title: A rare form of persistent right aorta arch in linkage disequilibrium with the DiGeorge critical region on CFA26 in German Pinschers.
abstract: Persistent right aortic arch (PRAA) is a congenital vascular ring anomaly common in several dog breeds. In German Pinscher, the disorder is characterized by a left retroesophageal subclavian artery in combination with a ligamentum arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). In this study, we genotyped 38 microsatellite markers on canine chromosome 26 (CFA26) in German Pinschers and tested them for linkage and association. We found a chromosome-wide significantly linked genomic region on CFA26, which corresponds to the human DiGeorge syndrome critical region (DGCR). Therefore, we analyzed sequences from 13 genes of DGCR and the canine t-box gene TBX1. We identified a total of 26 polymorphisms in German Pinschers. Three of these SNPs located within TBX1 and one in the mitochondrial ribosomal protein L40 gene (MRPL40) were associated with the PRAA-SA-LA phenotype in German Pinscher. Despite linkage and association between PRAA-SA-LA and the canine DGCR, none of these mutations appeared responsible for PRAA-SA-LA. As the orthologue human region on HSA22q11.2 is known for high susceptibility to genomic rearrangements, we suspect that in German Pinschers, chromosomal aberrations might cause PRAA-SA-LA.
authors.affiliation: Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17p, 30559 Hannover, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Philipp
authors.forename: Julia
authors.initials: J
authors.lastname: Menzel
authors.forename: Ottmar
authors.initials: O
authors.lastname: Distl
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities*; D001483:Base Sequence; D002874:Chromosome Mapping; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics*; D004285:Dogs / Q000002:abnormalities* / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D018895:Microsatellite Repeats / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: D017931:DNA Primers; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins; D020825:T-Box Domain Proteins