Test Detail

Multi-disease genetic panel for bulldog breeds (Old English Bulldog, Continental Bulldog, French Bulldog and English Bulldog, according to the laboratory's price list) grouping five molecular tests: type I-A cystinuria (SLC3A1 haplotype), hyperuricosuria (HUU, SLC2A9), degenerative myelopathy (DM, SOD1 exon 2 variant), canine multifocal retinopathy 1 (CMR1, BEST1) and the DVL2 variant associated with screw tail and caudal vertebral anomalies (Robinow-like phenotype of the Bulldog). The panel is complementary to, not a substitute for, the urological, ophthalmological and orthopaedic examination in breeding selection.

Applicable breeds: Old English Bulldog, Continental Bulldog, French Bulldog and English Bulldog (according to price list). Cystinuria: allele frequency 0.40 per variant in Danish English Bulldog (Fitzwilliams 2023); Spanish population data limited. HUU: documented in English Bulldog (OMIA:001033-9615), with no published evidence in French Bulldog or in Olde English Bulldogge/Continental Bulldog. DM: documented in French Bulldog (OMIA:000263-9615), not in English Bulldog. Olde English Bulldogge and Continental Bulldog do not appear in OMIA for any of the five variants, so their applicability in these breeds is not supported. CMR1: listed in OMIA:001444-9615 in mastiff-type breeds (American bulldog, Bullmastiff, Dogue de Bordeaux, English Bulldog, English Mastiff, Great Pyrenees, Cane Corso, Presa Canario, etc.); the French Bulldog does not appear in OMIA and there is no publication confirming cmr1 in that breed (limited data). DVL2: associated with screw tail in English/French Bulldog, Dogue de Bordeaux and other brachycephalic breeds, with high allele frequency in these breeds (Mansour 2018). There are no reliable carrier frequencies in the breeding population.

- Genotype breeding animals with the panel before mating\n- Cystinuria: do not cross two carriers/homozygotes; with a high allele frequency, use the test as a guide for prophylaxis and diversity, not for mass culling; remember that type I-A is not androgen-dependent (castration does not resolve it, unlike type III)\n- HUU, DM and CMR1 (recessive): do not cross two carriers (25 % of affected homozygotes); carrier x free is admissible if the offspring intended for breeding is tested\n- DVL2 (recessive, OMIA): consider not crossing two carriers; the DVL2 test does not explain all hemivertebrae in the breed\n- In HUU/cystinuria homozygotes: high hydration, pH and crystalluria control, and monitoring for obstruction (especially in males)\n- Confirm the breed of the animal before interpreting the panel: CMR1 is documented in English Bulldog and mastiff-type breeds (not in French Bulldog), HUU in English Bulldog and DM in French Bulldog; there is no published evidence for Olde English Bulldogge or Continental Bulldog\n- After a confirmed clinical case, do not repeat the parental mating

Bulldog urolithiasis can be cystine or urate (and also oxalate): stone analysis is key and metabolic screening (nitroprusside, urinary amino acids) detects cystinuria before the clinical picture. CMR1 is confirmed by ophthalmoscopy and molecular test; cmr1 (BEST1 c.73C>T) must be distinguished from cmr2/cmr3 (other BEST1 variants). The DVL2 phenotype (screw tail and caudal vertebral anomalies) must be differentiated from other causes of hemivertebrae and spinal dysraphism in the breed; the test does not explain all hemivertebrae. DM is a diagnosis of exclusion (rule out spinal compression and disc herniation).

1. Cistinuria tipo I-A: Harnevik L et al. 2006. SLC7A9 cDNA cloning and mutational analysis of SLC3A1 and SLC7A9 in canine cystinuria. Mamm Genome. PMID: 16845473; Ruggerone B et al. 2016. Genetic evaluation of English bulldogs with cystine uroliths. Vet Rec. PMID: 27388977; Fitzwilliams T et al. 2023. Evaluation of the value of genetic testing for cystinuria in the Danish population of English bulldogs. Anim Genet. PMID: 36971195; Brons AK et al. 2013. SLC3A1 and SLC7A9 mutations in autosomal recessive or dominant canine cystinuria. J Vet Intern Med. PMID: 24001348; OMIA:000256-9615
2. HUU (SLC2A9): Bannasch D et al. 2008. Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet. PMID: 18989453; Karmi N et al. 2010. Validation of a urine test. Am J Vet Res. PMID: 20673090; OMIA:001033-9615
3. DM (SOD1): Awano T et al. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy. Proc Natl Acad Sci U S A. PMID: 19188595; Coates JR et al. 2010. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. PMID: 20732599; OMIA:000263-9615
4. CMR1 (BEST1): Guziewicz KE et al. 2007. Bestrophin gene mutations cause canine multifocal retinopathy. Invest Ophthalmol Vis Sci. PMID: 17460247; Gornik KR et al. 2014. Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel. Vet Ophthalmol. PMID: 23998685; Grahn BH et al. 1998. Multifocal retinopathy of Great Pyrenees dogs. Vet Ophthalmol. PMID: 11397233; OMIA:001444-9615; OMIA:001553-9615; OMIA:001554-9615
5. DVL2 (cola en tornillo): Mansour TA et al. 2018. Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2. PLoS Genet. PMID: 30521570; Niskanen JE et al. 2021. Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies. Hum Genet. PMID: 33599851; OMIA:002186-9615