Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength.
Lagerholm, Sofia LU ; Park, Hee-Bok LU ; Luthman, Holger LU ; Grynpas, Marc ; McGuigan, Fiona LU
; Swanberg, Maria
LU
and Åkesson, Kristina
LU
(2011)
In PLoS ONE
6(7).
- Abstract
- 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)... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2151394
- author
- Lagerholm, Sofia
LU
; Park, Hee-Bok
LU
; Luthman, Holger
LU
; Grynpas, Marc
; McGuigan, Fiona
LU
; Swanberg, Maria
LU
and Åkesson, Kristina
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 6
- issue
- 7
- article number
- e22462
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000293282700032
- pmid:21818327
- scopus:79960823768
- pmid:21818327
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0022462
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical and Molecular Osteoporosis Research Unit (013242930), Neuronal Survival (013212041), Medical Genetics Unit (013241550), Neurodegeneration and Inflammation Genetics (013210062)
- id
- 791bfbc4-2fbd-4c60-ad6f-fe3921abbff2 (old id 2151394)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21818327?dopt=Abstract
- date added to LUP
- 2016-04-04 09:40:55
- date last changed
- 2023-09-06 02:48:24
@article{791bfbc4-2fbd-4c60-ad6f-fe3921abbff2,
abstract = {{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 = {{Lagerholm, Sofia and Park, Hee-Bok and Luthman, Holger and Grynpas, Marc and McGuigan, Fiona and Swanberg, Maria and Åkesson, Kristina}},
issn = {{1932-6203}},
language = {{eng}},
number = {{7}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength.}},
url = {{https://lup.lub.lu.se/search/files/5389128/2213167.pdf}},
doi = {{10.1371/journal.pone.0022462}},
volume = {{6}},
year = {{2011}},
}