ICCFGG 2022
#26 Genetic investigation of spontaneous harlequin coat patterning in a family of Australian Shepherds Katherine Singleton1 , Rooksana E. Noorai1, 2, Jacquelyn M. Evans1,3, Leigh Anne Clark1 kgsingl@g.clemson.edu 1Department of Genetics and Biochemistry, Clemson University, Clemson, SC, USA; 2Clemson University Genomics and Bioinformatics Facility, Clemson University; Clemson, SC, USA; 3Baker Institute for Animal Health, Cornell University, Ithaca, NY, USA The ubiquitin-proteasome system is a highly complex process through which damaged proteins are degraded. In the Great Dane breed, a coat pattern known as harlequin is caused by heterozygosity for a missense mutation in PSMB7, impacting the catalytic beta-2 subunit of the proteasome. All harlequins are also heterozygous for the Merle allele of SILV, which harbors a retrotransposon that leads to production of abnormal protein. In melanocytes with impaired protein degradation, aberrant SILV is thought to accumulate and cause cell death, resulting in the characteristic white base coat of a harlequin dog. We identified a novel spontaneous harlequin pattern in a family of Australian shepherds. Pedigree analysis confirmed transmission of a dominant allele, independent of Merle, by the tricolored sire. We generated genome-wide SNP profiles for the sire and five het- erozygous Merle family members and identified 32 chromosomal regions with genotype patterns consistent with the mode of inheritance: heterozygous in the sire and harlequin offspring (n=4) and absent from the non-harlequin merles (n=2). To identify candidate causal variants in these regions, we generated whole genome and skin transcriptome sequences from a harlequin dog. High quality, heterozygous variants were filtered against multibreed VCFs representing over 1300 canines to identify protein coding changes private to the Australian shepherd dog family. Variant effect was predicted for remaining variants using in silico programs. The identification of novel mutations that cause harlequin patterning in merle dogs will provide insight into genes and sequences critical for proper function of the ubiquitin-proteasome system. #27 Whole genome sequencing of an Old English Sheepdog with multiple-ocular defect identifies a candidate causal variant with a probable dominant mode of inheritance in a collagen-type gene Stanbury, K.1 , Pettitt, L.1, Schofield, E.C1, Oliver, J.A.3, Dixon, C.2, Burmeister, L.M.1, Ricketts, S.L.1, Mellersh, C.S.1 ks2017@cam.ac.uk 1Kennel Club Genetics Centre, Department of Veterinary Medicine, University of Cambridge, UK, 2Veterinary Vision, UK, 3Ophthalmology Department, Dick White Referrals, UK. Multiple-ocular defect (MOD) is an inherited ocular syndrome that has an increased prevalence in a number of breeds including the Old English Sheepdog (OES). Affected dogs typically present with multiple and various ocular abnormalities. Our objectives were to describe the clinical presentation of MOD in the OES and use whole genome sequence (WGS) analysis to identify the causal variant. A seven-year-old female OES that had been diagnosed with hereditary cataracts (HC) at the age of five was referred to a board-certified veterinary ophthalmologist due to owner-reported visual de- terioration. An ophthalmic assessment revealed that in addition to the cataracts there was bilateral
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