1 / 47

Det humane genom

ward
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

    2. er ganske stort

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

    4. Antall kromosomer i forskjellige organismer

    6. Strrelse av genomer

    8. Det humane genom

    10. En oversikt over det humane genom

    11. Hvor mange gener i genomet?

    12. Genomstrrelser hvor mange gener?

    14. Sammensetning av genomet

    16. Den molekylre 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 menneske 42, bananflue 9, orm 6 Gener som koder for proteiner med immunglobulindomener menneske 765, bananflue 140, orm 64 Sinkfinger-proteiner menneske dobbelt s mange som bananflue og 5 ganger flere enn orm

    20. Mouse-human synteny. Human chromosomes can be cut into ~150 pieces, then shuffled into a reasonable approximation of the mouse genome.Mouse-human synteny. Human chromosomes can be cut into ~150 pieces, then shuffled into a reasonable approximation of the mouse genome.

    21. CpG-frekvens og CpG-yer

    22. CpG-yer Diagram showing the structure of three human CpG island genes of different sizes. Vertical lines show the positions of CpGs in the first 10 kb of (a) the desmin (EMBL hsdes01), (b)hypoxanthine phosphoribosyl transferase (HPRT; EMBL hshprt8a) and(c) retinoblastoma (EMBL L11910) genes. The locations of the exons are shown by boxes. Open and tinted portions denote translated and untranslated regions, respectively. Any exons not present in the first 10 kb of genomic DNA are shown fused together to the right. The total genomic length of each gene (in kb) is given in brackets Diagram showing the structure of three human CpG island genes of different sizes. Vertical lines show the positions of CpGs in the first 10 kb of (a) the desmin (EMBL hsdes01), (b)hypoxanthine phosphoribosyl transferase (HPRT; EMBL hshprt8a) and(c) retinoblastoma (EMBL L11910) genes. The locations of the exons are shown by boxes. Open and tinted portions denote translated and untranslated regions, respectively. Any exons not present in the first 10 kb of genomic DNA are shown fused together to the right. The total genomic length of each gene (in kb) is given in brackets

    23. Vedlikeholdsmetylering

    24. CpG underrepresentert i genomet

    25. Cytosin, metylcytosin og tymin

    27. Repeterte sekvenser skaper problemer

    28. Klasser av intersperserte repetisjoner i det humane genom

    29. Elementer i det humane genom som kan transposeres p en RNA-formidlet mte RNA-mediated transposable elements in the human genome. Each contains the characteristic flanking direct repeats (arrows). The human endogenous retrovirus containing long terminal repeats (LTRs) (speckled region), gag (group-specific antigen gene), pol (polymerase gene) and env (envelope gene). The THE-1 retrotransposon consists of an open reading frame (ORF) and LTRs. The non-LTR retrotransposon (LINE) contains internal RNA polymerase II promoter sequences (P), two open reading frames, and an A-tail. The Alu element has a dimeric structure of homologous halves separated by a middle A-rich region (striped). The left half contains A- and B-box RNA polymerase III promoter sequences, and the right half contains an additional internal 31 bp. Other shaded regions are sequences unique to the element. RNA-mediated transposable elements in the human genome. Each contains the characteristic flanking direct repeats (arrows). The human endogenous retrovirus containing long terminal repeats (LTRs) (speckled region), gag (group-specific antigen gene), pol (polymerase gene) and env (envelope gene). The THE-1 retrotransposon consists of an open reading frame (ORF) and LTRs. The non-LTR retrotransposon (LINE) contains internal RNA polymerase II promoter sequences (P), two open reading frames, and an A-tail. The Alu element has a dimeric structure of homologous halves separated by a middle A-rich region (striped). The left half contains A- and B-box RNA polymerase III promoter sequences, and the right half contains an additional internal 31 bp. Other shaded regions are sequences unique to the element.

    30. SINEs og utledning av fylogenetiske forhold En SINE er enten der eller ikke SINEs innsettes p tilfeldig mte i ikke-kodende omrder. Samme plassering i to arter tyder p at innsettingen foregitt i en felles stamfar Innsetting av en SINE er irreversibel, fravr er derfor et ancestralt trekk

    31. 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).

    32. Evolution of Alu elements

    33. Alu elements can be divided into subfamilies

    34. Sekvenssammenstilling av Alu-familier Alignment of Alu-subfamily consensus sequences. The consensus sequence for the Alu Sx subfamily is shown at the top, with the sequences of progressively younger Alu subfamilies underneath. The dots represent the same nucleotides as the consensus sequence. Deletions are shown as dashes, and mutations are shown in coloured boxes; all are colour-coded according to the family in which the ancestral mutation arose. Each of the newer subfamilies, such as Ya5 or Yb8, has all the mutations of the ancestral Alu elements, as well as five or eight extra mutations, respectively, that are diagnostic for the particular Alu subfamily. This figure primarily illustrates the newer subfamilies and does not attempt to show many of the older Alu subfamilies. Alignment of Alu-subfamily consensus sequences. The consensus sequence for the Alu Sx subfamily is shown at the top, with the sequences of progressively younger Alu subfamilies underneath. The dots represent the same nucleotides as the consensus sequence. Deletions are shown as dashes, and mutations are shown in coloured boxes; all are colour-coded according to the family in which the ancestral mutation arose. Each of the newer subfamilies, such as Ya5 or Yb8, has all the mutations of the ancestral Alu elements, as well as five or eight extra mutations, respectively, that are diagnostic for the particular Alu subfamily. This figure primarily illustrates the newer subfamilies and does not attempt to show many of the older Alu subfamilies.

    35. Evolusjon av Alu-elementer

    36. Transposisjonering av et typisk humant Alu-element The structure of each Alu element is bi-partite,with the 3' half containing an additional 31-bp insertion (not shown) relative to the 5' half. The total length of each Alu sequence is ~300 bp, depending on the length of the 3' oligo(dA)-rich tail. The elements also contain a central A-rich region and are flanked by short intact direct repeats that are derived from the site of insertion (black arrows). The 5' half of each sequence contains an RNA-polymerase-III promoter (A and B boxes). The 3' terminus of the Alu element almost always consists of a run of As that is only occasionally interspersed with other bases (a). Alu elements increase in number by retrotransposition a process that involves reverse transcription of an Alu-derived RNA polymerase III transcript.As the Alu element does not code for an RNA-polymerase-III termination signal, its transcript will therefore extend into the flanking unique sequence (b). The typical RNA-polymerase-III terminator signal is a run of four or more Ts on the sense strand,which results in three Us at the 3' terminus of most transcripts. It has been proposed that the run of As at the 3' end of the Alu might anneal directly at the site of integration in the genome for target-primed reverse transcription (mauve arrow indicates reverse transcription) (c). It seems likely that the first nick at the site of insertion is often made by the L1 endonuclease at the TTAAAA consensus site. The mechanism for making the second-site nick on the other strand and integrating the other end of the Alu element remains unclear.A new set of direct repeats (red arrows) is created during the insertion of the new Alu element (d). The structure of each Alu element is bi-partite,with the 3' half containing an additional 31-bp insertion (not shown) relative to the 5' half. The total length of each Alu sequence is ~300 bp, depending on the length of the 3' oligo(dA)-rich tail. The elements also contain a central A-rich region and are flanked by short intact direct repeats that are derived from the site of insertion (black arrows). The 5' half of each sequence contains an RNA-polymerase-III promoter (A and B boxes). The 3' terminus of the Alu element almost always consists of a run of As that is only occasionally interspersed with other bases (a). Alu elements increase in number by retrotransposition a process that involves reverse transcription of an Alu-derived RNA polymerase III transcript.As the Alu element does not code for an RNA-polymerase-III termination signal, its transcript will therefore extend into the flanking unique sequence (b). The typical RNA-polymerase-III terminator signal is a run of four or more Ts on the sense strand,which results in three Us at the 3' terminus of most transcripts. It has been proposed that the run of As at the 3' end of the Alu might anneal directly at the site of integration in the genome for target-primed reverse transcription (mauve arrow indicates reverse transcription) (c). It seems likely that the first nick at the site of insertion is often made by the L1 endonuclease at the TTAAAA consensus site. The mechanism for making the second-site nick on the other strand and integrating the other end of the Alu element remains unclear.A new set of direct repeats (red arrows) is created during the insertion of the new Alu element (d).

    37. Alu-elementer hos primater

    38. Eukaryotic genes (exons & introns)

    39. Alternative splicing: One gene, several proteins!

    41. Cassette exon or internal-exon skipping

    42. Signals of splicing

    43. Because mRNAs and Alus are frequently reverse transcribed and incorporated into the genome, pyrimidine tracts are ubiquitous

    44. 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 that resemble the consensus donor site: Consensus donor site: CAG/GTRAGT Alu-J: (25-17) : CAG/GTGtGA

    45. 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.

    46. 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%.

    47. Proposed model for Alu exonization

    48. Hvordan studere genomet?

More Related