1 / 48

Det humane genom

Det humane genom. Menneskekroppen har 100 billioner celler, hver med 46 kromosomer. Samlet lengde av DNA: 2 meter/celle. …er ganske stort. Andre genomer som kan lære oss mye om det humane genom. Antall kromosomer i forskjellige organismer.

nhung
Download Presentation

Det humane genom

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Det humane genom Menneskekroppen har 100 billioner celler, hver med 46 kromosomer. Samlet lengde av DNA: 2 meter/celle

  2. …er ganske stort

  3. Andre genomer som kan lære oss mye om det humane genom

  4. Antall kromosomer i forskjellige organismer

  5. K-value paradox: Complexity does not correlate with chromosome number. Homo sapiens Lysandra atlantica Ophioglossum reticulatum 46 250 1260

  6. Størrelse av genomer

  7. C-value paradox: Complexity does not correlate with genome size.

  8. Det humane genom

  9. The human genome is disappointing: • It is small • It is empty • It is unoriginal • It is repetitive

  10. En oversikt over det humane genom

  11. Hvor mange gener i genomet?

  12. Genomstørrelser – hvor mange gener?

  13. N-value paradox: Complexity does not correlate with gene number. ~31,000 genes ~26,000 genes ~50,000 genes

  14. Sammensetning av genomet

  15. 1.5% Exons Introns (junk) Intergenic regions (junk) The genome is empty.

  16. Den molekylære funksjonen til 26383 humane gener

  17. Funksjonelle kategorier i eukaryote proteomer

  18. Flere proteiner fra samme gen (alternativ spleising) • Menneske: 60 % av genene koder for mer enn ett protein • Orm: 22 % av genene koder for mer enn ett protein

  19. Forskjeller i geninhold • Fibroblastvekstfaktor – menneske 30, bananflue og orm 2 hver • Transformerende vekstfaktor β – menneske 42, bananflue 9, orm 6 • Gener som koder for proteiner med immunglobulindomener – menneske 765, bananflue 140, orm 64 • ”Sinkfinger”-proteiner – menneske dobbelt så mange som bananflue og 5 ganger flere enn orm

  20. CpG-frekvens og CpG-øyer The typical density of CpG doublets in mammalian DNA is ~1/100 bp, as seen for a -globin gene. In a CpG-rich island, the density is increased to >10 doublets/100 bp. The island in the APRT gene starts ~100 bp upstream of the promoter and extends ~400 bp into the gene. Each vertical line represents a CpG doublet.

  21. CpG-øyer

  22. Vedlikeholdsmetylering Ved maintenance-metylering induserer metyleringsmønsteret i en parental DNA-tråd det tilsvarende metyleringsmønster i den komplementære tråden. Slik kan et stabilt metyleringsmønster opprettholdes i en cellelinje

  23. CpG – underrepresentert i genomet The CpG doublet occurs in vertebrate DNA at only ~20% of the frequency that would be expected from the proportion of G·C base pairs. (this is because CpG doublets are methylated on C, and spontaneous deamination of methyl-C converts it to T, introducing a mutation that removes the doublet.) In certain regions, however, the density of CpG doublets reaches the predicted value; in fact, it is increased by 10× relative to the rest of the genome. The CpG doublets in these regions are unmethylated

  24. Cytosin, metylcytosin og tymin T me

  25. Repetitive DNA Alus are like that! interspersed in tandem I

  26. Repeterte sekvenser skaper problemer

  27. Klasser av intersperserte repetisjoner i det humane genom

  28. Elementer i det humane genom som kan transposeres på en RNA-formidlet måte

  29. SINEs og utledning av fylogenetiske forhold • En SINE er enten der eller ikke • SINEs innsettes på tilfeldig måte i ikke-kodende områder. Samme plassering i to arter tyder på at innsettingen foregitt i en felles stamfar • Innsetting av en SINE er irreversibel, fravær er derfor et ancestralt trekk

  30. Alu elements • Length = ~300 bp • Repetitive: > 1,000,000 times in the human genome • Constitute >10% of the human genome • Found mostly in intergenic regions and introns • Propagate in the genome through retroposition (RNA intermediates).

  31. Evolution of Alu elements

  32. Alu elements can be divided into subfamilies The subfamilies are distinguished by ~16 diagnostic positions.

  33. Sekvenssammenstilling av Alu-familier 14 Alu-familier hos mennesket, hvorav 1 ikke hos andre primater. 2000 Alu-insersjoner spesifikke for mennesket. J, S, Y

  34. Evolusjon av Alu-elementer

  35. Transposisjonering av et typisk humant Alu-element

  36. Alu-elementer hos primater

  37. Translation Splicing Eukaryotic genes (exons & introns)

  38. Alternative Splicing Mature splice variant I Mature splice variant II Alternative splicing: One gene, several proteins!

  39. Types of alternative splicing

  40. Cassette exon or internal-exon skipping

  41. Donor site Branch point Acceptor site 1 2 CAG GTRAGT A YYYYYYYYYNCAG G 1 2 -OH A A 1 2 Signals of splicing Pyrimidine tract Lariat

  42. Because mRNAs and Alus are frequently reversetranscribed and incorporated into the genome, pyrimidinetractsareubiquitous The complementary strand of polyA is polyT = pyrimidine tract.

  43. The minus strand of Alu elements contains “near” splice sites • The minus strand of Alu contains ~3 sites that resemble the acceptor recognition site: Consensus acceptor site:YYYYYYNCAG/R Alu-J: (127-114) :TTTTTTGtAG/A • The minus strand of Alu contains ~9 sites thatresemble the consensus donor site: Consensus donor site: CAG/GTRAGT Alu-J: (25-17) : CAG/GTGtGA

  44. Our findings • Out of 1,182 alternatively spliced cassette exons, 62 have a significant hit to an Alu sequence. • Out of 4,151 constitutively spliced exons, none has a significant hit to an Alu sequence.  all Alu-containing exons are alternatively spliced.

  45. Retention Ratio • Retention ratio = number of mRNA molecules containing the alternatively spliced exon divided by total number of mRNA molecules. • Retention ratio for Alu-containing exons was ~10%. • Retention ratio for alternatively spliced exons that do not contain Alu was ~45%.

  46. Exon Exon Proposed model for Alu exonization

  47. Hvordan studere genomet? http://www.genome.ucsc.edu/cgi-bin/hgGateway?org=human http://www.ensembl.org/ Men NCBI har også en genombrowser: MapView!

More Related