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The Human Genome Project - Part III


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Part III

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The Human Genome Project - Part III

  1. 1. The Human Genome Dr. Hasan Alhaddad Guest lecturer: Molecular Basis of Human Diseases October 12th, 14th, 16th 2014 Room 244 (1 PM)
  2. 2. Lectures structure • Part I (Sunday Oct 12th): • The book of life (Matt Ridely’s analogy with modifications). • Introduction to the technologies at the time. • Part II (Tuesday Oct 14th): • Why sequencing genomes/the human genome? • Genome war (public and private projects). • Sequencing the genome. • Part III (Thursday Oct 16th): • Genome assembly revisited. • Genome annotation. • Genome outcome. • The Genomic era.
  3. 3. AIMS (part III) • Learn the basic principles and terminology of genome assembly. • Understand the importance of genome annotation. • Become familiar with the outcomes of the human genome. • Understand the technologies and applications that were developed due to the human genome project. • Become familiar with the OMICS.
  4. 4. Genome Assembly Revisited
  5. 5. Genome Assembly Revisited DNA sequence: The sequence reads that gets produced by sequencing machine. This can be considered the primary sequence of the genome.
  6. 6. Genome Assembly Revisited Sequence alignment: order and connect overlapping sequence reads to for a Contig. This is something you are likely to do when you sequence a gene.
  7. 7. Genome Assembly Revisited We can consider Contigs the secondary level of genome assembly.
  8. 8. Genome Assembly Revisited Scaffolds are the tertiary level of genome assembly. Scaffolds are also referred to as Super Contigs. Scaffolds are formed by connecting ordered Contigs.
  9. 9. Genome Assembly Revisited Scaffolds are formed by connecting ordered and Contigs. How?
  10. 10. Genome Assembly Revisited
  11. 11. Genome Assembly Revisited Genome assembly quality is measured by Contig/scaffold N50 or similar measures.
  12. 12. Genome Assembly Revisited What affects the quality of genome assembly? 1.Repeat elements. 2.Variations between the individuals sequenced (segmental duplications).
  13. 13. Genome Annotation Genome annotation is very important to study the biology of an organism. Without a proper annotation, the sequence is useless. Remember! A book that cannot be read and understood is useless knowledge
  14. 14. Genome Annotation The genome sequence can be classified into different groups based on the overall sequence composition and structure. Genome Coding Non-coding Genes Proteins or RNA Introns Regulators Etc. Repetitive DNA Interspersed Tandem SINE LINE LTR Transposons Satellite Minisatellite Microsatellite
  15. 15. Genome Annotation Genome annotation can be divided into two approaches: 1.Structural annotation: 1. Largely in silico. 2. Utilizing the accumulated knowledge of genes and genomes to identify sequence signatures. 2.Functional annotation: 1. Requires a lot of work and time. 2. Studying the function of the book/code. 3. Involves biochemical analyses of the genome. 4. Gene expression and regulation.
  16. 16. Structural annotation Start End Introns Exons 5’ UTR 3’ UTR Un-Translated Region Promoter sequence Regulation sequence
  17. 17. Structural annotation Hidden Markov Models are used for bioinformatic annotation
  18. 18. Genome Outcome
  19. 19. Genome Outcome A time line of the developments in genomics
  20. 20. Genome Outcome Number of genes in the human genome ~ 22K and constitute ~1.5% of the genome
  21. 21. Genome Outcome Genes categorized
  22. 22. Genome Outcome Genes categorized
  23. 23. Genome Outcome Disease genes
  24. 24. Genome Outcome Potential Drug targets
  25. 25. Genome Outcome RNA gene are present in multiple copies in the human genome. WHY?
  26. 26. Genome Outcome Exon and intron size compared to other taxa
  27. 27. Genome Outcome Overall GC content of the human genome
  28. 28. Genome Outcome GC is correlated with genes
  29. 29. Genome Outcome GC is correlated with genes CpG islands in the promoter region can regulate gene expression
  30. 30. Genome Outcome We are repeat elements with some genes :-)
  31. 31. Tandem Repeat elements Microsatellite: Short Tandem Repeats (STR) – Simple Sequence Repeats (SSR) Minisatellite: Variable Number Tandem Repeats (VNTR) Repeat unit size = hundreds base pairs Repeated 4 times Repeat unit size = 2 - 6 base pairs Repeated 8 times Repeated 20 times
  32. 32. Tandem Repeat elements
  33. 33. Genome Outcome • Evolutionary relationship. • Syntenic region are the conserved regions across taxa.
  34. 34. Genome Outcome A summary of each chromosome
  35. 35. Genome Outcome
  36. 36. SNP as a marker Single Nucleotide Polymorphism 1. Many are found in through out the genome. 2. Found in nuclear and mitochondrial DNA. 3. No need for a lot of DNA. 4. Can be used on degraded DNA. 5. Easy to detect – many platforms. 6. Polymorphism lower than microsatellites.
  37. 37. SNP as a marker The SNPs identified by the human genome project allowed the development of SNP arrays (SNP chip). SNP array allows surveying the genome for variations between individuals easily at a low price.
  38. 38. SNP as a marker
  39. 39. SNP as a marker Commercial uses of SNP markers to learn about ancestry and health
  40. 40. SNP as a marker Genome-wide Association studies (GWAS)
  41. 41. Beyond the genome The ENCycleopedia Of DNA Elements 1. Transcripts 2. Regulatory elements 3. Enhancers 4. Silencers 5. Origins of replication 6. CpG islands 7. Histone modification sites 8. Open chromatin sites
  42. 42. Beyond the genome Genome papers are no longer news
  43. 43. The OME Era
  44. 44. The OME Era