Categories: Immune system phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2024

Species-specific name: Increased susceptibility to Mycobacterium avium complex infection

Inheritance: Mizukami et al. (2024): "Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait."

Mapping: Mizukami et al. (2024): "A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9." ... "There were 118 genes annotated in the ~ 2.5 Mb homozygous segment flanked by the heterozygous markers at positions 47,266,853 and 49,753,465, which we considered as a critical interval for the causal variant". The coordinates of the critical interval refer to the CanFam3.1 assembly.

Molecular basis: Mizukami et al. (2024): " Whole genome sequencing of 2 MAC-infected [Miniature Schnauzer] dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide β-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1."

Breed: Miniature Schnauzer (Dog) (VBO_0200896).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: