1311: Genome-wide association mapping study of hypertrophic osteodystrophy in Irish Setters

Grant Status: Closed

Grant Amount: $74,237
Alison Starr-Moss, PhD; Clemson University
January 1, 2010 - June 30, 2014

Sponsor(s): Irish Setter Club of America Foundation

Breed(s): Irish Setter
Research Program Area: Musculoskeletal Conditions and Disease
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Project Summary

Hypertrophic osteodystrophy (HOD) is a complex disorder of the musculoskeletal and inflammatory systems in dogs. HOD has been recognized as an animal model of chronic recurrent multifocal osteomyelitis (CRMO). In humans, mutations causing CRMO have been described in the genes LPIN2 and IL1RN. A mouse model of CRMO results from defects of pstpip2. Defects of any of these genes results in syndromic forms of CRMO, and the disease affects multiple body systems. The etiology of HOD remains poorly understood, and genetic and environmental factors are expected to play a role in the disease. HOD commonly affects breeds of large stature, including the Irish Setter, Great Dane, and Weimaraner. A genome-wide association study was undertaken to identify genes contributing to HOD.

The primary aim of this study was to identify genes associated with HOD in Irish Setters. To this end, we completed a genomic study using a population of 89 dogs (40 affected, 49 control). Optimally, we hoped to identify a major locus contributing to HOD in dogs, and identify a genetic marker that could be reliably used to predict and prevent cases of HOD.

Our initial goal was to collect blood samples from 200 Irish Setters; however, insufficient numbers of study participants were obtained. We modified our aims to complete the genetic screen with fewer dogs, while adding a new aim: whole genome re-sequencing from healthy and HOD-affected Irish Setters. We planned to have whole genome sequence augment the data generated from the genomic screen. We were able to generate whole genome sequence for three Irish Setters: 2 HOD-affected, and 1 healthy. Using the boxer reference as a control, as well as data from several other breeds from our laboratory, we were able to compare the coding sequence in regions identified by the genomic screen and CRMO candidate genes in HOD-affected dogs to healthy dogs. Several variants were detected and are currently being investigated further. The combination of two whole-genome approaches did not yield a major locus contributing to HOD in Irish Setters. Two genomic regions appear interesting, but further research is needed to understand the genetic contribution to the onset of HOD. The availability of whole-genome sequence will allow for immediate assessment of candidate genes identified from the genomic screen and/or future studies. There is no test at this time that can reliably detect HOD risk alleles. Additional analyses with new software programs are being carried out. It is our hope that these secondary analyses will help dissect the complex genetic control of HOD. Further work remains necessary to elucidate these mechanisms.


None at this time.

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