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Gregor Mendel (1823-1884)

Gregor Mendel (1823-1884). DNA (gene). Transcription. RNA processing (splicing etc). mRNA. Translation. Folding. Post translational modifications. Protein. Proteolysis. Peptides/amino acids. William Bateson (1861-1926) coined the name “genetics” in 1909.

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Gregor Mendel (1823-1884)

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  1. Gregor Mendel (1823-1884)

  2. DNA (gene) Transcription RNA processing (splicing etc) mRNA Translation Folding Post translational modifications Protein Proteolysis Peptides/amino acids

  3. William Bateson (1861-1926)coined the name “genetics” in 1909

  4. Genetics is the study of genes Whether geneticists study at the molecular, cellular, organismal, familial, population, or evolutionary level, genes are always central to their studies.

  5. Topics studied in the department of Genetics • Telomeres of chromosomes • Cell cycle • Nuclear architecture • Population genetics • Genetics of tomatoes • Quantitative traits of milk production in cows • Chromosome X inactivation • RNA splicing • Yeast meiosis • Genetics of the CF disease • Chromosomal fragile sites • Human stem cells • Oncogenes

  6. Transcription

  7. Translation

  8. Promoters

  9. Promoters, enhancers, silencers etc.

  10. Alternative splicing- gives rise to different proteins from the same gene

  11. How many genes do we have ?

  12. How many genes do we have ? The answer to this question is almost meaningless because:

  13. How many genes do we have ? The answer to this question is almost meaningless because: • Each gene can give rise to several proteins by alternative splicing

  14. How many genes do we have ? The answer to this question is almost meaningless because: • Each gene can give rise to several proteins by alternative splicing • And each protein can be modified in multiple ways by phosphorylation, methylation, acetylation, glycosylation etc.

  15. How many genes do we have ? The answer to this question is almost meaningless because: • Each gene can give rise to several proteins by alternative splicing • And each protein can be modified in multiple ways by phosphorylation, methylation, acetylation, glycosylation etc. • These modified proteins can further take part in different protein complexes.

  16. All the cells in the organism have the same DNA

  17. DNA is packed together with histones and other proteins into chromatin. • Chromatin is a highly dynamic material which carries a substantial amount of epigentic information. • All cells in the organism carry the same genetic material, however each cell type expresses different genes.

  18. Epigenetics • Epigenetics - Heritable changes in gene expression that operate outside of changes in DNA itself

  19. Chromatin remodeling • Protein expression can be induced and repressed over many orders of magnitude. An important part of this regulation is exerted via chromatin remodeling by DNA methylation and numerous modifications mainly of the N-termini of histones - acetylation, methylation, phosphorylation and ubiquitilation.

  20. Epigenetic chromatin regulation A. Modification at the DNA level 1. cytosine methylation B. Histone modification - the histone code 1. Histone acetylation 2. Histone methylation 3. Histone phosphorylation 4. Histone ubiquitilation 5. Different types of histones

  21. The five nucleotides that make up the DNA

  22. Mutations at 5’ methyl cytosine cannot be identified and repaired

  23. CpG dinocleotides are palindromic 5’ CpG 3’ 3’ GpC 5’

  24. CpG dinocleotides are palindromic 5’ CpG 3’ 3’ GpC 5’

  25. Maintenance of methylation

  26. Methylation is globally erased during gametogenesis and embryogenesis

  27. DNA demethylation of early embryos 3h 6h 8h Aphidicolin First met. P P P M M M P M 22h 2 cells 45h 4 cells

  28. Establishment of DNA methylation pattern • The methylation pattern of the genome is established anew every generation. In that sense methylation is an epigentic phenomenon - it influences the genetic material but it is not inherited from one generation to another. • All methylation (or at least almost all) is erased during early embryogenesis and reestablished

  29. Genomic imprinting Some genes are expressed only from the maternal genome and some only from the paternal genome

  30. Genomic imprinting Some genes are expressed only from the maternal genome and some only from the paternal genome It is estimated that about 40 genes are imprinted and they can be found on several different chromosomes

  31. Genomic imprinting Some genes are expressed only from the maternal genome and some only from the paternal genome It is estimated that about 40 genes are imprinted and they can be found on several different chromosomes For example - igf2, h19, igf2r and genes involved in the Angelman and Prader Willi syndromes

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