Genetic test for liver copper accumulation in dogs

Abstract

The present disclosure provides methods of determining the susceptibility of a dog to liver copper accumulation, comprising detecting in a biological sample obtained from the dog the presence or absence in the genome of the dog of one or more polymorphisms, and methods of treating or breeding the dog based on such determination.

What is claimed is: 
     
         1 . A method of treating or breeding a dog, comprising:
 (a) genotyping a biological sample obtained from the dog to determine in a genome of the dog presence or absence of a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), wherein the polymorphism is present if T allele is present at Chr10_65209946 (position 101 of SEQ ID NO: 155), and the polymorphism is absent if A allele is present at Chr10_65209946 (position 101 of SEQ ID NO: 155); and   (b) administering to the dog a low copper food stuff or a therapeutic amount of a copper chelator when the polymorphism is present; or   breeding the dog when the polymorphism is absent.   
     
     
         2 . The method of  claim 1 , wherein step (a) further comprises genotyping the biological sample obtained from the dog to determine in the genome of the dog presence or absence of one or more polymorphisms selected from the group consisting of:
 (i) Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), and CGCCCC repeat at chromosome location 22 starting at genomic location 3135287;   (ii) Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157) and Chr8_4880518 (position 101 of SEQ ID NO: 158); and   (iii) ChrX_63338063 (position 102 of SEQ ID NO: 142).   
     
     
         3 . The method of  claim 2 , wherein the one or more polymorphisms are single nucleotide polymorphisms (SNPs). 
     
     
         4 . The method of  claim 1 , wherein step (a) further comprises genotyping the biological sample obtained from the dog to determine presence or absence of one or more SNPs selected from the group consisting of BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141). 
     
     
         5 . The method of  claim 4 , wherein the one or more SNPs comprise BICF2P506595 (position 61 of SEQ ID NO:1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), and BICF2P591872 (position 61 of SEQ ID NO:5). 
     
     
         6 . The method of  claim 1 , wherein step (a) comprises genotyping the biological sample obtained from the dog to determine in the genome of the dog the presence or absence of one or more polymorphisms comprising Chr10_65209946 (position 101 of SEQ ID NO: 155), Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr3_86838677 (position 101 of SEQ ID NO: 152), and ChrX_63338063 (position 102 of SEQ ID NO: 142). 
     
     
         7 . A method of treating or breeding a dog, comprising:
 (a) inputting to a computer system genotyping data concerning presence or absence in a genome of the dog a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), and optionally one or more polymorphisms selected from the group consisting of Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), CGCCCC repeat at chromosome location 22 starting at genomic location 3135287, Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157), Chr8_4880518 (position 101 of SEQ ID NO: 158), ChrX_63338063 (position 102 of SEQ ID NO: 142), BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141);   (b) comparing the genotyping data to a computer database, wherein the computer database comprises information of the risk of dog liver copper accumulation associated with the polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), and optionally one or more polymorphisms selected from the group consisting of Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), CGCCCC repeat at chromosome location 22 starting at genomic location 3135287, Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157), Chr8_4880518 (position 101 of SEQ ID NO: 158), ChrX_63338063 (position 102 of SEQ ID NO: 142), BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141);   (c) determining whether the dog is at risk of liver copper accumulation based on the comparison; and   (d) administering to the dog a low copper food stuff or a therapeutic amount of a copper chelator if the dog is determined to be at risk of liver copper accumulation, or   breeding the dog if the dog is determined to be not at risk of liver copper accumulation.   
     
     
         8 . A computer program comprising program code means that, when executed on a computer system, instruct the computer system to perform steps (a)-(c) of  claim 7 . 
     
     
         9 . A computer storage medium comprising the computer program according to  claim 8  and a database comprising information of the risk of dog liver copper accumulation associated with a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), and optionally one or more polymorphisms selected from the group consisting of Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), CGCCCC repeat at chromosome location 22 starting at genomic location 3135287, Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157), Chr8_4880518 (position 101 of SEQ ID NO: 158), ChrX_63338063 (position 102 of SEQ ID NO: 142), BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141). 
     
     
         10 . A computer system arranged to perform steps (a)-(c) of  claim 7  comprising:
 (a) means for receiving genotyping data concerning presence or absence in the genome of the dog of a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), and optionally one or more polymorphisms selected from the group consisting of Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), CGCCCC repeat at chromosome location 22 starting at genomic location 3135287, Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157), Chr8_4880518 (position 101 of SEQ ID NO: 158), ChrX_63338063 (position 102 of SEQ ID NO: 142), BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141); 
 (b) a database comprising information of the risk of dog liver copper accumulation associated with a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), and optionally one or more polymorphisms selected from the group consisting of Chr22_3167534 (position 101 of SEQ ID NO: 144), Chr22_3135144 (position 101 of SEQ ID NO: 145), Chr20_55461150 (position 101 of SEQ ID NO: 146), ChrX_120879711 (position 101 of SEQ ID NO: 147), Chr19_6078084 (position 101 of SEQ ID NO: 148), Chr15_62625262 (position 101 of SEQ ID NO: 149), Chr14_39437543 (position 101 of SEQ ID NO: 150), Chr15_62625024 (position 101 of SEQ ID NO: 151), Chr3_86838677 (position 101 of SEQ ID NO: 152), Chr24_4011833 (position 101 of SEQ ID NO: 153), Chr18_60812198 (position 101 of SEQ ID NO: 154), CGCCCC repeat at chromosome location 22 starting at genomic location 3135287, Chr32_38904515 (position 101 of SEQ ID NO: 156), Chr8_4892743 (position 101 of SEQ ID NO: 157), Chr8_4880518 (position 101 of SEQ ID NO: 158), ChrX_63338063 (position 102 of SEQ ID NO: 142), BICF2P506595 (position 61 of SEQ ID NO: 1), BICF2P772765 (position 61 of SEQ ID NO:2), BICF2S2333187 (position 61 of SEQ ID NO:3), BICF2P1324008 (position 61 of SEQ ID NO:4), BICF2P591872 (position 61 of SEQ ID NO:5), ATP7a_Reg4_F_9 (position 164 of SEQ ID NO: 131), UBL5_Reg1F_16 (position 97 of SEQ ID NO: 132), golga5_Reg1_24 (position 70 of SEQ ID NO: 133), golga5_26 (position 88 of SEQ ID NO: 134), golga5_27 (position 104 of SEQ ID NO: 135), golga5_28 (position 139 of SEQ ID NO: 136), golga5_29 (position 128 of SEQ ID NO: 137), golga5_30 (position 95 of SEQ ID NO: 138), golga5_31 (position 106 of SEQ ID NO: 139), atp7areg17_32 (position 95 of SEQ ID NO: 140), and atp7areg17_33 (position 90 of SEQ ID NO: 141); 
 (c) a module for comparing the genotyping data with the database; and 
 (d) means for determining on the basis of said comparison the risk of the dog to liver copper accumulation. 
 
     
     
         11 . A method of selecting a first dog for producing offspring that are likely to be protected from liver copper accumulation comprising:
 (a) genotyping a biological sample obtained from the first dog to determine in a genome of the first dog presence or absence of a polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155), wherein the polymorphism is present if T allele is present at Chr10_65209946 (position 101 of SEQ ID NO: 155), and the polymorphism is absent if A allele is present at Chr10_65209946 of (position 101 of SEQ ID NO: 155); and   (b) breeding the first dog when the polymorphism is absent, wherein the first dog produces offspring that are likely to be protected from liver copper accumulation, or   administering to the first dog a low copper food stuff or a therapeutic amount of a copper chelator when the polymorphism is present; and optionally   (c) genotyping a biological sample obtained from a second dog to determine in a genome of the second dog the presence or absence of the polymorphism at Chr10_65209946 (position 101 of SEQ ID NO: 155).   
     
     
         12 . The method of  claim 1 , wherein the dog has genetic inheritance of the Labrador Retriever breed.