Sir
In a recent issue of Nature Reviews Genetics, Froguel and collaborators1 described different approaches to identify genes that are involved in human obesity. In their review, the authors did not mention the use of model organisms such as the mouse or the rat. These two species are often advocated for use in obesity research. Here we would like to propose that commercial pigs represent a useful model to dissect the genetics of obesity.
The pig has many similarities in structure and function to humans, including size, digestive physiology and dietary habits. During its domestication, the pig has undergone an intense selection and selective breeding has produced pig populations that differ for various phenotypes, such as growth rate and fat deposition. In commercial pig breeding farms, growth and body-fat are routinely measured for each tested pig and in a subset, daily feed intake and feeding behaviour are also measured. All of these traits are relevant to phenotypes that are commonly used in obesity research. In addition, more detailed studies can be conducted to further define phenotypes2. Some pig breeding companies have accumulated millions of pedigreed phenotypic records and DNA samples. These resources are already being used to discover genetic markers for marker-assisted selection to improve pig lines. Different approaches have been taken, including the candidate gene approach, which takes advantage of the knowledge we have of human or mouse genes and genomes. For example, a variant of the porcine melanocortin-4 receptor (MC4R) gene — a gene that is involved in human and mouse obesity — has been shown to be associated with variation in fatness, growth and feed intake3. Pig genome analysis has lagged behind that of some other farm animals, such as chickens or cattle, but recently several large-scale genomic projects have been initiated and a call to sequence the pig genome has been made4. For example, more than 5,500 pig SNPs have been identified and deposited in the public domain5. Analysis within commercial pig populations of a subset of these SNPs showed a high percentage of polymorphic markers and demonstrates the usefulness of these public SNPs in identifying loci that significantly influence economically important traits6. Some commercial pig breeding companies also have large private collections of SNPs that are segregating in their commercial populations. Because of the availability of samples from large numbers of animals with defined genetic and environmental backgrounds and the relatively large extent of linkage disequilibrium7, some whole-genome SNP association studies are already underway in the pig, including those targeted to obesity-related traits.
Since domestication, human and pig lives have been intertwined. In recent years, animal scientists have identified, based on information from the human genome, genes that are involved in pig growth and fatness. With the current developments in pig genomics, we believe that now it is time to add commercial pigs and the plethora of associated data to the weaponry to fight human obesity.
References
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Rocha, D., Plastow, G. Using commercial pigs in the search for genes behind human obesity. Nat Rev Genet 6, 248 (2005). https://doi.org/10.1038/nrg1556-c1
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DOI: https://doi.org/10.1038/nrg1556-c1
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