RGD Reference Report - Fine mapping of bone structure and strength QTLs in heterogeneous stock rat. - Rat Genome Database

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Fine mapping of bone structure and strength QTLs in heterogeneous stock rat.

Authors: Alam, I  Koller, DL  Canete, T  Blazquez, G  Mont-Cardona, C  Lopez-Aumatell, R  Martinez-Membrives, E  Diaz-Moran, S  Tobena, A  Fernandez-Teruel, A  Stridh, P  Diez, M  Olsson, T  Johannesson, M  Baud, A  Econs, MJ  Foroud, T 
Citation: Alam I, etal., Bone. 2015 Dec;81:417-26. doi: 10.1016/j.bone.2015.08.013. Epub 2015 Aug 19.
RGD ID: 11528619
Pubmed: PMID:26297441   (View Abstract at PubMed)
PMCID: PMC4641024   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bone.2015.08.013   (Journal Full-text)

We previously demonstrated that skeletal structure and strength phenotypes vary considerably in heterogeneous stock (HS) rats. These phenotypes were found to be strongly heritable, suggesting that the HS rat model represents a unique genetic resource for dissecting the complex genetic etiology underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone structure and strength phenotypes using 1524 adult male and female HS rats between 17 to 20 weeks of age. Structure measures included femur length, neck width, head width; femur and lumbar spine (L3-5) areas obtained by DXA; and cross-sectional areas (CSA) at the midshaft, distal femur and femoral neck, and the 5th lumbar vertebra measured by CT. In addition, measures of strength of the whole femur and femoral neck were obtained. Approximately 70,000 polymorphic SNPs distributed throughout the rat genome were selected for genotyping, with a mean linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes were estimated across the entire genome for each rat using a multipoint haplotype reconstruction method, which calculates the probability of descent at each locus from each of the 8 HS founder strains. The haplotypes were then tested for association with each structure and strength phenotype via a mixed model with covariate adjustment. We identified quantitative trait loci (QTLs) for structure phenotypes on chromosomes 3, 8, 10, 12, 17 and 20, and QTLs for strength phenotypes on chromosomes 5, 10 and 11 that met a conservative genome-wide empiric significance threshold (FDR=5%; P<3x10(-6)). Importantly, most QTLs were localized to very narrow genomic regions (as small as 0.3 Mb and up to 3 Mb), each harboring a small set of candidate genes, both novel and previously shown to have roles in skeletal development and homeostasis.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

QTLs
Bss113  (Bone structure and strength QTL 113)
Bss114  (Bone structure and strength QTL 114)
Bss115  (Bone structure and strength QTL 115)
Bss116  (Bone structure and strength QTL 116)
Bss117  (Bone structure and strength QTL 117)
Bss118  (Bone structure and strength QTL 118)
Bss119  (Bone structure and strength QTL 119)
Bss120  (Bone structure and strength QTL 120)
Bss121  (Bone structure and strength QTL 121)

Strains
NAft:HS  (Heterogeneous stock)

Objects referenced in this article
Marker rs106984956 rs106984956 Rattus norvegicus
Marker rs106758500 rs106758500 Rattus norvegicus
Marker rs106987644 rs106987644 Rattus norvegicus
Marker rs198651987 rs198651987 Rattus norvegicus
Marker rs197434291 rs197434291 Rattus norvegicus
Marker rs105692231 rs105692231 Rattus norvegicus
Marker rs105872339 rs105872339 Rattus norvegicus
Marker rs198350962 rs198350962 Rattus norvegicus
Marker rs105202638 rs105202638 Rattus norvegicus
Marker rs105809441 rs105809441 Rattus norvegicus
Marker rs106226950 rs106226950 Rattus norvegicus
Marker rs198863294 rs198863294 Rattus norvegicus
Marker rs197277061 rs197277061 Rattus norvegicus
Marker rs197861804 rs197861804 Rattus norvegicus
Marker rs105739537 rs105739537 Rattus norvegicus
Marker rs197893447 rs197893447 Rattus norvegicus
Marker rs105033786 rs105033786 Rattus norvegicus
Marker rs197056246 rs197056246 Rattus norvegicus
Marker rs198738055 rs198738055 Rattus norvegicus
Marker rs198380959 rs198380959 Rattus norvegicus
Marker rs105204296 rs105204296 Rattus norvegicus
Marker rs107420884 rs107420884 Rattus norvegicus
Marker rs198448974 rs198448974 Rattus norvegicus
Marker rs196994347 rs196994347 Rattus norvegicus
Marker rs197969186 rs197969186 Rattus norvegicus
Marker rs197046678 rs197046678 Rattus norvegicus

Additional Information