OMIA 001592-9615 : Episodic falling in Canis lupus familiaris

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Mapping: By conducting a GWAS on 5 affected, one obligate carrier and 9 control Cavalier King Charles spaniels, each of which had been genotyped with the Affymetrix Canine SNP Array version 2 (yielding 58,873 informative SNPs for analysis), Gill et al. (2012) mapped this disorder to a 3.48Mb region on chromosome CFA7.

By conducting a GWAS on 31 affected and 38 control Cavalier King Charles Spaniels, each genotyped with the Illumina Canine HD SNP chip (yielding 91,427 SNPs for analysis), Forman et al. (2012) highlighted the same region on chromosome CFA7 as had been reported by Gill et al. (2012).

Molecular basis: By sequencing the most likely positional candidate gene in the candidate region they had identified (see Mapping section), Gill et al. (2012) reported that this disorder in Cavalier King Charles Spaniels is due to a 15.7kb deletion in the BCAN gene, which encodes brain-specific extracellular matrix proteoglycan brevican. By sequencing 5 affected dogs within their candidate region (see Mapping section), Forman et al. (2012) reported the same mutation.

Genetic testing: As explained on the web site of the Animal Health Trust (http://www.aht.org.uk/genetics_curleycoat.html), a DNA test for this disorder in Cavalier King Charles Spaniels was discovered by geneticists at the Trust in early 2011, and is available from the Trust. Their discovery was reported by Forman et al. (2012). As described under "Molecular basis", another research group independently discovered and published a causal mutation in 2012.

Breed: Cavalier King Charles Spaniel.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
BCAN brevican Canis lupus familiaris 7 NC_006589.3 (41330178..41313578) BCAN 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
Cavalier King Charles Spaniel Episodic falling BCAN deletion, gross (>20) a 15.7kb deletion in the BCAN gene 2012 21821125

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.
2012 Forman, O.P., Penderis, J., Hartley, C., Hayward, L.J., Ricketts, S.L., Mellersh, C.S. :
Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83H Associated with Discrete Inherited Disorders in a Domestic Dog Breed. PLoS Genet 8:e1002462, 2012. Pubmed reference: 22253609. DOI: 10.1371/journal.pgen.1002462.
Gill, J.L., Tsai, K.L., Krey, C., Noorai, R.E., Vanbellinghen, J.F., Garosi, L.S., Shelton, G.D., Clark, L.A., Harvey, R.J. :
A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiol Dis 45:130-6, 2012. Pubmed reference: 21821125. DOI: 10.1016/j.nbd.2011.07.014.
1983 Herrtage, ME., Palmer, AC. :
Episodic falling in the cavalier King Charles spaniel. Vet Rec 112:458-9, 1983. Pubmed reference: 6868317.

Edit History


  • Created by Frank Nicholas on 01 Aug 2011
  • Changed by Frank Nicholas on 18 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
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  • Changed by Frank Nicholas on 13 Jul 2017