Syncq4^LG/J
QTL Variant Detail

Summary

• QTL variant: Syncq4^LG/J
• Name: synovial calcification QTL 4; LG/J
• MGI ID: MGI:6342146
• QTL: Syncq4 Location: Chr1:180673565-182085565 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: LG/J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:276925

Pathological mineralization of synovial connective tissues leads to chondromatosis or loose bodies in the knee. This study reports on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice.

Here, the authors report the development of synovial and meniscal ectopic calcifications in response to knee trauma in an F44 advanced intercross of LG/J and SM/J mice (Wustl:LG, SM-G44). Using 347 mice in 98 full-sibships, destabilization of medial meniscus (DMM) was performed to induce joint injury. The authors found that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT.

Each mouse was scored for presence/absence of synovial and/or meniscal ectopic calcifications as well as according to a graded scale: 0 = no nodules, 1 = less than 5

nodules, 2 = more than 5 nodules.

QTL analysis was performed to map ectopic calcification phenotypes to discrete genomic locations.

Individuals of the F44 and their F43 parents were genotyped at 4,588 SNPs distributed across the 19 autosomes of the mouse genome. A genetic map was constructed based on the physical ordering of SNPs along each autosome according to NCBI build 37/mm9 using R/qtl. Using the Hapi software, ordered heterozygous genotypes were estimated twice from family data. Heterozygous genotypes were input initially as LG/J:SM/J and then SM/J:LG/J. Loci with discrepant calls between the two analyses were treated as having missing phase information.

Based on each individuals marker genotypes, the authors utilized HaleyKnott regression to impute additional genotypes every 1 centimorgan (cM), assigning additive, dominance, and imprinting genotypic scores at each marker and imputed position. Then two mapping models were compared using the Mixed Procedure in SAS v9.1 (SAS Institute, Cary, NC). The full-model included sex plus genomic location effects and their interactions with sex as fixed effects, and family assignment and its interaction with sex as random effects.

Since meniscal and synovial calcifications were scored twice according to binary and graded classifications, QTL of a given full- or reduced-model were considered valid only when they achieved at least chromosome-wise significance on one scale and at least point-wise significance at 10% level on the other scale.

Overall, the authors detected 21 QTL affecting synovial and meniscus calcification phenotypes:

(LPR = -log[probability])

Syncq1 (synovial calcification QTL 1) maps to Chr 1: 38.094 - 38.932 with a peak LPR score of 3.99 at 38.746. Syncq1 exerts an additive effect in males.

Syncq2 (synovial calcification QTL 2) maps to Chr 1: 39.657 - 40.460 with a peak LPR score of 5.20 at 40.035. Syncq2 exerts additive and dominance effects in males and an additive effect in females.

Syncq3 (synovial calcification QTL 3) maps to Chr 1: 155.549 - 156.758 with a peak LPR score of 3.08 at 155.851. Syncq3 exerts imprinting effects in males and females.

Syncq4 (synovial calcification QTL 4) maps to Chr 1: 180.846 - 182.258 with a peak LPR score of 3.77 at 181.640. Syncq4 exerts an additive effect in females.

Syncq5 (synovial calcification QTL 5) maps to Chr 4: 37.705 - 38.537 with a peak LPR score of 4.04 at 38.157. Syncq5 exerts additive and dominance effects in females.

Syncq6 (synovial calcification QTL 6) maps to Chr 6: 4.177 - 5.219 with a peak LPR score of 3.48 at 4.608. Syncq6 exerts additive and dominance effects in pooled data from both males and females.

Syncq7 (synovial calcification QTL 7) maps to Chr 9: 60.553 -61.490 with a peak LPR score of 3.25 at 61.044. Syncq7 exerts dominance effects in pooled data from both males and females.

Syncq8 (synovial calcification QTL 8) maps to Chr 9: 69.607 - 70.785 with a peak LPR score of 3.51 at 70.435. Syncq8 exerts additive effects in pooled data from both males and females.

Syncq9 (synovial calcification QTL 9) maps to Chr 11: 96.047 - 97.102 with a peak LPR score of 3.73 at 96.433. Syncq9 exerts imprinting effects in females.

Syncq10 (synovial calcification QTL 10) maps to Chr 13: 32.257 - 33.510 with a peak LPR score of 3.20 at 32.496. Syncq10 exerts additive, dominance, and imprinting effects in pooled data from both males and females.

Syncq11 (synovial calcification QTL 11) maps to Chr 19: 50.737 - 51.891 with a peak LPR score of 3.58 at 51.468. Syncq11 exerts additive and dominance effects in pooled data from both males and females.

Mencq1 (meniscus calcification QTL 1) maps to Chr 1: 187.601 - 189.319 with a peak LPR score of 3.15 at 189.133. Mencq1 exerts dominance and imprinting effects in pooled data from both males and females.

Mencq2 (meniscus calcification QTL 2) maps to Chr 1: 191.851 - 192.530 with a peak LPR score of 3.06 at 192.193. Mencq2 exerts additive and dominance effects in females.

Mencq3 (meniscus calcification QTL 3) maps to Chr 5: 74.281 - 75.687 with a peak LPR score of 3.71 at 74.537. Mencq3 exerts additive and dominance effects in pooled data from both males and females.

Mencq4 (meniscus calcification QTL 4) maps to Chr 5: 135.867 - 136.190 with a peak LPR score of 4.06 at 136.041. Mencq4 exerts imprinting effects in males and females.

Mencq5 (meniscus calcification QTL 5) maps to Chr 6: 59.615 - 63.355 with a peak LPR score of 3.17 at 61.571. Mencq5 exerts imprinting effects in males.

Mencq6 (meniscus calcification QTL 6) maps to Chr 8: 10.972 - 12.150 with a peak LPR score of 3.20 at 11.324. Mencq6 exerts an additive effect in males and additive and dominance effects in females.

Mencq7 (meniscus calcification QTL 7) maps to Chr 10: 85.478 - 86.812 with a peak LPR score of 3.19 at 86.056. Mencq7 exerts dominance effects in males and females.

Mencq8 (meniscus calcification QTL 8) maps to Chr 14: 120.062 - 120.872 with a peak LPR score of 3.57 at 120.301. Mencq8 exerts imprinting effects in males.

Mencq9 (meniscus calcification QTL 9) maps to Chr 15: 27.316 - 27.624 with a peak LPR score of 3.51 at 27.470. Mencq9 exerts dominance effects in pooled data from both males and females.

Mencq10 (meniscus calcification QTL 10) maps to Chr 19: 50.982 - 51.894 with a peak LPR score of 3.10 at 51.517. Mencq10 exerts an additive effect in females.

Functional and bioinformatic analyses of SNP identified functional classifications relevant to angiogenesis, bone metabolism/calcification, arthritis, and ankylosing-spondylitis. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification.

References

• Original: J:276925 Rai MF, et al., Genetic loci that regulate ectopic calcification in response to knee trauma in LG/J by SM/J advanced intercross mice. J Orthop Res. 2015 Oct;33(10):1412-23
• All: 1 reference(s)