Genetic test for liver copper accumulation in dogs and low copper pet diet

Abstract

The present invention provides a method of determining the susceptibility of a dog to liver copper accumulation, comprising detecting the presence or absence in the genome of the dog of (a) a polymorphism in the GOLGA5, ATP7a or UBL5 gene that is indicative of susceptibility to liver copper accumulation and/or (b) a polymorphism in linkage disequilibrium with a said polymorphism (a). The invention also provides a method of determining the likelihood that a dog is protected from liver copper accumulation comprising detecting the presence or absence in the genome of the dog of one or more polymorphisms selected from (a) SNP ATP7a_Reg3_F_6 (SEQ ID NO: 142) and (b) one or more polymorphisms in linkage disequilibrium with (a).

1 . A method of determining the susceptibility of a dog to liver copper accumulation, comprising detecting the presence or absence in the genome of the dog of (a) a polymorphism in the GOLGA5, ATP7a or UBL5 gene that is indicative of susceptibility to liver copper accumulation and/or (b) a polymorphism in linkage disequilibrium with a said polymorphism (a). 
     
     
         2 . The method according to  claim 1 , comprising detecting the presence or absence of at least one polymorphism (a) and at least one polymorphism (b). 
     
     
         3 . The method according to  claim 1 , wherein the polymorphism is a single nucleotide polymorphism (SNP). 
     
     
         4 . The method according to  claim 3 , comprising detecting the presence or absence of one or more SNPs selected from BICF2P506595 (SEQ ID NO:1), BICF2P772765 (SEQ ID NO:2), BICF2S2333187 (SEQ ID NO:3), BICF2P1324008 (SEQ ID NO:4), BICF2P591872 (SEQ ID NO:5), ATP7a_Reg4_F — 9 (SEQ ID NO: 131), UBL5_Reg1F — 16 (SEQ ID NO: 132), golga5_Reg1 — 24 (SEQ ID NO: 133), golga5 — 26 (SEQ ID NO: 134), golga5 — 27 (SEQ ID NO: 135), golga5 — 28 (SEQ ID NO: 136), golga5 — 29 (SEQ ID NO: 137), golga5 — 30 (SEQ ID NO: 138), golga5 — 31 (SEQ ID NO: 139), atp7areg17 — 32 (SEQ ID NO: 140), atp7areg17 — 33 (SEQ ID NO: 141) and one or more SNPs in linkage disequilibrium thereof. 
     
     
         5 . The method according to  claim 4 , comprising detecting the presence or absence of the SNPs BICF2P506595 (SEQ ID NO:1), BICF2P772765 (SEQ ID NO:2), BICF2S2333187 (SEQ ID NO:3), BICF2P1324008 (SEQ ID NO:4), and BICF2P591872 (SEQ ID NO:5). 
     
     
         6 . The method according to  claim 1  wherein the dog has genetic inheritance of the Labrador Retriever breed. 
     
     
         7 . A database comprising information relating to one or more polymorphisms in the GOLGA5, ATP7a or UBL5 genes and/or one or more polymorphisms in linkage disequilibrium thereof and their association with the susceptibility of a dog to liver copper accumulation. 
     
     
         8 . A method of determining the susceptibility of a dog to liver copper accumulation, comprising:
 (a) inputting to a computer system data concerning the presence or absence in the genome of the dog of a polymorphism as defined in  claim 1 ;   (b) comparing the data to a computer database, which database comprises information relating to one or more polymorphisms in the GOLGA5, ATP7a or UBL5 genes and/or one or more polymorphisms in linkage disequilibrium thereof and their association with the susceptibility of a dog to liver copper accumulation; and   (c) determining on the basis of the comparison the susceptibility of the dog to liver copper accumulation.   
     
     
         9 . A computer program comprising program code means that, when executed on a computer system, instruct the computer system to perform all the steps of  claim 8 . 
     
     
         10 . A computer storage medium comprising the computer program according to  claim 9  and the database according to  claim 7 . 
     
     
         11 . A computer system arranged to perform a method according to  claim 8  comprising:
 (a) means for receiving data concerning the presence or absence in the genome of the dog of a polymorphism as defined in  claim 1 ; 
 (b) a database comprising information relating to one or more polymorphisms in the GOLGA5, ATP7a or UBL5 genes and/or one or more polymorphisms in linkage disequilibrium thereof and their association with the susceptibility of a dog to liver copper accumulation; 
 (c) a module for comparing the data with the database; and 
 (d) means for determining on the basis of said comparison the susceptibility of the dog to liver copper accumulation. 
 
     
     
         12 . A method of testing a dog for susceptibility to liver copper accumulation, comprising detecting in a sample the presence or absence in the genome of the dog of (a) a polymorphism in the GOLGA5, ATP7a or UBL5 gene that is indicative of susceptibility to liver copper accumulation and/or (b) a polymorphism in linkage disequilibrium with a said polymorphism (a). 
     
     
         13 . Use of (a) a polymorphism in the GOLGA5, ATP7a or UBL5 gene of a dog that is indicative of susceptibility to liver copper accumulation and/or (b) a polymorphism in linkage disequilibrium with a said polymorphism (a) for determining the susceptibility of a dog to liver copper accumulation. 
     
     
         14 . A method of selecting a dog for producing offspring likely to be protected from liver copper accumulation comprising:
 determining whether the genome of a candidate first dog comprises one or more polymorphisms indicative of susceptibility to liver copper accumulation according to the method of  claim 1  and thereby determining whether the candidate first dog is suitable for producing offspring likely to be protected from liver copper accumulation;   optionally, determining whether the genome of a second dog of the opposite sex to the first dog comprises one or more polymorphisms indicative of susceptibility to liver copper accumulation according to the method of  claim 1 ; and   optionally, mating the first dog with the second dog in order to produce offspring likely to be protected from liver copper accumulation.   
     
     
         15 . The method according to  claim 14 , wherein the dog has genetic inheritance of the Labrador Retriever breed. 
     
     
         16 . A method of preventing a disease attributable to liver copper accumulation in a dog having genetic inheritance of the Labrador Retriever breed, comprising feeding the dog a foodstuff comprising copper at a concentration of at least 4.5 to less than 12 mg/kg dry matter, wherein the dog has been determined to be susceptible to liver copper accumulation by a method of  claim 1 . 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled)