环境微生物基因组技术研究进展

环境微生物基因组学是基于功能和序列的基础上对得到的环境样品基因组进行分析的科学,是目前国际生物技术研究开发的最新热点之一。对环境微生物基因组技术的概念、研究策略和筛选方式进行了介绍,并对该技术存在的问题和未来发展方向做了展望。     

癌肿基因组解剖计划

1 .引言肿瘤是多因子多步骤引起的疾病。肿瘤的发生与发展实质是一个克隆演化过程。在收稿日期 :2 0 0 1 0 2 2 2作者简介 :何祥火 (1972— ) ,男 ,博士生。此过程中伴随一系列细胞核内遗传物质的改变 ,包括序列改变如点突变、缺失、插入 ;结构畸变 ,如大范围缺失、重排、基因扩增[1] 。越来越多的证据表明 ,在克隆演化过程中的不同阶段存在不同基因的激活和 /或失活及其复杂的相互作用[2 ,3 ] ,给研究肿瘤发生的分子机制带来很大的挑战。同时 ,肿瘤细胞有遗传物质不稳定的倾向 ,其中哪些基因的改变起了至关重要的作用、哪些基因的改变只是…     

人类肿瘤基因组系统性突变分析带来的机遇

最近发表于《科学》杂志(Science)的“人类乳腺癌和结直肠癌共有编码序列”一文,是继人类基因组计划完成后,对人类疾病状态下基因组改变的首次无偏倚系统性分析.对如何利用该研究发现的候选癌基因获得肿瘤治疗药物的新靶标作初步分析,并介绍这些候选癌基因在识别肿瘤高危人群和依据分子机制更新肿瘤分型方面的潜在应用价值.     

基于全基因组关联的中国常见肿瘤遗传病因学研究

肿瘤是基因-环境交互作用引起的复杂性疾病.在同样的环境暴露下,不同遗传背景的个体发生肿瘤的风险有很大差异.研究肿瘤相关遗传因素对理解肿瘤发生发展乃至诊断治疗都有重要意义.近年来发展的全基因组关联研究(genome-wide association study,GWAS)可在全基因组范围内发现与复杂疾病或表型关联的遗传因素,为复杂疾病遗传学研究提供了强有力的手段.欧美研究者运用全基因组关联研究的方法,对各种常见肿瘤进行了研究,获得了重要成果.2010年以来,中国科学家在国际核心期刊发表了一系列高水平的肿瘤全基因组关联研究成果,在中国常见肿瘤的遗传病因学研究方面取得了重要进展.     

GADD45α参与维持基因组稳定性并发挥肿瘤抑制效应的多样性分子机制

哺乳动物细胞在遭受应激损伤因素刺激时会启动一系列信号传导通路,从而引发细胞周期阻滞、DNA修复或细胞凋亡等效应,这些机制的异常与肿瘤的发生发展密切相关。GADD45α作为生长阻滞及DNA损伤诱导基因编码家族的一员,参与维持基因组稳定性、调控细胞周期行进、DNA损伤修复、细胞衰老及细胞凋亡等多种生物学过程,在肿瘤发生发展和肿瘤抑制反应中具有重要作用。我们简要综述了GADD45α参与维持基因组稳定性并发挥肿瘤抑制效应的分子机制。     

环境微生物基因组技术研究

绝大多数微生物难以有效地进行人工培养,而且实验室工程菌几乎没有野生型功能,因此限制了基于自然微生物多样性的生物技术的应用.为了把对生物群落的结构、功能和细菌在自然环境中进化的认识应用到微生物工艺学中、微生物学家们正致力于把基因组学和相关的高通量技术应用到微生物培养体系和环境样品中,而这必将增添对生态系统及其生物学功能的新见解并带动生物技术的发展.从微生物鉴别及其基因功能的分析、确证和评价等方面综述了基因组技术在环境样品中的应用,提出了现今面临的问题,同时也对环境基因组技术做了展望.     

番茄RAPD分析有效引物3′端序列的偏倚分布及其与基因组序列结构的关系

对番茄RAPD分析的有效引物与Operon引物系列(OP系列)的3′端序列作了统计比较。研究结果指出,番茄有效引物系列不是OP系列的随机样本,而是3′端序列的种类和分布上有偏倚性的选择性样本。虽然两个系列的引物都具有3′端同序现象,但对其分布频率正交比较结果差异极显著,此类同序性3′端在番茄基因组的RAPD座位中是普遍分布的。RAPD引物3′端序列的非随机分布,反映了番茄基因组内的多态性区段侧翼具有序列的特异性,这种特异性结构应是番茄基因组序列的一种属性,这种属性为番茄属基因组所共有。 Abstract：The study of compared effectual primers 3′ end sequences between RAPD analysis used in tomato and Operon system. It is suggested that 3′ end sequences of primers for tomato RAPD are not the random samples of OP system, their 3′ end sequences are partial distribution in kinds and frequency. Though there have homologous sequences at 3′ end in both systems. But their distribution of frequency shows significant difference in orthogonal comparison. The 3′ ending homologous sequences in RAPD loci are found all over in tomato genome.Therefore the nonrandom distribution of 3′ end sequences of effectual primers in tomato RAPD reflected the sequence-specific structure may occur in tomato genome at flank of polymorphic regions. It is probably an attribute of tomato genomic sequence and is common in Lycopersicon.     

桉树基因组和功能基因组

本文就桉树基因组和功能基因组的研究进展作介绍。     

肿瘤表观基因组学、生物芯片和生物信息学

肿瘤的分子生物学研究一直是生命科学和医学研究的热点,随着科学技术的发展,高通量的分析方法在分子生物学研究中的广泛应用,使其成为肿瘤研究的一种高效手段,同时表观基因组学和生物信息学也促进了肿瘤学的发展,本文就表观基因组学、生物芯片和生物信息学方法在肿瘤研究中的应用进行综述,并对未来的发展和展望进行了讨论。     

线虫染色体研究揭示肿瘤基因组发生机制

近日一项针对线虫染色体DNA重排的研究揭示了肿瘤发生中大规模的基因组重复的机制.这一重要发现发表在4月22日在线刊出的Science杂志上.来自美国北卡罗莱纳大学教堂山分校医学院的科学家研究了线虫的端粒,也就是位于染色体末端的一     

肿瘤基因组研究进展

所有的肿瘤都源自于细胞基因组DNA序列的异常。在整个生命过程中,甚至从最初的受精卵开始,人体细胞的基因组就暴露于各种突变诱变因素和自身的复制错误之中,这些不利影响可能导致任何细胞的DNA序列渐进的、细微的突变。过去的25年中,这些突变和基因异常如何调控肿瘤的成长已经越来越多地为人们所认识,在此基础上,大量获得肿瘤基因组的完整DNA序列已经成为可能。这些研究将为人类提供肿瘤发生和成长的重要线索。     

Integrative Analysis of Genome, 3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples

Genomic studies of cancer cell alterations, such as mutations, copy number variations (CNVs), and translocations, greatly promote our understanding of the genesis and development of cancers. However, the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties. To explore the 3D genome structure in clinical lung cancer, we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer, combining with RNA sequenceing analysis. We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells (1 × 10⁴), compared the genome architecture between clinical samples and cell lines of lung cancer, and identified conserved and changed spatial chromatin structures between normal and cancer samples. We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer. By integrating those different types of cancer alterations, we showed significant associations between CNVs, 3D genome, and gene expression. We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures. Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.     

DNA损伤检验点与损伤修复及基因组稳定性

生物有机体基因组DNA经常会受到内源或外源因素的影响而导致结构发生变化,产生损伤;在长期进化过程中,有机体也相应形成了一系列应对与修复损伤DNA,并维持染色体基因组正常结构功能的机制。其中DNA损伤检验点（DNA damage checkpoint）就是在感应DNA损伤的基础上,对损伤感应信号进行转导,或引起细胞周期的暂停,从而使细胞有足够的时间对损伤DNA进行修复,或最终导致细胞发生凋亡。DNA损伤检验点信号转导途径是一个高度保守的信号感应过程,整个途径大致可以分为损伤感应、信号传递及信号效应3个组成部分。其中3-磷脂酰肌醇激酶家族类成员ATM（ataxia-telangiectasia mutated）和ATR（ataxia-telangiectasia and Rad3-related）活性的增加构成整个途径活化的第一步。它们通过激活下游的效应激酶,Chk2／Chk1,通过协同作用许多其他调控细胞周期、DNA复制、DNA损伤修复及细胞凋亡等过程的蛋白质因子来实现细胞对DNA损伤的高度协调反应。近十几年,随着此领域研究的不断深入,人们逐步揭示了DNA损伤检验点途径发生过程中,各种核心组分通过与不同调节因子、效应因子及DNA损伤修复蛋白间的复杂相互作用,以实现监测感应异常DNA结构并实施相应反应的机制;其中,检验点衔接因子（mediators）及染色质结构,尤其是核小体组蛋白的共价修饰在调控ATM／ATR活性,促进ATM／ATR与底物间的相互作用以及介导DNA损伤位点周围染色质区域上多蛋白复合物在时间与空间上的动态形成发挥着重要的作用。同时,人们也开始发现DNA损伤检验点途径与DNA损伤修复、基因组稳定性以及肿瘤发生等过程之间某些内在的联系。该反应途径在通过协调细胞针对DNA损伤做出各种反应的基础上,直接或间接地参与或调控DNA损伤修复过程,并与DNA损伤修复途径协同作用最终保证染色体基凶组结构的完整性,而检验点途径的改变,则会引起基因组不稳定的发生,包括从突变频率的提高到大范围的染色体重排,以及染色体数量的畸变。如：突变发生在肿瘤形成早期,会大大增加肿瘤发生的几率。文章将对DNA损伤检验点途径机制及其对DNA损伤修复、基因组稳定性影响的最新进展进行综述。     

DNA Damage Checkpoint, Damage Repair, and Genome Stability

Genomic DNA is under constant attack from both endogenous and exogenous sources of DNA damaging agents. Without proper care, the ensuing DNA damages would lead to alteration of genomic structure thus affecting the faithful transmission of genetic information. During the process of evolution, organisms have acquired a series of mechanisms responding to and repairing DNA damage, thus assuring the maintenance of genome stability and faithful transmission of genetic information. DNA damage checkpoint is one such important mechanism by which, in the face of DNA damage, a cell can respond to amplified damage signals, either by actively halting the cell cycle until it ensures that critical processes such as DNA replication or mitosis are complete or by initiating apoptosis as a last resort. Over the last decade, complex hierarchical interactions between the key components like ATM/ATR in the checkpoint pathway and various other mediators, effectors including DNA damage repair proteins have begun to emerge. In the meantime, an intimate relationship between mechanisms of damage checkpoint pathway, DNA damage repair, and genome stability was also uncovered. Reviewed hereinare the recent findings on both the mechanisms of activation of checkpoint pathways and their coordination with DNA damage repair machinery as well as their effect on genomic integrity.     

人类基因组计划与后基因组时代

2003年4月14日生命科学诞生了一个新的重要里程碑,人类基因组计划完成,后基因组时代正式来临。着重介绍了人类基因组计划的提出、目标与任务、实施与进展等方面的基本情况,讨论了后基因组时代的时间界定,分析展望了后基因组时代与人类基因组计划密切相关的生物信息学、功能基因组学、蛋白质组学、药物基因组学等几个重要研究领域 。     

环境因素对肺癌发生的影响

肺癌每年夺走人类几百万条生命,是当今一个重大的公共健康问题.吸烟是肺癌发生的重要诱因,但仅有10%～15%的吸烟者患肺癌.随着人类生活环境及生活方式的不断变化,肺癌患者正日益增多.研究发现,除遗传因素外,肺癌的发生主要与环境因素相关,包括吸烟、空气污染、饮水及食品污染、饮食习惯的改变等;环境致癌物透过皮肤等机体自然屏障和代谢屏障而进入细胞并损伤D NA,导致细胞生长、分化及凋亡失衡而形成肿瘤.因此,改善环境对于降低肺癌发生率具有积极的影响.     

Genome and stresses: Reactions against aggressions,behavior of transposable elements

The action of stresses on the genome can be considered as responses of cells or organisms to external aggressions. Stress factors are of environmental origin (climatic or trophic) or of genomic nature (introduction of foreign genetic material, for example). In both cases, important perturbations can occur and modify hereditary potentialities, creating new combinations compatible with survival; such a situation may increase the variability of the genome, and allow evolutive processes to take place. The behavior of transposable elements under stress conditions is thus of particular interest, since these sequences are sources of mutations and therefore of genetic variability; they may play an important role in population adaptation. The survey of the available experimental results suggests that, although some examples of mutations and transposable elements movements induced by external factors are clearly described, environmental injuries or introduction of foreign material into a genome are not systematically followed by drastic genomic changes.     

Comprehensive Draft Genome Analyses of Three Rockfishes (Scorpaeniformes,Sebastiscus) via Genome Survey Sequencing

Sebastiscus species, marine rockfishes, are of essential economic value. However, the genomic data of this genus is lacking and incomplete. Here, whole genome sequencing of all species of Sebastiscus was conducted to provide fundamental genomic information. The genome sizes were estimated to be 802.49 Mb (S. albofasciatus), 786.79 Mb (S. tertius), and 776.00 Mb (S. marmoratus) by using k-mer analyses. The draft genome sequences were initially assembled, and genome-wide microsatellite motifs were identified. The heterozygosity, repeat ratios, and numbers of microsatellite motifs all suggested possibly that S. tertius is more closely related to S. albofasciatus than S. marmoratus at the genetic level. Moreover, the complete mitochondrial genome sequences were assembled from the whole genome data and the phylogenetic analyses genetically supported the validation of Sebastiscus species. This study provides an important genome resource for further studies of Sebastiscus species.     

Systematic Deciphering of Cancer Genome Networks

When growth regulatory genes are damaged in a cell, it may become cancerous.Current technological advances in the last decade have allowed thecharacterization of the whole genome of these cells by directly or indirectlymeasuring DNA changes. Complementary analyses were developed to make sense ofthe massive amounts of data generated. A large majority of these analyses weredeveloped to construct interaction networks between genes from, primarily,expression array data. We review the current technologies and analyses that havedeveloped in the last decade. We further argue that as cancer genomics evolvesfrom single gene validations to gene network inferences, new analyses must bedeveloped for the different technological platforms.     

比较基因组学和人类基因组研究

在人类基因组计划突飞猛进地开展的同时,模式生物基因组计划也在轰轰烈烈地进行,并取得许多实质性的进展,是人类对于模式生物基因组有了更广泛更深刻的认识。这些知识的积累,从根本上推动了人类基因组计划的进行。