Mining the draft human genome

Now that the draft human genome sequence is available, everyone wants to be able to use it. However, we have perhaps become complacent about our ability to turn new genomes into lists of genes. The higher volume of data associated with a larger genome is accompanied by a much greater increase in complexity. We need to appreciate both the scale of the challenge of vertebrate genome analysis and the limitations of current gene prediction methods and understanding.     

Guide to the draft human genome

There are a number of ways to investigate the structure, function and evolution of the human genome. These include examining the morphology of normal and abnormal chromosomes, constructing maps of genomic landmarks, following the genetic transmission of phenotypes and DNA sequence variations, and characterizing thousands of individual genes. To this list we can now add the elucidation of the genomic DNA sequence, albeit at 'working draft' accuracy. The current challenge is to weave together these disparate types of data to produce the information infrastructure needed to support the next generation of biomedical research. Here we provide an overview of the different sources of information about the human genome and how modern information technology, in particular the internet, allows us to link them together.     

Genome sequence of Yersinia pestis, the causative agent of plague

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.     

Computational comparison of two draft sequences of the human genome

We are in the enviable position of having two distinct drafts of the human genome sequence. Although gaps, errors, redundancy and incomplete annotation mean that individually each falls short of the ideal, many of these problems can be assessed by comparison. Here we present some comparative analyses of these drafts. We look at a number of features of the sequences, including sequence gaps, continuity, consistency between the two sequences and patterns of DNA-binding protein motifs.     

Integration of telomere sequences with the draft human genome sequence

Telomeres are the ends of linear eukaryotic chromosomes. To ensure that no large stretches of uncharacterized DNA remain between the ends of the human working draft sequence and the ends of each chromosome, we would need to connect the sequences of the telomeres to the working draft sequence. But telomeres have an unusual DNA sequence composition and organization that makes them particularly difficult to isolate and analyse. Here we use specialized linear yeast artificial chromosome clones, each carrying a large telomere-terminal fragment of human DNA, to integrate most human telomeres with the working draft sequence. Subtelomeric sequence structure appears to vary widely, mainly as a result of large differences in subtelomeric repeat sequence abundance and organization at individual telomeres. Many subtelomeric regions appear to be gene-rich, matching both known and unknown expressed genes. This indicates that human subtelomeric regions are not simply buffers of nonfunctional 'junk DNA' next to the molecular telomere, but are instead functional parts of the expressed genome.     

云南鼠疫菌随机引物扩增DNA多态性指纹图谱分析

目的：分析云南不同地区、不同年代分离鼠疫菌的基因表型。方法：采用随机引物扩增技术（RAPD）对菌株进行分析。结果：共检测了28株鼠疫菌，除一株外，27株均显示有13条带型，并与假结核菌和小肠结肠炎菌有明显的区别。结论：云南家、野两型鼠疫菌株可能具有相同的随机引物扩增基因表征。     

Integration of cytogenetic landmarks into the draft sequence of the human genome

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.     

中世纪欧洲鼠疫及其对当时社会经济的影响

鼠疫在中世纪的欧洲曾经大规模流行，给当时的欧洲造成了巨大灾难：人口锐减，土地荒芜，农产品价格大跌。但灾难的发生最终却加速了采邑制度和契约义务在农村的瓦解。     

中世纪英国政府对黑死病的反应及应对措施

面对黑死病疾风暴雨式的肆虐,为了维持与安定社会统治秩序,英国教俗两界权力组织都采取了诸多的应对措施。中世纪的欧洲社会,基督教教会所拥有的社会感召力和控制力,使其在瘟疫降临之际首当其冲。以英王为首的世俗权力,在黑死病肆虐期间采取积极的应对措施,其价值极其值得关注。英国政府在此期间的基本理念是敬天命,尽人事,积极地发挥政府职能作用。     

The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.     

黑死病与中世纪英国经济转型探析

黑死病爆发前,英国农业已进入滞胀阶段,在进一步恶化过程中,黑死病的降临导致英国人口锐减,劳动力严重缺乏,农民斗争加剧,土地、人口和粮食之间比例失调,加速了庄园农奴体制的瓦解,商品经济萌芽、成长,英国农业生产转向商业性畜牧经营.黑死病所造成的后果在一定程度上为后来英国资本主义的发展做好了铺垫.     

A map of human genome variation from population-scale sequencing

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.     

非溢流重力坝基本剖面的拟定

阐述了非溢流重力坝基本剖面设计的原则是在自重、静水压力和渗透压力三项主要荷载作用下，满足强度、稳定、施工、经济要求的最小剖面。     

Learning about addiction from the genome

Drug addiction can be defined as the compulsive seeking and taking of a drug despite adverse consequences. Although addiction involves many psychological and social factors, it also represents a biological process: the effects of repeated drug exposure on a vulnerable brain. The sequencing of the human and other mammalian genomes will help us to understand the biology of addiction by enabling us to identify both genes that contribute to individual risk for addiction and those through which drugs cause addiction. We illustrate this potential impact by searching a draft sequence of the human genome for genes related to desensitization of receptors that mediate the actions of drugs of abuse on the nervous system.     

猪粪中间型耶氏菌的分离和特性

从海南岛昌江县和乐东县的农村家养猪猪粪便中，分离到三株中间型耶氏菌．这些菌株的主要特性是分解多种糖，均能分解鼠李糖、密二糖和棉子糖．     

非标机械设计图样的管理

从事非标设备设计制造的企业,因为所涉及图样量大,因而图样管理难度也较大,如果没有明确的制度规范,势必造成管理的混乱。所以,需要依据本企业的产品性质,针对图样设计编号、CAD图保存、打印出图、校对审核签字、复印分发、底图归档、借阅、完工图回收处理等各环节进行制度化、规范化管理。     

A physical map of the chicken genome

Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones. In an accompanying paper we describe the draft genome sequence of the chicken, Gallus gallus, the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes.     

A physical map of the human genome

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.