Mapping Genetic Loci which Influence Recurrent Airway Obstruction

The half-sibling offspring from two warmblood RAO-affected sires were recruited into a study of RAO (see abstract by V. Gerber for details). In brief, these horses were subjected to a rigorous phenotyping protocol (Ramseyer et al., 2007) based on their extensive history of clinical signs. In addition details of their management and other diseases were collected. Peripheral blood samples were collected for genomic DNA extraction from each horse. This provided a large collection of 239 samples ideal for the mapping of genetic loci conferring an inherited risk of RAO.
The offspring were genotyped using a panel of 250 microsatellite markers, chosen as evenly-spaced and polymorphic. Correlated segregation, or “linkage”, of these markers with the RAO phenotype, as defined by HOARSI (see abstract by V. Gerber), was used to identify implicated chromosome regions. In addition, individual clinical signs, such as coughing, nasal discharge, and so on, were independently examined for linkage. The data was analysed using a regression analysis approach provided by the remote access freeware “QTL Express” (http://qtl.cap.ed.ac.uk/). The two families were analysed separately, and the results indicate that there is a genetic heterogeneity between them. This conclusion is in agreement with segregation analysis of the families (Gerber et al., 2009). The results of the linkage analysis will be presented. In brief, two chromosome regions showed a genome-wide significant association with RAO, one in each family (Figure 1). This data supports the linkage seen between RAO and IL4R (Jost et al., 2007). An additional 11 chromosome region showed a more modest association. Potential candidate genes in these regions, identified as implicated in human asthma, or involved in the immune response, have been identified and will be discussed. […]