In other species: taurine cattle

Categories: Embryo phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 603245 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: A heterogeneous group of congenital spinal anomalies that result from defective closure of the neural tube early in fetal life. [HP:0010301]; Neural tube defect (NTD), also called spinal cord dysraphism

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."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Dalmatian, German Shepherd Dog, Pekingese, Toy Poodle, Weimaraner.
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: