Předmět Introduction to Genomics (KMB / 358)

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Materiál	Typ	Datum	Počet stažení

Obsah

Content of courses:- Introduction to the 'Genome' (definition of the genome/genetic material, types and variety of genome in biology, genome-transcriptome-proteome central dogma, genome structure i.e. concept of genes, regulatory elements and repetitive DNA, genome organisation i.e. chromosomes and histones/ chromatin, DNA replication).- Historical overview of first 'Genomic' methods i.e. chromosome mapping, laborious genetic linkage analyses, chromosome walking, QTLs. Introduction to nucleic acid sequencing from a historical perspective; first organisms - bacteriophages (MS2 PhiX174), bacteria (Haemophilus influenza, E. coli). Individual research group led DNA sequencing of specific loci of more complex organisms. Creation of common databases for this information - need to consolidate and coordinate DNA sequencing efforts- Scaled-up DNA sequencing to tackle larger genomes (use of human genome project as a case study). - Historical perspective and public versus private initiatives. Techniques used to perform large scale sequencing, Genome sequencing of model organisms - which, how and why? Creation of synthetic organisms (Craig Venter).- Interpreting the sequenced genome - identifying genes/ transcripts in the sequence and cataloguing them - birth of 'Bioinformatics'. Databases, Development of more sophisticated genome browsers with increasing amounts of annotation. 'Gene cards' and gene specific information features and using BLAST searches to identify experimentally derived sequences against the genome sequence reference.- Using the genomic sequence and bioinformatics to identify functionally important information e.g. Comparative genomics - phylogenetic analyses of bacteria or viruses (e.g. H5N1 influenza), identification of specific transcription factor binding sites and candidate target genes (e.g. REST and neurogenesis)- Applying genomics at the bench (development of numerous experimental strategies e.g. originally microarray based now based on novel large scale sequencing technologies) - inclusion of relevant case study examples e.g. the international ENCODE consortium- Depositing, retrieving and interpreting bench-based genomic experiment data/ results - cross referencing with our experimental databases and web resources

Literatura

Combinatorial patterns of histone acetylations and methylations in the human genome. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K. Nat Genet. 2008 Jul;40(7):897-903. Epub 2008 Jun 15. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B. Nat Genet. 2007 Mar;39(3):311-8. Epub 2007 Feb 4. ENCODE whole-genome data in the UCSC Genome Browser. Rosenbloom KR, Dreszer TR, Pheasant M, Barber GP, Meyer LR, Pohl A, Raney BJ, Wang T, Hinrichs AS, Zweig AS, Fujita PA, Learned K, Rhead B, Smith KE, Kuhn RM, Karolchik D, Haussler D, Kent WJ. Nucleic Acids Res. 2010 Jan;38(Database issue):D620-5. Epub 2009 Nov 17. Functional diversity for REST (NRSF) is defined by in vivo binding affinity hierarchies at the DNA sequence level. Bruce AW, López-Contreras AJ, Flicek P, Down TA, Dhami P, Dillon SC, Koch CM, Langford CF, Dunham I, Andrews RM, Vetrie D. Genome Res. 2009 Jun;19(6):994-1005. Epub 2009 Apr 28. Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns. Roh TY, Wei G, Farrell CM, Zhao K. Genome Res. 2007 Jan;17(1):74-81. Epub 2006 Nov 29. Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T, Fejes AP, Wederell ED, Cullum R, Euskirchen G, Krzywinski M, Birol I, Snyder M, Hoodless PA, Hirst M, Marra MA, Jones SJ. Genome Res. 2008 Dec;18(12):1906-17. Epub 2008 Sep 11. Genomic approaches uncover increasing complexities in the regulatory landscape at the human SCL (TAL1) locus. Dhami P, Bruce AW, Jim JH, Dillon SC, Hall A, Cooper JL, Bonhoure N, Chiang K, Ellis PD, Langford C, Andrews RM, Vetrie D. PLoS One. 2010 Feb 5;5(2):e9059. High-resolution profiling of histone methylations in the human genome. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. Cell. 2007 May 18;129(4):823-37. Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication. Johnson R, Gamblin RJ, Ooi L, Bruce AW, Donaldson IJ, Westhead DR, Wood IC, Jackson RM, Buckley NJ. Nucleic Acids Res. 2006;34(14):3862-77. Epub 2006 Aug 9. Prediction of regulatory elements in mammalian genomes using chromatin signatures. Won KJ, Chepelev I, Ren B, Wang W. BMC Bioinformatics. 2008 Dec 18;9:547. The landscape of histone modifications across 1% of the human genome in five human cell lines. Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, Wilcox S, Beare DM, Fowler JC, Couttet P, James KD, Lefebvre GC, Bruce AW, Dovey OM, Ellis PD, Dhami P, Langford CF, Weng Z, Birney E, Carter NP, Vetrie D, Dunham I. Genome Res. 2007 Jun;17(6):691-707.

Požadavky

Periodicity: each academic year.

Garant

Alexander W. Bruce, Ph.D.

Vyučující

Alexander W. Bruce, Ph.D.Mgr. Aleš Horák, Ph.D.Miluše Hroudová, Ph.D.Mgr. Jan MichálekMgr. Jan Pačes, Ph.D.