Experiment
Linkage analysis was performed on 400 animals from a (C57BL/6J x DBA/2J)F2 intercross to identify QTLs for skeletal phenotypes. Ninety-six microsatellite markers at a 15 cM to 20 cM resolution were used for the genome scan. Measurement of the right tibiaand femur was performed on 200 day old animals. Multiple regression analysis performed on the body mass index (BMI) ratio method was used to adjust for co-factors influencing skeletal phenotypes.
Significant linkage to tibia length mapped to 74 cM on mouse Chromosome 1 with LOD=9.89. This locus is named Mskt1 (musculoskeletal traits 1) and also exhibits linkage to femur length (LOD=4.75), femur sagital width (LOD=4.05), femur epiphyseal width (LOD=3.18), tibia total area (LOD=3.94), and tibia cross sectional moment of inertia (CSMI) (LOD=3.83). Unadjusted data shows linkage of Mskt1 to body weight (LOD=3.42), body length (LOD=3.54), and BMI (LOD=3.74). C57BL/6J-derived alleles at Mskt1 confer increased femur length, femur sagital width, tibia length, tibia total area, tibia CSMI, and body length. DBA/2J-derived alleles at Mskt1 confer increased femur epiphyseal width, body weight, and BMI.
Significant linkage to gastrocnemius muscle weight (LOD=5.11), body length (LOD=3), tibia length (LOD=4.4), and alkaline phosphatase (LOD=4.2) mapped to 6.4 cM on mouse Chromosome 3 in the unadjusted data set. This locus is named Mskt2 (musculoskeletal traits 2). C57BL/6J-derived alleles at Mskt2 confer increased gastrocnemius muscle weight, body length, tibia length,and alkaline phosphatase.
Significant linkage to body length (LOD=3.58), femur length (LOD=3.5), and tibia ultimate load (LOD=3.13) mapped to 27.9 cM on mouse Chromosome 4 in the unadjusted data set. This locus is named Mskt3 (musculoskeletal traits 3).DBA/2J-derived alleles confer increased body length, femur length, and tibia ultimate load.
Significant linkage to femur coronal width mapped to 52 cM on mouse Chromosome 6 (LOD=6.74). This locus is named Mskt4 (musculoskeletal traits 4). Mskt4 also shows linkage to tibia length (LOD=4.25), tibia total area (LOD=3.11), tibia CSMI (LOD=3.05), tibia stiffness (LOD=3.68), gastrocnemius muscle weight (LOD=3.48), and tibialis anterior mass (LOD=3.06). C57BL/6J-derived alleles at Mskt4 confer increased valuesfor the above traits.
Significant linkage to femur ultimate load mapped to 19.4 cM on mouse Chromosome 7 (LOD=5.36). This locus is named Mskt5 (musculoskeletal traits 5). Mskt5 is also linked to femur yield load (LOD=4.37), femur ultimate work (LOD=3.26), tibialis anterior mass (LOD=3.64), and femur ash mass (LOD=3.95). DBA/2J-derived alleles at Mskt5 confer increased values for the above traits. In the unadjusted data set, Mskt5 shows linkage to BMI (LOD=3.36) and body weight (LOD=3.21) with C57BL/6J-derived alleles conferring increased values for these traits. Bntq8 (15 cM) and Bdt4 (18 cM) are previously identified body trait QTLs mapping near Mskt5.
In the unadjusted data set, significant linkage to body length (LOD=3.86), femur coronal width (LOD=3.75), femur length (LOD=3.3), and tibia length (LOD=3.69) mapped to 38 cM on mouse Chromosome 11. This locus is named Mskt6 (musculoskeletal traits 6). DBA/2J-derived alleles at Mskt6 confer increased body length and tibia/femur traits.
In the unadjusted data set, significant linkage to body weight mapped to 24 cM on mouse Chromosome 13 (LOD=6.61). This locus is also linked to femur stiffness (LOD=3.54), BMI (LOD=4.64), tibia length (LOD=4.37), and body length (LOD=3.13). DBA/2J-derived alleles at thislocus, designated Mskt7 (musculoskeletal traits 7), confer increased values for the above traits. Bmd13 (35 cM), Bmch6 (38 cM), and Bntq14 (31 cM) are previously identified body trait QTLs mapping near Mskt7.
Significant linkage to femur ultimate loadmapped to 51.9 cM on mouse Chromosome 15. C57BL/6J-derived alleles at this locus, designated Mskt8 (musculoskeletal traits 8), confer increased femur ultimate load.
Significant linkage to femur stiffness mapped to 54.5 cM on mouse Chromosome 17 (LOD=5.14). This locus is named Mskt9 (musculoskeletal traits 9). DBA/2J-derived alleles at Mskt9 confer increased femur stiffness. Bntq17 (57 cM), a previously identified QTL associated with femur stiffness and other bone traits, may be identical to Mskt9.
Analysis Tools