Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  10
• Reference
  J:307888 Al-Barghouthi BM, et al., Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength. Nat Commun. 2021 Jun 7;12(1):3408
• ID
  MGI:6751721

Genes

Gene	Assay Type
Tmd2	visible phenotype
Towq1	visible phenotype
Wpy1	visible phenotype
Daf1	visible phenotype
Daml1	visible phenotype

Notes

• Reference
  The Diversity Outbred heterogeneous stock (J:DO) is a developing mouse population derived from progenitor lines of the Collaborative Cross (CC). The CC is a panel of recombinant inbred (RI) mouse strains that combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture nearly 90% of the known variation present in laboratory mice (Churchill et al. 2004). Animals from 160 incipient CC lines at early stages of inbreeding were used to establish the DO population, which is maintained by a randomized outbreeding strategy that avoids brother-sister matings. The DO and CC populations thus capture the same set of natural allelic variants derived from a common set of eight founder strains, with DO mice being outbred and the CC population being inbred.
  
  CTC (2004), Churchill, G. A., et al. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 36, 1133-7.
• Experiment
  Osteoporosis is a condition of low bone strength and an increased risk of fracture. Genome-wide association studies (GWAS) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, the authors use Diversity Outbred (DO) mice (J:DO) to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes.
  
  The authors measured 55 complex skeletal phenotypes in a cohort of J:DO mice (n = 619; 314 males, 305 females; breeding generations 23-33) at 12 weeks of age. All 619 mice were genotyped using the GigaMUGA19 array (~110,000 SNPs) and these data were used to reconstruct the genome-wide haplotype structures of each mouse.
  
  The authors identified 28 QTL for various osteoporotic traits (genome coordinates relative to GRCm38/mm10):
  
  Tmd1 (tissue mineral density 1) maps to Chr 1: 154.8 - 155.6 Mb with a peak LOD score of 23.9 at 155.1 Mb.
  
  Maq1 (medullary area QTL 1) maps to Chr 1: 155.1 - 155.7 Mb with a peak LOD score of 12.8 at 155.3 Mb.
  
  Tcsa1 (total cross sectional area 1) maps to Chr 1: 155.1 - 156.2 Mb with a peak LOD score of 11.5 at 155.2 Mb.
  
  Cpq1 (cortical porosity QTL 1) maps to Chr 1: 155.1 - 156.4 Mb with a peak LOD score of 11.4 at 155.4 Mb.
  
  Mlfw1 (medial-lateral femoral width 1) maps to Chr 1: 155.1 - 155.7 Mb with a peak LOD score of 10 at 155.4 Mb.
  
  Pmi1 (polar moment of inertia 1) maps to Chr 1: 154.8 - 158.2 Mb with a peak LOD score of 8.8 at 155.1 Mb.
  
  Cbaf1 (cortical bone area fraction 1) maps to Chr 1: 154.3 - 155.7 Mb with a peak LOD score of 8.5 at 155.3 Mb.
  
  Mmi1 (maximum moment of inertia 1) maps to Chr 1: 155.1 - 158.2 Mb with a peak LOD score of 8.3 at 155.1 Mb.
  
  Mlfw2 (medial-lateral femoral width 2) maps to Chr 2: 144.1 - 145.6 Mb with a peak LOD score of 7.9 at 145.4 Mb.
  
  Maq2 (medullary area QTL 2) maps to Chr 3: 66.6 - 70 Mb with a peak LOD score of 8.8 at 68.1 Mb.
  
  Maq3 (medullary area QTL 3) maps to Chr 4: 113 - 118.4 Mb with a peak LOD score of 8 at 114.6 Mb.
  
  Tcsa2 (total cross sectional area 2) maps to Chr 4: 113.6 - 114.8 Mb with a peak LOD score of 8.2 at 114.6 Mb.
  
  Cbaf2 (cortical bone area fraction 2) maps to Chr 4: 125.4 - 128.1 Mb with a peak LOD score of 8.1 at 127.7 Mb.
  
  Bmd66 (bone mineral density 66) maps to Chr 8: 102.7 - 104.4 Mb with a peak LOD score of 7.8 at 103.5 Mb.
  
  Tmd2 (tissue mineral density 2) maps to Chr 10: 23.1 - 24.6 Mb with a peak LOD score of 14.6 at 23.5 Mb.
  
  Towq1 (total work QTL 1) maps to Chr 10: 23.5 - 24.6 Mb with a peak LOD score of 13.6 at 24.3 Mb.
  
  Wpy1 (work post-yield 1) maps to Chr 10: 23.5 - 25.3 Mb with a peak LOD score of 11.9 at 23.8 Mb.
  
  Daf1 (displacement at fracture 1) maps to Chr 10: 23.3 - 24.6 Mb with a peak LOD score of 10.7 at 23.7 Mb.
  
  Daml1 (displacement at max load 1) maps to Chr 10: 21.8 - 25.2 Mb with a peak LOD score of 9.4 at 23.7 Mb.
  
  Mlq1 (max load QTL 1) maps to Chr 16: 22.3 - 23.4 Mb with a peak LOD score of 8.8 at 23.3 Mb.
  
  Flq1 (fracture load QTL 1) maps to Chr 16: 22.6 - 23.4 Mb with a peak LOD score of 8.2 at 23.1 Mb.
  
  Baq12 (bone area QTL 12) maps to Chr X: 58.4 - 71.2 Mb with a peak LOD score of 13.5 at 59.4 Mb.
  
  Mxmi2 (maximum moment of inertia 2) maps to Chr X: 58.4 - 69.6 Mb with a peak LOD score of 11 at 59.5 Mb.
  
  Pmi2 (polar moment of inertia 2) maps to Chr X: 58.4 - 61.4 Mb with a peak LOD score of 10.4 at 59.4 Mb.
  
  Mnmi1 (minimum moment of inertia 1) maps to Chr X: 57.3 - 61.2 Mb with a peak LOD score of 8.4 at 59.5 Mb.
  
  Ctq1 (cortical thickness QTL 1) maps to Chr X: 58.4 - 74.1 Mb with a peak LOD score of 9.9 at 73.4 Mb.
  
  Tsq1 (trabecular separation QTL 1) maps to Chr X: 72.7 - 77.5 Mb with a peak LOD score of 8.6 at 73.8 Mb.
  
  Tnq1 (trabecular number QTL 1) maps to Chr X: 72.7 - 76.8 Mb with a peak LOD score of 7.9 at 74 Mb.
  
  The results supported the presence of at least two loci on Chr 1, both driven by WSB/EiJ alleles, one influencing cortical bone morphology and cortical porosity and the other influencing cortical tissue mineral density, as well as possibly influencing cortical bone morphology and cortical porosity.
  
  The authors identify Qsox1 as a gene influencing cortical bone accrual and bone strength.