Mapping quantitative trait loci that influence femoral cross-sectional area in mice

Robert Klein, Renn J. Turner, Lisa D. Skinner, Kristina A. Vartanian, Maqsood Serang, Amy S. Carlos, Marie Shea, John Belknap, Eric Orwoll

Research output: Contribution to journalArticle

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Abstract

Size and shape are critical determinants of the mechanical properties of skeletal elements and can be anticipated to be highly heritable. Moreover, the genes responsible may be independent of those that regulate bone mineral density (BMD). To begin to identify the heritable determinants of skeletal geometry, we have examined femoral cross-sectional area (FCSA) in male and female mice from two inbred strains of mice with divergent FCSA (C57BL/6 [B6] and DBA/2 [D2]), a large genetically heterogeneous population (n = 964) of B6D2F2 mice and 18 BXD recombinant inbred (RI) strains derived from their F2 cross. Femora were harvested from 16-week-old mice and FCSA (bone and marrow space enclosed within the periosteum) was measured at the midshaft by digital image analysis. In all mouse populations examined, FCSA was positively correlated with body weight and weight-corrected FCSA (WC-FCSA) values were normally distributed in the BXD-RI and F2 populations, suggesting polygenic control of this trait. Genome-wide quantitative trait locus (QTL) analysis of the B6D2F2 population revealed regions on four different chromosomes that were very strongly linked to WC-FCSA (chromosomes 6, 8, 10, and X) in both genders. Evidence of gender-specific genetic influences on femoral geometry was also identified at three other chromosomal sites (chromosomes 2, 7, and 12). Supporting evidence for the WC-FCSA QTLs on chromosomes 2, 7, 8, 10, and 12 also was present in the RI strains. Interestingly, none of these WC-FCSA QTLs were identified in our previous QTL analysis of whole body BMD in the same B6D2F2 population. Thus, the genetic determinants of bone size appear to be largely, if not entirely, distinct from those that regulate BMD attainment. The identification of the genes responsible for geometric differences in bone development should reveal fundamentally important processes in the control of skeletal integrity.

Original languageEnglish (US)
Pages (from-to)1752-1760
Number of pages9
JournalJournal of Bone and Mineral Research
Volume17
Issue number10
StatePublished - Oct 1 2002

Fingerprint

Quantitative Trait Loci
Thigh
Bone Density
Weights and Measures
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 2
Population
Multifactorial Inheritance
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 8
Periosteum
Chromosomes, Human, Pair 6
Inbred Strains Mice
Bone Development
Femur
Genes
Chromosomes
Bone Marrow
Body Weight
Genome

Keywords

  • Femoral cross-sectional area
  • Heredity
  • Osteoporosis
  • Quantitative trait
  • Quantitative trait locus analysis

ASJC Scopus subject areas

  • Surgery

Cite this

Klein, R., Turner, R. J., Skinner, L. D., Vartanian, K. A., Serang, M., Carlos, A. S., ... Orwoll, E. (2002). Mapping quantitative trait loci that influence femoral cross-sectional area in mice. Journal of Bone and Mineral Research, 17(10), 1752-1760.

Mapping quantitative trait loci that influence femoral cross-sectional area in mice. / Klein, Robert; Turner, Renn J.; Skinner, Lisa D.; Vartanian, Kristina A.; Serang, Maqsood; Carlos, Amy S.; Shea, Marie; Belknap, John; Orwoll, Eric.

In: Journal of Bone and Mineral Research, Vol. 17, No. 10, 01.10.2002, p. 1752-1760.

Research output: Contribution to journalArticle

Klein, R, Turner, RJ, Skinner, LD, Vartanian, KA, Serang, M, Carlos, AS, Shea, M, Belknap, J & Orwoll, E 2002, 'Mapping quantitative trait loci that influence femoral cross-sectional area in mice', Journal of Bone and Mineral Research, vol. 17, no. 10, pp. 1752-1760.
Klein R, Turner RJ, Skinner LD, Vartanian KA, Serang M, Carlos AS et al. Mapping quantitative trait loci that influence femoral cross-sectional area in mice. Journal of Bone and Mineral Research. 2002 Oct 1;17(10):1752-1760.
Klein, Robert ; Turner, Renn J. ; Skinner, Lisa D. ; Vartanian, Kristina A. ; Serang, Maqsood ; Carlos, Amy S. ; Shea, Marie ; Belknap, John ; Orwoll, Eric. / Mapping quantitative trait loci that influence femoral cross-sectional area in mice. In: Journal of Bone and Mineral Research. 2002 ; Vol. 17, No. 10. pp. 1752-1760.
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