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 13. 10. 15 KS2 Struktur von Genen und Chromosomen 20. 10. 15 KS3 Genfunktion 27. 10. 15 KS4 Transmission der DNA während der Zellteilung 03. 11. 15 KS5 Vererbung von Einzelgenveränderungen 10. 11. 15 KS6 Genetische Rekombination (Eukaryonten) 17. 11. 15 KS7 Genetische Rekombination (Bakterien/Viren) 24. 11. 15 KS8 Rekombinante DNA-Technologie 01. 12. 15 CS9 Kartierung/Charakterisierung ganzer Genome 08. 12. 15 CS

10 Genmutationen: Ursache und Reparatur 15. 12. 15 CS11 Veränderungen der Chromosomen 22. 12. 15 CS12 Genetische Analyse biologischer Prozesse 12. 01. 16 CS13 Transposons bei Eukaryonten 19. 01. 16 CS14 Regulation der Genexpression 26. 01. 16 KS15 Regulation der Zellzahl - Onkogene 02. 02. 16 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

“Natural” carcinogens - aflatoxins

Aspergillus fumigatus

Quantitating mutagenicity and carcinogenicity

Ames test

Ames test - classifying the mechanisms

TA100 - sensitive to reversion through base pair substitution

TA1535 and TA1538 - sensitive to reversions through frame shift mutation

Biological repair mechanisms

Photolyases repair UV-induced photodimers

Homology-dependent repair - base excision repair

deoxyribophosphodiesterase

apurinic/apyrimidinic endonuclease

Homology-dependent repair - GGR and NER

Homology-dependent repair - GGR and NER

Xeroderma pigmentosum - Mutants in TFIIH

Mutations and cancer

Mutations can induce cancer

The ras oncogene

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

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