Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
J Hered. 2011 Sep-Oct;102 Suppl 1:S40-6. doi: 10.1093/jhered/esr048.
Due to their unique population structure, purebred dogs have emerged as a key model for the study of complex genetic disorders. To evaluate the utility of a newly available high-density canine whole-genome array with >170,000 single nucleotide polymorphisms (SNPs), genome-wide association was performed on a small number of case and control dogs to determine disease susceptibility loci in canine necrotizing meningoencephalitis (NME), a disorder with known non-Mendelian inheritance that shares clinical similarities with atypical variants of multiple sclerosis in humans. Genotyping of 30 NME-affected Pug dogs and 68 healthy control Pugs identified 2 loci associated with NME, including a region within dog leukocyte antigen class II on chromosome 12 that remained significant after Bonferroni correction. Our results support the utility of this high-density SNP array, confirm that dogs are a powerful model for mapping complex genetic disorders and provide important preliminary data to support in depth genetic analysis of NME in numerous affected breeds.
由于其独特的种群结构,纯种狗已成为研究复杂遗传疾病的重要模型。为了评估一种新的、包含超过 17 万个单核苷酸多态性(SNP)的高密度犬全基因组基因芯片的效用,对少量病例和对照犬进行了全基因组关联分析,以确定犬坏死性脑膜脑炎(NME)的易感基因座。NME 是一种具有已知非孟德尔遗传的疾病,与人类的多发性硬化症的非典型变异具有临床相似性。对 30 只患有 NME 的哈巴狗和 68 只健康的哈巴狗对照组进行基因分型,确定了与 NME 相关的 2 个基因座,包括位于 12 号染色体上的犬白细胞抗原 II 类的一个区域,该区域在经过 Bonferroni 校正后仍然显著。我们的研究结果支持了这种高密度 SNP 基因芯片的效用,证实了狗是一种强大的用于绘制复杂遗传疾病图谱的模型,并提供了重要的初步数据,以支持对众多受影响品种的 NME 进行深入的遗传分析。