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Char9C57BL/6J
QTL Variant Detail
Nomenclature
QTL variant: Char9C57BL/6J
Name: P. chabaudi malaria resistance QTL 9; C57BL/6J
MGI ID: MGI:3714005
QTL: Char9  Location: unknown  Genetic Position: Chr10, Syntenic
Variant
origin
Strain of Specimen:  C57BL/6J
Variant
description
Allele Type:    QTL
Mutation:    Undefined
    This allele confers resistance to Plasmodium chabaudi infection compared to A/J. (J:122131)
Inheritance:    Codominant
Phenotypes
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View phenotypes and curated references for all genotypes (concatenated display).
Notes
Char9 has a stronger effect in males compared to females.

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

J:122131

Recombinant congenic strain AcB55 is resistant to malaria and is derived from parental strains A/J (susceptible) and C57BL/6J (resistant). An F2 cross between AcB55 and A/J was analyzed for linkage to malaria resistance. PklrChar4 on mouse Chromosome 3controls 30% of the phenotypic variance. A suggestive locus near D10Mit189 (7 cM) on mouse Chromosome 10 was further analyzed while controlling for PklrChar4. This resulted in significant linkage to malaria resistance at 4 cM near D10Mit167 (LOD=4.57).This locus controls 8% of the variance and is designated Char9 (P. chabaudi malaria resistance QTL 9). C57BL/6J-derived alleles at Char9 confer codominant malaria resistance.

The Char9 locus spans 14 Mb and contains 77 genes. RT-PCR analysis of A/J andAcB55 mRNA revealed highly significant differential expression of Vnn3, with AcB55 expressing 12-fold more Vnn3 mRNA compared to A/J (p<0.0001).

SNP analysis revealed a 4 Mb haplotype block conserved among 5 out of 6 known malaria-susceptible strains (SJL/J, C3H/HeJ, BALB/cJ, AKR/J, and A/J). Vnn3 maps to this haplotype block and displays 100% correlation between genotype and transcript expression level. The A/J-derived Vnn3 transcript carries a C1592T nucleotide substitution resulting in premature stop codon and 7 amino acid truncation.

In addition, Vnn3 and Vnn1, a similar gene 30 Kb downstream from Vnn3, are present in liver mRNA from C57BL/6 and AcB55 resistant strains but are absent in liver mRNA from susceptible A/J and AcB61 strains. Analysis of the Vnn3 putative proximal promoter region revealed the A/J sequence contains complex rearrangements that could possibly explain the lack of transcriptional activity in this strain.

References
Original:  J:122131 Min-Oo G, et al., Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus. J Exp Med. 2007 Mar 19;204(3):511-24
All:  1 reference(s)

Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/16/2021
MGI 6.16
The Jackson Laboratory