Experiment
Linkage analysis was performed on 914 adult female (C57BL/6J x C3H/HeJ)F2 using 118 polymorphic markers on 19 autosomes at an average spacing of 13 cM - 14 cM to identify QTLs associated with bone traits. The fifth lumbar vertebra was examined for several quantitative traits such as total volume, trabecular thickness, bone volume, and bone volume fraction. Parental strain C3H/HeJ exhibits lower vertebral trabecular bone volume fraction, trabecular number, and higher trabecular separation compared to C57BL/6J. Trabecular thickness is similar between both strains.
On mouse Chromosome 1, two QTLs were identified at 37 cM (Vtbt1, vertebral trabecular bone trait 1) and 82 cM (Vtbt2). Vtbt1 shows linkage to bone volume fraction at D1Mit282 (LOD=4.3) and Vtbt2shows linkage to total volume (LOD=4.5), trabecular number (LOD=11.4), and bone volume fraction (LOD=10.4) at D1Mit14. C57BL/6J-derived alleles confer increased bone volume fraction with recessive inheritance at Vtbt1. Vtbt2 exhibits additive inheritancewith C3H/HeJ-derived alleles conferring increased trabecular number and bone volume fraction and C57BL/6J-derived alleles conferring increased total volume.
On mouse Chromosome 4 Vtbt3 mapped to 50 cM in linkage to bone volume (LOD=5.5), bone volume fraction (LOD=13.1), trabecular thickness (LOD=14.4), and trabecular number (15.4) at D4Mit187. C3H/HeJ-derived alleles confer increased bone trait values with an additive mode of inheritance.
On mouse Chromosome 7 Vtbt4 mapped to 53 cM in linkage to trabecular thickness (LOD=3.4) at D7Mit238. C57BL/6J-derived alleles confer increased trabecular thickness with additive inheritance at Vtbt4.
On mouse Chromosome 8 Vtbt5 mapped to 38 cM in linkage to bone volume (LOD=4.1), bone volume fraction (LOD=12.9), trabecular thickness (LOD=6.2), and trabecular number (LOD=8.6) at D8Mit75. C57BL/6J-derived alleles confer increased bone trait values with a dominant effect for bone volume and trabecular thickness and an additive effect for bone volume fraction and trabecular number.
On mouse Chromosome 9, Vtbt6 mapped to 15 cM in linkage to bone volume (LOD=4.8), bone volume fraction (LOD=5.7), and trabecular thickness (LOD=3.9) at D9Mit297. Vtbt7 mapped to 27 cM in linkage to trabecular number (LOD=4.8) at D9Mit95. Vtbt8 mapped to 48 cM in linkage to total volume (LOD=6.8), bone volume fraction (LOD=7.4), and trabecular number (LOD=3.7) at D9Mit196. C57BL/6J-derived alleles increase bone trait values with dominant inheritance at Vtbt6 and with additive inheritance atVtbt7. At Vtbt8 C57BL/6J-derived alleles confer additively inherited increase in trabecular thickness and dominantly inherited increase in bone volume while C3H/HeJ-derived alleles confer additively inherited increase in total volume.
On mouse Chromosome 10 Vtbt9 mapped to 51 cM in linkage to total volume (LOD=3.3) at D10Mit95 and Vtbt10 mapped to 62 cM in linkage to bone volume fraction (LOD=3.5) and trabecular number (LOD=3.1) at D10Mit233. C57BL/6J-derived alleles confer increased total volume with dominant inheritance at Vtbt9 while C3H/HeJ-derived alleles confer dominantly inherited increase in bone volume fraction and trabecular number at Vtbt10.
Vtbt11 mapped to 1 cM on mouse Chromosome 11 in linkage to total volume at D11Mit71 (LOD=3.8). C3H/HeJ-derived alleles confer additively inherited increased total volume at this locus.
On mouse Chromosome 12, Vtbt12 mapped to 2 cM in linkage to bone volume (LOD=5.8), bone volume fraction (LOD=4.8), and trabecular number (LOD=4.3) at D12Mit215. C57BL/6J-derived alleles confer increased bone trait values with additive inheritance at Vtbt12. Vtbt13 mapped to 29 cM in linkage to bone volume fraction (LOD=5.4), trabecular thickness (LOD=4.6), and trabecular number (LOD=3.4) at D12Mit114. C57BL/6J-derived alleles confer additively increased bone volume fraction and trabecular number and dominantly increased trabecular thickness at Vtbt13. Vtbt14 mapped to 53 cM in linkage to bone volume fraction (LOD=6.7), trabecular thickness (LOD=3.9), and trabecular number (LOD=4.1) at D12Mit79. C3H/HeJ-derived alleles confer dominantly increased trabecular thickness and trabecular number and additively increased bone volume fraction at Vtbt14.
Vtbt15 mapped to 30 cM on mouse Chromosome 13 in linkage to bone volume (LOD=4.2), bone volume fraction (LOD=9.8), and trabecular number (LOD=9.2) at D13Mit245. C57BL/6J-derived alleles increase bone trait values with dominant inheritance at this locus.
Vtbt16 mapped to 40 cM on mouse Chromosome 14 in linkage to bone volume fraction(LOD=5) and trabecular thickness (LOD=8.3) at D14Mit160. C3H/HeJ-derived alleles confer dominantly inherited increase in bone volume fraction and recessively inherited increased in trabecular thickness.
Vtbt17 mapped to 32 cM on mouse Chromosome 15 in linkage to total volume (LOD=7) at D15Mit209. C3H/HeJ-derived alleles confer additively inherited increase in total volume at this locus.
Vtbt18 mapped to 4 cM on mouse Chromosome 17 in linkage to bone volume (LOD=5.8), bone volume fraction (LOD=6.8), andtrabecular thickness (LOD=7) at D17Mit164. C57BL/6J-derived alleles increase bone trait values with additive inheritance at this locus.
Vtbt19 mapped to 24 cM on mouse Chromosome 18 in linkage to trabecular thickness (LOD=4.3) at D18Mit24. C3H/HeJ-derived alleles confer increased trabecular thickness with dominant inheritance at this locus.
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