OMIA:000938-9615 : Spinal dysraphism in Canis lupus familiaris (dog) |
In other species: taurine cattle
Categories: Skeleton phene (incl. short stature & teeth) , Nervous system phene , Embryo phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 603245 (gene)
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: 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
Inheritance: In Weimaraner dogs the condition has an autosomal recessive mode of inheritance. Sporadic forms that may not be heritable have been reported in many other breeds.
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."
Breeds:
Alaskan Malamute (Dog) (VBO_0200017),
Chihuahua (Dog) (VBO_0200338),
Collie (Dog) (VBO_0200375),
Dalmatian (Dog) (VBO_0200427),
English Bulldog (Dog) (VBO_0200485),
German Shepherd Dog (Dog) (VBO_0200577),
Golden Retriever (Dog) (VBO_0200610),
Irish Setter (Dog) (VBO_0200702),
Pekingese (Dog) (VBO_0200994),
Poodle, Toy (Dog) (VBO_0201061),
Rottweiler (Dog) (VBO_0201143),
Samoyed (Dog) (VBO_0201174),
Weimaraner (Dog) (VBO_0201401),
West Highland White Terrier (Dog) (VBO_0201415).
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:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| NKX2-8 | NK2 homeobox 8 | Canis lupus familiaris | 8 | NC_051812.1 (15263403..15261532) | NKX2-8 | Homologene, Ensembl , NCBI gene |
Variants
By default, variants are sorted chronologically by year of publication, to provide a historical perspective.
Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending
order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column
headers.
WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 622 | Weimaraner (Dog) | Spinal dysraphism | NKX2-8 | delins, small (<=20) | Naturally occurring variant | CanFam3.1 | 8 | g.15149895delinsAA | c.449delinsTT | p.(A150Vfs*6) | XM_847109.4; XP_852202.1 | 2013 | 23874236 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000938-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2017 | De Rycke, L., Saunders, J.H. : |
| Congenital anomalies of the vertebrae in dogs. Vlaams Diergeneeskundig Tijdschrift 86:105-118, 2017. DOI: 10.21825/vdt.v86i2.16296. | |
| 2016 | Song, R.B., Glass, E.N., Kent, M. : |
| Spina bifida, meningomyelocele, and meningocele. Vet Clin North Am Small Anim Pract 46:327-45, 2016. Pubmed reference: 26725976. DOI: 10.1016/j.cvsm.2015.10.007. | |
| 2013 | Safra, N., Bassuk, A.G., Ferguson, P.J., Aguilar, M., Coulson, R.L., Thomas, N., Hitchens, P.L., Dickinson, P.J., Vernau, K.M., Wolf, Z.T., Bannasch, D.L. : |
| Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans. PLoS Genet 9:e1003646, 2013. Pubmed reference: 23874236. DOI: 10.1371/journal.pgen.1003646. | |
| 2012 | Allett, B., Broome, M.R., Hager, D. : |
| MRI of a split cord malformation in a German shepherd dog. J Am Anim Hosp Assoc 48:344-51, 2012. Pubmed reference: 22843830. DOI: 10.5326/JAAHA-MS-5780. | |
| Gómez, M., Mieres, M., Gutiérrez, J.C., Jones, J.C. : | |
| CT myelography characteristics of spinal dysraphism in a young mixed breed dog. Arch. med. Vet 44:191–194, 2012. DOI: 10.4067/S0301-732X2012000200014. | |
| 1995 | Ruberte, J., Añor, S., Carretero, A., Vilafranca, M., Navarro, M., Mascort, J., Pumarola, M. : |
| Malformations of the vertebral bodies and the ribs associated to spinal dysraphism without spina bifida in a Pekingese dog. Zentralbl Veterinarmed A 42:307-13, 1995. Pubmed reference: 8578905. DOI: 10.1111/j.1439-0442.1995.tb00382.x. | |
| 1992 | Bailey, C.S., Morgan, J.P. : |
| Congenital spinal malformations. Vet Clin North Am Small Anim Pract 22:985-1015, 1992. Pubmed reference: 1641930. DOI: 10.1016/s0195-5616(92)50089-4. | |
| 1991 | Vandenbroek, A.H.M., Else, R.W., Abercromby, R., France, M. : |
| Spinal dysraphism in the Weimaraner Journal of Small Animal Practice 32:258-260, 1991. | |
| 1982 | Engel, H.N., Draper, D.D. : |
| Comparative prenatal development of the spinal cord in normal and dysraphic dogs: fetal stage. Am J Vet Res 43:1735-43, 1982. Pubmed reference: 6756222. | |
| Engel, H.N., Draper, D.D. : | |
| Comparative prenatal development of the spinal cord in normal and dysraphic dogs: embryonic stage. Am J Vet Res 43:1729-34, 1982. Pubmed reference: 6756221. | |
| 1979 | Wilson, J.W., Kurtz, H.J., Leipold, H.W., Lees, G.E. : |
| Spina bifida in the dog. Vet Pathol 16:165-79, 1979. Pubmed reference: 375559. DOI: 10.1177/030098587901600202. | |
| 1976 | Draper, D.D., Kluge, J.P., Millerw, J. : |
| Clinical and pathological aspects of spinal dysraphism in dogs. Thessaloniki 1:134-137, 1976. | |
| 1974 | Neufeld, J.L., Little, P.B. : |
| Spinal dysraphism in a Dalmatian dog. Can Vet J 15:335-6, 1974. Pubmed reference: 4434313. | |
| 1973 | Klaus, B. : |
| [Picture report. Spinal dysraphism in a German shepherd]. Berl Munch Tierarztl Wochenschr 86:95, 1973. Pubmed reference: 4732250. | |
| 1972 | Confer, A.W., Ward, B.C. : |
| Spinal dysraphism: a congenital myelodysplasia in the Weimaraner Journal of the American Veterinary Medical Association 160:1423-1426, 1972. Pubmed reference: 5023160. | |
| 1967 | Geib, L.W., Bistner, S.I. : |
| Spinal cord dysraphism in a dog. J Am Vet Med Assoc 150:618-20, 1967. Pubmed reference: 5339905. | |
| 1965 | Foster, S.J. : |
| A case of sternal dysraphism and two cases of suspected congenital diaphragmatic hernia in the dog. Vet Rec 77:1112-4, 1965. Pubmed reference: 5318050. DOI: 10.1136/vr.77.38.1112. | |
| McGrath, J.T. : | |
| Spinal dysraphism in the dog, with comments on syringomylia Pathologia Veterinaria 2:1-36 (Supplement), 1965. Pubmed reference: 5893238. |
Edit History
- Created by Frank Nicholas on 06 Sep 2005
- Changed by Frank Nicholas on 19 Aug 2013
- Changed by Imke Tammen2 on 12 Jun 2023
- Changed by Imke Tammen2 on 13 Jun 2024