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Silence of the Genes

Silence of the Genes. Genetics. The study of inheritance. Gregor Mendel (1823-1884). Mendelian Ratios. ATGCGA G CGAGT. ATGCGATCGAGT. Mutation. Phenotype. Genotype. Epigenetics. Heritable changes in gene expression that do not involve changes in DNA sequence. ATGCGA A CGAGT.

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Silence of the Genes

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  1. Silence of the Genes

  2. Genetics • The study of inheritance

  3. Gregor Mendel(1823-1884)

  4. Mendelian Ratios

  5. ATGCGAGCGAGT ATGCGATCGAGT Mutation Phenotype Genotype

  6. Epigenetics • Heritable changes in gene expression that do not involve changes in DNA sequence.

  7. ATGCGAACGAGT ATGCGATCGAGT Epi-mutation Phenotype Genotype DNA Modifications Histone Modifications Proteins

  8. Nucleosome DNA histones

  9. CH3 DNAMethylation histones

  10. CH3 HistoneMethylation histones

  11. Examples of Epigenetics

  12. male female X Y X X inactivation X Y X X X-Inactivation unequal expression equal expression Barr Body

  13. Barr Body

  14. Calico Cat orange allele black allele X X o O X X o O O o X X orange sector black sector

  15. Other Examples of Epigenetics

  16. Imprinting • Imprinted genes are expressed differently depending on whether they are inherited through the maternal or paternal parent.

  17. Horses and Donkeys male female male female

  18. Gynogenotes • Embryos containing two female genomes • do not develop normally • fail due to underdeveloped extraembryonic placental tissue

  19. Androgenotes • Embryos containing two paternal genomes • result in abnormal (often overgrown) embryo • display overdeveloped extraembryonic placental tissue

  20. Maternal vs. Paternal Imprinting • Male genome wants to promote growth. • Female genome wants to inhibit growth.

  21. Resetting Methylation Patterns Primordial Germ Cells male methylation female developmental time

  22. Battle for Maintaining DNA Methylation

  23. Battle to Maintain Methylation Fertilization methylation developmental time

  24. Female Strategy Genes that promote growth Fertilization

  25. Antisense Male Strategy Genes that inhibit growth Fertilization

  26. Resetting Imprints is Important for Proper Development

  27. Dolly • First mammal to be cloned from an adult cell. • Developed illness common in older sheep (arthritis) • Probably due to abnormal imprinting

  28. Gene Silencing

  29. Heterochromatin Densely staining condensed chromosomal regions; believed to be transcriptionally inert. Euchromatin A chromosomal region that stains normally; thought to contain the normally functioning genes.

  30. IV Heterochromatin B. McClintock Paul Fransz

  31. Heterochromatin • Centromeric regions • Telomeric regions

  32. Position Effect Variegation W+ heterochromatin W+ spreading W+ suppressed W+ enhanced

  33. Post-Transcriptional Gene Silencing

  34. Anti-Sense

  35. Sense Also Works? Guo and Kemphues, (1995)

  36. What is Causing Silencing? ?

  37. dsRNAPost Transcriptional ? Fire et al. (1998)

  38. RNAi ? Fire et al. (1998)

  39. Dicer RISC A A A A A A RNAi dsRNA

  40. Dicer A A A A A A RNAi dsRNA RISC

  41. cosuppression RNA Silencing

  42. RNA Silencing quelling

  43. RNA Silencing Post Transcriptional Gene Silencing (PTGS)

  44. RNA Silencing RNA Interference (RNAi)

  45. RNA Interference

  46. DNA Methylation Mette et al. (2000)

  47. RNAi and Transcriptional Silencing

  48. Transcriptional Silencing Mette et al. (2000)

  49. Micro RNAs dicer Grishok et al. (2001)

  50. RNAi Genes in S. pombe?

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