Cnes1^CBA/J
QTL Variant Detail

Summary

• QTL variant: Cnes1^CBA/J
• Name: C. neoformans susceptibility locus 1; CBA/J
• MGI ID: MGI:6379264
• QTL: Cnes1 Location: unknown Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: CBA/J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:279066

Cryptococcus neoformans is a major cause of fungal pneumonia, meningitis and disseminated disease in the immune compromised host. The authors used a clinically relevant model to investigate the genetic determinants of susceptibility to progressive cryptococcal pneumonia in C57BL/6J and CBA/J inbred mice. At 5 weeks after infection, the lung fungal burden was over 1000-fold higher in C57BL/6J compared to CBA/J mice. A genome-wide scan was performed on 210 male and 203 female (CBA/J x C57BL/6J)F2 progeny using lung colony-forming units as a quantitative trait.

The entire (CBA/J x C57BL/6J)F2 population was initially genotyped with 95 markers distributed across the genome at an average distance of 40 Mb. An additional 17 SNPs were subsequently genotyped on chromosomes 3, 6, 9, and 17 for further analysis of regions that were initially suggestive of linkage (LOD >= 2.0). All coordinates are relative to NCBI Build 36.

Genetic linkage analysis revealed three loci associated with susceptibility to cryptococcal pneumonia:

Cnes1 (C. neoformans susceptibility locus 1) maps to Chr 3 with a peak LOD score of 4.09 at 18.83 Mb. Cnes1 is significant in females with a dominant mode of inheritance and explains 8.9% of the phenotypic variance.

Cnes2 (C. neoformans susceptibility locus 2) maps to Chr 17 with a peak LOD score of 7.30 at 14.06 Mb. Cnes2 is significant in females with a dominant mode of inheritance and explains 15.9% of the phenotypic variance.

Cnes3 (C. neoformans susceptibility locus 3) maps to Chr 17 with a peak LOD score of 4.04 at 67.90 Mb. Cnes3 is significant in males with an overdominant mode of inheritance and explains 8.6% of the phenotypic variance.

Genome-wide pair-wise analysis revealed significant QTL interactions in both the female and male (CBA/J x C57BL/6J)F2 progeny that collectively explained 43.8 and 19.5% of phenotypic variance in each sex, respectively.

In the female (CBA/J x C57BL/6J)F2 progeny, interaction between Cnes2 (17-013493244-M) and marker 08-092730657-N explained 26.5% (LOD = 12.80, P < 0.0001) of the total phenotypic variance.

Pair-wise interaction between marker 03-051281956-M and 09-076920055-M, and pair-wise interaction between marker 06-017592278-N and 12-006490502-M in female (CBA/J x C57BL/6J)F2 progeny explained 15.6% (LOD = 7.23, P = 0.001) and 13.0% (LOD = 5.82,P = 0.006) of the total phenotypic variance, respectively.

Within the male (CBA/J x C57BL/6J)F2 progeny, one significant interaction was observed between Cnes3 (17-067130590-M) and marker 03-051281956-M that explained 19.5% (LOD = 9.84, < 0.0001) of the total phenotypic variance.

Four suggestive QTL were mapped for females:

Chr 1: 140.90 Mb with a peak LOD score of 2.20 at rs3677464.

Chr 6: 148.27 Mb with a peak LOD score of 3.07 at rs3711088.

Chr 8: 24.79 Mb with a peak LOD score of 2.06 at rs3671390.

Chr 14: 16.45 Mb with a peak LOD score of 2.47 at rs3678171.

Three suggestive QTL were mapped for males:

Chr 6: 144.37 Mb with a peak LOD score of 2.90 at rs3685482.

Chr 8: 95.83 Mb with a peak LOD score of 2.16 at rs3089148.

Chr 9: 40.39 Mb with a peak LOD score of 2.74 at rs3705734.

References

• Original: J:279066 Carroll SF, et al., Sex differences in the genetic architecture of susceptibility to Cryptococcus neoformans pulmonary infection. Genes Immun. 2008 Sep;9(6):536-45
• All: 1 reference(s)