A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis
A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis
复制标题
DOI：
10.1016/j.bbrc.2004.12.038
复制
发表时间：
2005-02-11
影响因子：
3.1
通讯作者：
Johnson, GS
中科院分区：
文献类型：
--
作者：
Katz, ML;Khan, S;Johnson, GS
英国塞特犬的遗传性神经退行性疾病长期以来一直作为人类神经元蜡样脂褐质沉积症（NCL）的模型进行研究。Megablast搜索犬基因组的第一个构建的潜在致病基因，将CLAW基因定位在犬37号染色体的q端粒附近，靠近先前与英国塞特犬NCL相关的标记。从受影响的狗的编码区的序列分析显示，在CLN 8基因的预测p.L164P错义突变的T到C的转变。亮氨酸1644在其他四种哺乳动物中是保守的。C等位基因共分离的疾病表型在两代英国塞特家庭的模式符合自染色体隐性遗传。NCL家系4名成员均为C/C纯合子，4名携带者均为C/T杂合子。103只无关犬均为T/T纯合子。这些结果表明，CLN 8 T-到-C转换是可能的原因，英语二传手NCL。(C)2004爱思唯尔公司All rights reserved.
A heritable neurodegenerative disease of English Setters has long been studied as a model of human neuronal ceroid-lipofuscinosis (NCL). Megablast searches of the first build of the canine genome for potential causative genes located the CLAW gene near the q telomere of canine chromosome 37, close to a marker previously linked to English Setter NCL. Sequence analysis of the coding region from affected dogs revealed a T-to-C transition in the CLN8 gene that predicts a p.L164P missense mutation. Leucine 1644 is conserved in four other mammalian species. The C allele co-segregated with the disease phenotype in a two generation English Setter family in a pattern consistent with autosornal recessive inheritance. All four NCL-affected family members were C/C homozyrMes and all four obligate carriers were C/T heterozygotes; whereas. 103 unrelated dogs were all T/T homozygotes. These findings indicate that the CLN8 T-to-C transition is the likely cause of English Setter NCL. (C) 2004 Elsevier Inc. All rights reserved.