Human encodeproject


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Human encodeproject

  1. 1. A consortium of 440 scientists, 32 laboratories Sucheta Tripathy, IICB, 17th Sept. 2012
  2. 2.  ards.html
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  4. 4. Characterization of intergenic region and gene definition
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  6. 6. NHGRI Solicited RFAs were First pilot sought for Publicat proposal full ion in for ENCODE ENCODE 2000 In October GWAS -1990 Human Finished 90% lies First Report ENCODE Genome paper in outside on Encode published project 2003 coding Published 2005 2012 started in 2007
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  8. 8. Treasure Hunt?It is like google map says Eric Lander : Map of earthfrom outer space
  9. 9.  95% of the genome is “junk”. ◦ 2.94% of the genome is coding cis regulatory elements occur within a limited genome distance. Most of the genome is transposable elements that are of obscure origin are dying. Transcribed elements are most often translated than not.
  10. 10.  80% of the human genome is active!! ◦ 70,000 promoters and 400,000 enhancers 75% of the genome transcribed in some tissue or other during life time. Environment plays great role in switching on or off of a lot many genes. [Epigenetics] Most of the diseases don‟t lie with the genes but the switches!! Dark matters controlling the genes are physically close to the genes they control.
  11. 11.  Genes and the switches don‟t hold one to one relationship! 4 million switches controlling 21,000 genes!! Identical twins are NOT identical – greatly influenced by environments. Astronomy and genetic Biology looks similar(95% of the Universe is called as dark matter – we don‟t understand)
  12. 12.  “This explains why 6.5 billion people on earth don‟t look alike”.. Intelligent Design (Creationism) believers are excited that it is handiwork of God. Natural selectionists (Darwinists) excited that natural selection at its best. ◦ This has raged a war between democrats and republicans as usual. Junk DNA is an “Oxymoron”. Some are still wondering about the remaining 20%.
  13. 13.  „I hope this information stirs the mind of those researchers that have ignored "trace minerals" in food as part of the nutritional package‟. The more we think we are close to finding an answer – the far we find ourselves. Reminds me of Aristotle Who once said “The more you know, the more you know you dont know”
  14. 14.  Most part of DNA was considered “Garbage” but later upgraded to “junk”. Most people are actually happy because it is happening during their “life time”. Switches are software and genes are hardware. Ancient Egyptians considered “torso” has a divine role and discarded grey matter in head as “junk”.
  15. 15.  Sean Eddy “At least 40% of the human genome is composed of the decaying DNA remains of transposable elements (TEs), different species of which have replicated in great waves during the evolution of our genome.” “I sure wish I‟d gotten the memo, because this week a collaboration of labs led by myself, Arian Smit, and Jerzy Jurka just released a new data resource that annotates nearly 50% of the human genome as transposable element-derived, and transposon-derived repetitive sequence is the poster child for what we colloquially call “junk DNA”.”
  16. 16. PLoS Biol.2011April; 9(4):e1001046.
  17. 17. PLoS Biol.2011 April;9(4):e1001046.
  18. 18. PLoS Biol.2011 April;9(4):e1001046.
  19. 19. The Cell TypesCell Type Tier Description SourceGM12878 1 B-Lymphoblastoid cell line Coriell GM12878 ChronicK562 1 Myelogenous/Erythroleukemia ATCC CCL-243 cell line Human Embryonic Stem Cells, Cellular DynamicsH1-hESC 1 line H1 InternationalHepG2 2 Hepatoblastoma cell line ATCC HB-8065HeLa-S3 2 Cervical carcinoma cell line ATCC CCL-2.2 Human Umbilical VeinHUVEC 2 Lonza CC-2517 Endothelial Cells PLoS Biol.Various (Tier 3) 3 Various cell lines, cultured primary cells, and primary Various 2011 tissues April; 9(4): e1001046 .
  20. 20.  DNAseI -> Transcription factor binding sites (2.9 million sites, 1/3 rd in one cell type and remaining in others) Chip-seq -> sequence transcription factor and histone binding sites (HeLA and GM12878 – qualified to be called as new species) 5C technology -> Finding proximity between regulatory and regulated regions High density 5 bp tiling DNA micro arrays
  21. 21.  Cap Analysis of Gene Expression Paired-End diTag (PET) Reduced Representation Bisulphite Sequencing (RRBS)
  22. 22.  33.45% exon and 66.55% intron. 62% of the genome is transcribed reproducibly. 231 MB of genome has protein binding sites. ◦ 80% of which are low affinity sites ( ◦ Many are highly conserved cell selective type 96% of the CpG exhibited differential methylation pattern. GWAS SNPs had overlaps with ENCODE elements.
  23. 23.  Chromosome confirmation capture carbon copy(5C) ◦ 1% of the genome is distally regulated (>1000 bp) ◦ On an average 3.9 distal elements interacted with TSS. ◦ Distance could be several KBs to MBs
  24. 24.  cis-regulatory elements - Enhancers, promoters, insulators, silencers. 2.9 million DHS encompassing 125 diverse cell and tissue types. 20-50 bp length DHS mapped uniquely to 86.9% of genome ◦ 580,000 distal DHS with target promoters ◦ 3% lie in TSS ◦ 5% lie within 2.5 KB of TSS ◦ 95% lie distally (introns and intergenic regions) ◦ Strongly enriched in LTRs
  25. 25.  3/4th of genome is capable of transcription – redefine concept of gene? ◦ 62.1% AND 74.7% are processed or primary transcripts. ◦ 10-12 expressed isoforms per gene per cell. ◦ Coding and non-coding transcripts are localized in cytoplasm and nucleus respectively. ◦ 6% of the coding and non-coding transcripts overlap with small RNAs – precursors? ◦ Most of the novel transcripts lacked protein coding ability.
  26. 26.  Mapping job is only half done. Characterizing everything a genome does is 10% done. Finding Network of switches for genes. A number of correlations…..
  27. 27.  Where does gene therapy go from here? Our fundamental understanding of genes as the functional units are flawed?? Epigenetics becomes the key player… Gives impetus to holistic approach in treating a disease. Do we still believe that human genome is most efficient?