Analysis of candidate regions for ectopic ureter in dog (Canis familiaris) genomeMulac, Roberta (Avtor) Dovč, Peter (Mentor) ectopic ureterKarst ShepherdGWAS analysisSNPGEMMAEctopic ureter (EU) is a congenital anomaly in which one or both ureters terminate in a site other than trigone of the urinary bladder. Ectopic ureter is classified according to the location of their termination as extravesicular (EVEU) or intravesicular (IVEU). Other classification is according to their course until their terminal orifice as extramural or intramural. Ectopic ureter can be accompanied by other urogenital system abnormalities such as dysplasia or hypoplasia, ureter dilatation, renal agenesis, hydronephrosis, hypoplastic bladder, vaginal septum, dual vagina and many others. Study made in Slovenia showed a higher incidence of ectopic ureter in Karst Shepherds. The Karst Shepherd is a Slovenian autochthonous livestock guard breed. Since it is a very small population and due to high level of inbreeding, many diseases, including ectopic ureter, are inherited from generation to generation. Nowadays, most of the animals are screened for the disease to avoid transmission to the new generations. Applying GWAS analysis for samples with known family relationship, we aimed to find a possible candidate gene for ectopic ureter in Karst Shepherd population and compare them to other dog breeds and candidate genes in humans. GWAS analysis was performed using genome-wide efficient mixed model (GEMMA). The results were shown in Manhattan plot and the most significant peaks were found on chromosomes 5, 21 and 30. The most significant p-values falls into area of genes MAPK6, GALK2, SEMA6D, TLN2, ALDH1A2, ANO5, ANO3, BDNF, LUZP2, NFIA and ATP84B. Peaks with significant p-value are found at a higher frequency in cases than control, which suggest that genes mentioned above can be associated with EU. The highest peak falls into area of gene MAPK6. Mitogen-Activated Protein Kinase 6 encodes a member of the Ser/Thr protein kinase family and is closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases (also known as extracellular signal-regulated kinases (ERKs)) are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. Molecules from the RAS/ERK MAP kinase signalling pathway are strongly expressed in the Wolffian duct. As mentioned above, his pathway is one of the signalling pathways activated by GDNF/ret signalling. GDNF and c-ret are highly expressed in ureteric bud and Wolffian duct and have a role in development and branching of ureteric bud.20212021-10-20 08:50:00Magistrsko delo/naloga132281VisID: 19061COBISS_ID: 88545027sl