Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17p, 30559 Hannover, Germany.
J Hered. 2011 Sep-Oct;102 Suppl 1:S68-73. doi: 10.1093/jhered/esr053.
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.
持续性右主动脉弓（PRAA）是一种常见于几种犬种的先天性血管环异常。在德国牧羊犬中，该疾病的特征是左食管后锁骨下动脉与起源于异常左锁骨下动脉（PRAA-SA-LA）的动脉韧带相结合。在这项研究中，我们对德国牧羊犬的 26 号染色体（CFA26）上的 38 个微卫星标记进行了基因分型，并对其进行了连锁和关联测试。我们在 CFA26 上发现了一个全染色体显著连锁的基因组区域，该区域与人类 DiGeorge 综合征关键区域（DGCR）相对应。因此，我们分析了 DGCR 中的 13 个基因和犬 T 盒基因 TBX1 的序列。我们在德国牧羊犬中总共发现了 26 个多态性。其中 3 个 SNP 位于 TBX1 内，1 个位于线粒体核糖体蛋白 L40 基因（MRPL40）内，与德国牧羊犬的 PRAA-SA-LA 表型相关。尽管 PRAA-SA-LA 与犬科 DGCR 之间存在连锁和关联，但这些突变似乎都不是导致 PRAA-SA-LA 的原因。由于人类 22q11.2 上的同源区域易发生基因组重排，我们怀疑在德国牧羊犬中，染色体异常可能导致 PRAA-SA-LA。
