Semmelweis University. Genetic and epigenetic regulation of. Dept. GCI. the immune response. András Falus. November

Transkript

1 Genetic and epigenetic regulation of the immune response András Falus Do-Re-Mi November Semmelweis University Dept. GCI

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3 Encyclopedy of DNA elements of human genome released: April, 2012

4 The human genome Exon (1.5%) Intron (5%) mobile jumping elements (45%) Regulatory elements ( 20%) L1 elements (17%) Alu elements (10%) Repetitive elements (14%) individual non-coding DNA (15%) large, common non-coding (5 6%)

5 Expert Rev. Mol. Diagn. 11(3), (2011)

6 Some diseases with relevant environmental (epigenetic) background Fetal and neonatal disorders Autism Schizophrenia Crohn s disease Neuromuscular disorders Psychotic diseases Tumors Type 1 and 2 diabetes Multiple sclerosis Asthma Gout and pseudogout..

7 MISSING HERITABILITY (after a disappointment) as a major challenge Ethnic differences Multifactorial biological networks Environment-epigenetics coding-non-coding genome rare disease alleles metagenomics- (microbiota) EPIGENETICS

8 Definition of EPIGENETICS Covalent and reversible modifications of chromatin without changes in nucleotide sequence Regulates gene expression ( )

9 eukromatin heterokromatin

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11 Epigenetics of twins

12 exercise eating Social status gut microbiome viruses medical care food excess in utero development environmental pollution psychology doi: /journal.pgen g002 hormones technology development social effects

13 2 m CpG-meth Hist-acet

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15 Human mirnas block mrna translation Total number of mirnas known 21,513 Number human mirnas identified 3,756 Number of human mrna targets 49,887 mirnas can have multiple targets Target mrnas can have multiple mirna binding sites (July 31, 2013)

16 Ornish D, Lin J, Daubenmier J, Weidner G, Epel E, Kemp C, Magbanua MJ, Marlin R, Yglecias L, Carroll PR, Blackburn EH. Department of Medicine, University of California, San Francisco, CA, USA. Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol Nov;9(11): Epub 2008 Sep 15.

17 2006.

18 Epigenetic inputs maternal effect food medications, drugs, toxins infections radiation physical activity, sport light stress, behaviour, psychosocial effects etc.

19 immunoregulation 1. danger requires rapid reaction 2. Restitution and maintenance of homeostasis (reversible changes) epigenetics chromatin rearrangement covalent, reversible

20 The immune genome 1,375 25,000 = 5.5% Kelley, de Bono & Trowsdale, 2005

21 GWAS analysis of SNP associations in asthma by Bayes informatics tool Csorba et al, PlosOne, 2013

22 DC, monocyte/macrophage

23 PAMP/MAMP/DAMP signals are regulated by mirna

24 B-lymphocyte

25 T-lymphocyte

26 An epigenetic model of helper T cell differentiation Reiner S L Hum. Mol. Genet. 2005;14:R41-R46 The Author Published by Oxford University Press. All rights reserved. For Permissions, please journals.permissions@oupjournals.org

27 Methylation regulates T cell polarization

28 A Pivarcsi 2013

29 Network Medicine Barabási, New England Journal of Medicine (2007)

30 Genomics-epigenomics Heredity (genetics) is irreversible Egigenetic changes are reversible LIFESTYLE!!!

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