In other species: cattle

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Mapping: In a GWAS on just 4 unrelated affected Weimaraners and 96 controls from the same breed were each genotyped with the Illumina 170K CanineHD BeadChip (yielding 114,775 informative SNPs for analysis), Safra et al. (2013) used GWAS to identified a 1.5Mb candidate region on chromosome CFA8 that includes 18 genes.

Molecular basis: By sequencing the most likely of the genes (based on clinical signs in mice that are mutant for this gene) in the candidate region on CFA8, namely NKX2-8, Safra et al. (2013) identified a causal mutation as "a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein" (p.A150VfsX1). Importantly, Safra et al. (2013) then sequenced the "exons of NKX2-8 . . . in human patients with spina bifida and rare variants (rs61755040 and rs10135525) were found to be significantly over-represented (p = 0.036). This is the first documentation of a potential role for NKX2-8 in the etiology of [human] NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs."

Breed: Weimaraner.

Associated gene: