OMIA 000527-9913 : Hypomyelinogenesis, congenital in Bos taurus

In other species: pig , sheep , dog

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; Progress 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".

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIF1C kinesin family member 1C Bos taurus 19 NC_037346.1 (26412297..26390125) KIF1C 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Charolais Progressive ataxia KIF1C missense UMD3.1 19 g.27041449C/T c.608G>A p.R203Q; p.RT203-204QStop Duchesne et al. (2018): "Using a combination of next generation sequencing and whole genome SNP analysis, we determined that in the majority of cases with this phenotype, the disease is caused by a single substitution, c.608G>A, in the KIF1C gene. 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." 2018 30067756

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.
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.

Edit History


  • Created by Frank Nicholas on 12 May 2010
  • Changed by Frank Nicholas on 17 Sep 2014
  • Changed by Frank Nicholas on 08 Aug 2018