954: Identification of Genes Causing Chiari I Malformation with Syringomelia in the Cavalier King Charles Spaniel
Grant Status: Closed
Chiari-like malformation (CM) is a deformity that occurs in the region where the brain joins the spinal cord and that is present at birth. The lower portions of the brain protrude into the vertebral canal causing a variety of clinical signs. CM is often associated with syringomyelia (SM), which describes an abnormal collection of cerebral spinal fluid within the spine. The symptoms of CM/SM vary in severity from mild pain to more devastating neuropathic pain which includes persistent scratching at one side of the shoulder/neck. Some dogs have other neurological deficits including paresis, poor coordination (ataxia) and spinal curvature (scoliosis) abnormalities. This condition is particularly common in the Cavalier king Charles Spaniels (CKCS) as compared to other breeds, suggesting the involvement of genetic factors in the etiology of this disease. In this study, we will identify and characterize the gene(s) defective in this disease. We conducted a first scan of the whole genome and identified six candidate genomic regions that could harbour the CM/SM gene(s). Genetic investigation of these candidate regions confirmed linkage of CM/SM to one region on chromosome 4. We have identified a set of alleles that are over-represented in the unaffected dogs and hence might confer protection against the disease. We are currently identifying all genes residing in this region and resequencing them in affected and unaffected dogs. Identification of the CM/SM gene(s) will allow the development of a DNA test that will allow breeders to identify carriers and devise breeding strategies with the aim of reducing or eliminating this devastating condition in the dog. These studies will also help us better understand the pathogenic mechanisms involved in CM/SM for better treatment strategies.
Lemay, P., Knowler, S. P., Bouasker, S., Nédélec, Y., Platt, S., Freeman, C., … Kibar, Z. (2014). Quantitative Trait Loci (QTL) Study Identifies Novel Genomic Regions Associated to Chiari-Like Malformation in Griffon Bruxellois Dogs. PLoS ONE, 9(4), e89816. https://doi.org/10.1371/journal.pone.0089816
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