OMIA 001466-9615 : Exercise-induced collapse in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 602377 (gene) , 616346 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Species-specific symbol: EIC

Species-specific description: Exercise-induced collapse (EIC) is an inherited neuromuscular disorder characterized by exercise intolerance in otherwise healthy young adult dogs. Clinical signs are precipitated by strenuous exercise. A causative mutation in dynamin 1 has been identified in retriever breeds listed below, but not yet in Border Collies. [Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT in 2011; revised by FN 29 Oct 2020]

History: EIC was first identified in Labrador Retrievers (Taylor et al., 2008).

Inheritance: Exercise-induced callapse in Labrador retrievers is a Mendelian trait.

Norton et al. (2021) concluded that the disease in border collies (BCC) is a moderately- to highly-heritable complex polygenetic disease.

Mapping: A genome-wide scan with 459 microsatellites in six families of Labrador Retrievers mapped the disorder to 60.4Mb on CFA9 (Patterson et al., 2008)

Norton et al. (2021) aimed to "estimate the heritability (h2SNP) of BCC [Border Collie Collapse], define its underlying genetic architecture, and identify associated genomic loci using dense whole-genome single-nucleotide polymorphism (SNP) genotyping data. Genotype data were obtained for ~440,000 SNPs from 343 border collies (168 BCC cases and 175 controls). ... Genome-wide association analyses identified significantly associated loci on chromosomes 1, 6, 11, 20, and 28, which accounted for ~5% of the total BCC h2SNP."

Molecular basis: The causative mutation in Labrador retrievers, Chesapeake Bay retrievers and curly-coated retrievers is a G to T substitution in exon 6 that changes the amino acid codon from arginine to leucine (R256L) in a highly conserved region of DNM1 (Patterson et al., 2008).

Clinical features: Affected dogs have normal muscle mass, normal patellar reflexes before an episode of EIC, normal findings on muscle biopsy and are capable of moderate exertion without showing signs (Taylor et al., 2008, Patterson et al., 2008). Signs begin within 2 minutes after cessation of 5 to 15 minutes of strenuous exercise. Affected dogs develop a wobbly gait with hindlimb weakness and incoordination, wide based stance, and walking with crouched hind legs. Signs can progress to full body weakness, extensor rigidity, confusion, loss of consciousness, and rarely death. Episodes frequently last 5-10 minutes, often with complete recovery after 30 minutes. Loss of patellar reflexes persists after initial recovery.

Pathology: Dynamin 1 is a type of GTPase that facilitates continuous neurotransmission across synapses. At the presynaptic terminal membrane, it assists in release of membrane vesicles containing neurotransmitter, which is needed for continuous synaptic communication (Patterson et al 2008). During high intensity exercise, DNM1 activity is inadequate to maintain synaptic transmission, which causes reversible loss of motor function (Patterson et al., 2008).

Prevalence: In a population of 400 Labrador Retrievers from the Midwestern US, 37% were carriers and 3% were homozygous for the causative mutation. This suggests a high frequency of this mutation in Labrador Retrievers. Homozygous Labrador Retrievers have also been found in Europe, the Middle East, and Australia (Patterson et al., 2008).

Control: It is recommended that working dogs or those showing signs be tested, as well as relatives of affected dogs. Breeding of homozygous dogs should be avoided. Breeding of carriers to noncarriers will avoid production of affected dogs. [updated 29 Oct 2020, with thanks to Frank Coopman]

Genetic testing: A test is available to detect carriers and homozygotes (Patterson et al, 2008).

Breeds: Border Collie, Boykin Spaniel, Chesapeake Bay Retriever, Curly-coated retriever, Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DNM1 dynamin 1 Canis lupus familiaris 9 NC_051813.1 (56220232..56174435) DNM1 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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
39 Chesapeake Bay Retriever Curly-coated retriever Labrador Retriever Exercise-induced collapse DNM1 missense Naturally occurring variant CanFam3.1 9 g.55282762C>A c.767G>T p.(R256L) ROS_Cfam_1.0:g.56204742C>A ENSCAFT00845051951.1:c.767G>T ENSCAFP00845040760.1:p.Arg256Leu rs852832685 rs852832685 2008 18806795 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2021 Norton, E.M., Minor, K.M., Taylor, S.M., McCue, M.E., Mickelson, J.R. :
Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies. Genes (Basel) 12:1927, 2021. Pubmed reference: 34946876. DOI: 10.3390/genes12121927.
2019 Lewis, T.W., Mellersh, C.S. :
Changes in mutation frequency of eight Mendelian inherited disorders in eight pedigree dog populations following introduction of a commercial DNA test. PLoS One 14:e0209864, 2019. Pubmed reference: 30650096. DOI: 10.1371/journal.pone.0209864.
2016 Taylor, S., Shmon, C., Su, L., Epp, T., Minor, K., Mickelson, J., Patterson, E., Shelton, G.D. :
Evaluation of Dogs with Border Collie Collapse, Including Response to Two Standardized Strenuous Exercise Protocols. J Am Anim Hosp Assoc :, 2016. Pubmed reference: 27487345. DOI: 10.5326/JAAHA-MS-6361.
Taylor, S., Minor, K., Shmon, C.L., Shelton, G.D., Patterson, E.E., Mickelson, J.R. :
Border Collie Collapse: Owner Survey Results and Veterinary Description of Videotaped Episodes. J Am Anim Hosp Assoc :, 2016. Pubmed reference: 27685362. DOI: 10.5326/JAAHA-MS-6436.
2013 Broeckx, B.J., Coopman, F., Verhoeven, G.E., Van Haeringen, W., van de Goor, L., Bosmans, T., Gielen, I., Saunders, J.H., Soetaert, S.S., Van Bree, H., Van Neste, C., Van Nieuwerburgh, F., Van Ryssen, B., Verelst, E., Van Steendam, K., Deforce, D. :
The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany. PLoS One 8:e74811, 2013. Pubmed reference: 24069350. DOI: 10.1371/journal.pone.0074811.
Furrow, E., Minor, K.M., Taylor, S.M., Mickelson, J.R., Patterson, E.E. :
Relationship between dynamin 1 mutation status and characteristics of recurrent episodes of exercise-induced collapse in Labrador Retrievers. J Am Vet Med Assoc 242:786-91, 2013. Pubmed reference: 23445289. DOI: 10.2460/javma.242.6.786.
Motta, L., Dutton, E. :
Suspected exercise-induced seizures in a young dog. J Small Anim Pract 54:213-8, 2013. Pubmed reference: 23387942. DOI: 10.1111/jsap.12028.
2011 Minor, KM., Patterson, EE., Keating, MK., Gross, SD., Ekenstedt, KJ., Taylor, SM., Mickelson, JR. :
Presence and impact of the exercise-induced collapse associated DNM1 mutation in Labrador retrievers and other breeds. Vet J :, 2011. Pubmed reference: 21782486. DOI: 10.1016/j.tvjl.2011.06.022.
Owczarek-Lipska, M., Thomas, A., André, C., Hölzer, S., Leeb, T. :
[Frequency of gene defects in selected European retriever populations]. Schweiz Arch Tierheilkd 153:418-20, 2011. Pubmed reference: 21866517. DOI: 10.1024/0036-7281/a000236.
Takanosu, M., Mori, H., Suzuki, H., Suzuki, K. :
Genotyping of exercise-induced collapse in Labrador retrievers using an allele-specific PCR. Vet J :, 2011. Pubmed reference: 22104507. DOI: 10.1016/j.tvjl.2011.10.018.
2009 Taylor, SM., Shmon, CL., Adams, VJ., Mickelson, JR., Patterson, EN., Shelton, GD. :
Evaluations of labrador retrievers with exercise-induced collapse, including response to a standardized strenuous exercise protocol. J Am Anim Hosp Assoc 45:3-13, 2009. Pubmed reference: 19122058.
2008 Patterson, EE., Minor, KM., Tchernatynskaia, AV., Taylor, SM., Shelton, GD., Ekenstedt, KJ., Mickelson, JR. :
A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. Nat Genet 40:1235-9, 2008. Pubmed reference: 18806795. DOI: 10.1038/ng.224.
Taylor, SM., Shmon, CL., Shelton, GD., Patterson, EN., Minor, K., Mickelson, JR. :
Exercise-induced collapse of Labrador retrievers: survey results and preliminary investigation of heritability. J Am Anim Hosp Assoc 44:295-301, 2008. Pubmed reference: 18981194.
1999 Matwichuk, CL., Taylor, S., Shmon, CL., Kass, PH., Shelton, GD. :
Changes in rectal temperature and hematologic, biochemical, blood gas, and acid-base values in healthy Labrador Retrievers before and after strenuous exercise. Am J Vet Res 60:88-92, 1999. Pubmed reference: 9918153.

Edit History


  • Created by Frank Nicholas on 30 Oct 2008
  • Changed by Martha MaloneyHuss on 09 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 05 Aug 2016
  • Changed by Frank Nicholas on 29 Oct 2020
  • Changed by Imke Tammen2 on 12 Jan 2022