Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

Henthorn, Paula S.; Liu, Junlong; Gidalevich, Tanya; Fang, Jun; Casal, Margret L.; Patterson, Donald F.; Giger, Urs

doi:10.1007/s004390000392

Cited by 52 publications

(12 citation statements)

References 38 publications

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“…Neither the mutation found to cause cystinuria in the Newfoundlands, 18 nor the formerly described amino acid polymorphisms in exon 6 (I192V) and 10 (S698G) of SLC3A1 and exon 5 (A217T) of SLC7A9 in English Bulldogs were observed in any of the dogs studied here. 22 The sequence differences resulting in cystinuria are detailed below for each breed studied.…”

Section: Resultscontrasting

confidence: 65%

“…17 Among all the cystinuric dogs to date, only 1 mutation in SLC3A1, an early stop codon precluding the production of the rBAT protein, and leading to the loss of b 0,+ function, was identified in cystinuric Newfoundlands in 2000. 18 And although the disease was widely recognized in the breed, screening programs for the mutation have markedly decreased the incidence of cystinuria in Newfoundlands and Landseers worldwide.…”

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confidence: 99%

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SLC3A1andSLC7A9Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System

Brons

Henthorn

Raj

et al. 2013

Veterinary Internal Medicne

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Background Cystinuria, one of the first recognized inborn errors of metabolism, has been reported in many dog breeds. Hypothesis/Objectives To determine urinary cystine concentrations, inheritance and mutations in the SLC3A1 and SLC7A9 genes associated with cystinuria in 3 breeds. Animals Mixed and purebred Labrador Retrievers (n=6), Australian Cattle Dogs (6), Miniature Pinschers (4) and 1 mixed breed dog with cystine urolithiasis, relatives and control dogs. Methods Urinary cystinuria and aminoaciduria was assessed and exons of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA. Results In each breed, male and female dogs, independent of neuter status, were found to form calculi. A frameshift mutation in SLC3A1 (c.350delG) resulting in a premature stop codon was identified in autosomal-recessive (AR) cystinuria in Labrador Retrievers and mixed breed dogs. A 6 bp deletion (c.1095_1100del) removing 2 threonines in SLC3A1 was found in autosomal-dominant (AD) cystinuria with a more severe phenotype in homozygous than in heterozygous Australian Cattle Dogs. A missense mutation in SLC7A9 (c.964G>A) was discovered in AD cystinuria in Miniature Pinschers with only heterozygous affected dogs observed to date. Breed specific DNA tests were developed, but the prevalence of each mutation remains unknown. Conclusions and clinical importance These studies describe the first AD inheritance and the first putative SLC7A9 mutation to cause cystinuria in dogs and expand our understanding of this phenotypically and genetically heterogeneous disease, leading to a new classification system for canine cystinuria and better therapeutic management and genetic control in these breeds.

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Section: Resultscontrasting

confidence: 65%

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confidence: 99%

SLC3A1andSLC7A9Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System

Brons

Henthorn

Raj

et al. 2013

Veterinary Internal Medicne

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“…Indeed, the canine DLA locus appears to be associated with several diseases, including early-onset systemic lupus erythematosus (SLE), as seen in the Nova Scotia duck tolling retriever, which is associated with variant alleles in DLA class II genes (163). By way of a final example, mutations in the SLC3A1 gene cause type 1 cystinuria in humans and a similarly severe form of the disease in the Newfoundland (60). …”

Section: Canine Disease Mapping Informs Human Diseasementioning

confidence: 99%

Man's Best Friend Becomes Biology's Best in Show: Genome Analyses in the Domestic Dog

2010

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In the last five years, canine genetics has gone from map construction to complex disease deconstruction. The availability of a draft canine genome sequence, dense marker chips, and an understanding of the genome architecture has changed the types of studies canine geneticists can undertake. There is now a clear recognition that the dog system offers the opportunity to understand the genetics of both simple and complex traits, including those associated with morphology, disease susceptibility, and behavior. In this review, we summarize recent findings regarding canine domestication and review new information on the organization of the canine genome. We discuss studies aimed at finding genes controlling morphological phenotypes and provide examples of the way such paradigms may be applied to studies of behavior. We also discuss the many ways in which the dog has illuminated our understanding of human disease and conclude with a discussion on where the field is likely headed in the next five years.

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“…Cystinuria was one of the first “inborn errors of metabolism” in humans coined by Sir Archibald Garrod (6) and has since been described in many other species such as dogs (2, 8, 10) cats (4, 24, 25, 34), maned wolves (3), a caracal lynx (39), servals (8), ferrets (29), and mice (37). The impaired renal reabsorption of the amino acids cystine, ornithine, lysine and arginine, combined known as COLA (normally >98%), results in increased urinary concentrations of these amino acids.…”

Section: Introductionmentioning

confidence: 99%

Cystinurie aufgrund einer SLC7A9-Missense-Mutation bei Siammischlingskatzen eines Wurfs in Deutschland

Hilton¹,

Mizukami²,

Giger³

2017

Tierarztl Prax Ausg K

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Summary Cystinuria is caused by defective proximal renal tubular reabsorption of the amino acids cystine, ornithine, lysine and arginine (COLA). The low solubility of cystine in mildly acidic urine may lead to the formation of urinary cystine crystals and uroliths. Much progress has been made recently in the diagnosis and understanding of cystinuria in companion animals. In cats, cystinuria affects equally both genders independent of neutering status and, despite being rare, already more cystinuria-causing mutations have been detected in cats compared to dogs. In this study a litter of Siamese-crossbred cats in Germany was assessed clinically for cystinuria and screened for mutations known to cause cystinuria in cats. An adult male castrated cat was presented with cystine crystalluria and calculi-related urinary obstruction and treated with perineal urethrostomy, cystotomy and medical management. This cat and a neutered male littermate without evidence of urinary tract disease were found to be positive for cystine by urinary nitroprusside test, to have increased urinary COLA values and to be homozygous for the p.Val294Glu mutation in the SLC7A9 gene coding for b0,+AT subunit of the b0,+ renal COLA transporter. Another littermate was non-cystinuric and did not carry this mutation. The same SLC7A9 mutation was previously found in a Maine coon, a Sphinx and a medium-haired cat in North America suggesting a common ancestor and likely first widespread SLC7A9 mutation causing cystinuria in cats. Genetic screening for this mutation may offer a simple and precise mean to diagnose other cats for cystinuria and offer specific management.

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Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

Cited by 52 publications

References 38 publications

SLC3A1andSLC7A9Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System

SLC3A1andSLC7A9Mutations in Autosomal Recessive or Dominant Canine Cystinuria: A New Classification System

Man's Best Friend Becomes Biology's Best in Show: Genome Analyses in the Domestic Dog

Cystinurie aufgrund einer SLC7A9-Missense-Mutation bei Siammischlingskatzen eines Wurfs in Deutschland

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