Recent activities of the Microbiology in Schools Advisory Committee

Ecology and evolution

Agricultural education

Evolution and education

Education division elections

ISII in Europe

Tree project

Science teaching scholarship

Biology of terrestrial arthropods

A microscopied museum     

Germline genome editing versus preimplantation genetic diagnosis: Is there a case in favour of germline interventions?

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made.     

分子生物学技术在遗传病诊断中的应用

论述了遗传性疾病的发病机理和遗传病诊断的途径和策略,着重介绍了人类遗传疾病基因诊断技术的原理和发展状况,对该领域的新成果作了介绍和总结,对发展动向和存在的问题作了简要论述。Abstract:The mechanisms of human genetic diseases and strategies to test human genetic diseases are discussed in the review.The development of the gene diagnosis techniques to genetic diseases and their principles are introduced emphatically.The new achievements in the field are valued and concluded,and the prospect and the difficulties in genetic diseases diagnosis are also briefly discussed.     

基因诊断中测序技术的应用及优缺点

基因突变是当今生命科学研究的热点之一,其检测方法和诊断技术发展迅猛。测序技术在基因病的确诊、分型等方面发挥着不可或缺的作用。文章重点围绕第一~三代测序技术的研究进展、优缺点及其在基因诊断中的应用进行评述 ,并对未来的发展趋势进行了预测和展望。     

猪伪狂犬病综合诊断及分离毒株gE和TK基因遗传变异分析

2012年以来,许多使用gE基因缺失活疫苗免疫过的猪场广泛性出现伪狂犬病毒(PRV)感染,gE抗体阳性率不断升高,伪狂犬典型病例不断增加。2018年3月鲁南地区几个种猪场先后发生疑似伪狂犬病疫情,怀孕母猪流产、产死胎和木乃伊胎,仔猪出现神经症状且死亡率高。通过对病死猪及死胚剖检进行初步诊断,取病料进一步进行病理组织学诊断及病毒分离鉴定。结果显示,病死猪均可见病毒性脑炎、肝细胞变性坏死及淋巴组织坏死等病理变化,在病变的神经元、肝细胞、扁桃体隐窝上皮细胞等细胞核内见红染包涵体。对分离到的4株PRV进行了gE和TK基因的序列测定及遗传变异分析发现,4株PRV的gE和TK核苷酸序列的同源性分别为98.8%~99.3%和98.9%~99.6%,与国内流行毒株其核苷酸序列的同源性分别99.1%~99.7%和98.6%~99.8%,与匈牙利和美国等流行毒株核苷酸序列的同源性分别为97.3%~97.8%和98.8%~99.5%,表明4株分离株高度同源,与国内PRV变异株处在同一分支,而与匈牙利和美国等毒株遗传距离较远。传统疫苗对PRV变异毒株不能提供有效保护,给猪场伪狂犬病的防控和净化工作带来了新的挑战。     

The evolutionary demography of duplicate genes

Although gene duplication has generally been viewed as a necessary source of material for the origin of evolutionary novelties, the rates of origin, loss, and preservation of gene duplicates are not well understood. Applying steady-state demographic techniques to the age distributions of duplicate genes censused in seven completely sequenced genomes, we estimate the average rate of duplication of a eukaryotic gene to be on the order of 0.01/gene/million years, which is of the same order of magnitude as the mutation rate per nucleotide site. However, the average half-life of duplicate genes is relatively small, on the order of 4.0 million years. Significant interspecific variation in these rates appears to be responsible for differences in species-specific genome sizes that arise as a consequence of a quasi-equilibrium birth-death process. Most duplicated genes experience a brief period of relaxed selection early in their history and a minority exhibit the signature of directional selection, but those that survive more than a few million years eventually experience strong purifying selection. Thus, although most theoretical work on the gene-duplication process has focused on issues related to adaptive evolution, the origin of a new function appears to be a very rare fate for a duplicate gene. A more significant role of the duplication process may be the generation of microchromosomal rearrangements through reciprocal silencing of alternative copies, which can lead to the passive origin of post-zygotic reproductive barriers in descendant lineages of incipient species.     

大肠杆菌最小基因组分析和删减进展

大肠杆菌是基础研究最透彻、应用广泛的微生物,构建含减小甚至是最小基因组的大肠杆菌将为合成生物学的研究和应用提供理想的底盘生物。介绍了大肠杆菌最小基因组的生长与繁殖必需基因的生物信息学分析和实验鉴定,基因组敲除技术,以及删减基因组的大肠杆菌菌株的构建和应用等方面的研究进展。     

Exploration and grading of possible genes from 183 bacterial strains by a common protocol to identification of new genes: Gene Trek in Prokaryote Space (GTPS).

A large number of complete microorganism genomes has been sequenced and submitted to the public database and then incorporated into our complete genome database, Genome Information Broker (GIB, http://gib.genes.nig.ac.jp/). However, when comparative genomics is carried out, researchers must be aware that there are protein-coding genes not confirmed by homology or motif search and that reliable protein-coding genes are missing. Therefore, we developed a protocol (Gene Trek in Prokaryote Space, GTPS) for finding possible protein-coding genes in bacterial genomes. GTPS assigns a degree of reliability to predicted protein-coding genes. We first systematically applied the protocol to the complete genomes of all 123 bacterial species and strains that were publicly available as of July 2003, and then to those of 183 species and strains available as of September 2004. We found a number of incorrect genes and several new ones in the genome data in question. We also found a way to estimate the total number of orthologous genes in the bacterial world.     

Differential genome duplication and fish diversity

The duplication of genes and entire genomes arebelieved to be important mechanisms underlyingmorphological variation and functionalinnovation in the evolution of life andespecially for the broad diversity observed inthe speciation of fishes. How did these fishspecies and their genetic diversity arise? Theoccurrence of three rounds of genomeduplication during vertebrate evolution mightexplain why many gene families are typicallyabout half the size in land vertebrates as theyare in fishes. However, mechanisms of geneticdiversity in fish lineages need to be furtherexplained. Here we propose that differentialgenome duplication of from two to six roundsoccurred in different fish lines, offering newopportunities during the radiation of fishlineages. This model provides a fundamentalbasis for the understanding of theirspeciation, diversity and evolution.     

β-内酰胺酶耐药基因blaOKP进化及其侧翼序列特征研究

为研究β-内酰胺酶耐药基因bla_OKP进化及其侧翼序列情况,本文通过全基因组测序技术对肺炎克雷伯氏菌进行测定,分析了其中bla_OKP基因及其侧翼序列的特征,同时与不同亚型的bla_SHV侧翼序列进行了对比。研究发现,bla_OKP、bla_SHV基因进化差异明显,分为两个进化支,其中bla_OKP分为两个进化亚组(bla_OKP-A和bla_OKP-B)。侧翼序列分析结果表明,bla_OKP基因的侧翼序列中无可移动遗传元件,与染色体介导的基因bla_SHV的侧翼序列结构相似,但存在差异,主要表现为bla_OKP基因的一侧与KdpC相连,bla_SHV基因的一侧与RecF相连并具有ygbN-ygbM-ygbK结构。同时由质粒介导的bla_SHV基因的两侧存在多种可移动遗传元件。这些结构差异可能是导致bla_OKP耐药基因进化缓慢的原因之一。本研究通过对bla_OKP基因及其侧翼序列特征进行研究, 研究发现bla_OKP基因及其侧翼序列结构保守是其相对bla_SHV基因进化速度缓慢的重要原因。     

Molecular medicine: Molecular diagnostics, preventive medicine, and gene therapy

New trends in molecular medicine that have emerged owing to the success of the national Human Genome program are characterized. The major attention is paid to molecular diagnostics, preventive medicine, and gene therapy. Preventive medicine is a product of synthesis of the current notions on genetics and biochemistry of human diseases; it comprises pharmacogenetics, presymptomatic diagnosis, and testing of genes of predisposition to the most frequent multifactor diseases. In the Gene Therapy section, advantages and drawbacks of the main methods of delivery of nucleic acids into the cells are considered; diseases that are attempted to be rectified using gene therapy are listed. Exemplified with Duchenne myodystrophy, the problems encountered in correction of a genetic defect with the aid of foreign genes are considered. Results are summarized for assessing the efficiency of various methods of introduction of dystrophin cDNA (gene gun, liposomes, microspheres, viral oligopeptides, and lactoferrin) conducted on the Duchenne myodystrophy model, mdx mice.     

The Performance of Whole Genome Amplification Methods and Next-Generation Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities

Reliable and accurate pre-implantation genetic diagnosis(PGD) of patient’s embryos by next-generation sequencing(NGS) is dependent on efficient whole genome amplification(WGA) of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA(15 pg) and single cells, we showed that the two PCR-based WGA systems Sure Plex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification(MDA) system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing(CNV-Seq) was applied to single cell WGA products derived by either Sure Plex or MALBAC amplification, we showed that known disease CNVs in the range of 3e15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either Sure Plex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient’s cohort for uterine transplantation.     

最小基因组研究进展

随着许多生物体全基因组测序的完成,兴起了最小基因组的研究,即一个能营独立生活的生物体最少需要多少个基因。已知最小细胞支原体基因组是研究最小基因组的重要内容,还通过比较多种已测序基因组COG分析最小基因组,目前通过转座子插入基因突主为和同源重组删除基因的分析,进行最小基因组研究。