Recurrent airway obstruction and Genomics
Just yesterday we highlighted a paper that discussed the great progress that has been made in the equine genome, and how the thoroughbred industry at large can use genetics to truly improve the breed. The paper specifically mentioned the good ground that can be mede in identifying and selecting against diseases and heritable traits that impinge on performance.
Recurrent airway obstruction (RAO) is a common, performance-limiting, allergic respiratory disease of horses characterized by chronic cough, nasal discharge, and respiratory difficulty. Episodes of airway obstruction are observed when susceptible horses are stabled, bedded on straw, and fed hay, whereas elimination of these inciting factors results in remission or attenuation of clinical signs. Approximately 12% of mature horses have some degree of allergen-induced lower airway inflammation. There is no breed or gender predilection; however, there does appear to be a heritable component to susceptibility.
Much of the work on identifying the genes behind RAO has been done in the Warmblood breed. One of the first papers that we saw on RAO was published back in 2009 with the lead coming from the Animal Health Trust in the UK. The paper (click here), identified chromosomal regions on Chromosome 13 and 15 that had significant association with RAO. Once a scientists, or a team of scientists identify the chromosomal regions that may be responsible for a phenotype/disease, the next steps are to map it down to the gene (and its expression), and then, if possible, bring it down to identifying the single nucleotide polymorphism (SNP), or change(s) in the genetic code, that may be responsible for the phenotype.
Following that initial paper in 2009, a slew of papers have been published doing exactly that. Some of these have come out of the same group at the Animal Health Trust while others have come out of a team headed by J. Klukowska-Rötzle, or in some cases a combination of both. In November 2010 there was a paper looking at serum antibodies in two sires affected by RAO and the heritability of RAO. In May this year the same team looked at the ITGAX gene and it's role in RAO. In July this year a different research group out of Brazil looked at the Spi2 gene as a possibility given that Spi2 is a gene that is associated with chronic obstructive pulmonary disease (COPD) in humans (humans and horses share a lot of similar genetic code). This paper did not find any association with Spi2 gene and RAO in horses.
In August this year a comparison between genomic and proteomic data really started to narrow the search down to the IL21R gene, and in October this year the same research group did a full sequence of that gene identifying it as being responsible for some cases of RAO.Now, the latest paper from Klukowska-Rötzle's team, published this week, identifies the SNP's on the IL21R gene that are most likely to be responsible for RAO. It is important to understand that while they have narrowed it down to one gene (there still may be more), there are multiple SNP's or changes in DNA code that make a horse predisposed to RAO.
This type of complex work is going to become more and more prevalent in genetic research in the horse. We are aware of a number of similar studies looking at wobbler syndrome and laryngeal paralysis in the thoroughbred. The challenge is going to be, once we identify these genetic components and presuming that they are not in some way linked to elite performance (it is possible that variants for a disease may be also linked to superior performance), how willing is the thoroughbred industry going to be to use genomic technology to select away from these diseases? Is this something that the Jockey Club or Stud Books around the world should be testing for?