Whole-genome scan for linkage to bone strength and structure in inbred Fischer 344 and Lewis rats

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

Research output: Contribution to journalArticle

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Abstract

A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 × Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 × LEW rats were phenotyped for measures of bone strength (ultimate force [Fu]; energy to break [U]; stiffness [S]) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia [Ip]; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found; to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 × LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes.

Original languageEnglish
Pages (from-to)1589-1596
Number of pages8
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume20
Issue number9
DOIs
StatePublished - Sep 2005

Fingerprint

Inbred Lew Rats
Inbred F344 Rats
Genome
Femur
Bone and Bones
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 1
Quantitative Trait Loci
Thigh
Phenotype
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 10
Lumbar Vertebrae
Chromosomes, Human, Pair 5
Genetic Linkage
Chromosomes, Human, Pair 7
Genetic Loci
Human Chromosomes

Keywords

  • Biomechanics
  • BMD
  • Genes
  • Phenotype
  • Quantitative trait loci

ASJC Scopus subject areas

  • Surgery

Cite this

Whole-genome scan for linkage to bone strength and structure in inbred Fischer 344 and Lewis rats. / Alam, Imranul; Sun, Qiwei; Liu, Lixiang; Koller, Daniel L.; Fishburn, Tonya; Carr, Lucinda G.; Econs, Michael; Foroud, Tatiana; Turner, Charles H.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 20, No. 9, 09.2005, p. 1589-1596.

Research output: Contribution to journalArticle

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T1 - Whole-genome scan for linkage to bone strength and structure in inbred Fischer 344 and Lewis rats

AU - Alam, Imranul

AU - Sun, Qiwei

AU - Liu, Lixiang

AU - Koller, Daniel L.

AU - Fishburn, Tonya

AU - Carr, Lucinda G.

AU - Econs, Michael

AU - Foroud, Tatiana

AU - Turner, Charles H.

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AB - A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 × Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 × LEW rats were phenotyped for measures of bone strength (ultimate force [Fu]; energy to break [U]; stiffness [S]) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia [Ip]; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found; to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 × LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes.

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