RGD Reference Report - Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat. - Rat Genome Database

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Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat.

Authors: Lagerholm, S  Park, HB  Luthman, H  Nilsson, M  McGuigan, F  Swanberg, M  Akesson, K 
Citation: Lagerholm S, etal., Bone. 2010 Dec;47(6):1039-47. Epub 2010 Aug 10.
RGD ID: 4889918
Pubmed: PMID:20699128   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bone.2010.08.003   (Journal Full-text)

The F344 rat carries alleles contributing to bone fragility while the GK rat spontaneously develops type-2 diabetes. These characteristics make F344xGK crosses well suited for the identification of genes related to bone size and allow for future investigation on the association with type-2 diabetes. The aim of this study was to identify quantitative trait loci (QTLs) for bone size phenotypes measured by a new application of three-dimensional computed tomography (3DCT) and to investigate the effects of sex- and reciprocal cross. Tibia from male and female GK and F344 rats, representing the parental, F1 and F2 generations, were examined with 3DCT and analyzed for: total and cortical volumetric BMD, straight and curved length, peri- and endosteal area at mid-shaft. F2 progeny (108 male and 98 female) were genotyped with 192 genome-wide microsatellite markers (average distance 10 cM). Sex- and reciprocal cross-separated QTL analyses were performed for the identification of QTLs linked to 3DCT phenotypes and true interactions were confirmed by likelihood ratio analysis in all F2 animals. Several genome-wide significant QTLs were found in the sex- and reciprocal cross-separated progeny on chromosomes (chr) 1, 3, 4, 9, 10, 14, and 17. Overlapping QTLs for both males and females in the (GKxF344)F2 progeny were located on chr 1 (39-67 cM). This region confirms previously reported pQCT QTLs and overlaps loci for fasting glucose. Sex separated linkage analysis confirmed a male specific QTL on chr 9 (67-82 cM) for endosteal area at the fibula site. Analyses separating the F2 population both by sex and reciprocal cross identified cross specific QTLs on chr 14 (males) and chr 3 and 4 (females). Two loci, chr 4 and 6, are unique to 3DCT and separate from pQCT generated loci. The 3DCT method was highly reproducible and provided high precision measurements of bone size in the rat enabling identification of new sex- and cross-specific loci. The QTLs on chr 1 indicate potential genetic association between bone-related phenotypes and traits affecting type-2 diabetes. The results illustrate the complexity of the genetic architecture of bone size phenotypes and demonstrate the importance of complementary methods for bone analysis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bmd81Ratosteoporosis  IAGP  RGD 
Bss86Ratosteoporosis  IAGP  RGD 
Bss87Ratosteoporosis  IAGP  RGD 
Bss88Ratosteoporosis  IAGP  RGD 
Bss89Ratosteoporosis  IAGP  RGD 
Bss90Ratosteoporosis  IAGP  RGD 
Bss91Ratosteoporosis  IAGP  RGD 
Bss92Ratosteoporosis  IAGP  RGD 
Bss93Ratosteoporosis  IAGP  RGD 
Bss94Ratosteoporosis  IAGP  RGD 
Bss95Ratosteoporosis  IAGP  RGD 
Bss96Ratosteoporosis  IAGP  RGD 
Bss97Ratosteoporosis  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

QTLs
Bmd81  (Bone mineral density QTL 81)
Bss86  (Bone structure and strength QTL 86)
Bss87  (Bone structure and strength QTL 87)
Bss88  (Bone structure and strength QTL 88)
Bss89  (Bone structure and strength QTL 89)
Bss90  (Bone structure and strength QTL 90)
Bss91  (Bone structure and strength QTL 91)
Bss92  (Bone structure and strength QTL 92)
Bss93  (Bone structure and strength QTL 93)
Bss94  (Bone structure and strength QTL 94)
Bss95  (Bone structure and strength QTL 95)
Bss96  (Bone structure and strength QTL 96)
Bss97  (Bone structure and strength QTL 97)

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


Additional Information