Selecting animals for desired genotypic or potential phenotypic properties

Abstract

The invention relates to methods to select animals, such as mammals, in particular, domestic animals such as 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 or, in the case of mammals, to teat number. The invention provides a method for selecting an animal for 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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of PCT International Patent Application No. PCT / EP04 / 000149, filed on Jan. 9, 2004, designating the United States of America, and published, in English, as PCT International Publication No. WO 2004 / 063386 A2 on Jul. 29, 2004, which application claims priority to European Patent Application Serial No. 03075091.3 filed on Jan. 10, 2003, the contents of the entirety of each are incorporated herein by this reference.TECHNICAL FIELD [0002] The invention relates to methods to select animals, such as mammals, in particular, domestic animals such as 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 or, in the case of mammals, to teat number. Herein, a domestic animal is defined as an animal being purposely selected or having been derived from an animal having been purposely selected for...

AI Technical Summary

Benefits of technology

[0013] In a preferred embodiment, the invention provides a method wherein the nucleic acid modification comprises a nucleotide substitution, whereby in the pig, the substitution comprises a G to A transition at IGF2-intron3-nt3072 (SEQ ID NO:6 and SEQ ID NO:5). Abrogating or reducing binding of the nuclear factor to the IGF2 gene allows for modulating IGF2 mRNA transcription in a cell provided (naturally or by recombinant means) with the gene.

[0018] Accordingly, a method according to the invention is herein provided allowing testing for, and modulation of, desired genotypic or potential phenotypic properties comprising muscle mass, fat deposition or teat numbers (of mammals). Such testing is applicable in man and animals alike (animals herein defined as including humans). In humans, it is, for example, worthwhile to test for the presence 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 or affecting binding of a nuclear factor to an IGF2 gene, as provided herein, to test, for example, the propensity or genetic predisposition or likelihood of muscle growth or muscularity in humans versus propensity or genetic predisposition or the likelihood of obesity. In domestic animals, such testing may be undertaken to select the best or most suitable animals for breeding, or to preselect domestic animals destined for slaughter. An additional trait to be selected for concerns teat number, a quality highly valued in sow lines to allow for suckling large litters. A desirable breeding combination as provided herein comprises, for example, increased teat number in the female line with increased growth rates, reduced back fat and / or increased muscle mass in the male lines. It is herein also shown that the mutation influences teat number. The Q allele that is favorable with respect to muscle mass and reduced back fat is the unfavorable allele for teat number. This strengthens the possibility of using the paternal imprinting character of this QTL in breeding programs. Selecting maternal lines for the q allele will enhance teat number, a characteristic that is favorable for the maternal side. On the other hand, paternal lines can be selected for the Q allele that will increase muscle mass and reduce back fat, characteristics that are of more importance in the paternal lines. Terminal sires that are homozygous QQ will pass the full effect of increased muscle mass and reduced back fat to the slaughter pigs, while selection of parental sows that express the q allele will allow for the selection of sows that have more teats and suckle more piglets without affecting slaughter quality.

[0024] The results have important practical implications. The IGF2*Q mutation increases the amount of meat produced, at the expense of fat, by 3-4 kg for an animal slaughtered at the usual weight of about 100 kg. The high frequency of IGF2*Q among major pig breeds implies that this mutation affects the productivity of many millions of pigs in the Western world. The development of a simple diagnostic DNA test now facilitates the introgression of this mutation to additional breeds. This could be an attractive way to improve productivity in local breeds as a measure to maintain biological diversity. The diagnostic test will also make it possible to investigate if the IGF2*Q mutation is associated with any unfavorable effects on meat quality or any other trait. It has been previously demonstrated that European and Asian pigs were domesticated from different subspecies of the Wild Boar, and that Asian germplasm has been introgressed into European pig breeds (17). The IGF2*Q mutation apparently occurred on an Asian chromosome as it showed a very close relationship to the haplotype carried by Chinese Meishan pigs. This explains the large genetic distance observed between Q- and q-haplotypes (FIG. 4). However, it is an open question whether the Q mutation occurred before after the Asian chromosome was introduced into European pigs.

Problems solved by technology

One of the major problems in breeding programs of domestic animals is the negative genetic correlation between reproductive capacity and production traits.

The phenomenon of genetic or parental imprinting has never been earlier utilized in selecting domestic animals, nor was it ever considered feasible to employ this elusive genetic characteristic in practical breeding programs.

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