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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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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
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.
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
Alternative splicing- gives rise to different proteins from the same gene
How many genes do we have ? The answer to this question is almost meaningless because:
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
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.
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.
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.
Epigenetics • Epigenetics - Heritable changes in gene expression that operate outside of changes in DNA itself
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.
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
Mutations at 5’ methyl cytosine cannot be identified and repaired
CpG dinocleotides are palindromic 5’ CpG 3’ 3’ GpC 5’
CpG dinocleotides are palindromic 5’ CpG 3’ 3’ GpC 5’
Methylation is globally erased during gametogenesis and embryogenesis
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
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
Genomic imprinting Some genes are expressed only from the maternal genome and some only from the paternal genome
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
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