OMIA:000527-9913 : Hypomyelinogenesis, congenital in Bos taurus (taurine cattle)
Categories: Nervous system phene
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: 2018
Cross-species summary: Congenital deficiency of myelin, especially in the cerebellum and brainstem; includes failure of formation of myelin, plus incomplete and delayed myelination of axons. Clinical signs include inability to rise, and severe muscle tremor with periods of spasticity. Also known as oligodendroglial dysplasia.
Species-specific name: Charolais ataxia; Progressive ataxia of Charolais
Inheritance: From the published literature, Duchesne and Eggen (2005) concluded that this disorder is "probably autosomal and recessive".
Mapping: Noting that this disorder is similar to Long Evans Shanker (LES) rats, for which the causal gene is MBP (myelin basic protein), Duchesne and Eggen (2005) used Radiation-Hybrid mapping to identify 12 genes and 11 microsatellite markers in the region of chromosome BTA24 that (according to comparative rat-human-cattle mapping) was most likely to contain the bovine MBP gene. The purpose of this study was to provide markers in a likely location of the disorder locus.
Duchesne et al. (2018) reported that "Genotyping of 46 suspected cases was done using the Illumina bovine 50K SNP chip (including 8 cases confirmed by histopathological analysis) . . . , followed by homozygosity mapping and haplotype analysis identified a single homozygous interval on bovine chromosome 19 . . . shared by 41 animals. The minimal common interval was 681 kb long (chr19: 26848700–27529700), and contained more than 40 genes as predicted in the Ensembl database".
Molecular basis: By comparing whole-genome sequenced data (from 2 affecteds and one control) in the candidate region (see Mapping section), and filtering resultant candidate variants, Duchesne et al. (2018) narrowed the field down to "a single substitution in exon 5 of KIF1C (chr19:27041449 C/T). For easier comprehension and since KIF1C gene in cattle is on the reverse strand, the substitution will be referred as KIF1C G>A in order to match with the transcription sense". Subsequent testing for this variant in "143 Charolais animals, including 70 of the 71 cases suspected of progressive ataxia for which DNA was available" enabled Duchesne et al. (2018) to report that "most of the suspected ataxia cases (60/70) were homozygous for the KIF1C G>A substitution, including the histopathologically confirmed cases. The other 10 cases were either heterozygous for this mutation or WT, which indicates the possibility of other neurodegenerative syndromes in the Charolais breed, especially because the analysis of the genotypes in these cases was not concordant with the defined genetic interval".
Prevalence: Bischofberger et al. (2020) genotyped "88 Uckermärker cattle [a new (1993) Charolais-Fleckvieh composite breed from Germany], including 58 female and 30 male" for the Charolais c.608G>A variant, and reported "three homozygous and 15 heterozygous KIF1C mutant animals", giving the frequency of the c.608A variant as 0.12. It was not mentioned whether the homozygotes were affected with the disorder.
Charolais (Cattle) (VBO_0000177),
Uckermärker, Germany (Cattle) (VBO_0004643).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|KIF1C||kinesin family member 1C||Bos taurus||19||NC_037346.1 (26412273..26390125)||KIF1C||Homologene, Ensembl , NCBI gene|
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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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1005||Charolais (Cattle) Uckermärker, Germany (Cattle)||Progressive ataxia||KIF1C||missense||Naturally occurring variant||ARS-UCD1.2||19||g.26407668C>T||c.608G>A||p.(R203Q); p.(R203_T204delinsQ*)||ENSBTAT00000081136.1:c.608G>A ENSBTAP00000062635.1:p.Arg203Gln Duchesne et al. (2018): "This substitution has two effects: firstly, it modifies a conserved amino acid (p.R203Q). Secondly, it causes an alternative splicing event, resulting in exon 5 skipping in most of the transcripts (p.RT203-204QStop) associated with a drastic reduction of overall mRNA expression and leading to the absence of detectable KIF1C protein in brain extracts from affected cattle."||rs800926237||rs800926237||2018||30067756|
Cite this entry
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.
|2020||Bischofberger, F., Reinartz, S., Distl, O. :|
|Genotyping KIF1C (c.608G>A) mutant reveals a high prevalence of progressive ataxia in Uckermärker cattle. Anim Genet :, 2020. Pubmed reference: 32281115 . DOI: 10.1111/age.12935.|
|2018||Duchesne, A., Vaiman, A., Frah, M., Floriot, S., Legoueix-Rodriguez, S., Desmazières, A., Fritz, S., Beauvallet, C., Albaric, O., Venot, E., Bertaud, M., Saintilan, R., Guatteo, R., Esquerré, D., Branchu, J., Fleming, A., Brice, A., Darios, F., Vilotte, J.L., Stevanin, G., Boichard, D., El Hachimi, K.H. :|
|Progressive ataxia of Charolais cattle highlights a role of KIF1C in sustainable myelination. PLoS Genet 14:e1007550, 2018. Pubmed reference: 30067756 . DOI: 10.1371/journal.pgen.1007550.|
|2005||Duchesne, A., Eggen, A. :|
|Radiation hybrid mapping of genes and newly identified microsatellites in candidate regions for bovine arthrogryposis-palatoschisis and progressive ataxia based on comparative data from man, mouse and rat. J Anim Breed Genet 122 Suppl 1:28-35, 2005. Pubmed reference: 16130454 .|
|2004||Millar, M., Scholes, S., Morris, M. :|
|Progressive ataxia of Charolais cattle. Vet Rec 154:379, 2004. Pubmed reference: 15074334 .|
|2003||Hill, F.I. :|
|A triad of bovine inherited diseases (abstract). N Z Vet J 51:46, 2003. Pubmed reference: 16032297 .|
|2002||Hill, F.I., Julian, A.F., Roiri, J. :|
|Progressive ataxia' in a Charolais steer in New Zealand. N Z Vet J 50:166, 2002. Pubmed reference: 16032264 . DOI: 10.1080/00480169.2002.36304.|
|1998||Niskanen, R., Berg, A. L., Johanson, A. :|
|Progressiv ataxi hos charolaisboskap - en fallbeskrivning. [Progressive ataxia in Charolais cattle - a case report] Svensk Veterinartidning 50:693-696, 1998.|
|1991||Palmer, A.C., Jackson, P.G.G., Blakemore, W.F. :|
|A Primary Demyelinating Disorder of Young Cattle Neuropathology and Applied Neurobiology 17:457-467, 1991. Pubmed reference: 1800911 .|
|1988||Zicker, SC., Kasari, TR., Scruggs, DW., Read, WK., Edwards, JF. :|
|Progressive ataxia in a Charolais bull. J Am Vet Med Assoc 192:1590-2, 1988. Pubmed reference: 3410779 .|
|1986||Cordy, DR. :|
|Progressive ataxia of Charolais cattle--an oligodendroglial dysplasia. Vet Pathol 23:78-80, 1986. Pubmed reference: 2418576 .|
|Montgomery, D.L., Mayer, J.C. :|
|Progressive ataxia of Charolais cattle. Southwestern Veterinarian 37:247-250, 1986.|
|1982||Daniel, R.C.W., Kelly, W.R. :|
|Progressive ataxia in Charolais cattle Australian Veterinary Journal 58:32, 1982. Pubmed reference: 7082227 .|
|1977||Patton, CS. :|
|Progressive ataxia in Charolais cattle. Vet Pathol 14:535-7, 1977. Pubmed reference: 919246 .|
|1975||Palmer, A.C., Blakemore, W.F. :|
|Progressive ataxia of Charolais cattle Bovine Practitioner :84-85, 1975.|
|1974||Blakemore, W.F., Palmer, A.C., Barlow, R.M. :|
|Progressive ataxia of Charolais cattle associated with disordered myelin Acta Neuropathologia 29:127-139, 1974. Pubmed reference: 4446942 .|
|Ogden, A.L., Palmer, A.C., Blakemore, W.F. :|
|Progressive ataxia in Charolais cattle Veterinary Record 94:555 only, 1974. Pubmed reference: 4428597 .|
|1972||Palmer, A.C., Blakemore, W.F., Barlow, R.M., Fraser, J.A., Ogden, A.L. :|
|Progressive ataxia of Charolais cattle associated with a myelin disorder Veterinary Record 91:592-594, 1972. Pubmed reference: 4649036 .|
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