Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength.

Summary, in English

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.

• Author: Sofia Lagerholm; Hee-Bok Park; Holger Luthman; Marc Grynpas; Fiona McGuigan; Maria Swanberg; Kristina Åkesson
• Department/s: Orthopedics - Clinical and Molecular Osteoporosis Research; Genetics; Department of Experimental Medical Science; EpiHealth: Epidemiology for Health; MultiPark: Multidisciplinary research focused on Parkinson´s disease
• Publishing year: 2011
• Language: English
• Publication/Series: PLoS ONE
• Volume: 6
• Issue: 7
• Full text: - 243 kB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/21818327?dopt=Abstract; http://dx.doi.org/10.1371/journal.pone.0022462
• Document type: Journal article
• Publisher: Public Library of Science (PLoS)
• Topic: Medical Genetics; Neurosciences; Orthopedics
• Status: Published
• Research group: Orthopedics - Clinical and Molecular Osteoporosis Research; Genetics
• ISBN/ISSN/Other: ISSN: 1932-6203