POSTER ABSTRACTS
#18 Genetic loci associated with thoracolumbar myelopathy in pugs harbor candidate Brander G.1,2* , Rohdin C.3*, Bianchi M.1, Andersson A.4, Hedhammar A.3, Lindblad-Toh K1,2*, Tengvall K.1* *Authors contributed equally gbrander@broadinstitute.org 1Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden, 2Broad Institute of MIT and Harvard, Cambridge, MA, USA, 3Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden, 4Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden The pug has been bred to promote characteristics such as small stature, flat face, large head, bulging eyes, and soft and thin ears. The breed has a well-known predisposition to the brachy- cephalic obstructive airway syndrome but also to several other disorders including spinal cord disease (myelopathy). Pugs with thoracolumbar myelopathy presents with pelvic limb ataxia and paresis and a predictive, progressive, clinical course. Affected pugs are usually euthanized by the time they are unable to ambulate or develop incontinence. Different etiologies for the condition, including meningeal and vertebral column pathologies, have been proposed. Due to the breed specific appearance of thoracolumbar myelopathy in pugs and common clinical and pathological findings, genetic components are likely to be involved. We performed genome wide association analyses using a mixed linear model (GWAS), a bayesian model adapted for mapping complex traits (BayesR), and a cross-population extended haplotype test (XP-EHH) to search for disease-associated loci in 51 pugs affected by thoracolumbar my- elopathy and 38 pug controls. Five associated regions were defined; one locus on chr4 reached genome-wide significance in GWAS, one locus on chr17 (53Mb) was defined by the top effect variant in BayesR, and three loci on chr15, chr17 (57Mb), and chr30, presented with differences in extended haplotype homozygosity between cases and controls. Candidate genes from the five regions included BICC1, TFAM, CASQ2, VANGL1, MGAT4C, NOTCH2, and EHD4, all having reported association with cartilage from previous studies. In conclusion, we identified candidate genes with a common denominator in cartilage with potential relevance to the pathogenesis of thoracolumbar myelopathies in pugs.
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