RGD Reference Report - Identification of candidate gene regions in the rat by co-localization of QTLs for bone density, size, structure and strength. - Rat Genome Database

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Identification of candidate gene regions in the rat by co-localization of QTLs for bone density, size, structure and strength.

Authors: Lagerholm, S  Park, HB  Luthman, H  Grynpas, M  McGuigan, F  Swanberg, M  Akesson, K 
Citation: Lagerholm S, etal., PLoS One. 2011;6(7):e22462. Epub 2011 Jul 27.
RGD ID: 5684953
Pubmed: PMID:21818327   (View Abstract at PubMed)
PMCID: PMC3144887   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0022462   (Journal Full-text)

Susceptibility to osteoporotic fracture is influenced by genetic factors that can be dissected by whole-genome linkage analysis in experimental animal crosses. The aim of this study was to characterize quantitative trait loci (QTLs) for biomechanical and two-dimensional dual-energy X-ray absorptiometry (DXA) phenotypes in reciprocal F2 crosses between diabetic GK and normo-glycemic F344 rat strains and to identify possible co-localization with previously reported QTLs for bone size and structure. The biomechanical measurements of rat tibia included ultimate force, stiffness and work to failure while DXA was used to characterize tibial area, bone mineral content (BMC) and areal bone mineral density (aBMD). F2 progeny (108 males, 98 females) were genotyped with 192 genome-wide markers followed by sex- and reciprocal cross-separated whole-genome QTL analyses. Significant QTLs were identified on chromosome 8 (tibial area; logarithm of odds (LOD) = 4.7 and BMC; LOD = 4.1) in males and on chromosome 1 (stiffness; LOD = 5.5) in females. No QTLs showed significant sex-specific interactions. In contrast, significant cross-specific interactions were identified on chromosome 2 (aBMD; LOD = 4.7) and chromosome 6 (BMC; LOD = 4.8) for males carrying F344mtDNA, and on chromosome 15 (ultimate force; LOD = 3.9) for males carrying GKmtDNA, confirming the effect of reciprocal cross on osteoporosis-related phenotypes. By combining identified QTLs for biomechanical-, size- and qualitative phenotypes (pQCT and 3D CT) from the same population, overlapping regions were detected on chromosomes 1, 3, 4, 6, 8 and 10. These are strong candidate regions in the search for genetic risk factors for osteoporosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
osteopetrosis  IAGP 5684953; 5684953 RGD 
osteoporosis  IAGP 5684953; 5684953; 5684953; 5684953; 5684953; 5684953; 5684953; 5684953; 5684953; 5684953; 5684953 RGD 

Objects Annotated

QTLs
Bmd82  (Bone mineral density QTL 82)
Bmd83  (Bone mineral density QTL 82)
Bmd84  (Bone mineral density QTL 84)
Bmd85  (Bone mineral density QTL 85)
Bmd86  (Bone mineral density QTL 86)
Bmd87  (Bone mineral density QTL 87)
Bss100  (Bone structure and strength QTL 100)
Bss101  (Bone structure and strength QTL 101)
Bss102  (Bone structure and strength QTL 102)
Bss103  (Bone structure and strength QTL 103)
Bss104  (Bone structure and strength QTL 104)
Bss98  (Bone structure and strength QTL 98)
Bss99  (Bone structure and strength QTL 99)

Strains
F344/DuCrlSwe  (NA)
GK/KyoSwe  (Goto Kakizaki)


Additional Information