A processed pseudogene contributes to apparent mule deer prion gene heterogeneity
A processed pseudogene contributes to apparent mule deer prion gene heterogeneity
复制标题
DOI：
10.1016/j.gene.2003.10.022
复制
发表时间：
2004-02-04
期刊：
影响因子：
3.5
通讯作者：
Knowles, DP
中科院分区：
文献类型：
--
作者：
Brayton, KA;O'Rourke, KI;Knowles, DP
朊病毒疾病（传染性海绵状脑病，TSE）的发病机制和传播是由修饰的朊病毒蛋白（PrP）亚型介导的。已经在绵羊、人类和可能的麋鹿中发现了与 TSE 相对易感性相关的朊病毒蛋白基因 (PRNP) 等位基因。长耳鹿是一种容易感染 TSE 慢性消耗性疾病 (CWD) 的物种，但尚未得出类似数据。对长耳鹿 PRNP 基因外显子 3 开放阅读框 (ORF) 的初步分析显示，所有 145 个分析样本均存在多态性，其中有 10 个潜在多态性位点。由于 144/145 (99.3%) 的样本在密码子 138 (bp 412) 处存在编码变化 (N/S) 且在 bp 418 处存在非编码多态性，因此是杂合的，并且鉴定出具有三个或四个不同等位基因的个体鹿，表明可能存在基因重复。对含有长耳鹿 PRNP 基因的 BAC 克隆的分析揭示了全长功能基因和加工后的假基因。假基因是先前描述的逆转录元件的特征，因为它缺乏内含子并且两侧是重复序列。鉴定出功能基因的三个等位基因，仅在密码子 20 (D/G) 和 225 (S/F) 处发生编码变化。对 47 只 CWD 阳性长耳鹿的 PRNP 功能基因等位基因的测定显示，主要等位基因编码 20D225S（频率 0.85）。当等位基因根据功能基因的编码变化进行分组时，在受感染的鹿中鉴定出了六种可能的肽组合中的四种。在所检查的长耳鹿样本中鉴定出三个外显子 3 中编码发生变化的假基因等位基因。由于 TSE 似乎是“仅蛋白质”疾病，因此未翻译的假基因的存在预计不会影响抗病性。因此，选择针对功能基因的基因分型方法对于大规模研究以确定 PRNP 基因在黑尾鹿 CWD 易感性中的作用至关重要。 (C) 2003 年，Elsevier B.V. 出版
Pathogenesis and transmission of the prion disorders (transmissible spongiform encephalopathies, TSEs) are mediated by a modified isoform of the prion protein (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility to TSE have been identified in sheep, humans and possibly elk. Comparable data have not been derived for mule deer, a species susceptible to the TSE chronic wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed, with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were heterozygous for a coding change (N/ S) at codon 138 (bp 412) and a non-coding polymorphism at bp 418, and individual deer with three or four different alleles were identified a possible gene duplication was indicated. Analysis of BAC clones containing mule deer PRNP genes revealed a full length functional gene and a processed pseudogene. The pseudogene was characteristic of previously described retroelements, in that it lacks introns and is flanked by repeat sequences. Three alleles of the functional gene were identified, with coding changes only at codons 20 (D/G) and 225 (S/F). Determination of PRNP functional gene alleles from 47 CWD-positive mule deer showed the predominant allele encoded 20D225S (frequency 0.85). When alleles were grouped by coding changes in the functional gene, four of the six possible peptide combinations were identified in infected deer. Three pseudogene alleles with coding changes in exon 3 were identified in the mule deer samples examined. Because the TSEs appear to be "protein only" disorders, the presence of an untranslated pseudogene is not expected to affect disease resistance. Therefore, selection of a genotyping method specific for the functional gene is critical for large-scale studies to identify the role of the PRNP gene in susceptibility to CWD in mule deer. (C) 2003 Published by Elsevier B.V.