Einführung in die GenetikProf. Dr. Kay Schneitz (EBio Pflanzen)

http://plantdev.wzw.tum.dekay.schneitz@tum.deTwitter: @PlantDevTUM, #genetikTUMFB: Plant Development TUM

Prof. Dr. Claus Schwechheimer (PlaSysBiol)http://wzw.tum.de/sysbiolclaus.schwechheimer@wzw.tum.de

Einführung in die Genetik - Inhalte1 Einführung 07. 10. 14 KS

2 Struktur von Genen und Chromosomen 14. 10. 14 KS

3 Genfunktion 21. 10. 14 KS

4 Transmission der DNA während der Zellteilung 28. 10. 14 KS

5 Vererbung von Einzelgenveränderungen 04. 11. 14 KS

6 Genetische Rekombination (Eukaryonten) 11. 11. 14 KS

7 Genetische Rekombination (Bakterien/Viren) 18. 11. 14 KS

8 Rekombinante DNA-Technologie 25. 11. 14 CS

9 Kartierung/Charakterisierung ganzer Genome 02. 12. 14 CS

10 Genmutationen: Ursache und Reparatur 09. 12. 14 CS

11 Regulation der Genexpression 16. 12. 14 KS

12 Veränderungen der Chromosomen 23. 12. 14 CS

13 Genetische Analyse biologischer Prozesse 13. 01. 15 CS

14 Transposons bei Eukaryonten 20. 01. 15 CS

15 Regulation der Zellzahl - Onkogene 27. 01. 15 CS

Gene mutations: their causes and repair mechanisms

Genetics 10

Based on Chapter 17 (Griffiths; 10th ed.)

Summary10

• Spontaneous and induced mutations

• Point mutations

• synonymous

• missense: conservative, nonconservative

• nonsense (STOP)

• Indels (insertion, deletion, frameshift)

• Mutagens and carcinogens

• Ames Test

• DNA Repair

• photolyases

• nucleotide excision repair

• global genomic repair

• transcription coupled nucleotide-excision repair

• etc.

• Point mutations and cancer

What you need to know and understand

for the exam and for your life....

...point mutations

... indels

... types of spontaneous mutations

... examples for induced mutations

... repair mechanisms

... Ames test

Summary11

• Cells respond to intrinsic and extrinsic signals by modulating transcriptional control of certain genes

• Gene activity is the result of the function of cis- and trans-acting factors

• Trans-acting proteins react to environmental signals by using built-in sensors that continually monitor cellular conditions

• Coordinated gene regulation in bacteria

• gene are often clustered into operons on the chro and transcribed together into multigenic mRNAs

• one cluster of regulatory sites per operon is sufficient to regulate expression of several genes

• Negative vs positive regulation

• repressor proteins bind to DNA at operator site thereby blocking transcription (e.g., lac operon)

• activator proteins activate transcription by binding to DNA at the promoter region (e.g., cAMP/CAP regulation of lac operon)

• Molecular anatomy of genetic switch

• regulatory proteins have DNA-binding domains (e.g., HLH) and protein-protein interaction domains (modular

• specificity of gene regulation depends on specific protein-DNA interactions mediated by the chemical interactions between aa side chains and chemical groups of DNA bases

Summary• Eukaryotic gene regulation resembles bacterial gene regulation

• trans-acting factors binding to cis-regulatory elements on the DNA

• this regulatory factors determine the level of transcription by regulating the binding of RNA pol II to the promoter of a gene

• Enhancers/UAS

• cis-regulatory elements, possibly located quite far away (>10-50kb) from promoter

• combinatorial interactions among different transcription factors

• enhanceosome: complexes of regulatory proteins that interact in cooperative and synergistic fashion --> high levels of transcription through recruitment of RNA pol II

• Gene regulation and chromatin

• eukaryotic genes are packed in chromatin

• activation/repression requires specific modifications to chromatin

• genes are mostly turned off and kept silent in part by nucleosomes and condensed chromatin

• histone code: pattern of posttranslational modifications of histone tails (acetylation, methylation, phosphorylation etc).

• histone code is an epigenetic mark involved in nucleosome positioning and chromatin condensation that can be altered by TFs

• TFs recruit for example ATP-dependent chromatin remodelers (e.g., SWI-SNF)

Chromosome mutationsGenetics 12

Based on Chapter 16 (Griffiths; 9th ed.); Chapter 7 (10th ed.)

Euploidy and Polyploidy

Aneuploidy and Gene Balance

Chromosomal Mutations and Disease

Changes in Chromosome Structure

Types of chromosome mutations

Euploidy and Polyploidy

Chromosome constitutions

Euploids have multiples of the basic wild type chromosome setAneuploids differ from the wild type by part of a chromosome set

monoploid vs. haploid

male bees, wasps, and ants are examples of monoploids

monoploids are sterile (no m e i o s i s p o s s i b l e a n d propagation via mitotic gametes)

Higher ploidy induces e.g. larger cell size

Diploid vs. tetraploid grapes

Stomata size in theepidermis of a plant leaf

Colchicine, a (chemical) trick to induce autopolyploidy

Chromosome pairing in an autotetraploid

Meiotic pairing in triploids

This happens for each chromosome so that the resulting gametes will certainly have intermediate (aneuploid) chromosome numbers-> high chance of infertility or complete sterility

Origin of the allodiploid Raphanobrassica

Origin of the varieties of Brassica oleracea

Origin of the three allopolyploid species of Brassica

Proposed origin of bread wheat byancestral allodiploidy

Monoploid plants from tissue culture

Polyploidization is a driving force in evolution

Aneuploidy and Gene Balance

Changes in chromosome number

Euploids have multiples of the basic wild type chromosome setAneuploids differ from the wild type by part of a chromosome set

monoploid vs. haploid

male bees, wasps, and ants are examples of monploids

monoploids are sterile (no meiosis possible and propagate via mitotic gametes)

Meiotic nondisjunction generates aneuploid products

Characteristics of Turner syndrome (X0)

Karyotypeabout 1:5000 of female births

Characteristics of Klinefelter Syndrome (XXY)

Karyotypeabout 1:1000 of births

Characteristics of Down syndrome (Trisomy 21)

Karyotypeabout 1.5:1000 of births

Down syndrome and maternal age

Types of chromosome mutations

Changes in Chromosome Structure

- Deletions -

Origins of chromosomal rearrangements

Non-allelic homologous recombination (NHAR)

Gene dosage and balance

Balanced vs. unbalanced rearrangements

Unbalanced arrangements alter the gene ratio/dosage

Deletion loops in Drosophila

Mapping mutant alleles by pseudo-dominance

Deletion and the Cri-du-chat Syndrome

about 1:50,000 of births

Changes in Chromosome Structure

- Duplications -

Origins of chromosomal rearrangements

Non-allelic homologous recombination (NHAR)

Map of segmental duplications in the human genome

tandem duplications vs. insertional duplications

Duplications by ancestral polypoloidy in theSaccharomyces genome

Changes in Chromosome Structure

- Inversions -

Origins of chromosomal rearrangements

Non-allelic homologous recombination (NHAR)

Structural changes in the DNA by inversions

Inversion loops at meiosis

Paracentric deletions can lead to deletion products

Pericentric inversions can lead to duplication-and-deletion products

The two main chromosome-segregation patterns in a reciprocal-translocation

heterozygote

Down Syndrome in the progeny of a translocation heterozygote

Chromosomal mutations and disease

Mutations can induce cancer

Somatic translocations and cancer

Somatic translocations and cancer

Fates of a million implanted zygotes

What you need to know and understand for

the exam and for your life....

...monoploidy, diploidy, etc.

... autotetraploidy vs. autotriploidy

... alloploidy (origin of wheat)

... meiotic nondysjunction and consequences

... Turner, Klinefelter, Down Syndromes

... deletion, inversion, translocation

The end