title: Quantitative trait loci for BMD and bone strength in an intercross between domestic and wildtype chickens.
abstract: With chicken used as a model species, we used QTL analysis to examine the genetic contribution to bone traits. We report the identification of four QTLs for femoral traits: one for bone strength, one for endosteal circumference, and two affecting mineral density of noncortical bone.
  
  
  BACKGROUND
  BMD is a highly heritable phenotype, governed by elements at numerous loci. In studies examining the genetic contribution to bone traits, many loci have been identified in humans and in other species. The goal of this study was to identify quantitative trait loci (QTLs) controlling BMD and bone strength in an intercross between wildtype and domestic chickens.
  
  
  METHODS
  A set of 164 markers, covering 30 chromosomes (chr.), were used to genotype 337 F2-individuals from an intercross of domesticated white Leghorn and wildtype red junglefowl chicken. DXA and pQCT were used to measure BMD and bone structure. Three-point bending tests and torsional strength tests were performed to determine the biomechanical strength of the bone. QTLs were mapped using forward selection for loci with significant marginal effects.
  
  
  RESULTS
  Four QTLs for femoral bone traits were identified in QTL analysis with body weight included as a covariate. A QTL on chr. 1 affected female noncortical BMD (LOD 4.6) and is syntenic to human 12q21-12q23. Also located on chr. 1, a locus with synteny to human 12q13-14 affected endosteal circumference (LOD 4.6). On chr. 2, a QTL corresponding to human 5p13-p15, 7p12, 18q12, 18q21, and 9q22-9q31 affected BMD in females; noncortical (LOD 4.0) and metaphyseal (LOD 7.0) BMD by pQCT and BMD by DXA (LOD 5.9). A QTL located on chr. 20 (LOD 5.2) affected bone biomechanical strength and had sex-dependent effects. In addition to the significant QTLs, 10 further loci with suggestive linkage to bone traits were identified.
  
  
  CONCLUSIONS
  Four QTLs were identified: two for noncortical BMD, one for endosteal circumference, and one affecting bone biomechanical strength. The future identification of genes responsible for these QTLs will increase the understanding of vertebrate skeletal biology.
authors.affiliation: Department of Medical Sciences, Uppsala University, and Department of Internal Medicine, The Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Rubin
authors.forename: Helena
authors.initials: H
authors.lastname: Brändström
authors.forename: Dominic
authors.initials: D
authors.lastname: Wright
authors.forename: Susanne
authors.initials: S
authors.lastname: Kerje
authors.forename: Ulrika
authors.initials: U
authors.lastname: Gunnarsson
authors.forename: Karin
authors.initials: K
authors.lastname: Schutz
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Per
authors.initials: P
authors.lastname: Jensen
authors.forename: Leif
authors.initials: L
authors.lastname: Andersson
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Hans
authors.initials: H
authors.lastname: Mallmin
authors.forename: Sune
authors.initials: S
authors.lastname: Larsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002645:Chickens / Q000235:genetics* / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D006614:Hindlimb / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics*; D016474:Weight-Bearing / Q000502:physiology