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  1. 1. Presented by : SheetalNarkar<br />
  2. 2. Epigenetics<br />Heritable changes in gene expression caused by the mechanisms other than changes in the underlying DNA sequence<br />Epigenetics<br /> However, there is no change in the underlying DNA sequence of the organism; Instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.<br />
  3. 3.
  5. 5. Molecular Basis of Epigenetics<br />
  6. 6. Molecular Basis of Epigenetics<br /><ul><li>It involves modificationsand activation of certain genes, but not the basic structure of DNA
  7. 7. Additionally, the chromatin proteins associated with DNA may be activated or silenced
  8. 8. This accounts for why the differentiated cells in a multi-cellular organism express only the genes that are necessary for their own activity</li></li></ul><li>What are those Modifications ?<br />1. Chromatin Remodeling :<br /><ul><li>It is the  post translational modification  of the amino acids that make up histoneproteins
  9. 9. As the histones increase the compaction of the DNA , it depresses the genetic activity ; and vice–a-versa</li></li></ul><li>What are those Modifications ?<br />2. DNA Methylation :<br /><ul><li>It is the addition of methyl groups to the DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine
  10. 10. Some areas of genome are methylated heavier than others and highly methylated areas tend to be transcriptionally less active</li></li></ul><li>Epigenetic Effects in Humans<br /><ul><li>Genomic imprinting and related disorders
  11. 11. Cancer and developmental abnormalities
  12. 12. Twin studies</li></li></ul><li>Epigenetic Effects in Humans<br /><ul><li>Genomic imprinting and related disorders
  13. 13. Most mammalian autosomal genes are expressed from both the maternally inherited and paternally inherited copies of the chromosomes
  14. 14. However, some genes are expressed in a parent-of-origin–specific manner. This phenomenon, known as genomic imprinting</li></li></ul><li>Genomic imprinting<br />Imprinted genes are either expressed only from the allele inherited from the mother (eg. H19 ), or in other instances from the allele inherited from the father (eg. IGF2).<br />
  15. 15. Importance of Imprinted Genes<br /><ul><li>Play a major role in the embryonic growth and development
  16. 16. Imprinting defects results in various genetic diseases including:
  17. 17. Beckwith-Wiedemann syndrome, 
  18. 18. Silver-Russell Syndrome, 
  19. 19. Angelman Syndrome and 
  20. 20. Prader-Willi Syndrome</li></li></ul><li>IGF2<br />Function in embryo growth & development<br />IGF2<br />Monoallelic Expression<br /> Genomic Imprinting… An Epigenetic Event… <br />The differential expression of a gene or chromosomal region according to parental origin of inheritance<br /><br />Insulin-like Growth Factor 2 (IGF2)<br />
  21. 21. Closer look at IGF2 Locus……<br />Enhancer competition at IGF2-H19 locus<br />
  22. 22. Epigenetics Research Institutes<br />There are a total of 4,877 institutions engaged in the research on Epigenetics<br />Among the top 20, fourteen of the institutions are US-based, four hail from the UK, and one is from Austria<br /> <br />
  23. 23. Top 10 Research Institutes<br />Johns Hopkins University tops the list, with 347 papers<br />Harvard University, with 307 papers <br />National Cancer Institute of the US with 284 papers<br />University of Southern California, with 114 papers<br />University of Virginia, with 45 papers  <br />
  24. 24. Top 10 Research Institutes<br />University of Cambridge with 155 papers <br />MIT, with 87 papers<br />Vienna Biocenter, with 25 papers<br />University of California, San Francisco, with 146 papers <br />UK's Babraham Institute, with 81 papers<br />
  25. 25. To date, approximately 50 imprinted genes have been identified in the human genome (Morison IM, Reeve AE 1998; Morison IM, Ramsay JP, Spencer HG 2005; Glaser RL, Ramsay JP, Morison IM 2006)<br />Worldwide Research Going On <br />
  26. 26. Worldwide Research Going On <br />Besides genetic contribution, epigenetic modifications of the paternal genome are also reported to be involved in embryogenesis<br />Benchaib et al. (2003) reported a significant correlation between the level of DNA methylation in human spermatozoa and their ability to fertilize the oocyte and lead to normal embryo development<br />
  27. 27. Worldwide Research Going On <br />Most of the genes involved in embryo development are imprinted<br /> Also developmental disorders like BeckwidthWeideman, Angelman, Silver Russell Syndrome and Prader-Willi syndrome occur due to loss of imprinting (Maher and Reik 2000; Nicholls & Knepper 2001, Delavalet al., 2006)<br />
  28. 28. IGF2-H19 imprinting plays a significant role in normal fetal development<br /> IGF2’s role in Beckwith Weidemann Syndrome (BWS), an embryo overgrowth disorder, is strongly implicated. The overgrowth observed in patients with BWS, occurs only in tissues in which IGF2 is expressed (Gicquel and Le Bouc, 2001)<br />Worldwide Research Going On <br />
  29. 29. Recent Studies have indicated that hypomethylation of the ICR in the IGF2-H19 domain on the paternal allele to be involved in about 1/3rd of patients having Silver Russell Syndrome, an intrauterine growth retardation disorder (reviewed in Delavalet al., 2006)<br />Worldwide Research Going On <br />
  30. 30. Worldwide Research Going On <br />Studies by Gopalakrishnanet al. (2001) have shown defective sperm chromatin compaction as one of the causes for repeated pregnancy loss<br />
  31. 31. Worldwide Research Going On <br />Marques et al. (2004) reported an association between abnormal genomic imprinting and hypospermatogenesis. The above studies indirectly suggest that abnormalities in sperm epigenome could also lead to repeated pregnancy loss<br />
  32. 32. Thank You<br />