title: A Carbohydrate Sulfotransferase-6 (CHST6) gene mutation is associated with Macular Corneal Dystrophy in Labrador Retrievers.
abstract: OBJECTIVE
  To locate and identify variants associated with macular corneal dystrophy (MCD) in Labrador Retriever (LR) dogs, in the candidate gene carbohydrate sulfotransferase-6 (CHST6).
  
  
  METHODS
  The single coding exon of canine CHST6 was sequenced in one affected LR with MCD and one control LR clinically clear of ocular disease. A further 71 control LR with unknown clinical status were sequenced for the putative causal variant in CHST6. A TaqMan SNP genotyping assay was developed and used to screen an additional 84 dogs (five affected LR and 79 clinically clear LR). Finally, the variant was screened in a third cohort of 89 unrelated LR with unknown clinical status to estimate its allele frequency in the population of LR in the United Kingdom.
  
  
  RESULTS
  A single nucleotide polymorphism (SNP) was identified within the coding exon of CHST6, resulting in a missense mutation (c.814C>A, p.R272S). All six LR affected with MCD were homozygous for the mutant allele, while 140/151 control LR were homozygous for the wild-type allele and 11/151 were heterozygous for the mutation, indicating an association with MCD (P < 10-5). The mutant allele was present in the unrelated LR cohort at a frequency of 0.017, suggesting carrier and affection rates of 3.3% and 0.028%, respectively.
  
  
  CONCLUSIONS
  A missense mutation in the CHST6 gene is strongly associated with autosomal recessive MCD in the LR.
authors.affiliation: Comparative Ophthalmology Unit, Animal Health Trust, Lanwades Park, Kentford, CB8 7UU, UK. roser.tetas@aht.org.uk.
authors.forename: Roser
authors.identifier: http://orcid.org/0000-0003-1201-9641
authors.initials: R
authors.lastname: Tetas Pont
authors.affiliation: Canine Genetics, Animal Health Trust, Lanwades Park, Kentford, CB8 7UU, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Downs
authors.affiliation: Canine Genetics, Animal Health Trust, Lanwades Park, Kentford, CB8 7UU, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Pettitt
authors.affiliation: Comparative Ophthalmology Unit, Animal Health Trust, Lanwades Park, Kentford, CB8 7UU, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Busse
authors.affiliation: Canine Genetics, Animal Health Trust, Lanwades Park, Kentford, CB8 7UU, UK.
authors.forename: Cathryn S
authors.initials: CS
authors.lastname: Mellersh
mesh_terms: D000818:Animals; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics / Q000662:veterinary*; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics*; D004285:Dogs; D005838:Genotype; D009154:Mutation; D015238:Sulfotransferases / Q000235:genetics*; D006113:United Kingdom; D000097811:Carbohydrate Sulfotransferases
chemical_list: D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases
keywords: 
  CHST6
  ; 
  MCD
  ; canine; corneal; dystrophy; macular