OMIA 001033-9615 : Urolithiasis in Canis lupus familiaris

In other species: kangaroo , Rhesus monkey , domestic ferret , domestic cat , horse , pig , llama , cattle , goat , sheep , short-tailed chinchilla

Possibly relevant human trait(s) and/or gene(s) (MIM number): 220150

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Cross-species summary: Formation of calculi ('stones') in the urinary tract, or the condition associated with the presence of such calculi.

Species-specific name: Hyperuricosuria and hyperuricemia

Species-specific symbol: huu

History: All Dalmations are homozygous for this mutation.

Mapping: Linkage mapping followed by positional cloning by Bannasch et al. (2008) localised this disorder to a 2.5Mb region on chromosome CFA3. Homozygosity mapping reduced the region to 333kb, containg just four genes.

By conducting a proof-of-principle across-breed GWAS on "10 total affected dogs from three breeds and 59 controls from 25 breeds", each genotyped with the Affymetrix Version 2 Custom Canine SNP (comprising 49,663 SNPs), Bannasch et al. (2010) confirmed the location of the causal gene on chromosome CFA3 first reported by Bannasch et al. (2008).

Molecular basis: Sequencing and expression analysis of one of the four positional candidate genes (see Mapping section) by Bannasch et al. (2008) identified the causal mutation as "a missense mutation (G616T;C188F)" in the SLC2A9 gene. All Dalmations are homozygous for this mutation.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC2A9 solute carrier family 2 (facilitated glucose transporter), member 9 Canis lupus familiaris 3 NC_006585.3 (69394304..69588462) SLC2A9 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
Dalmatian Urolithiasis SLC2A9 missense CanFam3.1 3 g.69456869G>T c.563G>T p.C188F 2008 18989453 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.
2015 Cosgrove, L., Hammond, G., Mclauchlan, G. :
Primary portal vein hypoplasia and SLC2A9 mutation associated with urate urolithiasis in a Spanish water dog. Can Vet J 56:1153-7, 2015. Pubmed reference: 26538670.
2013 Jacinto, A.M., Mellanby, R.J., Chandler, M., Bommer, N.X., Carruthers, H., Fairbanks, L.D., Gow, A.G. :
Urine concentrations of xanthine, hypoxanthine and uric acid in UK Cavalier King Charles spaniels. J Small Anim Pract 54:395-8, 2013. Pubmed reference: 23859747. DOI: 10.1111/jsap.12106.
Palma, D., Langston, C., Gisselman, K., McCue, J. :
Canine struvite urolithiasis. Compend Contin Educ Vet 35:E1; quiz E1, 2013. Pubmed reference: 23677867.
2012 Kaiser, J., Stĕpánková, K., Koř Istková, T., Sedo, O., Melnyk, G., Hartl, M., Paloušek, D., Kucera, J. :
Determination of the cause of selected canine urolith formation by advanced analytical methods. J Small Anim Pract 53:646-51, 2012. Pubmed reference: 23034064. DOI: 10.1111/j.1748-5827.2012.01292.x.
Roe, K., Pratt, A., Lulich, J., Osborne, C., Syme, H.M. :
Analysis of 14,008 uroliths from dogs in the UK over a 10-year period. J Small Anim Pract 53:634-40, 2012. Pubmed reference: 22957984. DOI: 10.1111/j.1748-5827.2012.01275.x.
2010 Bannasch, D., Young, A., Myers, J., Truvé, K., Dickinson, P., Gregg, J., Davis, R., Bongcam-Rudloff, E., Webster, M.T., Lindblad-Toh, K., Pedersen, N. :
Localization of canine brachycephaly using an across breed mapping approach. PLoS One 5:e9632, 2010. Pubmed reference: 20224736. DOI: 10.1371/journal.pone.0009632.
Karmi, N., Brown, EA., Hughes, SS., Mclaughlin, B., Mellersh, CS., Biourge, V., Bannasch, DL. :
Estimated frequency of the canine hyperuricosuria mutation in different dog breeds. J Vet Intern Med 24:1337-42, 2010. Pubmed reference: 21054540. DOI: 10.1111/j.1939-1676.2010.0631.x.
Karmi, N., Safra, N., Young, A., Bannasch, DL. :
Validation of a urine test and characterization of the putative genetic mutation for hyperuricosuria in Bulldogs and Black Russian Terriers. Am J Vet Res 71:909-14, 2010. Pubmed reference: 20673090. DOI: 10.2460/ajvr.71.8.909.
Speth, RC. :
Re: Inheritance of urinary calculi in the Dalmatian. J Vet Intern Med 24:1239-40; author reply 1241, 2010. Pubmed reference: 21054531. DOI: 10.1111/j.1939-1676.2010.0599.x.
Weiss, CH. :
The link between hyperuricosuria and urate urolithiasis. Am J Vet Res 71:1257; author reply 1257-8, 2010. Pubmed reference: 21034314. DOI: 10.2460/ajvr.71.11.1257.
Yoon, H.Y., Mann, F.A., Punke, J.P., Jeong, S.W. :
Bilateral ureteral ectopia with renal dysplasia and urolithiasis in a dog. J Am Anim Hosp Assoc 46:209-14, 2010. Pubmed reference: 20439946.
2009 Bannasch, D., Henthorn, PS. :
Changing paradigms in diagnosis of inherited defects associated with urolithiasis. Vet Clin North Am Small Anim Pract 39:111-25, 2009. Pubmed reference: 19038654. DOI: 10.1016/j.cvsm.2008.09.006.
Houston, DM., Moore, AE. :
Canine and feline urolithiasis: examination of over 50 000 urolith submissions to the Canadian veterinary urolith centre from 1998 to 2008. Can Vet J 50:1263-8, 2009. Pubmed reference: 20190975.
Osborne, C.A., Lulich, J.P., Kruger, J.M., Ulrich, L.K., Koehler, L.A. :
Analysis of 451,891 canine uroliths, feline uroliths, and feline urethral plugs from 1981 to 2007: perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract 39:183-97, 2009. Pubmed reference: 19038658. DOI: 10.1016/j.cvsm.2008.09.011.
2008 Bannasch, D., Safra, N., Young, A., Karmi, N., Schaible, RS., Ling, GV. :
Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet 4:e1000246, 2008. Pubmed reference: 18989453. DOI: 10.1371/journal.pgen.1000246.
2006 Safra, N., Schaible, RH., Bannasch, DL. :
Linkage analysis with an interbreed backcross maps Dalmatian hyperuricosuria to CFA03. Mamm Genome 17:340-5, 2006. Pubmed reference: 16596455. DOI: 10.1007/s00335-005-0137-5.
2005 Albasan, H., Lulich, JP., Osborne, CA., Lekcharoensuk, C. :
Evaluation of the association between sex and risk of forming urate uroliths in Dalmatians. J Am Vet Med Assoc 227:565-9, 2005. Pubmed reference: 16117063.
Safra, N., Ling, GV., Schaible, RH., Bannasch, DL. :
Exclusion of Urate Oxidase as a Candidate Gene for Hyperuricosuria in the Dalmatian Dog Using an Interbreed Backcross. J Hered :, 2005. Pubmed reference: 15958795. DOI: 10.1093/jhered/esi078.
Simkin, P.A. :
The Dalmatian defect: a hepatic endocrinopathy of urate transport. Arthritis Rheum 52:2257-62, 2005. Pubmed reference: 16052594. DOI: 10.1002/art.21241.
Snyder, DM., Steffey, MA., Mehler, SJ., Drobatz, KJ., Aronson, LR. :
Diagnosis and surgical management of ureteral calculi in dogs: 16 cases (1990-2003). N Z Vet J 53:19-25, 2005. Pubmed reference: 15731830. DOI: 10.1080/00480169.2005.36464.
Sosnar, M., Bulkova, T., Ruzicka, M. :
Epidemiology of canine urolithiasis in the Czech Republic from 1997 to 2002. J Small Anim Pract 46:177-84, 2005. Pubmed reference: 15835236.
2004 Bannasch, DL., Ling, GV., Bea, J., Famula, TR. :
Inheritance of urinary calculi in the Dalmatian. J Vet Intern Med 18:483-7, 2004. Pubmed reference: 15822555.
Bannasch, DL., Ryun, JR., Bannasch, MJ., Schaible, RH., Breen, M., Ling, G. :
Exclusion of galectin 9 as a candidate gene for hyperuricosuria in the Dalmatian dog. Anim Genet 35:326-8, 2004. Pubmed reference: 15265074. DOI: 10.1111/j.1365-2052.2004.01154.x.
Bende, B., Németh, T. :
High prevalence of urate urolithiosis in the Russian black terrier. Vet Rec 155:239-40, 2004. Pubmed reference: 15384507.
2003 Carvalho, M., Lulich, J.P., Osborne, C.A., Nakagawa, Y. :
Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: Dalmatian dog model Urology 62:566-70, 2003. Pubmed reference: 12946778.
2001 Bende, B., Dunay, M., Zsomboly, M. :
Cystine urolithiasis in dogs. Examination and treatment of a hereditary metabolic disorder and its consequences Magyar Allatorvosok Lapja 123:486-491, 2001.
2000 Lekcharoensuk, C., Lulich, J.P., Osborne, C.A., Pusoonthornthum, R., Allen, T.A., Koehler, L.A., Urlich, L.K., Carpenter, K.A., Swanson, L.L. :
Patient and environmental factors associated with calcium oxalate urolithiasis in dogs Journal of the American Veterinary Medical Association 217:515-519, 2000. Pubmed reference: 10953715.
1999 Bartges, J.W., Osborne, C.A., Lulich, J.P., Kruger, J.M., Sanderson, S.L., Koehler, L.A., Ulrich, L.K. :
Canine urate urolithiasis. Etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 29:161-91, xii-xiii, 1999. Pubmed reference: 10028157.
Feeney, D.A., Weichselbaum, R.C., Jessen, C.R., Osborne, C.A. :
Imaging canine urocystoliths. Detection and prediction of mineral content. Vet Clin North Am Small Anim Pract 29:59-72, x-xi, 1999. Pubmed reference: 10028152.
Franti, C.E., Ling, G.V., Ruby, A.L., Johnson, D.L. :
Urolithiasis in dogs - V: Regional comparisons of breed, age, sex, anatomic location, and mineral type of calculus American Journal of Veterinary Research 60:29-42, 1999. Pubmed reference: 9918145.
Hulsen, J. :
Urolithiasis in cats and dogs [Dutch] Tijdschrift voor Diergeneeskunde 124:351-+, 1999. Pubmed reference: 10372422.
Kruger, J.M., Osborne, C.A., Lulich, J.P. :
Canine calcium phosphate uroliths. Etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 29:141-59, xii, 1999. Pubmed reference: 10028156.
Leidinger, J. :
Urolith diagnosis in dogs and cats [German] Wiener Tierarztliche Monatsschrift 86:18-23, 1999.
Lulich, J.P., Osborne, C.A., Lekcharoensuk, C., Allen, T.A., Nakagawa, Y. :
Canine calcium oxalate urolithiasis. Case-based applications of therapeutic principles. Vet Clin North Am Small Anim Pract 29:123-39, 1999. Pubmed reference: 10028155.
Lulich, J.P., Osborne, C.A., Thumchai, R., Lekcharoensuk, C., Ulrich, L.K., Koehler, L.A., Bird, K.A., Swanson, L.L., Nakagawa, Y. :
Epidemiology of canine calcium oxalate uroliths. Identifying risk factors. Vet Clin North Am Small Anim Pract 29:113-22, xi, 1999. Pubmed reference: 10028154.
Osborne, C.A. :
Medical dissolution and prevention of canine uroliths. Seven steps from science to service. Vet Clin North Am Small Anim Pract 29:1-15, ix, 1999. Pubmed reference: 10028148.
Osborne, C.A., Jacob, F., Lulich, J.P., Hansen, M.J., Lekcharoensul, C., Ulrich, L.K., Koehler, L.A., Bird, K.A., Swanson, L.L. :
Canine silica urolithiasis. Risk factors, detection, treatment, and prevention. Vet Clin North Am Small Anim Pract 29:213-30, xiii, 1999. Pubmed reference: 10028159.
Osborne, C.A., Lulich, J.P. :
Risk and protective factors for urolithiasis. What do they mean? Vet Clin North Am Small Anim Pract 29:39-43, x, 1999. Pubmed reference: 10028150.
Osborne, C.A., Lulich, J.P., Bartges, J.W. :
The rocket science of canine urolithiasis - Preface Veterinary Clinics of North America - Small Animal Practice 29:XVII-XVIII, 1999.
Osborne, C.A., Lulich, J.P., Bartges, J.W., Ulrich, L.K., Koehler, L.A., Bird, K.A., Swanson, L.L., Austin, G.W., Prien, E.L., Steinam, K.U. :
Drug-induced urolithiasis. Vet Clin North Am Small Anim Pract 29:251-66, xiv, 1999. Pubmed reference: 10028161.
Osborne, C.A., Lulich, J.P., Polzin, D.J. :
Canine retrograde urohydropropulsion. Lessons from 25 years of experience. Vet Clin North Am Small Anim Pract 29:267-81, xiv, 1999. Pubmed reference: 10028162.
Osborne, C.A., Lulich, J.P., Polzin, D.J., Allen, T.A., Kruger, J.M., Bartges, J.W., Koehler, L.A., Ulrich, L.K., Bird, K.A., Swanson, L.L. :
Medical dissolution and prevention of canine struvite urolithiasis. Twenty years of experience. Vet Clin North Am Small Anim Pract 29:73-111, xi, 1999. Pubmed reference: 10028153.
Osborne, C.A., Lulich, J.P., Polzin, D.J., Sanderson, S.L., Koehler, L.A., Ulrich, L.K., Bird, K.A., Swanson, L.L., Pederson, L.A., Sudo, S.Z. :
Analysis of 77,000 canine uroliths - Perspectives from the Minnesota Urolith Center Veterinary Clinics of North America - Small Animal Practice 29:17-, 1999.
Osborne, C.A., Sanderson, S.L., Lulich, J.P., Bartges, J.W., Ulrich, L.K., Koehler, L.A., Bird, K.A., Swanson, L.L. :
Canine cystine urolithiasis. Cause, detection, treatment, and prevention. Vet Clin North Am Small Anim Pract 29:193-211, xiii, 1999. Pubmed reference: 10028158.
Schafer, S., Remtisch, C., Iben, C. :
Urolithiasis in a bitch during pregnancy [German] Wiener Tierarztliche Monatsschrift 86:281-285, 1999.
1998 Hess, R.S., Kass, P.H., Ward, C.R. :
Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis Journal of the American Veterinary Medical Association 212:1889 ff., 1998.
Jones, B.R., Kirkman, J.H., Hogan, J., Holmes, S. :
Analysis of uroliths from cats and dogs in New Zealand, 1993-96 New Zealand Veterinary Journal 46:233-236, 1998.
Ling, G.V., Franti, C.E., Johnson, D.L., Ruby, A.L. :
Urolithiasis in dogs iv - survey of interrelations among breed, mineral composition, and anatomic location of calculi, and presence of urinary tract infection American Journal of Veterinary Research 59:650-660, 1998. Pubmed reference: 9582971.
Ling, G.V., Franti, C.E., Johnson, D.L., Ruby, A.L. :
Urolithiasis in dogs iii - prevalence of urinary tract infection and interrelations of infection, age, sex, and mineral composition American Journal of Veterinary Research 59:643-649, 1998. Pubmed reference: 9582970.
Ling, G.V., Franti, C.E., Ruby, A.L., Johnson, D.L. :
Urolithiasis in dogs ii - breed prevalence, and interrelations of breed, sex, age, and mineral composition American Journal of Veterinary Research 59:630-642, 1998. Pubmed reference: 9582969.
Ling, G.V., Franti, C.E., Ruby, A.L., Johnson, D.L., Thurmond, M. :
Urolithiasis in dogs i - mineral prevalence and interrelations of mineral composition, age, and sex American Journal of Veterinary Research 59:624-629, 1998. Pubmed reference: 9582968.
1993 Case, L.C., Ling, G.V., Ruby, A.L., Johnson, D.L., Franti, C.E., Stevens, F. :
Urolithiasis in Dalmatians - 275 Cases (1981-1990) Journal of the American Veterinary Medical Association 203:96-100, 1993. Pubmed reference: 8407468.
Sorenson, J.L., Ling, G.V. :
Diagnosis, Prevention, and Treatment of Urate Urolithiasis in Dalmatians Journal of the American Veterinary Medical Association 203:863-869, 1993. Pubmed reference: 8226243.
Sorenson, J.L., Ling, G.V. :
Metabolic and Genetic Aspects of Urate Urolithiasis in Dalmatians Journal of the American Veterinary Medical Association 203:857-862, 1993. Pubmed reference: 8226242.
1986 Schaible, R.H. :
Genetic predisposition to purine uroliths in Dalmatian dogs. Vet Clin North Am Small Anim Pract 16:127-31, 1986. Pubmed reference: 3486508.
1971 Yu, T.F. :
Low uricase activity in the Dalmatian dog simulated in mongrels given uronic acid American Journal of Physiology 220:973-979, 1971. Pubmed reference: 5551153.
1955 Brodey, R.S. :
Canine urolithiasis: a survey and discussion of 52 clinical cases Journal of the American Veterinary Medical Association 126:1-9, 1955. Pubmed reference: 13221500.
1948 Friedman, M., Byers, S.O. :
Observations concerning the causes of the excess excretion of uric acid in the Dalmatian dog Journal of Biological Chemistry 175:727-735, 1948.
1938 Trimble, H.C., Keeler, C.E. :
The inheritance of "high uric acid excretion" in dogs Journal of Heredity 29:281-189, 1938.

Edit History


  • Created by Frank Nicholas on 02 Nov 2010
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 May 2013