Genetic loci affecting bone structure and strength in inbred COP and DA rats

Qiwei Sun, Imranul Alam, Lixiang Liu, Daniel L. Koller, Lucinda G. Carr, Michael Econs, Tatiana Foroud, Charles H. Turner

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Previous studies have shown that the Copenhagen 2331 (COP) and Dark Agouti (DA) rats have significant differences in bone structure and strength despite their similar body mass. Thus, these inbred rat strains may provide a unique resource to identify the genetics underlying the phenotypic variation in bone fragility. A sample of 828 (405 males and 423 females) COP×DA F2 progeny had extensive phenotyping for bone structure measures including cortical bone area and polar moment of inertia at the femur midshaft and total, cortical and trabecular bone areas, for the lumbar vertebra 5 (L5). Bone strength phenotypes included ultimate force, stiffness and work to failure of femur and L5. These skeletal phenotypes were measured using peripheral quantitative computed tomography (pQCT) and mechanical testing. A whole-genome screen was conducted in the F2 rats, using microsatellite markers spaced at approximately 20 cM intervals. Genetic marker maps were generated from the F2 data and used for genome-wide linkage analyses to detect linkage to the bone structure and strength phenotypes. Permutation testing was employed to obtain the thresholds for genome-wide significance (p < 0.01). Significant QTL for femur structure and strength were identified on chromosome (Chr) 1 with a maximum LOD score of 33.5; evidence of linkage was found in both the male and female rats. In addition, Chrs 6, 7, 10, 13, 15 and 18 were linked to femur midshaft structure. QTL linked to femur strength were identified on Chrs 5 and 10. For L5 vertebrae, Chrs 2, 16, and 18 harbored QTL for cortical structure and trabecular structure for L5 was linked to Chrs 1, 7, 12, and 18. One female-specific QTL for femur ultimate force was identified on Chr 5, and two male-specific QTL for L5 cortical area were found on Chrs 2 and 18. Our study demonstrates strong evidence of linkage for bone structure and strength to multiple rat chromosomes.

Original languageEnglish
Pages (from-to)547-553
Number of pages7
JournalBone
Volume42
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Genetic Loci
Lumbar Vertebrae
Femur
Bone and Bones
Genome
Phenotype
Inbred Strains Rats
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 1
Genetic Markers
Microsatellite Repeats
Dasyproctidae
Spine
Chromosomes
Tomography

Keywords

  • Bone biomechanics
  • Bone strength
  • Bone structure
  • Inbred rats
  • QTL

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Genetic loci affecting bone structure and strength in inbred COP and DA rats. / Sun, Qiwei; Alam, Imranul; Liu, Lixiang; Koller, Daniel L.; Carr, Lucinda G.; Econs, Michael; Foroud, Tatiana; Turner, Charles H.

In: Bone, Vol. 42, No. 3, 03.2008, p. 547-553.

Research output: Contribution to journalArticle

Sun, Qiwei ; Alam, Imranul ; Liu, Lixiang ; Koller, Daniel L. ; Carr, Lucinda G. ; Econs, Michael ; Foroud, Tatiana ; Turner, Charles H. / Genetic loci affecting bone structure and strength in inbred COP and DA rats. In: Bone. 2008 ; Vol. 42, No. 3. pp. 547-553.
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AU - Turner, Charles H.

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