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Statistics for Microarrays

Statistics for Microarrays. Biological background: Molecular Biology. Class web site: http://statwww.epfl.ch/davison/teaching/Microarrays/. Acknowledgements. http://www.accessexcellence.org/AB/GG http://www.oup.co.uk/best.textbooks/biochemistry/genesvii

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Statistics for Microarrays

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  1. Statistics for Microarrays Biological background: Molecular Biology Class web site: http://statwww.epfl.ch/davison/teaching/Microarrays/

  2. Acknowledgements • http://www.accessexcellence.org/AB/GG • http://www.oup.co.uk/best.textbooks/biochemistry/genesvii • Sandrine Dudoit, UC Berkeley Biostatistics • Yee Hwa Yang, UC Berkeley Statistics • Terry Speed, UC Berkeley Statistics and WEHI, Melbourne, Australia

  3. Two types of organisms* * Every biological ‘rule’ has exceptions!

  4. Timeline of Genetics Highlights

  5. Mendelian Genetics http://www.stg.brown.edu/webs/MendelWeb/MWtoc.html

  6. Human Chromosomes

  7. Human Chromosome Banding Patterns

  8. Chromosomes and DNA

  9. Cell Division -- Mitosis

  10. Cell Division -- Meiosis

  11. Crossing over and Recombination

  12. Mitosis and Meiosis Compared

  13. (BREAK)

  14. DNA Structure Discovery Nature (1953), 171:737 “We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.”

  15. DNA • A deoxyribonucleic acid or DNA molecule is a double-stranded linear polymer composed of four molecular subunits called nucleotides • Each nucleotide comprises a phosphate group, a deoxyribose sugar, and one of four nitrogen bases: adenine (A), guanine (G), cytosine (C), or thymine (T) • The two strands are held together by weak hydrogen bonds between complementary bases • Base-pairing occurs according to the rule: G pairs with C, and A pairs with T

  16. Polymorphic DNA Tertiary Structures DNA B-type (7BNA) (Watson-Crick form) DNA A-type (140D) (low water content) DNA Z-type (2ZNA) (high salt concentration)

  17. Genes are linearly arranged along chromosomes

  18. DNA Structure (overview)

  19. DNA Structure The monomeric units of nucleic acids are callednucleotides. A nucleotide is a phospate, a sugar, and apurine (A, G) or apyramidine (T, C) base.

  20. Nucleotide Bases Adenine (A) Guanine (G) (Purines) Uracil (U) (RNA) Thymine (T) (DNA) (Pyrimidines) Cytosine (C)

  21. Nucleotide codes

  22. Base Pairing

  23. Proteins • Proteins: macromolecules composed of one or more chains of amino acids • Amino acids: class of 20 different organic compounds containing a basic amino group (-NH2) and an acidic carboxyl group (-COOH) • The order of amino acids is determined by the base sequence of nucleotides in the gene coding for the protein • Proteins function as enzymes, antibodies, structures, etc.

  24. Amino acid codes

  25. Primary Protein Structure

  26. Multiple Levels of Protein Strucure ( Protein folding)

  27. Tertiary Structure ofSperm whale myoglobin (1MBN)

  28. (RT)

  29. DNA Replication Nature (1953), 171:737 “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

  30. DNA Replication • The DNA strand that is copied to form a new strand is called a template • In the replication of a double-stranded or duplex DNA molecule, both original (parental) DNA strands are copied • When copying is finished, the two new duplexes, each consisting of one of the original strands plus its copy, separate from each other (semiconservative replication)

  31. Semiconservative Replication

  32. DNA Replication, ctd • DNA synthesis occurs in the chemical direction 5’3’ • Nucleic acid chains are assembled from 5’ triphosphates of deoxyribonucleosides (the triphosphates supply energy) • DNA polymerases are enzymes that copy (replicate) DNA • DNA polymerases require a short preexisting DNA strand (primer) to begin chain growth. With a primer base-paired to the template strand, a DNA polymerase adds nucleotides to the free hydroxyl group at the 3’ end of the primer. • DNA replication requires assembly of many proteins (at least 30) at a growing replication fork: helicases to unwind, primases to prime, ligases to ligate (join), topisomerases to remove supercoils, RNA polymerase, etc.

  33. DNA Replication Fork

  34. DNA Synthesis DNA is unwinding 

  35. RNA • RNA, or ribonucleic acid, is similar to DNA, but -- RNA is single-stranded -- the sugar is ribose rather than deoxyribose -- uracil (U) is used instead of thymine • RNA is important for protein synthesis and other cell activities • There are several classes of RNA molecules, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and other small RNAs

  36. The Genetic Code • DNA: sequence of four different nucleotides • Protein: sequence of twenty different amino acids • The correspondence between the four-letter DNA alphabet and the twenty-letter protein alphabet is specified by the genetic code, which relates nucleotide triplets, or codons, to amino acids

  37. Standard Genetic Code

  38. Variation of genetic codes T1: standard T2: vert mt T3: yeast mt T4: other mt T5: invert. mt T6: cil. etc nuc. T9: ech. mt T10: eup. nuc. T12:alt yeast nuc T13: asc. mt T14: flat. mt T15: bleph. nuc.

  39. Protein Synthesis

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