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肺癌在生物学上具有侵袭性，并且是癌症相关死亡的主要原因。根据临床特征、预后、对治疗的反应和耐受性，每一例肺癌患者的进展均是独特的。传统上基于毛细管的单基因测序的第一代技术（如sanger测序法）已被允许大量平行测序且成本更低、通量更高的下一代测序技术（next-generation sequencing，NGS）所替代。与传统方法相比，NGS技术取得显著进步。我们希望这些方法可全面地解释癌症全球图谱，并提供更多信息以满足个体化用药的需求。本综述包括对不同NGS技术的简要说明，NGS在肺癌研究进展中的应用和重要发现的总结，包括对已知靶基因（EGFR、ALK和KRAS）的进一步探索、其它肺癌突变的鉴定和癌症基因组研究的全局协调。

目的 克隆、测序人类OPRM1-EXON1，并用非同位素-生物素标记法对该基因进行标记、制备探针，用于OPRM1-EXON1的表达及功能研究。方法 通过PCR法扩增目的基因片段，并将其连接到pGEM-T载体上，转入感受态细胞中进行重组并克隆，经酶切和基因测序进行鉴定，用非同位素-生物素标记法进行探针的标记与制备。结果 经过PCR扩增的目的基因片段大小(2．2kb)与理论上片段大小一致，经过测序证实其序列与NCBI提供的序列相同，用此片段成功的制备了用于研究阿片受体基因的探针。结论 从基因组中成功克隆了人类OPRM1-EX-ON1，并制备了探针，为深入研究吗啡依赖相关基因及基因表达创造了必要的条件。

目的 建立人eck是基因外显子3(exon-3)的克隆与鉴定方法，研究其在ZR-75-1细胞系中的突变情况。方法 设计一对eck是基因exon-3特异性引物，提取人正常皮肤组织和乳腺癌细胞系ZR-75-1基因组DNA，并以此作为模板，采用聚合酶链反应(PCR)技术扩增即是基因exon-3片段，克隆入中介载体pUCm-T中构建重组质粒，转化JMl09大肠杆菌，扩增后经酶切、PCR初步鉴定后，进行序列分析。结果 ①从正常皮肤组织上皮细胞、ZR-75-1细胞系基因组DNA中，经PCR扩增，获得了人eck基因exon-3片段；②建立了正常皮肤组织、ZR-75-1细胞系即是基因exon-3片段的克隆；③ZR-75-1细胞系中eck基因exon-3片段存在突变。结论 从人组织与细胞系基因组DNA中，成功地构建了人类eck基因exon-3的克隆，并证实eck基因exon-3在ZR-75-1乳腺癌细胞系中有突变，为进一步研究eck是基因exon-3在肿瘤形成中的作用奠定了基础。

目的 分析寻常型银屑病患者维甲酸受体α基因序列。方法 选取对维甲酸有不同反应性的寻常型银屑病患者有核细胞，提取其基因组DNA，通过聚合酶链反应扩增维甲酸受体α的第6外显子序列，并对扩增产物进行序列测定。结果 第6外显子第93位碱基存在差异，出现C→G的改变。但从我们选取的对维甲酸反应性不同的寻常型银屑病患者中，未发现彼此间外显子碱基序列存在差异。结论 银屑病患者维甲酸受体α第6外显子碱基序列发生突变，但目前还不能确定突变点在维甲酸反应性差异中的作用。

Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons （ASEs）, and that inhibition of DNA methylation results in aberrant splicing of ASEs. The methyl- CpG-binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased histone acetylation and aberrant ASE-skipping events. We further show that inhibition of histone deacetylase （HDAC） activity leads to exon skipping that shows a highly significant degree of overlap with that caused by MeCP2 knockdown. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative RNA splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through the subsequent recruitment of HDACs.

The incidence of lung cancer from never smokers has increased dramatically in China nowadays. Strikingly, approximately 30% of the lung cancer patients in East Asian population are never smokers [1, 2]. The majority of these patients are females with lung adenocarcinomas [2]. Identification of oncogenic drivers, which the tumors are ＂addicted to＂ and rely on for survival, has signifi- cantly reformed the current strategies for lung cancer treatment in clinic and initiated the era of personalized therapy [3]. Therapeutics specifically targeting EGFR mutations, frequently observed in never smoker patients with lung cancer, have been very helpful in improving the clinical symptoms as well as the progression-free sur- vival [4-6]. Similarly, patients with lung tumors positive for ALK fusions also benefit from ALK-targeted therapy [7, 8].

Background: Posttraumatic stress disorder (PTSD) involves a complex interaction of biological, psychological, and social factors. Numerous studies have demonstrated genetic variation associated with the development of PTSD, primarily in adults. However, the contribution of low frequency and rare genetic variants to PTSD is unknown to date. Moreover, there is limited work on genetic risk for PTSD in child and adolescent populations. Objective: This preliminary study aimed to identify the low frequency and rare genetic variation that contributes to PTSD using an exome array. Method: This post-disaster, adolescent sample (n = 707, 51% females, M age = 14.54) was assessed for PTSD diagnosis and symptom count following tornado exposure. Results: Gene-based models, covarying for ancestry principal components, age, sex, tornado severity, and previous trauma identified variants in four genes associated with diagnosis and 276 genes associated with symptom count (at p adj < .001). Functional class analyses suggested an association with variants in the nonsense class (nonsynonymous variant that results in truncation of, and usually non-functional, protein) with both outcomes. An exploratory gene network pathway analysis showed a great number of significant genes involved in brain and immune function, illustrating the usefulness of downstream examination of gene-based findings that may point to relevant biological processes. Conclusions: While further investigation in larger samples is warranted, findings align with extant PTSD literature that has identified variants associated with biological conditions such as immune function. * This study aimed to identify low frequency and rare genetic variation that contributes to PTSD using an exome array in a disaster-exposed adolescent sample. * Gene-based models, identified 4 genes associated with PTSD diagnosis and 276 genes associated with PTSD symptom count. * Functional class analyses suggested an association with the nonsense class with both outcomes. * Networks related to immune function appeared to be particularly relevant.

The zinc-finger DNA-binding protein CTCF has been known for being a constituent of insulators. A recent paper in Nature reports an unforeseen intragenic role for CTCF that links DNA methylation with alternative splicing. By binding to its target DNA site placed within an alternative exon, CTCF creates a roadblock to transcriptional elongation that favors inclusion of the exon into mature mRNA. DNA methylation prevents CTCF binding, which releases pol II transient blockage and promotes exon exclusion.

Alternative splicing （AS） is a post-transcriptional process that can add complexity to proteome greatly by producing multi- ple different mature transcripts from the same pre-RNA （Black, 2003）. Ever since its discovery, multiple kinds of different AS types have been identified, for example, exon skipping （or cassette exon）,

RNA-Seq technology is becoming widely used in various transcriptomics studies; however, analyzing and interpreting the RNA-Seq data face serious challenges. With the development of high-throughput sequencing technologies, the sequencing cost is dropping dramatically with the sequencing output increasing sharply. However, the sequencing reads are still short in length and contain various sequencing errors. Moreover, the intricate transcriptome is always more complicated than we expect. These challenges proffer the urgent need of efficient bioinformatics algorithms to effectively handle the large amount of tran- scriptome sequencing data and carry out diverse related studies. This review summarizes a number of frequently-used applica- tions of transcriptome sequencing and their related analyzing strategies, including short read mapping, exon-exon splice junc- tion detection, gene or isoform expression quantification, differential expression analysis and transcriptome reconstruction.