OMIA 001893-9615 : Upper airway syndrome in Canis lupus familiaris

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: [Brachycephalic Obstructive Airway Syndrome

Species-specific symbol: BOAS

Mapping: By conducting a GWAS on 401 Norwich Terrier dogs, each genotyped with the CanineHD bead chip (yielding 105,130 informative SNPs), Marchant et al. (2019) mapped this disorder to a ~2.9Mb region "58,941,974–61,830,084 bp on canine chromosome (CFA) 13". Subsequent fine-mapping revealed a "413 kb haplotype spanning chr13:61,166,179–61,579,985 that is shared among most severely affected Norwich Terriers".

Molecular basis: Whole-genome sequencing within the fine-mapped region (see Mapping section) led Marchant et al. (2019) "to the discovery of a c.2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3)" as a likely causal variant.

Prevalence: Marchant et al. (2019): "Over 1,300 dogs representing up to 114 diverse breeds including representatives of brachycephalic breeds diagnosed with BOAS [Brachycephalic Obstructive Airway Syndrome] were screened for the c.2789G>A variant . . . . The disease allele frequency (AF) was observed in the Norwich Terrier (AF = 0.57, n = 401), Bulldog (AF = 0.85, n = 41), French Bulldog (AF = 0.12, n = 23), Staffordshire Bull Terrier (AF = 0.125, n = 8), German Spitz (Mittel) (AF = 0.06, n = 8) and Pomeranian (AF = 0.06, n = 8) suggesting the variant may influence BOAS in the French and English Bulldogs."

Breed: Norwich Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3 Canis lupus familiaris 13 NC_006595.3 (61539545..61278193) ADAMTS3 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
Norwich Terrier Upper airway syndrome ADAMTS3 missense CanFam 3.1 13 g.61,287,796G>A c.2786G>A p.(Arg929His) 2019 31095560

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.
2019 Marchant, T.W., Dietschi, E., Rytz, U., Schawalder, P., Jagannathan, V., Hadji Rasouliha, S., Gurtner, C., Waldvogel, A.S., Harrington, R.S., Drögemüller, M., Kidd, J., Ostrander, E.A., Warr, A., Watson, M., Argyle, D., Ter Haar, G., Clements, D.N., Leeb, T., Schoenebeck, J.J. :
An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome. PLoS Genet 15:e1008102, 2019. Pubmed reference: 31095560. DOI: 10.1371/journal.pgen.1008102.
2013 Johnson, L.R., Mayhew, P.D., Steffey, M.A., Hunt, G.B., Carr, A.H., McKiernan, B.C. :
Upper Airway Obstruction in Norwich Terriers: 16 Cases. J Vet Intern Med :, 2013. Pubmed reference: 24112556. DOI: 10.1111/jvim.12206.

Edit History


  • Created by Frank Nicholas on 26 Nov 2013
  • Changed by Frank Nicholas on 28 May 2019
  • Changed by Frank Nicholas on 03 Jun 2019