基因学(Genics)--未来的新兴学科

遗传学的发展是从Heredity(以生物外部表现型为主的数量遗传研究）→Genetics(以生物体内染色体为主的细胞遗传研究）→Genics(以染色体上核酸为主的分子遗传研究）,基因是研究的核心。在二十世纪,在理论方面,基因的结构、功能和概念不断扩展,由单基因→基因家庭→基因簇→同源框基因→基因组学,在应用方面,从基因工程→基因克 隆→转基因→基因沉默→基因流→转基因安全性的研究,有了飞跃性的发展。基因研究已渗透到各个科学领域,出现了后基因组学,功能基因组学,蛋白组学,功能蛋白组学,功能酶学,生物信息学,生物计算机,药物基因组学,疾病基因组学,工业基因组学,转基因（食品）安全性,基因流,环境基因学等新的基因研究方向。基因产业和基因经济将会成为二十一世纪经济发展的新生点。基因学将在二十一世纪走向更加成熟和完善。     

家蚕基因组研究对蚕业学科和产业发展的影响

近年来，蚕业科学技术一直处于平台期，没有大的突破。影响产量、质量的关键性技术难题得不到有效解决，蚕丝业整体生产效益低下，严重影响产业稳定和持续发展。但是，随着家蚕基因组的完成，将为其注入新的活力与创新源泉，将使我们掌握参与蚕茧产量和质量形成的相关功能基因，了解这些基因的作用方式和特征，比较全面、准确地认识家蚕生物特性的遗传基础和分子调控机制，为提高蚕茧产量、改善蚕茧品质提供理论基础和技术支持。同时，家蚕作为模式昆虫，其基因组研究以及比较基因组学研究在农林科学与人类疾病研究等学科发展中意义重大，并将发挥着越来越重要的作用。因此家蚕基因组研究，在蚕丝产业与模式生物的研究方面均具有重要的科学价值。     

基因组学:生命科学的系统化研究和生物世纪的科学革命

DNA(脱氧核糖核酸)是基因的“文字”，基因是生命的“语言”，生命的“剧本”用基因来编写。基因组学则是生命剧本的“导演”。DNA序列因此就成了舞台剧本。基因组学是一门大规模地、系统地研究物种全部基因和它们生物学意义和运动的学问。如今，我们正站在一个革命性的转折点上，也就是基因组学正处于生命科学的领导前沿。我们不该为此恐慌、怀疑甚或因而改变方向。获得一个物种的基本的基因组信息，比如基因的图谱及其在细胞中的产物，是我们了解该物种生物学意义的第一步。我们应该根据基础研究、经济效益和社会的需要来考虑测序日程上物种的先后次序。     

单碱基基因编辑系统的研究进展

基因编辑技术是近年来取得突破性进展的颠覆性技术之一。CRISPR/Cas9基因编辑系统简便、高效,被广泛应用于基因功能研究和利用。尽管CRISPR/Cas9可以高效靶向目的基因,但其定点修饰依赖于效率低下的同源重组机制,因此精准编辑基因的能力有待提高。单碱基编辑技术通过将Cas9切口酶或无核酸酶活性的Cas9与胞嘧啶脱氨酶形成融合蛋白,并通过sgRNA(单链向导RNA)将融合蛋白靶向靶位点,在不切割双链DNA的情况下对靶基因位点的单个碱基进行胞嘧啶C→胸腺嘧啶T或鸟嘌呤G→腺嘌呤A的精准编辑。目前,单碱基编辑技术已在植物、动物以及人细胞中进行了高效的基因定点突变,在农业、生物医学研究甚至基因治疗中有广泛的应用前景。本综述就单碱基编辑系统的发展和应用进行回顾和展望。     

美科学家确定下一组基因测序目标

美国科学家确定了基因测序的下一组目标生物,包括1种负鼠、4种真菌、3种蛔虫和1种甲虫。据英国《自然》杂志网站报道,这些生物的基因测序工作将于今年内在美国的5家研究中心展开,研究所由美国国家卫生研究所资助。此前,科学家已经绘制出了人类、小鼠、蜜蜂和果蝇等动物的基因图谱,目前正在对紫海胆、大鼠、黑猩猩和牛等进行测序。对比不同物种的基因组,有助于研究生物进化过程辨别基因并分析其功能,了解人类发育和疾病的机理。南美负鼠是一种灰色、短尾的小型哺乳动物,它将成为基因密码被破解的第一种有袋动物。研究人员选中负鼠是由于这种…     

揭开世界性系统农牧渔业基因组研究的序幕

以基因组测序为先导的农牧渔业系统基因组学研究是一项需要国际间进行协同攻关和紧密合作的重大项目计划。这种以应用为目的的基础科学研究项目无论是对发达国家还是对发展中国家而言都是非常重要和必要的。然而，我们必须清醒地意识到，当人类基因组和其他许多同人类健康相关的基因组以及一些模式生物基因组已经或即将被测序时，重要的农作物、牲畜、水产品基因组所受到的重视还远远不够。虽然我们正面对诸如政策制订、资金申请、地方发展重点、研究团体共识及技术革新等多方面的问题和挑战，人们还是提出了许多有关大规模测序及其投资收益的倡议或计划。由于大规模测序即全基因组鸟枪法(Wh01e Genome Shotgun or WGS)所产生的序列草图能覆盖整个基因组95％至99％的区域，从基因组草图中识别的基因连带其他资源比如分子标记、大片段插入克隆和cDNA序列的知识，为农牧渔业和环境生物学提供了丰富的信息和大量的工具。一旦这项重大计划得以实施并取得成功，所有国家的分子生物学家、遗传学家、实验生物学家。无论富裕或贫穷，都将站在同一科学起点上，基础基因组学信息的又一次大爆发将使我们的生活和环境拥有一个更美好的未来。我们热切呼吁全世界的各个研究基金会，也呼吁各个国家和国际政府机构与组织共同支持这场伟大的项目计划。     

一种描述电磁场与电路的统一理论

本文在似稳任意线性网络里由网络场论在似稳电磁场情况下证明麦克斯韦方程组是电网络基本方程组,找到了电磁场基本方程组和电网络基本方程组有相同的物理起源都是麦克斯韦方程组,由此提岀一种描述电磁场与电路的统一理论.在证明过程推演表达网络线图基本概念时发现了对于B条支路和N个节点的电网络必有(BN+1)个独立回路乃起因于电荷守恒定律,在推演表达电路元件基本概念时发现了4种基本电路元件特性公式乃全部起源于电路上电磁场能量转换与守恒定律,以及在推演电路上真正的电路基本定律时阐明了由它的推论之一得到的基尔霍夫定律为什么不能是电路基本定律的充分理由.     

胃癌侧群细胞耐药性研究及干细胞相关基因检测

目的研究胃癌侧群（Side Population，sP）细胞对化疗药物5-Fu（氟尿嘧啶）的耐药性及可能机制，并检测干细胞相关基因Nanog、Musashi-1及cD44的表达情况。方法选择人胃癌细胞株sGc-7901，以荧光染料H0echst 33342染色，维拉帕米桔抗对照，应用流式细胞仪分选sP细胞和nonsP细胞。细胞耐药实验比较sP细胞与nonsP细胞对化疗药物5．Fu的耐药性差异；westem_h10t检测ABcG2和bcl-2蛋白表达情况；流式细胞仪分析细胞周期；荧光定量PcR检测两组细胞中干细胞相关基因Nanog、Musashi-1及cD44mRNA的表达差异。结果胃癌细胞株sGc．790l中sP细胞的比例为2．8％，sP细胞对5-Fu的耐药存活率明显高于non-sP细胞（P〈0．05），与nonsP细胞相比，sP细胞高表达耐药蛋白ABcG2和抗凋亡蛋白bcl-2，有更多的细胞处于c0／G1期（P〈0．05），并高表达干细胞相关基因Musashi-1和cD44。结论胃癌sGC_7901细胞株中sP细胞对化疗药物5．Fu的耐药性明显高于nonsP细胞，其耐药机制可能与sP细胞高表达耐药蛋白ABcG2和抗凋亡蛋白bcl-2，有更多细胞处于G0／Gl期有关；Musashi-1和cD44可能是相对特异性的胃癌干细胞标志物。     

RNA干扰CD133基因对结肠癌干细胞生物学行为的影响

目的探讨CD133基因表达、活化被阻断后对结肠癌干细胞生物学行为的影响。方法从EpcAMhighCD44＋结肠癌干细胞中流式分选获得CD133＋细胞，感染LV-CD133shRNA载体慢病毒后观察CD133＋结肠癌干细胞在生长方式、成球能力、克隆形成率、成瘤能力以及ABCC2mRNA的变化；Westernblot分析CD133-细胞中CD133蛋白表达情况。结果EpcAMhighCD44＋结肠癌干细胞中CD133＋细胞比例为89．2％。实验组经过LV-CD133shRNA载体病毒感染后，在干细胞养液中细胞改悬浮生长的方式为贴壁生长，不能形成细胞球。MTT法测定发现细胞增殖减慢，克隆形成率明显下降。将感染细胞移植在Balb／C裸鼠体内，在观察期间，感染LV—CD133shRNA载体病毒的CD133＋细胞无肿瘤形成。ABCG2mRNA表达水平明显降低（P〈0．01）。从EpcAMhighCD44＋结肠癌干细胞中流式分选获得CD133-细胞，其中也有CD133蛋白的表达。结论CD133维持结肠癌干细胞生物学特性。     

两种新生大鼠皮质发育障碍模型的差异基因表达谱研究

目的研究两种不同的方法构建皮质发育障碍(DCDs)动物模型中的共同差异表达基因,为进一步研究DCDs形成机制提供基因水平筛选的研究平台。方法用两种方法制备DCDs模型:①射线损伤模型(射线组):采用剂量为1.45 Gy的γ射线照射妊娠15 d的SD大鼠制作子代大鼠DCDs模型;②卡莫司汀(BCNU)药物损伤模型(药物组):妊娠15 d的SD大鼠,腹腔注射BCNU制作子代大鼠DCDs模型。同时设正常对照组。对两种DCDs模型的子代新生鼠(P0)全脑做基因芯片扫描,结果与正常对照组比较,获得两种模型共有的差异基因。结果射线组大鼠与正常比较得到170个差异基因,其中25个上调,145个下调;药物组大鼠与正常比较得到259个差异基因,其中67个上调,192个下调。两组重合的基因共54个,其中3个上调,51个下调。结论皮质发育障碍是一个复杂的病理过程,本实验运用基因芯片技术,对两种不同方法构建的DCDs模型进行了研究,获得两种DCDs模型共有的基因差异表达谱,为进一步研究DCDs形成机制提供了分子生物学平台。     

Where, when and how much: regulation of myelin proteolipid protein gene expression

The myelin proteolipid protein (PLP) gene (Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.Received 4 August 2003; received after revision 17 September 2003; accepted 24 September 2003     

脊椎动物基因注释中的大基因问题

为了找出编码蛋白质的基因，注释流程结合了“从头开始的基因预测方法”和“与已知基因相似性比较”这两种方法。“从头开始的基因预测方法”虽然有很高的假阳性但是假阴性却很低；相形之下，结合了相似性比对的方法之后虽然能够降低假阳性，但是却大大提高了假阴性。我们发现，在这当中与基因预测正确率相关的最重要因素就是基因大小(包括内含子在内)——大基因尤其容易产生预测错误。     

Genetic factors for human obesity

Obesity is a multifactorial and heterogeneous condition that results from alterations of various genes, each having a partial and additive effect. The inheritance pattern of obesity is thus complex, and environmental factors play an important role in promoting or delaying its development. The identification of susceptibility genes and genetic variants for obesity requires various methodological approaches. Obesity is classified into three main categories on the basis of genetic etiology: monogenic, syndromic, and polygenic obesity. Here we review monogenic and syndromic obesity. We also review the linkage analysis studies followed by the candidate gene approaches and genome-wide association studies. Identification of the underlying genetic causes of obesity will likely provide a basis both for the development of new therapeutic agents and for the personalized prevention of this condition. Received 2 October 2007; received after revision 15 November 2007; accepted 19 November 2007     

Current topics in genome evolution: Molecular mechanisms of new gene formation

Comparative genome analyses reveal that most functional domains of human genes have homologs in widely divergent species. These shared functional domains, however, are differentially shuffled among evolutionary lineages to produce an increasing number of domain architectures. Combined with duplication and adaptive evolution, domain shuffling is responsible for the great phenotypic complexity of higher eukaryotes. Although the domain-shuffling hypothesis is generally accepted, determining the molecular mechanisms that lead to domain shuffling and novel gene creation has been challenging, as sequence features accompanying the formation of known genes have been obscured by accumulated mutations. The growing availability of genome sequences and EST databases allows us to study the characteristics of newly emerged genes. Here we review recent genome-wide DNA and EST analyses, and discuss the three major molecular mechanisms of gene formation: (1) atypical spicing, both within and between genes, followed by adaptation, (2) tandem and interspersed segmental duplications, and (3) retrotransposition events. Received 18 October 2006; received after revision 18 November 2006; accepted 28 November 2006     

Lateral gene transfer in eukaryotes

Lateral gene transfer – the transfer of genetic material between species – has been acknowledged as a major mechanism in prokaryotic genome evolution for some time. Recently accumulating data indicate that the process also occurs in the evolution of eukaryotic genomes. However, there are large rate variations between groups of eukaryotes; animals and fungi seem to be largely unaffected, with a few exceptions, while lateral gene transfer frequently occurs in protists with phagotrophic lifestyles, possibly with rates comparable to prokaryotic organisms. Gene transfers often facilitate the acquisition of functions encoded in prokaryotic genomes by eukaryotic organisms, which may enable them to colonize new environments. Transfers between eukaryotes also occur, mainly into larger phagotrophic eukaryotes that ingest eukaryotic cells, but also between plant lineages. These findings have implications for eukaryotic genomic research in general, and studies of the origin and phylogeny of eukaryotes in particular.Received 3 December 2004; received after revision 24 January 2005; accepted 1 February 2005     

基于音乐基因的乐谱存储模型

本文提出一种基于音乐基因的乐谱存储模型S-MusicXML.将乐谱的存储和处理的基本单位由音阶提升到基因,有利于通过数据挖掘技术对音乐内涵的挖掘和存储.定义了旋律基因等概念,并通过实验进一步分析了挖掘音乐基因比挖掘音乐频繁模式更有优势.     

小麦转基因研究现状及展望

自二十世纪八十年代开始研究转基因植物以来，小麦作为世界主要粮食来源，其转基因遗传改良受到科学家的广泛关注。目前国内外已有近200例外源基因，主要是抗除草剂类基因、抗病虫基因、品质基因、抗旱耐盐等抗逆基因、雄性不育类基因等，通过基因枪法、农杆菌介导法、花粉管通道法等技术转入小麦的报道。从转单基因到进行多基因组装，从改良各种生物胁迫和非生物胁迫的抗逆性，到改良品质、高产等生理和农艺性状，是未来转基因小麦的研究方向。本文就近二十几年来转基因小麦研究进展及存在问题进行了全面系统的综述和探讨。     

Molecular cloning and analysis of the protein modules of aggrecans

The large aggregating chondroitin sulfate proteoglycan of cartilage, aggrecan, has served as a prototype of proteoglycan structure. Molecular cloning has elucidated its primary structure and revealed both known and unknown domains. To date the complete structures of chicken, rat and human aggrecans have been deduced, while partial sequences have been reported for bovine aggrecan. A related proteoglycan, human versican, has also been cloned and sequenced. Both aggrecan and versican have two lectin domains, one at the amino-terminus which binds hyaluronic acid and one at the carboxyl-terminus whose physiological ligand is unknown. Both lectins have homologous counterparts in other types of proteins. Within the aggrecans the keratan sulfate domain may be variably present and also has a prominent repeat in some species. The chondroitin sulfate domain has three distinct regions which vary in their prominence in different species. The complex molecular structure of aggrecans is consistent with the concept of exon shuffling and aggrecans serve as suitable prototypes for comprehending the evolution of multi-domain proteins.     

Phylogenetic origin of LI-cadherin revealed by protein and gene structure analysis

The intestine specific LI-cadherin differs in its overall structure from classical and desmosomal cadherins by the presence of seven instead of five cadherin repeats and a short cytoplasmic domain. Despite the low sequence similarity, a comparative protein structure analysis revealed that LI-cadherin may have originated from a five-repeat predecessor cadherin by a duplication of the first two aminoterminal repeats. To test this hypothesis, we cloned the murine LI-cadherin gene and compared its structure to that of other cadherins. The intron-exon organization, including the intron positions and phases, is perfectly conserved between repeats 3–7 of LI-cadherin and 1–5 of classical cadherins. Moreover, the genomic structure of the repeats 1–2 and 3–4 is identical for LI-cadherin and highly similar to that of the repeats 1–2 of classical cadherins. These findings strengthen our assumption that LI-cadherin originated from an ancestral cadherin with five domains by a partial gene duplication event.Received 22 December 2003; received after revision 9 February 2004; accepted 27 February 2004