text)

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.

Disease Annotations    
osteoporosis  (IAGP)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Bmd19  (Bone mineral density QTL 19)
Bmd20  (Bone mineral density QTL 20)
Bmd21  (Bone mineral density QTL 21)
Bmd22  (Bone mineral density QTL 22)
Bmd23  (Bone mineral density QTL 23)
Bmd24  (Bone mineral density QTL 24)
Bmd25  (Bone mineral density QTL 25)
Bmd26  (Bone mineral density QTL 26)
Bmd27  (Bone mineral density QTL 27)
Bmd28  (Bone mineral density QTL 28)
Bmd29  (Bone mineral density QTL 29)
Bmd30  (Bone mineral density QTL 30)
Bmd31  (Bone mineral density QTL 31)
Bmd32  (Bone mineral density QTL 32)
Bmd33  (Bone mineral density QTL 33)
Bmd34  (Bone mineral density QTL 34)
Bmd35  (Bone mineral density QTL 35)
Bmd36  (Bone mineral density QTL 36)
Bmd37  (Bone mineral density QTL 37)
Bmd38  (Bone mineral density QTL 38)
Bmd39  (Bone mineral density QTL 39)
Bmd88  (Bone mineral density QTL 88)
Bmd89  (Bone mineral density QTL 89)
Bmd90  (Bone mineral density QTL 90)
Bmd91  (Bone mineral density QTL 91)

COP/OlaHsd  (NA)
DA/OlaHsd  (NA)

Additional Information