INTRODUCTION: Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. MATERIALS AND METHODS: A total of 828 (405 males and 423 females) F(2) progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP x DA F(2) data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. RESULTS: Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. CONCLUSIONS: We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to QTLs contributing to femoral neck and related phenotypes.
INTRODUCTION:Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. MATERIALS AND METHODS: A total of 828 (405 males and 423 females) F(2) progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP x DA F(2) data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. RESULTS: Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. CONCLUSIONS: We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to QTLs contributing to femoral neck and related phenotypes.
Authors: D L Koller; G Liu; M J Econs; S L Hui; P A Morin; G Joslyn; L A Rodriguez; P M Conneally; J C Christian; C C Johnston; T Foroud; M Peacock Journal: J Bone Miner Res Date: 2001-06 Impact factor: 6.741
Authors: S G Wilson; P W Reed; A Bansal; M Chiano; M Lindersson; M Langdown; R L Prince; D Thompson; E Thompson; M Bailey; P W Kleyn; P Sambrook; M M Shi; T D Spector Journal: Am J Hum Genet Date: 2002-12-11 Impact factor: 11.025
Authors: D L Koller; K E White; G Liu; S L Hui; P M Conneally; C C Johnston; M J Econs; T Foroud; M Peacock Journal: J Bone Miner Res Date: 2003-06 Impact factor: 6.741
Authors: Katie L Stone; Dana G Seeley; Li-Yung Lui; Jane A Cauley; Kristine Ensrud; Warren S Browner; Michael C Nevitt; Steven R Cummings Journal: J Bone Miner Res Date: 2003-11 Impact factor: 6.741
Authors: Imranul Alam; Daniel L Koller; Toni Cañete; Gloria Blázquez; Carme Mont-Cardona; Regina López-Aumatell; Esther Martínez-Membrives; Sira Díaz-Morán; Adolf Tobeña; Alberto Fernández-Teruel; Pernilla Stridh; Margarita Diez; Tomas Olsson; Martina Johannesson; Amelie Baud; Michael J Econs; Tatiana Foroud Journal: Bone Date: 2015-08-19 Impact factor: 4.398
Authors: Imranul Alam; Daniel L Koller; Qiwei Sun; Ryan K Roeder; Toni Cañete; Gloria Blázquez; Regina López-Aumatell; Esther Martínez-Membrives; Elia Vicens-Costa; Carme Mont; Sira Díaz; Adolf Tobeña; Alberto Fernández-Teruel; Adam Whitley; Pernilla Strid; Margarita Diez; Martina Johannesson; Jonathan Flint; Michael J Econs; Charles H Turner; Tatiana Foroud Journal: Bone Date: 2011-02-18 Impact factor: 4.398
Authors: Imranul Alam; Daniel L Koller; Toni Cañete; Gloria Blázquez; Regina López-Aumatell; Esther Martínez-Membrives; Sira Díaz-Morán; Adolf Tobeña; Alberto Fernández-Teruel; Pernilla Stridh; Margarita Diez; Tomas Olsson; Martina Johannesson; Amelie Baud; Michael J Econs; Tatiana Foroud Journal: J Bone Miner Res Date: 2014-07 Impact factor: 6.741
Authors: Neema Saless; Gloria E Lopez Franco; Suzanne Litscher; Robbie S Kattappuram; Meghan J Houlihan; Ray Vanderby; Peter Demant; Robert D Blank Journal: Bone Date: 2010-01-25 Impact factor: 4.398
Authors: Lu Lu; Jinsong Huang; Fuyi Xu; Zhousheng Xiao; Jing Wang; Bing Zhang; Nicolae Valentin David; Danny Arends; Weikuan Gu; Cheryl Ackert-Bicknell; Olivia L Sabik; Charles R Farber; Leigh Darryl Quarles; Robert W Williams Journal: JBMR Plus Date: 2019-11-11