Nba4^SWR
QTL Variant Detail

Summary

• QTL variant: Nba4^SWR
• Name: New Zealand Black autoimmunity 4; SWR
• MGI ID: MGI:3576909
• QTL: Nba4 Location: unknown Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: SWR

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

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

J:96263

Linkage analysis was performed on 88 animals from a SWR x (SWR x NZB)F1 backcross population to identify QTLs associated with lupus phenotypes. (SWR x NZB)F1 hybrid animals are susceptible to lupus nephritis. Animals were sero-typed at 9-12 months of age. 116 autosomal microsatellite markers at an average spacing of 10.6 cM were used for the genome scan.

A suggestive locus at 11 cM on mouse Chromosome 5 showed linkage to serum IgG3 antibodies and IgG anti-histone antibodies near D5Mit55 (LOD=1.72). This locus is tentatively named Nba4. NZB-derived alleles confer increased serum IgG3 and IgG anti-histone antibodies with a dominant mode of inheritance.

A previously identified lupus QTL named Sle6 (28 cM) overlaps with this locus. Weak linkage to glomerulonephritis susceptibility mapped to 58 cM on mouse Chromosome 5 near D5Mit339 (LOD=1.58). SWR-derived alleles at D5Mit339 confer susceptibility to glomerulonephritis with a recessive mode of inheritance. This locus maps near a previously identified lupus QTL named Lprm4 (54 cM).

J:96060

Linkage analysis was performed on a population of 62 (SWR x NZB)F2 animals to identify QTLs associated with lupus nephritis. (SWR x NZB)F1 hybrid animals exhibit susceptibility to lupus nephritis. 95 polymorphic markers at a 12.2 cM resolution were used for the genome scan.

A novel QTL tentatively named Swrl5 was identified at 106 cM on mouse Chromosome 1. Swrl5 shows suggestive linkage to hypergammaglobulinemia with LOD=3.22 at Tgfbm2 (formerly D1Mit17; 106 cM). Animals homozygous for SWR-derived alleles at Swrl5 tend to have significantly increased levels of total serum IgG. Previously identified lupus QTL Sle1c at 106.3 cM overlaps with Swrl5. A potential candidate gene for both Swrl5 and Sle1c is Cr2 (106.6 cM). The Swrl5 region is syntenic to a human SLE locus on 1q.

Previously identified QTL Nba4 was detected and confirmed in this study. Nba4 maps to 15 cM on mouse Chromosome 5. This locus shows suggestive linkage to IgG anti-ssDNA antibodies, anti-dsDNA antibodies and glomerulonephritis with LOD=2.98 at D5Mit127. Animals homozygous for NZB-derived alleles at Nba4 exhibit increased autoantibody production and susceptibility to glomerulonephritis. Other autoimmunity QTLs mapping near Nba4 are Sle6 (28 cM) and Pgia18 (5 cM). Nba4 is syntenic to a human SLE locus on 4p named SLEB3.

A novel locus tentatively named Nba6 mapped to 28 cM on mouse Chromosome 13. Nba6 shows suggestive linkage to serum IgG anti-ssDNA antibodies with LOD=3.63 near D13Mit202. Animals homozygous for NZB-derived alleles at Nba6 exhibit increased autoantibody production. A previously identified arthritis QTL named Pgia15 maps near Nba6.

Previously identified QTL Swrl2 was detected and confirmed in this study. Swrl2 maps to mouse 30 cM on Chromosome 14 and shows suggestive linkage to serum IgG anti-ssDNA antibodies with LOD=2.91.

A previously identified QTL named Swrl3 on mouse Chromosome 18 was also confirmed in this study. Swrl3 maps to 13 cM and has an additive effect with SWR-derived alleles conferring increased IgG anti-dsDNA antibodies and anti-histone antibodies.

References

• Original: J:96060 Xie S, et al., Genetic origin of lupus in NZB/SWR hybrids: lessons from an intercross study. Arthritis Rheum. 2005 Feb;52(2):659-67
• All: 2 reference(s)