Department of Genetics and Biochemistry, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC 29634, USA.
Mamm Genome. 2012 Feb;23(1-2):203-11. doi: 10.1007/s00335-011-9376-9. Epub 2011 Nov 22.
The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.
德国牧羊犬（GSD）是一种受欢迎的工作犬和伴侣犬，已有超过 50 种遗传性疾病被记录在案。在这里，使用 Affymetrix v2 犬 SNP 阵列为 197 只 GSD 生成 SNP 图谱，进行全基因组关联研究，以确定与四种疾病相关的基因座：垂体侏儒症、进行性多灶性脑白质病（DM）、先天性巨食管（ME）和胰腺腺泡萎缩（PAA）。9 号染色体上的一个基因座与垂体侏儒症密切相关，并且靠近一个可能的候选基因 LHX3。DM 的结果证实了一个包含 SOD1 的主要基因座，其中先前已经确定了一个相关的点突变，但没有提示修饰基因座。12 号染色体上的几个 SNP 与 ME 相关，受影响的犬只存在一个 4.7 Mb 的单倍型块。对该单倍型内的 SNP 进行额外 ME 病例分析提供了对该关联的进一步支持。PAA 的结果表明其具有更复杂的遗传基础。多个染色体上的几个区域达到全基因组显著水平。然而，没有明显的主要基因座，只观察到两个相关的单倍型块，位于 7 号和 12 号染色体上。这些数据表明，PAA 可能由多个具有小效应的基因座控制，或者它可能是一种异质性疾病。
