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THE DEFLATION OF GENOMIC BUB B L E A ND THE HOPES OF EPIGENETIcs

The Pathogenesis of Diseases from Genetic and Genomic Point of View - 4. THE DEFLATION OF GENOMIC BUB B L E A ND THE HOPES OF EPIGENETIcs. PROBLEMS. Rose H, Rose S: Genes, Cells and Brains. Verso UK & USA 2013. Small genetics and big genomics (and strong commercial influence )

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THE DEFLATION OF GENOMIC BUB B L E A ND THE HOPES OF EPIGENETIcs

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  1. ThePathogenesisofDiseasesfromGenetic and Genomic Point ofView - 4 THE DEFLATION OF GENOMIC BUBBLE AND THE HOPES OFEPIGENETIcs

  2. PROBLEMS Rose H, Rose S: Genes, Cells and Brains. Verso UK & USA 2013 Smallgenetics and big genomics (and strongcommercialinfluence) Genomesequencingisalreadyroutine(cca 1000eur) State and consumereugenics? Is there an improvement in our knowledge about health and disease 15 years after the human genome project? (yes, but…) Is it possible to apply in everyday medicine? (Yes in oncology)

  3. WHERE THE THINGS WENT WRONG? DNA IS A “DEAD” MOLECULE WORKING ONLY IN ITS VERY COMPLEX ENVIRONMENT (CHROMOSOMES, CELLS…) Smallgenetics and big genomics (and strongcommercialinfulence) Genomereadingisalreadyroutine(cca 100 eur) State and consumereugenics? Is there an improvement in our knowledge about health and disease 15 years after the human genome project? Is it possible to apply in everyday medicine?

  4. C.H. WADDINGTON. CCA 1950EPIGENETICSAND LONG AGO LAMARCK (THE LONG NECK OF GIRAFFE) THE SECRETS OF CELL/TISSUE DIFFERENTIATION The term ‘epigenetic’ refers to all heritable changes in gene expression and chromatin organization that are independent of the DNA sequence itself

  5. EPIGENETICS Histone modifications DNA methylation microRNAs Goldberg AD et alCell. 2007 Feb 23;128(4):635-8.

  6. Identical twins, different hair colour

  7. THE BASIC EPIGENETIC PROCESSES METHYLATION OF DNA (GENE BLOCK) HISTONE ACETYLATION (ACTIVATION) RNA MODIFICATIONS(ALTERNATIVE SPLICING) TRANSLATION CONTROLL (siRNA) SOMATIC = DIFFERENTIATION AND OTHER CHANGES IN CELL FUNCTION TRANSGENERATIONAL! INTERACTION WITH THE ENVIRONMENT

  8. DNA CYTOSINE METHYLATION

  9. ALSO ON THE OTHER CHAIN (CG – GC) MITOSIS – YES? NO?

  10. COMPLICATED ENZYME SYSTEMS (CODED IN DNA!)

  11. METHYLATION OF GERM CELLS

  12. METHYLATION CHANGES DURING DEVELOPMENT AND AGING

  13. AND BACK ???

  14. DNA METHYLATION • DNA methylationsconsist of adding –CH3groups to cytosines in CpG islands • Methylations regulate gene expression (block) and maintain the stability of genome • Gene expression in general • Imprinting • Silencingof repetitivesequences, pseudogenes... • Inactivation of the 2ndX chromosome • AGING, CARCINOGENESIS.... • TRANSGENERATIONAL METHYLATION !!!

  15. Hongerwinter 1944 German’s blocked food to the Dutch in the winter of 1944. Calorie consumption dropped from 2,000 to 500 per day for 4.5 million. Children born or raised in this time were small, short in stature and had many diseases including, edema, anemia, diabetes and depression. The Dutch Famine Birth Cohort study showed that women living during this time had children 20-30 years later with the same problems despite being conceived and born during a normal dietary state.

  16. HISTONE MODIFICATIONS • Coating and packing of DNA? Yes, but… • Covalent modifications: acetylation, methylation, phosphorylations, etc. • Common: acetylation and methylation of amino terminal lysins H3 and H4 histones • These modifications are essential for the regulation of transcription, replication and also DNA maintenance • They are coordinated with DNA methylation • Catch 22: The histone structure and everything around them is coded in DNA

  17. EXTREMELY COMPLICATED BASIC PRINCIPLE: WRITER – makes modifications READER – reads the signs and gives instructions what to do in the cell ERASER

  18. All “nonheritable” diseases have (epi)genetic background Most “heritable” diseases are influenced by the environment OGOD is dead • Food • Infections • Trauma • Toxins • Life style • Psychical • Social • ………

  19. EPIGENETICS?? Frustrations from the results of modern genomics and other „omics“ from the point of view of everyday practical medicine Interpretation of the results from microchips and genome reading? Too many genes (and their polymorphisms) for common diseases The missing part of heritability – the genomeis cooperating very intensively with the environment! This cooperation is possible through „epigenetic“ processes

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