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Cows in a pasture. © INRA, DELABY Luc

Cattle are the next top (animal) model

The study of mutations underlying sporadic syndromes in cattle, which also occur in humans, offers an interesting alternative to laboratory animals for confirming the genetic aetiology of isolated clinical case reports and gaining insight into the molecular mechanisms involved. This is the conclusion of a report by an international team of researchers led by INRA in collaboration with ALLICE, the CEA and VetAgroSup for the French partners, which was published in the journal Scientific Reports on Wednesday September 13, 2017.

Updated on 10/20/2017
Published on 09/18/2017

In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. In contrast, the structure of cattle populations and the large amount of genomic and phenotypic data that are now available in this species, make it easy to quickly identify the causative mutations and to study their effects on important cohorts of affected animals.” explains the leader of the study, Dr. Aurélien Capitan, scientist at INRA and ALLICE. “In this article, our aim was to illustrate, with selected examples, the numerous opportunities offered by the bovine animal model.”

In their article, the researchers identified candidate mutations for seven dominant syndromes simply by sequencing the whole genome of a single affected animal and filtering out the polymorphisms found in the whole genomes of more than 1000 control individuals representing the main ancestors of their breeds. Then, by studying close relatives of the affected animals, they were able to confirm the de novo nature and the causality of these mutations.

In addition, the authors performed clinical examinations and reported perfect genotype-phenotype correlations between affected calves and human patients with mutations affecting the same domains of the same proteins, demonstrating that cattle may be a useful model for the study of human genetic diseases. Furthermore, they proved that the bovine model is, in certain instances, a better model than rodents who sometimes express an attenuated phenotype. They also demonstrated that large half-sib pedigrees allow for mapping modifier loci in clinically variable syndromes and that the study of rare conditions occurring in cattle can provide interesting models for basic research.

Finally, after studying dominant mutations, the scientists demonstrated the feasibility of anticipating the emergence of recessive genetic defects by detecting de novo deleterious mutations in the genome of healthy artificial insemination bulls.

In conclusion this study represents a convincing plea for the better consideration of livestock species as possible models in the post genomic era.

These findings of the international team of researchers from France, Germany, Switzerland, Austria, and Australia are published in the article “Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species” in Scientific Reports. (www.nature.com/articles/s41598-017-11523-3)

Contact(s)
Scientific contact(s):

  • Aurélien Capitan (01 34 65 26 45) Joint Research Unit for Animal Genetics and Integrative Biology (INRA, AgroParisTech)
Press Relations:
INRA News Office (33 (0)1 42 75 91 86)
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Animal Genetics
Associated Centre(s):
Jouy-en-Josas

Reference

E. Bourneuf, P. Otz and coll. Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species. Scientific Reports. 13 September 2017. DOI: 10.1038/s41598-017-11523-3