title: Quantitative trait loci that determine BMD in C57BL/6J and 129S1/SvImJ inbred mice.
abstract: BMD is highly heritable; however, little is known about the genes. To identify loci controlling BMD, we conducted a QTL analysis in a (B6 x 129) F2 population of mice. We report on additional QTLs and also narrow one QTL by combining the data from multiple crosses and through haplotype analysis.
  
  
  BACKGROUND
  Previous studies have identified quantitative trait loci (QTL) that determine BMD in mice; however, identification of genes underlying QTLs is impeded by the large size of QTL regions.
  
  
  METHODS
  To identify loci controlling BMD, we performed a QTL analysis of 291 (B6 x 129) F2 females. Total body and vertebral areal BMD (aBMD) were determined by peripheral DXA when mice were 20 weeks old and had consumed a high-fat diet for 14 weeks.
  
  
  CONCLUSIONS
  Two QTLs were common for both total body and vertebral aBMD: Bmd20 on chromosome (Chr) 6 (total aBMD; peak cM 26, logarithm of odds [LOD] 3.8, and vertebral aBMD; cM 32, LOD 3.6) and Bmd22 on Chr 1 (total aBMD; cM 104, LOD 2.5, and vertebral aBMD; cM 98, LOD 2.6). A QTL on Chr 10 (Bmd21, cM 68, LOD 3.0) affected total body aBMD and a QTL on Chr 7 (Bmd9, cM 44, LOD 2.7) affected vertebral aBMD. A pairwise genome-wide search did not reveal significant gene-gene interactions. Collectively, the QTLs accounted for 21.6% of total aBMD and 17.3% of vertebral aBMD of the F(2) population variances. Bmd9 was previously identified in a cross between C57BL/6J and C3H/HeJ mice, and we narrowed this QTL from 34 to 22 cM by combining the data from these crosses. By examining the Bmd9 region for conservation of ancestral alleles among the low allele strains (129S1/SvImJ and C3H/HeJ) that differed from the high allele strain (C57BL/6J), we further narrowed the region to approximately 9.9 cM, where the low allele strains share a common haplotype. Identifying the genes for these QTLs will enhance our understanding of skeletal biology.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA. bjp@jax.org
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishimori
authors.forename: Renhua
authors.initials: R
authors.lastname: Li
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Walsh
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.forename: Jarod A
authors.initials: JA
authors.lastname: Rollins
authors.forename: Petko
authors.initials: P
authors.lastname: Petkov
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Pletcher
authors.forename: Tim
authors.initials: T
authors.lastname: Wiltshire
authors.forename: Leah Rae
authors.initials: LR
authors.lastname: Donahue
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Wesley G
authors.initials: WG
authors.lastname: Beamer
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
authors.forename: Beverly
authors.initials: B
authors.lastname: Paigen
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D003433:Crosses, Genetic; D006239:Haplotypes; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci / Q000235:genetics*