Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  17
• Reference
  J:276523 Wiltshire SA, et al., Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis. Genes Immun. 2015 Jun;16(4):261-7
• ID
  MGI:6330771

Genes

Gene	Assay Type
Cihvtq1	visible phenotype

Notes

• Experiment
  The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. The authors used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis.
  
  Inbred C57BL/6J, C57BL/10J, and A/J mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). The set of 36 AcB/BcA RC strains, derived from A/J and C57BL/6J parents, were generated according to a previously described breeding scheme and genotyping protocol.
  
  Twenty-five AcB/BcA recombinant congenic mouse strains were screened. One, BcA86/Pgrs, was found to be particularly susceptible to early mortality; 100% of BcA86/Pgrs mice died by day 6 compared with 0% of B6 mice (P = 0.0012). This increased mortality was accompanied by an increased hepatic necrosis as measured by serum alanine aminotransferase (ALT) levels (19547 +/- 10556 vs 769 +/- 109, P = 0.0055). This occurred despite a predominantly resistant (C57BL/6J) genetic background.
  
  Most single-nucleotides polymorphic between C57BL/10J and C57BL/6J for use in the generation of a panel capable of distinguishing between C57BL/10J and BcA86/Pgrs were identified by using the JAX Diversity Array (Jackson Laboratory). In this panel, 7499 single-nucleotides were polymorphic between C57BL/6J and C57BL/10J, though these tended to be clustered and gaps remained. These gaps in the genetic map were filled in by comparing the genotype of C57BL/6J against all other C57BL strains available in all datasets contained within the Mouse Phenome Database. When the C57BL/6J genotype was divergent, C57BL/6J and C57BL/10J were genotyped by Sanger sequencing to confirm the private C57BL/6J single-nucleotide polypeptide. Finally, the map was completed with microsatellites identified by us previously, and in collaboration with others for a total of 106 markers that are informative between BcA86/Pgrs and C57BL/10J.
  
  Linkage analysis was performed with the package R/qtl version 3.02.
  Analysis of Serum ALT, liver and heart viral titre F2 phenotypes in a cohort (n = 210) of (BcA86/Pgrs x C57BL/10J)F2 animals revealed two new loci related to viral infection:
  
  QTL Cisaq1 (coxsackieviral infection serum ALT QTL 1) maps to Chr13: 86 - 120 Mb with a peak LOD score of 4.50 at 101.2 Mb (rs3702296) (P = 0.003). This locus controlled serum ALT levels as early as 48 h following the infection, led to an elevated expression of type I interferon, and explained 9.4% of the phenotypic variance.
  
  QTL Cihvtq1 (coxsackieviral infection heart viral titre QTL 1) maps to Chr17: 49.7 - 69.7 Mb with a peak LOD score of 3.4 at 57.2 Mb (P = 0.046)
  
  Allele effect plots indicated that the BcA86/Pgrs genotype conferred susceptibility at both Cisaq1 and Cihvtq1.