Zhao Hui, Du Yanli, Chen Shunmei, Qing Lili, Wang Xiaoyan, Huang Jingfei, Wu Dongdong, Zhang Yaping
Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091, China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Infect Genet Evol. 2015 Dec;36:531-538. doi: 10.1016/j.meegid.2015.08.031. Epub 2015 Aug 28.
Prion protein, encoded by the prion protein gene (PRNP), plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Several polymorphisms within the PRNP are known to be associated with influencing bovine spongiform encephalopathy (BSE) susceptibility in cattle, namely two insertion/deletion (indel) polymorphisms (a 23-bp indel in the putative promoter and a 12-bp indel in intron 1), the number of octapeptide repeats (octarepeats) present in coding sequence (CDS) and amino acid polymorphisms. The domestic buffaloes, Bubalus bubalis, are a ruminant involved in various aspects of agriculture. It is of interest to ask whether the PRNP polymorphisms differ between cattle and buffalo. In this study, we analyzed the previously reported polymorphisms associated with BSE susceptibility in Chinese buffalo breeds, and compared these polymorphisms in cattle with BSE, healthy cattle and buffalo by pooling data from the literature. Our analysis revealed three significant findings in buffalo: 1) extraordinarily low deletion allele frequencies of the 23- and 12-bp indel polymorphisms; 2) significantly low allelic frequencies of six octarepeats in CDS and 3) the presence of S4R, A16V, P54S, G108S, V123M, S154N and F257L substitutions in buffalo CDSs. Sequence alignments comparing the buffalo coding sequence to other species were analyzed using the McDonald-Kreitman test to reveal five groups (Bison bonasus, Bos indicus, Bos gaurus, Boselaphus tragocamelus, Syncerus caffer caffer) with significantly divergent non-synonymous substitutions from buffalo, suggesting potential divergence of buffalo PRNP and others. To the best of our knowledge this is the first study of PRNP polymorphisms associated with BSE susceptibility in Chinese buffalo. Our findings have provided evidence that buffaloes have a unique genetic background in the PRNP gene in comparison with cattle.
朊病毒蛋白由朊病毒蛋白基因（PRNP）编码，在传染性海绵状脑病（TSEs）的发病机制中起关键作用。已知PRNP内的几种多态性与影响牛海绵状脑病（BSE）易感性有关，即两种插入/缺失（indel）多态性（推定启动子中的23 bp indel和内含子1中的12 bp indel）、编码序列（CDS）中八肽重复序列（八肽重复）的数量以及氨基酸多态性。家养水牛（Bubalus bubalis）是一种参与农业各个方面的反刍动物。研究牛和水牛之间PRNP多态性是否存在差异很有意义。在本研究中，我们分析了先前报道的与中国水牛品种BSE易感性相关的多态性，并通过汇总文献数据，将这些多态性在患BSE的牛、健康牛和水牛中进行了比较。我们的分析在水牛中发现了三个重要发现：1）23 bp和12 bp indel多态性的缺失等位基因频率极低；2）CDS中六个八肽重复序列的等位基因频率显著较低；3）水牛CDS中存在S4R、A16V、P54S、G108S、V123M、S154N和F257L替代。使用麦克唐纳-克雷特曼检验分析了将水牛编码序列与其他物种进行比较的序列比对，以揭示五组（欧洲野牛、印度牛、白肢野牛、四角羚羊、南非水牛）与水牛有显著不同非同义替代的物种，这表明水牛PRNP与其他物种可能存在差异。据我们所知，这是首次对中国水牛中与BSE易感性相关的PRNP多态性进行研究。我们的研究结果提供了证据，表明与牛相比，水牛在PRNP基因中具有独特的遗传背景。
