RGD Reference Report - Genetic loci affecting bone structure and strength in inbred COP and DA rats. - Rat Genome Database

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Genetic loci affecting bone structure and strength in inbred COP and DA rats.

Authors: Sun, Q  Alam, I  Liu, L  Koller, DL  Carr, LG  Econs, MJ  Foroud, T  Turner, CH 
Citation: Sun Q, etal., Bone. 2008 Mar;42(3):547-53. Epub 2007 Nov 28.
RGD ID: 2293455
Pubmed: PMID:18158281   (View Abstract at PubMed)
PMCID: PMC2288735   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bone.2007.11.004   (Journal Full-text)

Previous studies have shown that the Copenhagen 2331 (COP) and Dark Agouti (DA) rats have significant differences in bone structure and strength despite their similar body mass. Thus, these inbred rat strains may provide a unique resource to identify the genetics underlying the phenotypic variation in bone fragility. A sample of 828 (405 males and 423 females) COPxDA F2 progeny had extensive phenotyping for bone structure measures including cortical bone area and polar moment of inertia at the femur midshaft and total, cortical and trabecular bone areas, for the lumbar vertebra 5 (L5). Bone strength phenotypes included ultimate force, stiffness and work to failure of femur and L5. These skeletal phenotypes were measured using peripheral quantitative computed tomography (pQCT) and mechanical testing. A whole-genome screen was conducted in the F2 rats, using microsatellite markers spaced at approximately 20 cM intervals. Genetic marker maps were generated from the F2 data and used for genome-wide linkage analyses to detect linkage to the bone structure and strength phenotypes. Permutation testing was employed to obtain the thresholds for genome-wide significance (p<0.01). Significant QTL for femur structure and strength were identified on chromosome (Chr) 1 with a maximum LOD score of 33.5; evidence of linkage was found in both the male and female rats. In addition, Chrs 6, 7, 10, 13, 15 and 18 were linked to femur midshaft structure. QTL linked to femur strength were identified on Chrs 5 and 10. For L5 vertebrae, Chrs 2, 16, and 18 harbored QTL for cortical structure and trabecular structure for L5 was linked to Chrs 1, 7, 12, and 18. One female-specific QTL for femur ultimate force was identified on Chr 5, and two male-specific QTL for L5 cortical area were found on Chrs 2 and 18. Our study demonstrates strong evidence of linkage for bone structure and strength to multiple rat chromosomes.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bss22Ratosteoporosis susceptibilityIAGP  RGD 
Bss23Ratosteoporosis susceptibilityIAGP  RGD 
Bss24Ratosteoporosis susceptibilityIAGP  RGD 
Bss25Ratosteoporosis susceptibilityIAGP  RGD 
Bss26Ratosteoporosis susceptibilityIAGP  RGD 
Bss27Ratosteoporosis susceptibilityIAGP  RGD 
Bss28Ratosteoporosis susceptibilityIAGP  RGD 
Bss29Ratosteoporosis susceptibilityIAGP  RGD 
Bss30Ratosteoporosis susceptibilityIAGP  RGD 
Bss31Ratosteoporosis susceptibilityIAGP  RGD 
Bss32Ratosteoporosis susceptibilityIAGP  RGD 
Bss33Ratosteoporosis susceptibilityIAGP  RGD 
Bss34Ratosteoporosis susceptibilityIAGP  RGD 
Bss35Ratosteoporosis susceptibilityIAGP  RGD 
Bss36Ratosteoporosis susceptibilityIAGP  RGD 
Bss37Ratosteoporosis susceptibilityIAGP  RGD 
Bss38Ratosteoporosis susceptibilityIAGP  RGD 
Bss39Ratosteoporosis susceptibilityIAGP  RGD 
Bss40Ratosteoporosis susceptibilityIAGP  RGD 
Bss41Ratosteoporosis susceptibilityIAGP  RGD 
Bss42Ratosteoporosis susceptibilityIAGP  RGD 
Bss43Ratosteoporosis susceptibilityIAGP  RGD 
Bss44Ratosteoporosis susceptibilityIAGP  RGD 
Bss45Ratosteoporosis susceptibilityIAGP  RGD 
Bss46Ratosteoporosis susceptibilityIAGP  RGD 
Bss47Ratosteoporosis susceptibilityIAGP  RGD 
Bss48Ratosteoporosis susceptibilityIAGP  RGD 
Bss49Ratosteoporosis susceptibilityIAGP  RGD 
Bss50Ratosteoporosis susceptibilityIAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bss41Ratabnormal bone strength susceptibilityIDA  RGD 
Bss42Ratabnormal bone strength susceptibilityIDA  RGD 
Bss43Ratabnormal bone strength susceptibilityIDA  RGD 
Bss44Ratabnormal bone strength susceptibilityIDA  RGD 
Bss45Ratabnormal bone strength susceptibilityIDA  RGD 
Bss46Ratabnormal bone strength susceptibilityIDA  RGD 
Bss47Ratabnormal bone strength susceptibilityIDA  RGD 
Bss48Ratabnormal bone strength susceptibilityIDA  RGD 
Bss49Ratabnormal bone strength susceptibilityIDA  RGD 
Bss50Ratabnormal bone strength susceptibilityIDA  RGD 
Bss22Ratabnormal bone structure susceptibilityIDA  RGD 
Bss23Ratabnormal bone structure susceptibilityIDA  RGD 
Bss24Ratabnormal bone structure susceptibilityIDA  RGD 
Bss25Ratabnormal bone structure susceptibilityIDA  RGD 
Bss26Ratabnormal bone structure susceptibilityIDA  RGD 
Bss27Ratabnormal bone structure susceptibilityIDA  RGD 
Bss28Ratabnormal bone structure susceptibilityIDA  RGD 
Bss29Ratabnormal bone structure susceptibilityIDA  RGD 
Bss30Ratabnormal bone structure susceptibilityIDA  RGD 
Bss31Ratabnormal bone structure susceptibilityIDA  RGD 
Bss32Ratabnormal bone structure susceptibilityIDA  RGD 
Bss33Ratabnormal bone structure susceptibilityIDA  RGD 
Bss34Ratabnormal bone structure susceptibilityIDA  RGD 
Bss35Ratabnormal bone structure susceptibilityIDA  RGD 
Bss36Ratabnormal bone structure susceptibilityIDA  RGD 
Bss37Ratabnormal bone structure susceptibilityIDA  RGD 
Bss38Ratabnormal bone structure susceptibilityIDA  RGD 
Bss39Ratabnormal bone structure susceptibilityIDA  RGD 
Bss40Ratabnormal bone structure susceptibilityIDA  RGD 
Objects Annotated

Bss22  (Bone structure and strength QTL 22)
Bss23  (Bone structure and strength QTL 23)
Bss24  (Bone structure and strength QTL 24)
Bss25  (Bone structure and strength QTL 25)
Bss26  (Bone structure and strength QTL 26)
Bss27  (Bone structure and strength QTL 27)
Bss28  (Bone structure and strength QTL 28)
Bss29  (Bone structure and strength QTL 29)
Bss30  (Bone structure and strength QTL 30)
Bss31  (Bone structure and strength QTL 31)
Bss32  (Bone structure and strength QTL 32)
Bss33  (Bone structure and strength QTL 33)
Bss34  (Bone structure and strength QTL 34)
Bss35  (Bone structure and strength QTL 35)
Bss36  (Bone structure and strength QTL 36)
Bss37  (Bone structure and strength QTL 37)
Bss38  (Bone structure and strength QTL 38)
Bss39  (Bone structure and strength QTL 39)
Bss40  (Bone structure and strength QTL 40)
Bss41  (Bone structure and strength QTL 41)
Bss42  (Bone structure and strength QTL 42)
Bss43  (Bone structure and strength QTL 43)
Bss44  (Bone structure and strength QTL 44)
Bss45  (Bone structure and strength QTL 45)
Bss46  (Bone structure and strength QTL 46)
Bss47  (Bone structure and strength QTL 47)
Bss48  (Bone structure and strength QTL 48)
Bss49  (Bone structure and strength QTL 49)
Bss50  (Bone structure and strength QTL 50)

COP/OlaHsd  (NA)
DA/OlaHsd  (NA)

Additional Information