A canine BCAN microdeletion associated with episodic falling syndrome

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A canine BCAN microdeletion associated with episodic falling syndrome

Gill, JL; Tsai, KL; Krey, C; Noorai, RE; Vanbellinghen, JF; Garosi, LS; Shelton, GD; ... Harvey, RJ; + view all (2012) A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiology of Disease , 45 (1) 130 - 136. 10.1016/j.nbd.2011.07.014. Green open access

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	Excel Spreadsheet (Table 1 BCAN genotypes in CKCS cohorts and other dog breeds) table.csv Download (339B)
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	MS Word (Suppl. Table 1. Primer sequences for canine BCAN and HAPLN2 exon amplification) mmc1.doc Download (48kB)
	MS Word (Suppl. Table 2. Chromosome 7 single nucleotide polymorphisms associated with EFS) mmc2.doc Download (49kB)
	MS Word (Suppl. Table 3. Probes for MLPA) mmc3.doc Download (39kB)

Abstract

Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a genome-wide association strategy to map the EFS locus to a 3.48 Mb critical interval on canine chromosome 7. By prioritizing candidate genes on the basis of biological plausibility, we found that a 15.7 kb deletion in BCAN, encoding the brain-specific extracellular matrix proteoglycan brevican, is associated with EFS. This represents a compelling causal mutation for EFS, since brevican has an essential role in the formation of perineuronal nets governing synapse stability and nerve conduction velocity. Mapping of the deletion breakpoint enabled the development of Multiplex PCR and Multiplex Ligation-dependent Probe Amplification (MLPA) genotyping tests that can accurately distinguish normal, carrier and affected animals. Wider testing of a larger population of CKCS dogs without a history of EFS from the USA revealed that carriers are extremely common (12.9%). The development of molecular genetic tests for the EFS microdeletion will allow the implementation of directed breeding programs aimed at minimizing the number of animals with EFS and enable confirmatory diagnosis and pharmacotherapy of affected dogs.

Type:	Article
Title:	A canine BCAN microdeletion associated with episodic falling syndrome
Location:	United States
Open access status:	An open access version is available from UCL Discovery
DOI:	10.1016/j.nbd.2011.07.014
Publisher version:	http://dx.doi.org/10.1016/j.nbd.2011.07.014
Language:	English
Additional information:	PMCID: PMC3898273 This an Elsevier Open Access article.
Keywords:	Animals, Breeding, Brevican, Dog Diseases, Dogs, Gene Deletion, Genome-Wide Association Study, Genotype, Muscle Hypertonia
UCL classification:	UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI:	https://discovery.ucl.ac.uk/id/eprint/1350217

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