Einführung in die Genetik
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1 Einführung in die Genetik Prof. Dr. Kay Schneitz (EBio Pflanzen) Prof. Dr. Claus Schwechheimer (PlaSysBiol)
2 Einführung in die Genetik - Inhalte 1 Einführung KS 2 Struktur von Genen und Chromosomen KS 3 Genfunktion KS 4 Transmission der DNA während der Zellteilung KS 5 Vererbung von Einzelgenveränderungen KS 6 Genetische Rekombination (Eukaryonten) KS 7 Genetische Rekombination (Bakterien/Viren) KS 8 Rekombinante DNA-Technologie CS 9 Kartierung/Charakterisierung ganzer Genome CS 10 Genmutationen: Ursache und Reparatur CS 11 Veränderungen der Chromosomen CS 12 Genetische Analyse biologischer Prozesse CS 13 Transposons bei Eukaryonten CS 14 Regulation der Genexpression KS 15 Regulation der Zellzahl - Onkogene CS
3 Chromosome mutations Genetics 11 Based on Chapter 16 (Griffiths; 9th ed.); Chapter 7 (10th ed.)
4 Summary Euploidy and polyploidy crop plants, brassica, wheat, breeding colchicin triploids, tetraploids autopolyploids, allopolyploids, bastards Aneuploidy Meiotic nondisjunction Turner syndrome Klinefelter syndrome Down syndrome Changes in chromosome structure DNA double strand breaks Cross over and repetitive elements Deletion (pseudodominance) Inversion (paracentric, pericentric) Duplication Translocations (Robertson s translocations) Chromosomal mutations and disease Burkitt lymphoma (Reg(IG) -> MYC) Chronic myelogenous leukemia (ABL:BCR1)
5 Genetic analysis Genetics 12 Based on Chapter 4 (9th or10th ed.)
6 Model organisms Arabidopsis Drosophila WT agamous WT antennapedia
7 Mutational analysis Recombination and linkage Phenotypic markers Molecular markers Insertional mutagenesis and reverse genetics
8 Mutational analysis
9 Mutational analysis and model organisms Arabidopsis Drosophila WT agamous WT antennapedia
10 Gene discovery through mutational analysis
11 Spontaneous and induced mutations Types of mutagens Base-substitution mutagens high rates of transitions alkylating agents best in some systems base analogs best in some systems Indel mutagens insertion/deletion of single base pairs proflavin, quinacrine mustards Insertional mutagens transposable elements (natural and engineered) Chromosomal rearrangement mutagens deletions, duplications, inversions, translocations formaldehyde, X-rays, transposable elements
12 Types of mutations Loss-of-function Gain-of-function null or amorphic leaky or hypomorphic recessive hypermorphic neomorphic dominant haploinsufficiency (semi-)dominant
13 Genetic selection vs. genetic screen
14 Dominance/recessivity
15 Dominance/recessivity
16 Recombination and linkage
17 Linkage: linked alleles are inherited together Figure 4-2 vestigial, vg wild type purple
18 Crossing over: produces new allelic combinations Figure 4-3
19 Crossing over: recombination of genetic material Red: Bivalent paired chromosomes Blue: Centromer Green: Chiasmata
20 Crossing over is between chromatids, not chromosomes Wrong! Figure 4-5 Correct!
21 Multiple crossovers can include more than two chromatids Figure 4-6
22 Recombinants are produced by crossovers Figure 4-7
23 For linked genes, recombinant frequencies are less than 50 percent Figure 4-8
24 Nomenclature Cis Trans AB/ab or ++/ab Ab/aB or +b/a+ Loci on the same chromosome AB/AB Loci on different chromosomes AB/AB ; CD/CD
25 Linkage When two genes/loci are close together on the same chromosome pair (they are linked), they do not assort independently but produce a recombinant frequency of less than 50 % Conversely, a recombination frequency of less than 50% is indicative for linkage Quantitating linkage is the basis of gene mapping
26 Calculating the recombinant frequency (RF) a b c RF = Nrec Total x 100 1% = 1 map unit (m.u.) = 1 cm (centimorgan) cm gives a rough idea of the distance between two loci
27 Map distances are generally additive Figure 4-9
28 Example: Mapping of the BRI1 gene Marker Marker Marker Marker Marker
29 Longer regions have more crossovers and thus higher recombinant frequencies
30 Phenotypic markers
31 Phenotypic markers of pea
32 Phenotypic markers on the tomato chromosomes Figure 4-13c
33 Molecular markers
34 Simple Sequence Length Polymorphisms (SSLPs) - microsatellite markers - Figure 4-19a
35 Simple Sequence Length Polymorphisms (SSLPs) - minisatellite markers - Figure 4-18
36 Single nucleotide polymorphisms (SNPs) - in humans one SNP every bp -...AAGGCTCAT......TTCCGAGTA.....AAAGCTCAT......TTTCGAGTA... SNP can be within genes but the sequence change does not lead to a phenotype; SNP can be within an intergenic region and not cause a phenotype; SNP can be within a gene, alter its function and lead to a single inheritence phenotype; SNP can, together with other genes, be responsible for a polygenic trait; SNP can lead to the creation or deletion of a target site for restriction enzymes and the two alleles can be examined as a restriction fragment length polymorphism (RFLP)
37 Restriction fragment length polymorphism (RFLP) Figure 4-15a
38 Restriction Fragment Length Polymorphism (RFLP) Figure 4-15b
39 Restriction fragment length polymorphism (RFLP) Figure 4-15c
40 Single nucleotide polymorphisms (SNPs) - in humans one SNP every bp -...AAGGCTCAT......TTCCGAGTA.....AAAGCTCAT......TTTCGAGTA... SNP can be within genes but the sequence change does not lead to a phenotype; SNP can be within an intergenic region and not cause a phenotype; SNP can be within a gene, alter its function and lead to a single inheritence phenotype; SNP can, together with other genes, be responsible for a polygenic trait; SNP can lead to the creation or deletion of a target site for restriction enzymes and the two alleles can be examined as a restriction fragment length polymorphism (RFLP)
41 Haplotypes and Single Nucleotide Polymorphisms (SNPs) Figure 4-16
42 Phenotypic and molecular markers mapped on human chromosome 1 Figure 4-20
43 Alignment of physical and recombination maps Figure 4-25
44 Insertional mutagenesis and reverse genetics
45 Gene discovery through mutational analysis
46 Targeted gene knockouts
47 Targeted gene knockouts
48 Insertional mutagenesis in the mouse Mus musculus - gene targeting -
49 Stable plant transformation produces random insertions
50 Insertional mutagenesis with T-DNA
51 What you need to know and understand for the exam and for your life genetic selection vs. genetic screen... use of mutagens in this context... types of mutations (gain-of-function, loss-of-function; morph nomenclature)... calculation of recombination frequencies... molecular markers (SNPs, RFLP, microsatellites)... types of insertional mutagenesis
52 The end
Einführung in die Genetik
Einführung in die Genetik Prof. Dr. Kay Schneitz (EBio Pflanzen) http://plantdev.bio.wzw.tum.de schneitz@wzw.tum.de Prof. Dr. Claus Schwechheimer (PlaSysBiol) http://wzw.tum.de/sysbiol claus.schwechheimer@wzw.tum.de
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Einführung in die Genetik Prof. Dr. Kay Schneitz (EBio Pflanzen) http://plantdev.wzw.tum.de kay.schneitz@tum.de Twitter: @PlantDevTUM, #genetiktum FB: Plant Development TUM Prof. Dr. Claus Schwechheimer
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