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

Abstract

The present invention provides a method of testing a dog to determine the likelihood that the dog is protected from liver copper accumulation, comprising detecting in a sample 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 testing a dog to determine the likelihood that the dog is protected from liver copper accumulation, comprising detecting in a sample 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). 
     
     
         2 . The method according to  claim 1 , comprising detecting the presence or absence of (a) SNP ATP7a_Reg3_F — 6 (SEQ ID NO:142) or (b) SNP ATP7a_Reg16_F — 42 (SEQ ID NO: 143). 
     
     
         3 . The method according to  claim 1 , wherein the dog is in the first year of its life. 
     
     
         4 . The method according to  claim 1 , wherein the dog has genetic inheritance of the Labrador Retriever, Golden Retriever or Miniature Poodle breed. 
     
     
         5 . The method according to  claim 4 , wherein the dog has genetic inheritance of the Labrador Retriever breed. 
     
     
         6 . The method according to  claim 1 , further comprising detecting the presence or absence in the genome of the dog of (c) a polymorphism in the GOLGA5, ATP7A or UBL5 gene that is indicative of susceptibility to liver copper accumulation and/or (d) a polymorphism in linkage disequilibrium with a said polymorphism (c). 
     
     
         7 . The method according to  claim 6 , 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. 
     
     
         8 . The method according to  claim 7 , 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). 
     
     
         9 . The method according to  claim 1 , wherein a polymorphism that is in linkage disequilibrium with a polymorphism (a) or (c) is within 680 kb of and on the same chromosome as polymorphism (a) or (c) and the calculated measure of linkage disequilibrium between the pair of polymorphisms, D′, is greater than or equal to 0.9. 
     
     
         10 . A database comprising information relating to SNP ATP7a_Reg3_F — 6 (SEQ ID NO:142) and/or one or more polymorphisms in linkage disequilibrium thereof and their association with the protection of a dog from liver copper accumulation. 
     
     
         11 . A method of determining the likelihood that a dog is protected from liver copper accumulation, the method 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 said polymorphisms and their association with the protection of a dog from, or susceptibility of a dog to, liver copper accumulation; and   (c) determining on the basis of the comparison the likelihood that the dog is protected from liver copper accumulation.   
     
     
         12 . 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 11 . 
     
     
         13 . A computer storage medium comprising the computer program according to  claim 12  and the database according to  claim 10 . 
     
     
         14 . A computer system arranged to perform a method according to  claim 11  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 said polymorphisms and their association with the protection of a dog from, or 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 likelihood that the dog is protected from liver copper accumulation. 
 
     
     
         15 . 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). 
     
     
         16 . Use of a polymorphism as defined in  claim 1  for determining the likelihood that a dog is protected from liver copper accumulation. 
     
     
         17 . 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 protection from 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 protection from liver copper accumulation according to  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.   
     
     
         18 . The method according to  claim 17 , wherein the dog has genetic inheritance of the Labrador Retriever, Golden Retriever or Miniature Poodle breed. 
     
     
         19 . The method of  claim 18 , wherein the dog has genetic inheritance of the Labrador Retriever breed. 
     
     
         20 . A method of preventing a disease attributable to liver copper accumulation in a dog having genetic inheritance of the Labrador Retriever breed, wherein the likelihood that the dog is protected from liver copper accumulation has been determined by a method according to  claim 1 , the method comprising feeding the dog a foodstuff comprising copper at a concentration of from 4.5 to 12 mg/kg dry matter. 
     
     
         21 . The method according to  claim 20 , wherein the foodstuff further comprises zinc at a concentration of at least 120 mg/kg dry matter. 
     
     
         22 . The method according to  claim 20 , wherein the foodstuff comprises copper at a concentration of 4.5 to 10 mg/kg or 4.5 to 8 mg; and/or comprises zinc at a concentration of 120 to 250 mg/kg or 150 to 250 mg/kg dry matter. 
     
     
         23 . The method according to  claim 20 , for preventing a disease attributable to liver copper accumulation in a dog:
 (i) having at least one parent that is a pure-bred Labrador Retriever;   (ii) that has no clinical symptoms associated with liver copper accumulation;   (iii) that has a liver copper concentration of less than 400 mg/kg of dry weight liver; and/or   (iv) that does not have detectable liver disease.   
     
     
         24 . The method according to  claim 20 , which is for preventing copper-associated chronic hepatitis. 
     
     
         25 . (canceled) 
     
     
         26 . The method according to  claim 20 , further comprising feeding the dog a foodstuff or supplement comprising zinc at a concentration of at least 120 mg/kg. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled)