Fmbmd4^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Fmbmd4^C3H/HeJ
• Name: femur bone mineral density 4; C3H/HeJ
• MGI ID: MGI:5906691
• QTL: Fmbmd4 Location: unknown Genetic Position: Chr6, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:238309

A large scale study of morphology and cortical micro-structure was performed on a population of mice raised in a controlled environment with known genetic lineage in an effort to link microstructure phenotypes of murine femur bones to specific gene loci.

The QTL mapping population were 2nd generation, intercrossed offspring from two commonly used inbred strains of mice with high C3H/HeJ (C3H) and low C57BL/6J (B6) bone mass. Both strains were homozygous for a mutation in the growth hormone releasing hormone receptor.

A pipelined approach using a fully automated framework based on Synchrotron-based X-ray Tomographic Microscopy (SRXTM) for performing a full 3D characterization of millions of substructures was used to measure 1300 (C3H/HeJ x C57BL/6J)F2 femurs. More than 50 million osteocyte lacunae (cell-sized hollows in the bone) were characterized.

From the metrics, a subset was selected to pursue further with QTL analysis based on a broad-sense heritability criterion of 40%. Genotype information was only available for 755 of the 1132 mice; thus for the rest of the study only those 755 were considered. The extended Haley-Knott method for performing the single-locus scans was used because of its robustness and utilization of genotype information. Gender was an interactive covariant to the model. Genome-wide thresholds for significance and interaction were selected by performing a 2 loci scan again over 1000 permutations of the phenotype over the genotypes.

The following QTL were identified [Table 2, Table S4]:

QTL Fmctv1 (femur cortical thickness variance 1) mapped to Chromosome 1 with a LOD score of 3.13 at 59 cM. The 95% confidence interval spanned from 19 to 73 cM with the C3H allele contributing to the higher phenotypic value. Fmctv1 accounted for 1.71% of trait variance.

QTL Fmlv1 (femur lacuna volume 1) mapped to Chromosome 1 with a LOD score of 6.16 at 81.5 cM. The 95% confidence interval spanned from 77 to 83 cM with the C3H allele contributing to the higher phenotypic value. Fmlv1 accounted for 2.28% of trait variance.

QTL Fmbmd1 (femur bone mineral density 1) mapped to Chromosome 1 with a LOD score of 12.77 at 89.9 cM. The 95% confidence interval spanned from 82 to 97 cM with the C3H allele inherited dominantly contributing to the higher phenotypic value. Fmbmd1 accounted for 5.73% of trait variance.

QTL Fmct1 (femur cortical thickness 1) mapped to Chromosome 1 with a LOD score of 8.53 at 22.3 cM. The C3H allele contributed to the higher phenotypic value. Fmct1 accounted for 4.07% of trait variance.

QTL Fmct2 (femur cortical thickness 2) mapped to Chromosome 1 with a LOD score of 7.20 at 97.1 cM. The 95% confidence interval spanned from 83 to 101 cM with the C3H allele contributing to the higher phenotypic value. Fmct2 accounted for 3.42% of trait variance.

QTL Fmctv2 (femur cortical thickness variance 2) mapped to Chromosome 3 with a LOD score of 3.32 at 39.2 cM. The 95% confidence interval spanned from 26 to 62 cM with the B6 allele contributing to the higher phenotypic value. Fmctv2 accounted for 1.81% of trait variance.

QTL Fmbmd2 (femur bone mineral density 2) mapped to Chromosome 4 with a LOD score of 10.81 at 52.1 cM. The 95% confidence interval spanned from 47 to 71 cM with the C3H allele contributing to the higher phenotypic value. Fmbmd2 accounted for 4.82% of trait variance.

QTL Fmlv2 (femur lacuna volume 2) mapped to Chromosome 5 with a LOD score of 4.55 at 53.8 cM. The C3H allele contributed to the higher phenotypic value. Fmlv2 accounted for 1.68% of trait variance.

QTL Fmlv3 (femur lacuna volume 3) mapped to Chromosome 5 with a LOD score of 18.11 at 68.0 cM. The C3H allele inherited dominantly contributed to the higher phenotypic value. Fmlv3 accounted for 6.97% of trait variance.

QTL Fmls1 (femur lacuna stretch 1) mapped to Chromosome 5 with a LOD score of 6.52 at 68.2 cM. The C3H allele inherited dominantly contributed to the higher phenotypic value. Fmls1 accounted for 3.45% of trait variance.

QTL Fmbmd3 (femur bone mineral density 3) mapped to Chromosome 6 with a LOD score of 7.55 at 20.8 cM. The B6 allele contributed to the higher phenotypic value. Fmbmd3 accounted for 3.33% of trait variance.

QTL Fmbmd4 (femur bone mineral density 4) mapped to Chromosome 6 with a LOD score of 4.80 at 61.7 cM. The C3H allele inherited dominantly contributed to the higher phenotypic value. Fmbmd4 accounted for 2.10% of trait variance.

QTL Fmct3 (femur cortical thickness 3) mapped to Chromosome 6 with a LOD score of 2.31 at 63.4 cM. The C3H allele contributed to the higher phenotypic value. Fmct3 accounted for 1.08% of trait variance.

QTL Fmctv3 (femur cortical thickness variance 3) mapped to Chromosome 6 with a LOD score of 4.29 at 63.4 cM. The C3H allele contributed to the higher phenotypic value. Fmctv3 accounted for 2.35% of trait variance.

QTL Fmld1 (femur lacuna density 1) mapped to Chromosome 6 with a LOD score of 1.00 at 4.1 cM. The 95% confidence interval spanned from 0 to 63 cM with the B6 allele contributing to the higher phenotypic value. Fmld1 accounted for 0.53% of trait variance.

QTL Fmls2 (femur lacuna stretch 2) mapped to Chromosome 6 with a LOD score of 5.25 at 18.9 cM. The 95% confidence interval spanned from 4 to 30 cM with the B6 allele inherited dominantly and contributing to the higher phenotypic value. Fmls2 accounted for 2.77% of trait variance.

QTL Fmbmd5 (femur bone mineral density 5) mapped to Chromosome 7 with a LOD score of 4.38 at 2.2 cM. The 95% confidence interval spanned from 2 to 12 cM with the C3H allele contributing to the higher phenotypic value. Fmbmd5 accounted for 1.91% of trait variance.

QTL Fmct4 (femur cortical thickness 4) mapped to Chromosome 7 with a LOD score of 8.89 at 60.6 cM. The 95% confidence interval spanned from 60 to 72 cM with the C3H allele contributing to the higher phenotypic value. Fmct4 accounted for 4.24% of trait variance.

QTL Fmlv4 (femur lacuna volume 4) mapped to Chromosome 7 with a LOD score of 7.00 at 43.3 cM. The 95% confidence interval spanned from 40 to 72 cM with the C3H allele contributing to the higher phenotypic value. Fmlv4 accounted for 2.60% of trait variance.

QTL Fmls3 (femur lacuna stretch 3) mapped to Chromosome 7 with a LOD score of 2.80 at 1.7 cM. The 95% confidence interval spanned from 2 to 68 cM with the B6 allele contributing to the higher phenotypic value. Fmls3 accounted for 1.46% of trait variance.

QTL Fmlv5 (femur lacuna volume 5) mapped to Chromosome 8 with a LOD score of 5.02 at 18.2 cM. The 95% confidence interval spanned from 6 to 20 cM with the B6 allele contributing to the higher phenotypic value. Fmlv5 accounted for 1.85% of trait variance.

QTL Fmbmd6 (femur bone mineral density 6) mapped to Chromosome 9 with a LOD score of 7.51 at 12.0 cM. The 95% confidence interval spanned from 9 to 31 cM with the B6 allele contributing to the higher phenotypic value. Fmbmd6 accounted for 3.32% of trait variance.

QTL Fmcd1 (femur canal density 1) mapped to Chromosome 9 with a LOD score of 7.25 at 13.2 cM. The 95% confidence interval spanned from 9 to 21 cM with the B6 allele contributing to the higher phenotypic value. Fmcd1 accounted for 4.15% of trait variance.

QTL Fmld2 (femur lacuna density 2) mapped to Chromosome 9 with a LOD score of 10.26 at 40.1 cM. The 95% confidence interval spanned from 31 to 51 cM with the C3H allele contributing to the higher phenotypic value. Fmld2 accounted for 5.59% of trait variance.

QTL Fmlv6 (femur lacuna volume 6) mapped to Chromosome 9 with a LOD score of 12.85 at 32.2 cM. The 95% confidence interval spanned from 25 to 39 cM with the B6 allele contributing to the higher phenotypic value. Fmlv6 accounted for 4.86% of trait variance.

QTL Fmld3 (femur lacuna density 3) mapped to Chromosome 10 with a LOD score of 7.19 at 17.8 cM. The 95% confidence interval spanned from 4 to 32 cM with the C3H allele contributing to the higher phenotypic value. Fmld3 accounted for 3.88% of trait variance.

QTL Fmct5 (femur cortical thickness 5) mapped to Chromosome 11 with a LOD score of 9.47 at 45.6 cM. The 95% confidence interval spanned from 40 to 52 cM with the C3H allele contributing to the higher phenotypic value. Fmct5 accounted for 4.53% of trait variance.

QTL Fmctv4 (femur cortical thickness variance 4) mapped to Chromosome 11 with a LOD score of 2.34 at 54.1 cM. The 95% confidence interval spanned from 32 to 70 cM with the C3H allele contributing to the higher phenotypic value. Fmctv4 accounted for 1.27% of trait variance.

QTL Fmls4 (femur lacuna stretch 4) mapped to Chromosome 11 with a LOD score of 4.52 at 8.8 cM. The 95% confidence interval spanned from 2 to 20 cM with the C3H allele contributing to the higher phenotypic value. Fmls4 accounted for 2.38% of trait variance.

QTL Fmct6 (femur cortical thickness 6) mapped to Chromosome 12 with a LOD score of 3.81 at 16.2 cM. The 95% confidence interval spanned from 5 to 21 cM with the B6 allele contributing to the higher phenotypic value. Fmct6 accounted for 1.79% of trait variance.

QTL Fmld4 (femur lacuna density 4) mapped to Chromosome 12 with a LOD score of 4.09 at 2.19 cM. The B6 allele contributed to the higher phenotypic value. Fmld4 accounted for 2.19% of trait variance.

QTL Fmlv7 (femur lacuna volume 7) mapped to Chromosome 12 with a LOD score of 9.20 at 3.6 cM. The B6 allele contributed to the higher phenotypic value. Fmlv7 accounted for 3.44% of trait variance.

QTL Fmct7 (femur cortical thickness 7) mapped to Chromosome 13 with a LOD score of 12.05 at 10.3 cM. The C3H allele contributed to the higher phenotypic value. Fmct7 accounted for 5.81% of trait variance.

QTL Fmls5 (femur lacuna stretch 5) mapped to Chromosome 13 with a LOD score of 4.28 at 46.2 cM. The 95% confidence interval spanned from 12 to 58 cM with the C3H allele contributing to the higher phenotypic value. Fmls5 accounted for 2.25% of trait variance.

QTL Fmbmd7 (femur bone mineral density 7) mapped to Chromosome 14 with a LOD score of 4.96 at 22.1 cM. The 95% confidence interval spanned from 21 to 39 cM with the C3H allele contributing to the higher phenotypic value. Fmbmd7 accounted for 2.17% of trait variance.

QTL Fmbmd8 (femur bone mineral density 8) mapped to Chromosome 15 with a LOD score of 6.63 at 21.5 cM. The C3H allele inherited dominantly contributed to the higher phenotypic value. Fmbmd8 accounted for 2.92% of trait variance.

QTL Fmlv8 (femur lacuna volume 8) mapped to Chromosome 15 with a LOD score of 6.35 at 27.7 cM. The 95% confidence interval spanned from 21 to 39 cM with the C3H allele contributing to the higher phenotypic value. Fmlv8 accounted for 2.36% of trait variance.

QTL Fmbmd9 (femur bone mineral density 9) mapped to Chromosome 17 with a LOD score of 9.99 at 4.9 cM. The B6 allele contributed to the higher phenotypic value. Fmbmd9 accounted for 4.44% of trait variance.

QTL Fmctv5 (femur cortical thickness variance 5) mapped to Chromosome 17 with a LOD score of 4.83 at 7.9 cM. The C3H allele contributed to the higher phenotypic value. Fmctv5 accounted for 2.65% of trait variance.

QTL Fmlv9 (femur lacuna volume 9) mapped to Chromosome 17 with a LOD score of 4.72 at 45.3 cM. The 95% confidence interval spanned from 34 to 52 cM with the B6 allele contributing to the higher phenotypic value. Fmlv9 accounted for 1.74% of trait variance.

QTL Fmbmd10 (femur bone mineral density 10) mapped to Chromosome 18 with a LOD score of 6.36 at 44.5 cM. The 95% confidence interval spanned from 18 to 48 cM with the C3H allele contributing to the higher phenotypic value. Fmbmd10 accounted for 2.80% of trait variance.

QTL Fmctv6 (femur cortical thickness variance 6) mapped to Chromosome 18 with a LOD score of 3.00 at 15.4 cM. The B6 allele contributed to the higher phenotypic value. Fmctv6 accounted for 1.64% of trait variance.

QTL Fmcd2 (femur canal density 2) mapped to Chromosome 18 with a LOD score of 6.73 at 23.5 cM. The 95% confidence interval spanned from 4 to 42 cM with the B6 allele contributing to the higher phenotypic value. Fmcd2 accounted for 1.64% of trait variance.

QTL Fmlv10 (femur lacuna volume 10) mapped to Chromosome 18 with a LOD score of 8.46 at 14.6 cM. The 95% confidence interval spanned from 8 to 26 cM with the C3H allele contributed to the higher phenotypic value. Fmlv10 accounted for 3.16% of trait variance.

Table S4 contains a list of previously identified bone and growth murine QTL that overlap with QTL listed above identified in the current study.

References

• Original: J:238309 Mader KS, et al., High-throughput phenotyping and genetic linkage of cortical bone microstructure in the mouse. BMC Genomics. 2015 Jul 03;16:493
• All: 1 reference(s)