Finishing the euchromatic sequence of the human genome

Collins F.S., Lander E.S., Rogers J., Waterson R.H.
Abstract: The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers 99% of the euchromatic genome and is accurate to an error rate of 1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The nearcomplete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead. Index Keywords: Biomedical engineering; Genes; Physiology; Proteins; Research; Biological analysis; Euchromatic sequence; Genome sequence; Nucleotides; Genetic engineering; DNA; genome; accuracy; analytic method; article; birth; death; euchromatin; evolution; gene duplication; gene number; gene sequence; human; human cell; human genome; international cooperation; medical research; nucleotide sequence; priority journal; process design; protein analysis; teamwork; vertebrate; Amino Acid Sequence; Base Sequence; Centromere; Chromosomes, Artificial, Bacterial; Chromosomes, Human; DNA, Complementary; Euchromatin; Gene Duplication; Genes; Genome, Human; Heterochromatin; Human Genome Project; Humans; Molecular Sequence Data; Multigene Family; Physical Chromosome Mapping; Plasmids; Pseudogenes; Research Design; Sensitivity and Specificity; Sequence Analysis, DNA; Telomere; Vertebrata Year: 2004 Source title: Nature Volume: 431 Issue: 7011 Page : 931-945 Cited by: 1209 Link: Scorpus Link Document Type: Article Source: Scopus Authors with affiliations:
1. Collins, F.S. 2. Lander, E.S. 3. Rogers, J.

2012-2018 14. M. 401. 429. 825-837 24. pp. 2185-2195 15. 7. Heilig. M.. 489-495 18. pp. A comprehensive genetic map of the mouse genome (1996) Nature. Waterson. 149-152 9. J. 3. 429.. The DNA sequence and comparative analysis of human chromosome 10 (2004) Nature. pp. 369-374 29. Maglott.. pp. Assessing the quality of the DNA sequence from the Human Genome Project (1999) Genome Res.. A physical map of the mouse genome (2002) Nature. pp. T.4. elegans: A platform for investigating biology (1998) Science. M.. The sequence of the human genome (2001) Science.. S..E. 282. R. 2049-2054 Dib. 365-368 33. Initial sequencing and analysis of the human genome (2001) Nature. 4. J. 743-750 10.D. J. pp. pp. 152-154 5. Gregory. 270. 431. 601-607 23. References: 1. A comprehensive genetic map of the human genome based on 5.. Adams. Guyer. 31. pp. pp. pp. 522-528 27. The DNA sequence of human chromosome 7 (2003) Nature.R. The DNA sequence of human chromosome 22 (1999) Nature. Venter. 9.. 744-746 7.D. A comprehensive human linkage map with centimorgan density (1994) Science. L. NCBI Reference Sequence Project: Update and current status (2003) Nucleic Acids Res. G... 311-319 21. pp. 8. 0079. pp. 380.. pp. A physical map of 30. The DNA sequence and analysis of human chromosome 14 (2003) Nature.. pp. A comprehensive genetic linkage map of the human genome (1992) Science.H. W. Hattori. 67-86 Gyapay. 805-811 26. 409. 1945-1954 Deloukas. 428. 418. 865-871 22. 529-535 28. 425.W. pp.L.. pp. pp. Hillier. Skaletsky. pp. P. Celniker. 282. 408.. 1453-1457 12. The DNA sequence and analysis of human chromosome 13 (2004) Nature. P. Dunham.000 genes (1996) Science.. I. The DNA sequence and biology of human chromosome 19 (2004) Nature. Life with 6. The DNA sequence of human chromosome 21 (2000) Nature. A.. 287. pp. A. A. 2.. A physical map of the human genome (2001) Nature. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd (1995) Science.G. An STS-based map of the human genome (1995) Science. pp. The genome sequence of Drosophila melanogaster (2000) Science. Genome sequence of the nematode C. T. R. Humphray. 246-339 Murray. pp.. H. The 1993-94 Genethon human genetic linkage map (1994) Nature Genet.264 microsatellites (1996) Nature. Dunham. S. DNA sequence and analysis of human chromosome 9 (2004) Nature. pp.J. 375-381 30. R.C. 496-512 11. D. 79.. R.D.. 34-37 34. 860-921 16. Goffeau. 423. Schmutz.J. 934-941 Dietrich. The complete genome sequence of Escherichia coli K-12 (1997) Science. 1-4 32. F. J. pp.... The male-specific regions of the human Y chromosome is a mosaic of discrete sequence classes (2003) Nature. pp. Schmutz. K. J.C. 414.000 human genes (1998) Science.. 421. 428. Grimwood. A.. S. 6. pp... 291. The DNA sequence and comparative analysis of human chromosome 5 (2004) Nature. 274. Hudson. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana (2000) Nature. The DNA sequence and comparative analysis of human chromosome 20 (2001) Nature.. 429.. Blattner. pp.R. pp. C. pp. Schloss.J.1-0079. Quality assessment of the human genome sequence (2004) Nature. pp. Deloukas.F. 380. Fleischmann.000 full-length human and mouse cDNA sequences (2002) .. 405. pp. 277. 269. 546-567 13.. The DNA sequence and analysis of human chromosome 6 (2003) Nature. 265. Strausberg. P. Pruitt. Feisenfeld. Peterson. J. Deloukas. 796-815 19. 409. pp.... 157-164 25. 258. Mungall. J.. Tatusova. 424. Generation and initial analysis of more than 15.14 20. 1304-1351 17. pp.. 268-274 31.. pp. Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence (2002) Genome Biol.

F... 413. Sequencing and comparison of yeast species to identify genes and regulatory elements (2003) Nature... Lessons from the human genome: Transitions between euchromatin and heterochromatin (2001) Hum. Storz.. M.. pp..... Johnson. 1175-1186 49. M. Willard. 18.. 857864 40..E. M. Sci. Roest Crollius. pp. T. 423.. Patterson... Ruvolo.A. Genet. pp.. Lai. mechanism.. polymorphisms. X. 27-36 48. D. 301. 6240-6244 37. Surveying Saccharomyces genomes to identify functional elements by comparative DNA sequence analysis (2001) Genome Res. pp.. in the press 41.. Ventura. 514-519 44.S. pp. D. 13.. Acad. Rocchi. 7176 50. pp. P. She.. 10.. Large-scale transcriptional activity in chromosomes 21 and 22 (2002) Science. Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence (2000) Nature Genet.A. biogenesis. X. R. D. Bailey. Chorionic gonadotropin has a recent origin within primates and an evolutionary history of .. Kapranov. Re-evaluating human gene annotation: A second-generation analysis of chromosome 22 (2003) Genome Res... Lupski. Noncoding regulatory RNAs database (2003) Nucleic Acids Res. P. P. 31. Natl. 13. Analysis of human mRNAs with the reference genome sequence reveals potential errors. E.. Genet... 14. M. Clark. 16. 11.. Finding functional features in Saccharomyces genomes by phylogenetic footprinting (2003) Science. Genome architecture. Natl..E. 252-255 42. Eichler. parent of origin and in situ distribution of centromeric sequences in human chromosomes 13 and 21 (1997) Nature Genet. 2215-2223 47.F. 429-431 55. 14. 235-238 52. Zdobnov. 1260-1263 54. H. Analysis of segmental duplications and genome assembly in the mouse (2004) Genome Res. pp. Bork. USA. Padlock probes reveal single-nucleotide differences. Genet. A genome-wide survey of human peudo genes (2003) Genome Res.. J. pp. R. A shotgun optical map of the entire Plasmodium falciparum genome (1999) Nature. Suyama. M.. The structure and evolution of centromeric transition regions within the human genome (2004) Nature. pp. Nilsson. Mol. E. Sci.. E.E.P. Positive selection of a novel gene family during the emergence of humans and great apes (2001) Nature.. Moyzis. 345-354 38.A.A. Kellis.. . D. Collins. 309-313 39. 23. Barciszewski. Torrents. 5.K. Erdmann. Bailey.. Meyne. P. 99. J. Birren.. MicroRNAs: Genomics.. pp. Maston. B. Eichler.... Cloning human telomeric DNA fragments into Saccharomyces cerevisiae using a yeast artificial chromosome vector (1989) Proc. An expanding universe of noncoding RNAs (2002) Science.. 25.. M.P. Stankiewicz.S. 7482 43. D. 241-254 51.. J. 86. pp. Szymanski. M.A. Analysis of the centromeric regions of the human genome assembly Trends Genet. Locke. M. 296.C.. E. 789-801 45. An assessment of the sequence gaps: Unfinished business in a finished human genome (2004) Nature Rev... P. E. 116.. J.Proc.. 16899-16903 35.. Burke. 430. pp.. in the press 36. M. pp. E. She. Lander.R. pp.T.. Cliften. Rudd..V. rearrangements and genomic disorders (2002) Trends Genet. Church. H. pp.. M. Recent segmental duplications in the working draft assembly of the brown Norway Rat (2004) Genome Res.. pp.. Z.. Furey. E.. 296.. . G. 916-919 56.A. Horvath. and function (2004) Cell. 281-297 53. 2559-2567 57. J.. Bartel. M. Endrizzi. pp. pp. pp.K... N. Riethman. Cliften. pp. Olson. Eichler. Bailey. and RNA editing Genome Res.E.E.. J.. Acad. USA. J. H. Eichler. V. pp. G.M. Tuzun.E. J. 493-506 46.E.

C.E.. pp. Loftus. Green.A.. 22-32 59.. Natl. 11. K.J. Sequencing multimegabase-template DNA with BigDye terminator chemistry (1998) Genome Res. Y.M. A vision for the future of genomics research (2003) Nature. 70. pp. pp. 8. Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q (1999) Genomics..L.. 11. J. Bailey. Heiner. 60.. Furguson-Smith. Structural variation in chromosome no.. pp.selection (2002) Mol. 320-355 58.. Old.. Biol. pp. Short-insert libraries as a method of problem solving in genome sequencing (1998) Genome Res. Istrail.O. 295-308 68. 557-561 . pp. 835-847 62. D.. pp.... C. 614-625 69. M. Yanai.-T. B. Chen. M.B.. C. Bobrow. 188. pp.. 520-562 61. Glusman.. Madan. Sci.S. Cancer/testis antigens: An expanding family of targets for cancer immunotherapy (2002) Immunol.. pp.S. Automated finishing with autofinish (2001) Genome Res. L.. Parameters of the human genome (1991) Proc. J. Hunkapiller. Lancet. McMurray. S.. Chen.A.E. M. P.. N.. 291-304 63.. Acad. Chen... 8..C. 19... 9 (1974) Ann. 422.. Human centromeric DNAs (1997) Hum. Genet. Desmarais.A. Green. D. pp. Initial sequencing and comparative analysis of the mouse genome (2002) Nature. Evol. Guyer. pp. M. Genet. pp. Lee.. Acad. The complete human olfactory subgenome (2001) Genome Res. S. A. Glass. K. R.A. Sulston. Rubin.I. USA. Rev.. Weverick. Collins.. Recent segmental duplications in the human genome (2002) Science. E. Morton. 685702 60.A.. E. J.Y...D. Hum..E. A.J.. USA. Lin.R... pp. Gordon. Jungbluth. 81-86 65. I. 17. pp.. A. Genet. M. Guttmacher. 88. 100.. I. G. Fisher. 7474-7476 64. 83-100 67. Gure. 420. J. Whole-genome shotgun assembly and comparison of human genome assemblies (2004) Proc. Bailey.. Quail..J. pp. 1003-1007 66. Scanlan. 101. Sci. J. 297. B... F. Natl. C.A.. 562-566 71. A. Human-specific duplication and mosaic transcripts: The recent paralogous structure of chromosome 22 (2002) Am. 1916-1921 70.

Sign up to vote on this title
UsefulNot useful