Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  1
• Reference
  J:93297 Bygrave AE, et al., Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice. PLoS Biol. 2004 Sep;2(8):E243
• ID
  MGI:3531333

Genes

Gene	Assay Type
Sle16	visible phenotype
D1Mit17	PCR amplified length variant
Apcs	reported elsewhere
D1Mit105	PCR amplified length variant
D1Mit223	PCR amplified length variant
Sle17	visible phenotype
D1Mit123	PCR amplified length variant
D1Mit139	PCR amplified length variant

Notes

• Experiment
  Linkage analysis was performed on 141 female animals from a (129S6/SvEvTac x C57BL/6)F2 intercross to identify QTLs associated with systemic lupus erythematosus phenotypes. (129S6/SvEvTac x C57BL/6)F1 hybrid animals develop spontaneous autoimmunity. 143 polymorphic microsatellite markers were used for the genome scan. 158 homozygous mutant female animals from a (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross were also evaluated separately.
  
  Significant linkage to antinuclear antibody (ANA) production mapped to 96 cM on mouse Chromosome 1 near Tgfbm2 (formerly D1Mit17; LOD=5.4). This locus is named Sle16. Sle16 also shows strong linkage to anti-ssDNA antibody production (LOD=5.6). 129S6/SvEvTac-derived alleles confer increased ANA production and anti-ssDNA production. Previously identified lupus QTLs mapping near Sle16 are Sle1 (88 cM), Nba2 (95 cM), and Sle9/Bsx3 (100 cM). Because Sle16 maps close to the Apcs gene at 94 cM, 33 (129S6/SvEvTac x C57BL/6)F2 intercross mice homozygous for 129S6/SvEvTac-derived alleles between 80cM - 100 cM were compared to the 158 homozygous mutant (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe animals. No difference in autoantibody levels was observed between the 2 groups suggesting that 129S6-derived DNA influences autoantibody phenotypes instead of a lack of Apcs genes. A congenic line was created by introgressing 129S6-derived DNA between D1Mit105 (80 cM) and D1Mit223 (106.3 cM) onto a C57BL/6 genetic background. Congenic animals display increased autoantibody production.
  
  Significant linkage to anti-ssDNA antibody production mapped to 50 cM - 60 cM on mouse Chromosome 1 between D1Mit123 (21 cM) and D1Mit139 (65 cM) (LOD=3.9). This locus is named Sle17. 129S6-derived alleles confer increased anti-ssDNAproduction. Sle17 was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population although with suggestive significance (LOD=2.9).
  
  Highly significant linkage to SLE susceptibility mapped to 51 cM on mouse Chromosome 3 between D3Mit40(39.7 cM) and D3Mit13 (61.8 cM). This locus is namedSle18. Sle18 contributes to ANA production (LOD=5.4) and shows weaker association to anti-ssDNA (LOD=1.9) and anti-chromatin antibody production (LOD=1.8). C57BL/6-derived alleles confer increased production of ANA, anti-ssDNA and anti-chromatin antibodies. Linkage analysis was performed while controlling for Sle16 on Chromosome 1 and the LOD score increased from LOD=5.4 to LOD=6.4. Sle18 was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpeintercross populationwith LOD=1.8.
  
  Suggestive linkageto anti-dsDNA antibody production mapped to mouse Chromosome 1 at 17 cM (LOD=2.2 between D1Mit3 and D1Mit213), 77 cM (LOD=3.2 between D1Mit139 and D1Mit105), and 92 cM. The locus at 17 cM was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population with LOD=2.9.
  
  Suggestive linkage to anti-chromatin antibody production mapped to 88 cM on mouse Chromosome 1 (LOD=3.0 between D1Mit83 and D1Mit115) and to 35 cM on mouse Chromosome3 (LOD=1.8 atD3Mit278). The chromsome 3 locus was also detected in the (129S6/SvEvTac x C57BL/6)F2-Apcs^tm1Mpe intercross population with LOD=2.4.
  
  Suggestive linkage to glomerulonephritis mapped to mouse Chromosome 7 between D7Mit246 (15 cM) and D7Mit145 (26.5 cM) (LOD=2.86) and to mouse Chromosome 17 between D17Mit100 (11.7 cM) andD17Mit216 (29.4 cM) (LOD=1.3).