Domestic animals: ideal models for studying complex characters

Predisposition to many common diseases – among which cancer, cardiovascular conditions, diabetes, asthma, etc. – is said to be a multifactor phenomenon as it results from numerous genes as well as environmental factors. Identifying such predisposition genes is one of the major challenges in modern genetics and could contribute to establishing new preventive medicine patterns and developing new specific drugs.

However, the identification of predisposition genes appeared to be extremely difficult in humans. Despite huge investments, “successes” can be counted on the fingers of one hand.

Considering our domestic animals’ history, such populations are particularly well-adapted to the analysis of multifactor characters. This was shown most dramatically by the recent identification of a mutation in an IGF2 gene regulatory element leading to a muscle mass increase in pigs. A particularly ingenious genetic analysis allowed experts to isolate the relevant mutation among 280 other mutations identified in the gene. Functional analyses subsequently indicated that the mutation inactivated an inhibitor of the IGF2 production in muscles. As a consequence, it increased IGF2 secretion and muscle growth.

The research work was carried out by the team of Prof. Dr Michel Georges from the University of Liège (Minh Nguyen, Carine Nezer, Catherine Collette, Laurence Moreau), a member of the Faculty of Veterinary Medicine and of the new Centre for Applied Genomics (GIGA) in cooperation with Prof. Dr Leif Andersson’s team from the University of Uppsala and was financed by the Belgian Federal Ministry of Agriculture and Belgian company Gentec. It will be published in journal Nature on October 23. This prestigious publication results from the extraordinary, so far unequalled resolution achieved in a multifactor character analysis.

The identification of this mutation in the IGF2 gene follows the recent identification of two other genes shown to influence complex characters in domestic animals: the DGAT1 gene in bovines and the CLPG gene in sheep. The team of Prof. Dr Michel Georges also played a decisive role in both genes’ identification. Despite negligible investments in animal genetics – compared to human genetics – the number of “successes” appears to be virtually equivalent, which clearly demonstrates these populations’ interest.

Numerous routinely assessed multifactor characters in domestic animals rely on metabolic pathways likely to be implied in human multifactor pathology determinism. Relationships were noted between fat depots in carcases and obesity, calcium metabolism in laying hens and osteoporosis, glycogen levels in meat and diabetes, etc. Identifying genes that influence such multifactor production characters might thus significantly contribute to improving the knowledge of molecular mechanisms implied in human complex pathology determinism.

This is one of the reasons why domestic species’ genome sequencing – in addition to its agronomic impact – is very seriously considered, in particular by the American National Institute of Health (NIH). In this respect, this valuable opportunity is most regrettably ignored by the European Community.