Selecting animals for desired genotypic or potential phenotypic properties

Abstract

Described are methods to select animals, such as mammals, particularly domestic animals, breeding animals or animals destined for slaughter, for having desired genotypic or potential phenotypic properties, in particular, related to muscle mass and/or fat deposition lean meat, lean back fat, sow prolificacy and/or sow longevity. Provided is a method for selecting an animal having desired genotypic or potential phenotypic properties comprising testing the animal, a parent of the animal or its progeny for the presence of a nucleic acid modification affecting the activity of an evolutionary conserved CpG island, located in intron 3 of an IGF2 gene and/or for the presence of a nucleic acid modification affecting binding of a nuclear factor to an IGF2 gene.

1 . A method for selecting an animal having desired genotypic or potential phenotypic properties, said method comprising:
 testing said animal, a parent of said animal, or its progeny for the presence of a nucleic acid modification affecting the activity of an evolutionary conserved CpG island, located in intron 3 of an IGF2 gene.   
     
     
         2 . A method for selecting an animal having desired genotypic or potential phenotypic properties, said method comprising:
 testing said animal, a parent of said animal or its progeny for the presence of a nucleic acid modification affecting binding of a nuclear factor to an IGF2 gene.   
     
     
         3 . The method according to  claim 2  wherein said nuclear factor is able to bind to a stretch of nucleotides which in the wild type pig, mouse or human IGF2 gene is part of an evolutionary conserved CpG island, located in intron 3 of said IGF2 gene. 
     
     
         4 . The method according to  claim 3  wherein said stretch is functionally equivalent to the sequence 5′-GATCCTTCGCCTAGGCTC(A/G)CAGCGCGGGAGCGA-3′ (SEQ ID NO:1). 
     
     
         5 . The method according to  claim 1 , wherein said nucleic acid modification comprises a nucleotide substitution. 
     
     
         6 . The method according to  claim 5  wherein said substitution in the pig comprises a G to A transition at IGF2-intron3-nt3072. 
     
     
         7 . A method according to  claim 2 , wherein inhibiting binding of said nuclear factor to said IGF2 gene allows for modulating IGF2 mRNA transcription in a cell provided with said gene. 
     
     
         8 . A method according to  claim 1 , wherein said desired genotypic or potential phenotypic properties comprise muscle mass, fat deposition, lean meat, lean back fat, sow prolificacy and/or sow longevity. 
     
     
         9 . The method according to  claim 8 , wherein said sow prolificacy includes such phenotypic expressions as teat number, number of piglets born alive, litter size, number of total born and/or number of weaned piglets. 
     
     
         10 . The method according to  claim 8 , wherein said sow longevity includes such phenotypic expressions as parity and/or average number of cycles per sow. 
     
     
         11 . A method for modulating mRNA transcription of an IGF2 gene in a cell or organism provided with said gene comprising modulating the activity of an evolutionary conserved CpG island, located in intron 3 of an IGF2 gene and/or modulating binding of a nuclear factor to an IGF2 gene. 
     
     
         12 . The method according to  claim 11  wherein said nuclear factor is capable of binding to a stretch of nucleotides which in the wild type pig, mouse or human IGF2 gene is part of an evolutionary conserved CpG island, located in intron 3 of said IGF2 gene. 
     
     
         13 . The method according to  claim 12  wherein said stretch is functionally equivalent to the sequence 5′-GATCCTTCGCCTAGGCTC(A/G)CAGCGCGGGAGCGA-3′ (SEQ ID NO:1). 
     
     
         14 . A method for identifying a compound capable of modulating mRNA transcription of an IGF2 gene in a cell or organism provided with said gene comprising providing a first cell or organism having a nucleic acid modification affecting the activity of an evolutionary conserved CpG island, located in intron 3 of an IGF2 gene and/or affecting binding of a nuclear factor to an IGF2 gene and a second cell or organism not having said modification further comprising providing said first or said second cell or organism with a test compound and determining IGF2 mRNA transcription in said first and second cell or organism. 
     
     
         15 . The method according to  claim 14  wherein said nuclear factor is capable of binding to a stretch of nucleotides which in the wild type pig, mouse or human IGF2 gene is part of an evolutionary conserved CpG island, located in intron 3 of said IGF2 gene. 
     
     
         16 . The method according to  claim 15  wherein said stretch is functionally equivalent to the sequence 5′-GATCCTTCGCCTAGGCTC(A/G)CAGCGCGGGAGCGA-3′ (SEQ ID NO:1). 
     
     
         17 . The method according to  claim 16  wherein said nucleic acid modification comprises a nucleotide substitution. 
     
     
         18 . The method according to  claim 17  wherein said substitution comprises a G to A transition which in the pig is located at IGF2-intron3-nt3072. 
     
     
         19 . A method for identifying a compound capable of modulating binding of a nuclear factor to an IFG2 gene, said method comprising:
 providing a stretch of nucleotides which, in the wild type pig, mouse or human IGF2 gene, is part of an evolutionary conserved CpG island, located in intron 3 of said IGF2 gene;   providing a mixture of DNA-binding proteins derived from a nuclear extract of a cell;   providing a test compound; and   determining competition of binding of said mixture of DNA-binding proteins to said stretch of nucleotides in the presence or absence of said test compound.   
     
     
         20 . The method according to  claim 19  wherein said stretch is functionally equivalent to the sequence 5′-GATCCTTCGCCTAGGCTC(A/G)CAGCGCGGGAGCGA-3′ (SEQ ID NO:1). 
     
     
         21 . A compound identified by the method according  claim 14 . 
     
     
         22 . The compound of  claim 21  comprising an oligonucleotide or analogue thereof functionally equivalent to the sequence 5′-GATCCTTCGCCTAGGCTC(A/G)CAGCGCGGGAGCGA-3′ (SEQ ID NO:1). 
     
     
         23 . A pharmaceutical composition comprising the compound of  claim 21 , together with a pharmaceutically acceptable excipient. 
     
     
         24 . A method of treating obesity in a subject, the method comprising:
 administering to the subject the compound of  claim 21  so as to treat obesity.   
     
     
         25 . A method of treating muscle deficiencies in a subject in need thereof, said method comprising administering to the subject the compound of  claim 21  so as to treat muscle deficiencies. 
     
     
         26 . A method for modulating mRNA transcription of an IGF2 gene in a cell or organism provided with said gene, said method comprising:
 providing said cell or organism with the compound of  claim 21 .