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Statistics for Microarrays. Biological background: Molecular Biology. Class web site: http://statwww.epfl.ch/davison/teaching/Microarrays/ETHZ/. Two types of organisms *. * Every biological ‘rule’ has exceptions!. Mendelian Genetics.
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Statistics for Microarrays Biological background: Molecular Biology Class web site: http://statwww.epfl.ch/davison/teaching/Microarrays/ETHZ/
Two types of organisms* * Every biological ‘rule’ has exceptions!
Mendelian Genetics http://www.stg.brown.edu/webs/MendelWeb/MWtoc.html
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.”
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
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)
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.
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.
Multiple Levels of Protein Strucure ( Protein folding)
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.”
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)
DNA Replication, ctd • 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 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.
DNA Synthesis DNA is unwinding
RNA • RNA, or ribonucleic acid, is similar to DNA, but -- RNA is (usually) 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
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
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.
Transcription • Transcription is a complex process involving several steps and many proteins (enzymes) • RNA polymerase synthesizes a single strand of RNA against the DNA template strand (anti-sense strand), adding nucleotides to the 3’ end of the RNA chain • Initiation is regulated by transcription factors, including promoters, usually an initiator element and TATA box, usually lying just upstream (at the 5’ end) of the coding region • 3’ end cleaved at AAUAAA, poly-A tail added
Exons and Introns • Most of the genome consists of non-coding regions • Some non-coding regions (centromeres and telomeres) may have specific chomosomal functions • Other non-coding regions have regulatory purposes • Non-coding, non-functional DNA often called junk DNA, but may have some effect on biological functions • The terms exon and intron refer to coding and non-coding DNA, respectively
Translation • The AUG start codon is recognized by methionyl-tRNAiMet • Once the start codon has been identified, the ribosome incorporates amino acids into a polypeptide chain • RNA is decoded by tRNA(transfer RNA) molecules, which each transport specific amino acids to the growing chain • Translation ends when a stop codon (UAA, UAG, UGA) is reached
Alternative Splicing (of Exons) • How is it possible that there are millions of human antibodies when there are only about 30,000 genes? • Alternative splicing refers to the different ways the exons of a gene may be combined, producing different forms of proteins within the same gene-coding region • Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in higher eukaryotes
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
