共查询到20条相似文献,搜索用时 31 毫秒
1.
The DNA sequence of human chromosome 22 总被引:75,自引:0,他引:75
Dunham I Shimizu N Roe BA Chissoe S Hunt AR Collins JE Bruskiewich R Beare DM Clamp M Smink LJ Ainscough R Almeida JP Babbage A Bagguley C Bailey J Barlow K Bates KN Beasley O Bird CP Blakey S Bridgeman AM Buck D Burgess J Burrill WD O'Brien KP 《Nature》1999,402(6761):489-495
Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome. 相似文献
2.
Wheeler DA Srinivasan M Egholm M Shen Y Chen L McGuire A He W Chen YJ Makhijani V Roth GT Gomes X Tartaro K Niazi F Turcotte CL Irzyk GP Lupski JR Chinault C Song XZ Liu Y Yuan Y Nazareth L Qin X Muzny DM Margulies M Weinstock GM Gibbs RA Rothberg JM 《Nature》2008,452(7189):872-876
The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'. 相似文献
3.
Muzny DM Scherer SE Kaul R Wang J Yu J Sudbrak R Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Wei S Wheeler DA Wright MW Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clendenning J Clerc-Blankenburg KP Chen R Chen Z Davis C Delgado O Dinh HH Dong W 《Nature》2006,440(7088):1194-1198
After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. 相似文献
4.
S Neph J Vierstra AB Stergachis AP Reynolds E Haugen B Vernot RE Thurman S John R Sandstrom AK Johnson MT Maurano R Humbert E Rynes H Wang S Vong K Lee D Bates M Diegel V Roach D Dunn J Neri A Schafer RS Hansen T Kutyavin E Giste M Weaver T Canfield P Sabo M Zhang G Balasundaram R Byron MJ MacCoss JM Akey MA Bender M Groudine R Kaul JA Stamatoyannopoulos 《Nature》2012,489(7414):83-90
5.
Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning 总被引:10,自引:0,他引:10
Cokus SJ Feng S Zhang X Chen Z Merriman B Haudenschild CD Pradhan S Nelson SF Pellegrini M Jacobsen SE 《Nature》2008,452(7184):215-219
6.
甲醛溶液保存的中华哲水蚤基因组DNA提取和PCR扩增 总被引:1,自引:1,他引:1
提取了保存于5%甲醛溶液中的单只中华哲水蚤基因组DNA.经凝胶电泳后虽无清晰条带.但PCR扩增后可得线粒体DNA细胞色素氧化酶Ⅰ亚基基因(mtCOI)片段.测序分析,该片段长度为710bp。与GenBank中的序列(索引号AF332769)比对后确定为中华哲水蚤mtCOI序列的一部分.利用本实验方法所提取的基因组DNA可适用于系统发生、种群遗传结构等领域的分子水平研究.为保存在甲醛溶液中的小型海洋浮游动物的基因信息利用提供实用技术。 相似文献
7.
DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae 总被引:23,自引:0,他引:23
Heidelberg JF Eisen JA Nelson WC Clayton RA Gwinn ML Dodson RJ Haft DH Hickey EK Peterson JD Umayam L Gill SR Nelson KE Read TD Tettelin H Richardson D Ermolaeva MD Vamathevan J Bass S Qin H Dragoi I Sellers P McDonald L Utterback T Fleishmann RD Nierman WC White O Salzberg SL Smith HO Colwell RR Mekalanos JJ Venter JC Fraser CM 《Nature》2000,406(6795):477-483
8.
Watanabe H Fujiyama A Hattori M Taylor TD Toyoda A Kuroki Y Noguchi H BenKahla A Lehrach H Sudbrak R Kube M Taenzer S Galgoczy P Platzer M Scharfe M Nordsiek G Blöcker H Hellmann I Khaitovich P Pääbo S Reinhardt R Zheng HJ Zhang XL Zhu GF Wang BF Fu G Ren SX Zhao GP Chen Z Lee YS Cheong JE Choi SH Wu KM Liu TT Hsiao KJ Tsai SF Kim CG OOta S Kitano T Kohara Y Saitou N Park HS Wang SY Yaspo ML Sakaki Y 《Nature》2004,429(6990):382-388
Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized. 相似文献
9.
Sequence identification of 2,375 human brain genes. 总被引:81,自引:0,他引:81
M D Adams M Dubnick A R Kerlavage R Moreno J M Kelley T R Utterback J W Nagle C Fields J C Venter 《Nature》1992,355(6361):632-634
We recently described a new approach for the rapid characterization of expressed genes by partial DNA sequencing to generate 'expressed sequence tags'. From a set of 600 human brain complementary DNA clones, 348 were informative nuclear-encoded messenger RNAs. We have now partially sequenced 2,672 new, independent cDNA clones isolated from four human brain cDNA libraries to generate 2,375 expressed sequence tags to nuclear-encoded genes. These sequences, together with 348 brain expressed sequence tags from our previous study, comprise more than 2,500 new human genes and 870,769 base pairs of DNA sequence. These data represent an approximate doubling of the number of human genes identified by DNA sequencing and may represent as many as 5% of the genes in the human genome. 相似文献
10.
Cancer and genomics 总被引:6,自引:0,他引:6
11.
M C Simmler F Rouyer G Vergnaud M Nystr?m-Lahti K Y Ngo A de la Chapelle J Weissenbach 《Nature》1985,317(6039):692-697
A DNA probe from a human Y chromosome-derived cosmid detects a single-copy genomic DNA fragment which can appear in different allelic forms shared by both sex chromosomes. Variants at this DNA locus show an autosomal pattern of inheritance, undergo recombination with sexual phenotype and can therefore be described as 'pseudoautosomal'. Another probe from the same cosmid detects a sequence repeated 15-20 times per haploid genome. These repeats also appear pseudoautosomal and map exclusively to the short-arm terminal region of each sex chromosome. 相似文献
12.
用聚合酶链式反应(PCR)法检测患者尿液中人巨细胞病毒(HCMV)DNA.结果表明,自行设计合成的引物位于HCMV基因组早期蛋白基因区,经PCR仪扩增一段长430bp的特异序列片段,对正常人基因组DNA或其它疱疹病毒DNA无交叉反应.此法可检测出少至10-16g(0.1fg)的病毒DNA.通过对35份尿液标本的检测,比较PCR法和组织培养法的检测结果完全一致 相似文献
13.
A human homoeo box gene specifically expressed in spinal cord during embryonic development 总被引:18,自引:0,他引:18
A Simeone F Mavilio L Bottero A Giampaolo G Russo A Faiella E Boncinelli C Peschle 《Nature》1986,320(6064):763-765
14.
There has been much progress in genomics in the ten years since a draft sequence of the human genome was published. Opportunities for understanding health and disease are now unprecedented, as advances in genomics are harnessed to obtain robust foundational knowledge about the structure and function of the human genome and about the genetic contributions to human health and disease. Here we articulate a 2011 vision for the future of genomics research and describe the path towards an era of genomic medicine. 相似文献
15.
DNA sequence alignment algorithms in computational molecular biology have been improved by diverse methods. In this paper, we propose a DNA sequence alignment that uses quality information and a fuzzy inference method developed based on characteristics of DNA fragments and a fuzzy logic system in order to improve conventional DNA sequence alignment methods that uses DNA sequence quality information. In conventional algorithms, DNA sequence alignment scores are calculated by the global sequence alignment algorithm proposed by Needleman-Wunsch, which is established by using quality information of each DNA fragment. However, there may be errors in the process of calculating DNA sequence alignment scores when the quality of DNA fragment tips is low, because only overall DNA sequence quality information are used. In our proposed method, an exact DNA sequence alignment can be achieved in spite of low quality of DNA fragment tips by improvement of conventional algorithms using quality information. Mapping score parameters used to calculate DNA sequence alignment scores are dynamically adjusted by the fuzzy logic system utilizing lengths of DNA fragments and frequencies of low quality DNA bases in the fragments. From the experiments by applying real genome data of National Center for Biotechnology Information, we could see that the proposed method is more efficient than conventional algorithms. 相似文献
16.
Comparison of human genetic and sequence-based physical maps 总被引:40,自引:0,他引:40
Yu A Zhao C Fan Y Jang W Mungall AJ Deloukas P Olsen A Doggett NA Ghebranious N Broman KW Weber JL 《Nature》2001,409(6822):951-953
Recombination is the exchange of information between two homologous chromosomes during meiosis. The rate of recombination per nucleotide, which profoundly affects the evolution of chromosomal segments, is calculated by comparing genetic and physical maps. Human physical maps have been constructed using cytogenetics, overlapping DNA clones and radiation hybrids; but the ultimate and by far the most accurate physical map is the actual nucleotide sequence. The completion of the draft human genomic sequence provides us with the best opportunity yet to compare the genetic and physical maps. Here we describe our estimates of female, male and sex-average recombination rates for about 60% of the genome. Recombination rates varied greatly along each chromosome, from 0 to at least 9 centiMorgans per megabase (cM Mb(-1)). Among several sequence and marker parameters tested, only relative marker position along the metacentric chromosomes in males correlated strongly with recombination rate. We identified several chromosomal regions up to 6 Mb in length with particularly low (deserts) or high (jungles) recombination rates. Linkage disequilibrium was much more common and extended for greater distances in the deserts than in the jungles. 相似文献
17.
The International HapMap Project 总被引:1,自引:0,他引:1
International HapMap Consortium 《Nature》2003,426(6968):789-796
The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention. 相似文献
18.
Thomas JW Touchman JW Blakesley RW Bouffard GG Beckstrom-Sternberg SM Margulies EH Blanchette M Siepel AC Thomas PJ McDowell JC Maskeri B Hansen NF Schwartz MS Weber RJ Kent WJ Karolchik D Bruen TC Bevan R Cutler DJ Schwartz S Elnitski L Idol JR Prasad AB Lee-Lin SQ Maduro VV Summers TJ Portnoy ME Dietrich NL Akhter N Ayele K Benjamin B Cariaga K Brinkley CP Brooks SY Granite S Guan X Gupta J Haghighi P Ho SL Huang MC Karlins E Laric PL Legaspi R Lim MJ Maduro QL Masiello CA Mastrian SD 《Nature》2003,424(6950):788-793
The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates. 相似文献
19.
Nucleotide sequence of cloned cDNA of human c-myc oncogene 总被引:4,自引:0,他引:4
Like other transforming genes of retroviruses, the v-myc gene of the avian virus, MC29, has a homologue in the genome of normal eukaryotic cells. The human cellular homologue, c-myc, located on human chromosome 8, region q24 leads to qter (refs 1, 2), is translocated into the immunoglobulin heavy-chain locus on human chromosome 14 (ref. 3) in Burkitt's lymphoma, suggesting that c-myc has a primary role in transformation of some human haematopoietic cells. In addition, c-myc is amplified in the human promyelocytic leukaemia cell line, HL60 (refs 6, 7) which also contains high levels of c-myc mRNA. Recently, Colby et al. reported the nucleotide sequence of the human c-myc DNA isolated from a genomic recombinant DNA library derived from human fetal liver. This 4,053-base pair (bp) sequence includes two exons and one intron of the myc gene, and the authors have suggested the existence of a human c-myc mRNA of 2,291 nucleotides that has a coding capacity for a protein of molecular weight (Mr) 48,812. We have approached the problem of accurately defining the characteristics of the human c-myc mRNA and c-myc protein by determining the sequence of the c-myc cDNA isolated from a cDNA library prepared from mRNA of a clone of the K562 human leukaemic cell line. K562 cells are known to contain c-myc mRNA which is similar in size to the c-myc mRNA of other human cell types. We report here the sequence of 2,121 nucleotides of a human c-myc mRNA and demonstrate that its 5' noncoding sequence does not correspond to the sequence of the reported genomic human sequence. However, our data confirm that the intact human c-myc mRNA can encode a 48,812-Mr protein with a sequence identical to that reported by Colby et al. 相似文献
20.
Bentley DR Balasubramanian S Swerdlow HP Smith GP Milton J Brown CG Hall KP Evers DJ Barnes CL Bignell HR Boutell JM Bryant J Carter RJ Keira Cheetham R Cox AJ Ellis DJ Flatbush MR Gormley NA Humphray SJ Irving LJ Karbelashvili MS Kirk SM Li H Liu X Maisinger KS Murray LJ Obradovic B Ost T Parkinson ML Pratt MR Rasolonjatovo IM Reed MT Rigatti R Rodighiero C Ross MT Sabot A Sankar SV Scally A Schroth GP Smith ME Smith VP Spiridou A Torrance PE Tzonev SS Vermaas EH Walter K Wu X Zhang L Alam MD 《Nature》2008,456(7218):53-59
DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications. 相似文献