The Genom of Homo sapiens.pdf

6 ROGERSFigure 4. Sequencing center contributions to the finished human genome sequence. Abbreviations: (BCM) Baylor College ofMedicine; (Beijing) Human Genome Center, Institute of Genetics, Chinese Academy of Sciences; (CSHL) Cold Spring Harbor Laboratory;(GBF) Gesellschaft fur Biotechnologische Forschung,mbH; (GTC) Genome Therapeutics Corporation; (IMB) Institute forMolecular Biology, Jena; (JGI) Joint Genome Institute, U.S. Department of Energy; (Keio) Keio University; (MPIMG) Max PlanckInstitute for Molecular Genetics; (RIKEN) RIKEN Genomic Sciences Center; (Sanger Institute) Wellcome Trust Sanger Institute;(SDSTDC) Stanford DNA Sequencing and Technology Center; (SHGC) Stanford Human Genome Center; (TIGR) The Institute forGenome Research; (UOKNOR) University of Oklahoma; (UTSW) University of Texas, Southwestern Medical Center; (UWGC) Universityof Washington Genome Center; University of Washington Multimegabase Sequencing Center; (WIBR) Whitehead Institutefor Biomedical Research, MIT; (WUGSC) Washington University Genome Sequencing Center.SEQUENCE ANNOTATIONWith the finished sequence in hand, the next key stepin understanding the biology of the genome is accurateannotation of the human gene set. Ultimately, we requireall genome features, including genes, alternative transcripts,sequence variations, promoters, enhancers, andother regulatory motifs to be accurately defined and displayedalong the single metric of the genome sequence.The assembly of the working draft sequence providedthe basis for the first completely automated and nonredundantannotation of the human genome. Key featuresof the sequence analysis method were that it was based onusing unfinished sequence and that the annotation couldbe updated rapidly as the sequence evolved. Ensembl (ajoint project between the European Bioinformatics Instituteand the Sanger Institute) (Hubbard and Birney 2000;Hubbard et al. 2002) annotates known genes and predictsnovel genes, with functional annotation from the InterPro(Apweiler et al. 2001) protein family databases and fromdisease expression and gene family databases (Enright etal. 1999; Antonarakis and McKusick 2000; Wheeler et al.2002). The Ensembl gene build system uses a three-stepprocess, incorporating information on exon structure andplacement from alignment of genes predicted from humanproteins in SPTREMBL (Bairoch and Apweiler2000); the alignment of paralogous human proteins andproteins from other organisms; and ab initio gene predictionusing genscan (Burge and Karlin 1997). Exons thatare supported by more than one prediction are clusteredto form genes. “Ensembl genes” are regarded as being accuratepredicted gene structures with a low false-positiverate, since they are all supported by experimental evidencefrom protein and nucleotide databases.Genome annotation can be viewed in genome browsersdeveloped by Ensembl (http://www.ensembl.org), theUniversity of California at Santa Cruz (http://genome.ucsc.edu), and the National Center for Biotechnology