Genetic variability of HPV-58 E6 and E7 genes in Southwest China
Genetic variability of HPV-58 E6 and E7 genes in Southwest China
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中国西南地区HPV-58 E6和E7基因的遗传变异性。
DOI：
10.1016/j.meegid.2013.12.009
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发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Sun, Qiangming
中科院分区：
文献类型：
--
作者：
Yang, Lijuan;Yang, Hongying;Sun, Qiangming
HPV占宫颈癌发病率的大部分。E6和E7的遗传变异可能与特定地理区域宫颈癌的发生有关。HPV-58是中国西南地区女性中相对流行的高危型HPV。为探讨西南地区HPV-58 E6和E7基因的遗传变异和多态性，收集2000例刮取细胞标本进行DNA提取和HPV分型。对22例HPV-58株E6和E7基因进行测序，并与GenBank中已发表的E6和E7基因进行比较，用DNASTAR软件分析其二级结构的多样性。用邻接法和Kimura 2-参数法构建系统发育树，用PAML软件分析E6/E7基因的选择压力。215例高危型标本中HPV-58阳性22例。22例HPV-58 E6序列中E6核苷酸变异率为86.36%（19/22）。在E6序列中发现了4个单核苷酸突变，其中3/4为同义突变（C187 T，A260 C，C307 T），1/4为非同义突变（A388 C，从Lys到Asn，在α螺旋中）。E6基因最常见的突变是C307 T和A388 C。在HPV-58 E7序列中发现了8个单核苷酸变异，其中2/8个同义突变（T726 C，T744 G）和6/8个非同义突变（G599 A，C632 T，G694 A，G760 A，G761 A，T803 C）。E7基因核苷酸变异率为72.73%（17/22）。E7基因最常见的突变是C632 T、G694 A、T744 G、G760 A（依次从Gly变为Ser）、G761 A和T803 C。系统发育分析表明，所有鉴定的HPV-58 E6/E7变异体都属于东南亚谱系。在HPV-58 E6和E7基因的序列比对中没有证据表明正选择。(C)2013年爱思唯尔B。V.保留所有权利。
HPV accounts for most of incidence of cervical cancer. Genetic variations of E6 and E7 may be associated with the development of cervical cancer in specific geographic regions. HPV-58 has been found to be a relatively prevalent high-risk HPV among southwest Chinese women. To explore gene intratypic variations and polymorphisms of HPV-58 E6 and E7 genes originating in Southwest China, a total of 2000 scraped cell samples were collected for DNA extraction and HPV typing. Then, the E6 and E7 genes of HPV-58 (n = 22) were sequenced and compared to others submitted to GenBank, followed by an analysis of the diversity of secondary structure by DNASTAR software. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods, followed by an analysis of selection pressures acting on the E6/E7 genes by PAML software. 22 were HPV-58 positive among 215 high-risk types' samples. The nucleotide variation rate of E6 was 86.36% (19/22) among the 22 HPV-58 E6 sequences studied. 4 single nucleotide changes were identified among the E6 sequences with 3/4 synonymous mutations (C187T, A260C, C307T) and 1/4 non-synonymous mutations (A388C, from Lys to Asn, in alpha helix). The most common mutations of E6 genes are the C307T and A388C. 8 single nucleotide changes were identified among the HPV-58 E7 sequences with 2/8 synonymous mutations (T726C, T744G) and 6/8 non-synonymous mutations (G599A, C632T, G694A, G760A, G761A, T803C). The nucleotide variation rate of E7 was 72.73% (17/22). The most common mutations of E7 genes are C632T, G694A, T744G, G760A (from Gly to Ser, in turn), G761A and T803C. The phylogenetic analyses demonstrate that all HPV-58 E6/E7 variants identified belonged to the Southeast Asia lineage. There was no evidence of positive selection in the sequence alignment of HPV-58 E6 and E7 genes. (C) 2013 Elsevier B. V. All rights reserved.