酿酒酵母功能基因组学研究进展

随着各种微生物基因组序列信息的积累和测序工作的不断完成,酿酒酵母基因组学研究的重点已由传统的结构基因组学发展到了功能基因组学,并从单一的基因功能研究转向多个或整个基因组系统地去了解真核生物生命活动的本能。对基因组学水平上酿酒酵母功能基因的生物芯片分析,代谢通路和功能图谱,以及比较基因组学研究进行综述。     

基于基因组学的栎树生物学研究进展

栎树(Quercus spp.)是北半球重要的经济与生态树种。夏栎(Q. robur)、加州白栎(Q. lobata)、麻栎(Q. acutissima)等树种基因组的公布,对栎树生物学研究产生了深刻的影响。近5年来,栎树生物学出现了包括系统进化与物种鉴定、基因渐渗与适应进化、景观基因组学与生态保育、生物共存与互作机制、次生代谢与生长发育、DNA甲基化与表观遗传调控及基因与长寿机制等方面的研究热点。虽然基于基因组学的栎树生物学若干研究前沿已经形成,但尚处于起步阶段,笔者预期未来会向4个方面深入:①强调栎树基因组资源的深度应用。应用景观基因组学途径,探究栎树的杂交渐渗与适应进化;联合基因组、转录组、蛋白组等多组学技术,探究栎树生长发育与胁迫响应过程中的基因调控网络与信号通路;优化体细胞发生和遗传转化体系,攻克栎树遗传改良和基因资源开发技术瓶颈。②促进栎树研究体系的广度拓展。随着壳斗科其他树种全基因组序列的公布,基于从分子到群落的不同生物层次的模式系统,将对欧亚大陆和北美不同区域的栎树,包括白栎组、红栎组、冬青栎组、麻栎组等不同栎树类群,以及壳斗科其他属树种基因组生物学研究产生深远影响。③关注栎树资源利用的遗传与发育主题。用栎树基因组资源对其结构的、代谢的和农艺性状的差异及其优化加以解析,全基因组关联研究(GWAS)也将应用于栎树,从而为阐释木材发育和木栓形成的机制奠定基础。④聚焦栎林保育的生态与进化主题。在全球气候变化背景下,通过增加耐受胁迫的基因型,以缓解气候变化对森林生态系统的影响。同时维持和保护栎树在自然生态系统中的生态与进化过程,阐明栎树多样性、迁移与适应、趋异与趋同生态适应等方面进化成功的机制。     

林木分子育种研究的基因组学信息资源述评

分子育种是指利用与性状相关的DNA标记进行选育,也称标记辅助选择或标记辅助育种,广义上还包括基因工程育种和基因组学辅助育种。林木分子育种为早期选择和加速育种提供了极具潜力的高效手段。笔者对林木分子育种研究的基因组学信息资源进行了进展综述和前景展望。近30年来,林木分子标记技术从早期的低通量方法发展到目前基于微阵列芯片和新一代测序的高通量技术,如测序分型、转录组测序、重测序、扩增子测序和外显子组测序等,并广泛用于连锁作图、关联分析和基因组选择等林木性状相关的DNA变异检测研究。随着2006年毛果杨基因组序列的发表,已有50余个树种完成了基因组测序。基于连锁作图和关联研究检测了林木10余个属生长、材性和抗逆及非木质产品品质等性状相关的大量基因组位点,主要趋势表现为：① 表型广泛,涵盖经济性状、生理指标和代谢成分等;②标记数量成千上万甚至上百万,覆盖全基因组;③转录组和降解组等多组学的分子变异开始应用;④ 利用大群体以提高位点检测的精度;⑤ 重视环境的影响,大田试验设置多个地点,解析QTL与环境、年份的互作效应;⑥ 结合参考基因组序列和/或转录组差异表达基因进一步挖掘性状相关的候选基因,建立了桉属、松属和云杉属等主要造林树种的基因组选择模型。此外,积累了泛基因组、相关软件和算法、功能基因、基因组编辑技术及网站和数据库等其他信息资源。林木分子育种面临的挑战主要包括：① 如何获得稳定性好的性状相关基因组位点和基因组选择（GS）模型;② 缺乏自动化、无损和高通量的表型测定技术;③对大基因组的针叶树和一些多倍体树种,仍难获得高质量的基因组序列;④ 标记辅助选择增加了常规育种之外的费用,且存在不确定性;⑤多数树种的加速育种仍较困难。后基因组时代的林木分子育种将有效结合到常规育种程序中,显著促进遗传增益的提高。     

基于高通量测序技术的松材线虫研究进展

松材线虫(Bursaphelenchus xylophilus)是松树萎蔫病的病原,严重威胁欧亚等国的松林资源和生态安全。自2011年松材线虫基因组首次公布以来,高通量测序技术成为该病害的重要研究手段之一。笔者从松材线虫的功能基因、非编码RNA、转录表达差异和基因组学等方面综述其致病机理,认为随着高通量测序技术的快速发展,在转录组相关研究方面,可尝试开展空间转录组、单细胞测序等新技术,在染色体基因组的支持下寻找松材线虫中具有潜在调控功能的长链非编码RNA、融合基因和环状RNA等罕见核酸分子,挖掘可能存在的甲基化、RNA编辑、结构变异等未知现象;在基因组学研究方面,可以开展基因家族扩增、大样本全基因组关联分析和数量性状定位等研究,以挖掘与松材线虫致病力和繁殖力等重要性状紧密关联的基因或位点,阐明松材线虫不同种群在进化过程中发生的适应性变化。     

水稻的起源与驯化——来自基因组学的证据

 水稻是世界上最重要的粮食作物, 约1 万年前开始被驯化。由于水稻与其祖先野生种存在一定的遗传分化, 水稻的起源和驯化问题长期存在争议。本文综述了水稻起源和驯化方面的研究成果, 特别是近年来基因组学方面的证据, 认为水稻2 个亚种独立起源于野生祖先种内很早就分化的不同类群, 但一些驯化基因--控制重要农艺性状的基因, 可能首先在一个亚种中被驯化, 然后通过基因渐渗, 扩散到另一个亚种中。因此, 水稻驯化的关键是研究驯化基因的起源和扩散方式。随着大规模基因组测序技术的发展和相应数据分析方法的建立, 在全基因组水平对水稻及其祖先进行大规模分析, 已成为揭示水稻起源与驯化之谜的必由之路。     

营养基因组学:制订专属菜单

正基因时代,人人都对自己的基因组很好奇,也希望利用新的科技成果来常保健康。如今,一个营养学与基因组学结合的崭新学科——营养基因组学,正渐渐进入我们的视野。跨越新门槛科学家研究后发现,基因缺陷虽是先天问题,但并非直接促发一些疾病的原因;每个人的基因组都是独特的,承载特有的讯息,终身不改变,个别基因却可能因受到后天的饮食、环境等影响而产生变异。     

功能基因组学研究

功能基因组学概述２０世纪有三大科学工程:曼哈顿原子弹计划、阿波罗人类登月计划和人类基因组工程计划。人类基因组研究发端于１９９０年启动的美国“人类基因组计划”（ＨＧＰ）。ＨＧＰ的科学目标是绘制遗传图和物理图,并于２００５年最终获得人类基因组ＤＮＡ全序列。此即通常所称的“结构基因组学”时代。世纪之交实施的这项宏伟的科学计划以其鲜明的前沿性、先进性和带动性,将使生命科学成为２１世纪的主流科学,并将成为新技术、新产业的基础和生长点。世人对之寄予厚望。ＨＧＰ启动以来,在构建遗传连锁图、物理图、测序和基因识别等…     

功能基因组学研究

 功能基因组学概述20世纪有三大科学工程：曼哈顿原子弹计划、阿波罗人类登月计划和人类基因组工程计划。人类基因组研究发端于1990年启动的美国”人类基因组计划“(HGP).HGP的科学目标是绘制遗传图和物理图, 并于2005年最终获得人类基因组DNA全序列。此即通常所称的”结构基因组学“时代。世纪之交实施的这项宏伟的科学计划以其鲜明的前沿性、先进性和带动性, 将使生命科学成为21世纪的主流科学, 并将成为新技术、新产业的基础和生长点。世人对之寄予厚望。HGP启动以来, 在构建遗传连锁图、物理图、测序和基因识别等方面取得了重要进展, 前二项任务已提前完成。     

植物数量遗传学研究团队简介

正"植物数量遗传学"研究团队由"国家自然科学基金优秀青年基金"获得者、"万人计划青年拔尖人才"入选者黄学辉教授作为学术带头人,开发并利用基因组学、数量遗传学及计算生物学领域的最新技术手段,在作物群体遗传学分析、复杂农艺性状的遗传解析、基因互作和调控网络构建,以及分子育种技术开发等领域为高产优质高抗作物育种提供理论和技术支持.已在水稻、谷子、芝麻等作物的全基因组遗传变异鉴定、复杂农艺性状的遗传基础解析、杂种优势机理的分析和起源驯化研究等方面取得重要进展,主要     

基因组学与蛋白质组学

介绍了基因组与基因组学、蛋白质与蛋白质组学的概念及功能基因组学和蛋白质组学的研究方法。     

Close linkage of c-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees

Affective disorder (AD) is one of the major forms of functional psychoses. Although the mode of transmission is uncertain, family, twin and adoption studies strongly suggest a genetic involvement. Because a basic biochemical abnormality is not known, direct analysis of the disease using a probe for the defective gene is not possible. However, a specific locus can be tested for its relevance to the aetiology of AD by genetic linkage, using restriction fragment length polymorphisms (RFLPs). Using probes for the c-Ha-ras-1 oncogene and the insulin gene, Gerhard et al. and Egeland et al. found convincing evidence for close linkage between these markers and a locus for AD in a large Old Order Amish pedigree. In an attempt to confirm this finding, we examined three bipolar pedigrees outside the Amish population. Our results indicate the absence of linkage from 0 to 15% recombination frequency between AD and the insulin gene-HRAS1 region in these pedigrees.     

阿尔茨海默症基因修饰小鼠模型

摘要:阿尔茨海默症( Alzheimer’ s disease,AD) 是一种神经退行性疾病,影响着全球 4 000 多万人的健康,预计在未来的几十年将呈指数级增长。 至今为止,该病还没有很好的治疗方法,也缺乏系统完整的病理及生理学研究,因此建立良好的动物模型是研究和治疗 AD 最有价值的科学工具。 本文总结了 4 种基因修饰的 AD 模型,讨论不同模型的表型特征、病理变化以及在科学研究中的应用。     

A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk

The identification of common variants that contribute to the genesis of human inherited disorders remains a significant challenge. Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes. We have used family-based association studies to identify a disease interval, and integrated this with comparative and functional genomic analysis to prioritize conserved and functional elements within which mutations can be sought. We now show that a common non-coding RET variant within a conserved enhancer-like sequence in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribution to risk than rare alleles do. This mutation reduces in vitro enhancer activity markedly, has low penetrance, has different genetic effects in males and females, and explains several features of the complex inheritance pattern of HSCR. Thus, common low-penetrance variants, identified by association studies, can underlie both common and rare diseases.     

Global variation in copy number in the human genome

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.     

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.     

The patterns and dynamics of genomic instability in metastatic pancreatic cancer

Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.     

A template of rat brain based on fMRI T*2 imaging

The development of functional magnetic resonance imaging (fMRI) technology has made it possible to carry out functional brain imaging experiments in small animals. Usually, group data is required to form the assessment of population, which can not only increase the sensitivity of the overall experiment, but also allow the generalization of the conclusion to the whole population. In order to average the signals of functional brain images from different subjects, it is necessary to put all the mapping images into the same standard space (template image). However, up to now, most animal brain templates remain unavailable and it must be done by ourselves. In this study, a template image based on the brains of eight male Wistar rats is obtained, and it is successfully used in our present Alzheimer disease (AD)-like rat model studies as template for spatially normalizing images to the same stereotaxical space. The fMRI results processed with statistical parametric mapping (SPM99) software are in agreement with the results from immunohistochemical experiment, which proves that this method is universally applicable to the pathologic models of other small animals and to human brain lesion studies.     

A template of rat brain based on fMRI T_2~* imaging

Thedevelopmentofnoninvasivefunctionalneu roimagingmethodshasmadeitpossibletoinvestigatelarge scaleactivationpatternsofbrain.FMRI,arep resentativeinhemodynamictechniques,hasbeen usedextensivelyinthestudiesofthephysiology,pathologyandpsychologyofbrains[1—3],foritslessinvasiveproperty,superiorresolution,andlowercost comparedtoPETtechniques.Itisimportanttopointoutthatcommonimage analysissoftwaressuchasstatisticalparametricmap ping(SPM),analysesoffunctionalneuroimages(AFNI),createdatabydoinga…