Einführung in die Genetik Prof. Dr. Kay Schneitz (EBio Pflanzen) http://plantdev.bio.wzw.tum.de [email protected] Twitter: @PlantDevTUM, #genetikTUM FB: Plant Development TUM Prof. Dr. Claus Schwechheimer (PlaSysBiol) http://wzw.tum.de/sysbiol [email protected] Einführung in die Genetik VO, 2 SWS / 3 ECTS im WS Dienstags, 08.30 - 10.00 Uhr, HS16, WZW Übung 1 SWS / 1 ECTS in SFerien, LV-Nr 2401237000 08. 04. - 12. 04. 2013, 09.00 - 17.00 Uhr, HS14, WZW, PD Dr. Erich Glawischnig, Dr. Lilla Römisch-Margl (Genetik) http://www.tum.de/genetik [email protected], [email protected] Einführung in die Genetik - Inhalte 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Einführung Struktur von Genen und Chromosomen Genfunktion Transmission der DNA während der Zellteilung Vererbung von Einzelgenveränderungen Genetische Rekombination (Eukaryonten) Genetische Rekombination (Bakterien/Viren) Rekombinante DNA-Technologie Kartierung/Charakterisierung ganzer Genome Genmutationen: Ursache und Reparatur Veränderungen der Chromosomen Genetische Analyse biologischer Prozesse Transposons bei Eukaryonten Regulation der Genexpression Regulation der Zellzahl - Onkogene 16. 10. 12 23. 10. 12 30. 10. 12 06. 11. 12 13. 11. 12 20. 11. 12 27. 11. 12 04. 12. 12 11. 12. 12 18. 12. 12 08. 01. 13 15. 01. 13 22. 01. 13 29. 01. 13 05. 02. 13 KS KS KS KS KS KS KS CS CS CS CS CS CS KS CS Prüfung 12. 04. 2013 HS 14, WZW 13.00 Uhr VO + Übung Prüfungsanmeldung • TUMonline zwingend!!! • https://campus.tum.de/tumonline/ webnav.ini • myTUM-Kennung / Password • Wenn angemeldet --> Rückzug nur mit Attest (Prüfungsamt), ansonsten --> nicht angetreten und eine 5.0 !! Downloads http://plantdev.bio.wzw.tum.de/lehre/anmeldung http://www.wzw.tum.de/sysbiol/index.php?id=10 user: gregor password: mendel Literatur • Introduction to Genetic Analysis. 10th Edition. • Genetik: Allgemeine Genetik - Molekulare Genetik Entwicklungsgenetik. 2. Auflage. Griffiths, A.J.F., Wessler, S.R., Carroll, S.B., Doebley, J. (2011). WH Freeman and Company, New York, USA. Janning, W., Knust, E. (2008). Georg Thieme Verlag, Stuttgart, BRD • Genetics Essentials: Concepts and Connections. Pierce, • Molecular Biology of the Cell, 5th Edition. B.A. (2010) WH Freeman and Company, New York, USA. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. (2008) Garland Science, Taylor & Francis Group, UK Fundamental concepts Cells prokaryotic, eukaryotic Multigenic traits e.g. human height Gene Genetic Information fundamental unit of heredity contained in DNA and RNA Alleles Chromosomes multiple forms of a gene genes are located on chro Mutations Mitosis/Meiosis permanent, heritable changes chro separation Genotype vs Phenotype Central Dogma genes confer phenotypes DNA to RNA to protein Evolution is genetic change Genetics and biology Transmission genetics Molecular genetics Population genetics Genetic dissection Biosynthetic pathway α γ β δ Enzymes A B C Genes A B C Mutation Gene Function Genetics and basic science Developmental genetics Evolution Human genetics Genetics and application Agriculture Medicine: congenital disorders Green revolution Cystic fibrosis (Mukoviszidose) Biotechnology The Structure of Genes and Chromosomes Genetics 02 Topics DNA Structure Chromosomes DNA Replication DNA: The genetic material Griffith, 1928 Transformation DNA: The genetic material Avery, MacLeod, McCarty, 1944 DNA: The genetic material Hershey and Case, 1952 DNA is transforming principle Genes are made of DNA The Structure of DNA The DNA double helix groove: Rinne/Furche 1953: The double helix James Watson Francis Crick Rosalind Franklin The building blocks of DNA Connecting the blocks: phosphodiester linkage 5’ 3’ The DNA double helix (Rinne/Furche) The DNA double helix 5’ pCpApGpTOH 3’ 5’ CAGT 3’ 1’000 b = 1 kb Summary • • • • genetic material is DNA building blocks of DNA: • nucleotides (base, deoxyribose, phosphate) nucleotides form a strand through phosphodiester linkage between phosphate and sugar (5’ to 3’ direction) DNA double helix: two, anti-parallel strands, kept together by hydrogen bonds between matching bases • A-T G-C Chromosomes Organizing the genome Cells Genome sizes Plasmid Chromosomes Drosophila E. coli Human Maize Chromosomal landscapes Specific human chromosomal landscape The nuclear genome The nucleosome Histone modifications Chromatin, the stuff of chromosomes Solenoid Chromosome condensation by supercoiling Chromatin structure varies along the chromosome Landmarks of tomato chromosome 2 The human karyotype 2n = 46 Karyotype of a patient with hereditary ataxia Chro 4 Chro 12* Summary • • • • • • • genomes are organized into chromosomes karyotype is species-specific diploid organism: pairs of homologous chro chromsomes are made of DNA and proteins chromatin • nucleosomes (histones plus DNA) chro landmarks: • • • • • centromer (CEN) NOR chromosomal bands euchromatin heterochromatin chromosomal condensation DNA Replication Making copies Model: Semiconservative DNA replication Fork New DNA strands are complementary to template Meselson-Stahl experiment Bacterial chro replication: two replication forks Bacterial chro replication: two replication forks Connecting the building blocks: DNA polymerase E. coli: DNA pol I (pol I - pol III) 5’-to-3’ polymerase activity 5’ chain growth 3’-to-5’ exonuclease activity removal of mismatched bases 5’-to-3’ exonuclease activity degrades single-stranded DNA or RNA 3’ DNA replication at growing fork Leading strand: Leitstrang Lagging strand: Folgestrang DNA replication at growing fork Leading strand: Leitstrang, führender Strang Lagging strand: Folgestrang, verzögerter Strang Synthesizing the lagging strand Leading strand: Leitstrang, führender Strang Lagging strand: Folgestrang, verzögerter Strang Movie Movie The replisome Origins: controlled start of replication Eukaryote: Starting replication Assembling nucleosomes during DNA replication How to terminate replication? How to terminate replication? Telomeres Telomere lengthening Telomere lengthening Protecting the telomeric ends Cap Summary • • • • • • • • DNA replication is semi-conservative replication occurs at the replication fork replication starts at oris 5’ to 3’ direction leading/lagging strands (primers/Okazaki fragments) DNA polymerases replisome telomers • • terminating replication protecting the ends THE END