Imraq1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Imraq1^DBA/2J
• Name: immune response to AAV2 QTL 1; DBA/2J
• MGI ID: MGI:3603768
• QTL: Imraq1 Location: unknown Genetic Position: Chr4, cM position of peak correlated region/allele: 32.54 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased anti-AAV2 IgG2b antibody response compared to C57BL/6J. (J:100370)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:100370

Linkage analysis was performed on animals from 18 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains to identify QTL associated with immune response to adeno-associated virus 2 (AAV2) and coagulation Factor IX. Animals at 2 months of age were injected with AAV2 and Factor IX and evaluated at several time points between 0 day -180 days post-injection. Parental strain C57BL/6J exhibits a higher IgG2b response to AAV2, and lower (but not statistically significant) IgG1 response to Factor IX comparedto parental strain DBA/2J.

Significant linkage to IgG2b anti-AAV2 response mapped to 29 cM on mouse Chromosome 4 near D4Mit164 (LOD=3.35). This locus is named Imraq1 (immune response to AAV2 QTL 1). DBA/2J-derived alleles at Imraq1 confer increased anti-AAV2 IgG2b antibody response. Suggestive linkage to IgG2b anti-AAV2 response also mapped to 30.5 cM on mouse Chromosome 6 near D6Mit16 (LOD=2.43) and to 47.7 cM on mouse Chromosome 17 near D17Mit187 (LOD=2.85). DBA/2J-derived alleles at D6Mit16 and C57BL/6J-derived alleles at D17Mit187 confer increased anti-AAV2 IgG2b antibody response.

Significant epistatic interaction was detected for a locus pair at 40 cM on mouse Chromosome 8 (D8Mit45) and 43 cM on mouse Chromosome 16 (D16Mit47) with LOD=6.54. Theseloci are named Imraq2 (immune response to AAV2 QTL 2) and Imraq3 (immune response to AAV2 QTL 3), respectively. Animals with DBA/2J-derived alleles at Imraq2 and C57BL/6J-derived alleles at Imraq3 exhibit significantly enhanced IgG2b anti-AAV2 response.

Suggestive linkage to IgG1 anti-Factor IX response mapped to 67 cM on mouse Chromosome 1 near D1Mit218 (LOD=3.07). DBA/2J-derived alleles at D1Mit218 confer increased IgG1 anti-Factor IX response.

Significant epistatic interaction was detected for a locus pair at 8 cM on mouse Chromosome 5 (D5Mit348) and 69 cM on mouse Chromosome 15 (D15Mit161) with LOD=7.66. These loci are named Imrfq1 (immune response to Factor IX QTL 1) and Imrfq2 (immune response to Factor IX QTL 2), respectively. Animals with C57BL/6J-derived alleles at both Imrfq1 and Imrfq2 exhibit significantly enhanced IgG1 anti-Factor IX response.

References

• Original: J:100370 Zhang HG, et al., Genetic analysis of the antibody response to AAV2 and factor IX. Mol Ther. 2005 Jun;11(6):866-74
• All: 1 reference(s)