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The Cell, Central Dogma and Human Genome Project. A Eukaryotic Cell (there is nucleus). Central Dogma. Transcription and translation. Fundamentals of Nucleic Acids. DNA Base Pair & Double Helix. Strands come in pairs. Alternating sugar-phosphate backbone
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DNA Base Pair & Double Helix
Strands come in pairs. Alternating sugar-phosphate backbone A,T,G,C variability in the side groups Nucleotide bonds are hydrogren bonds 3' ATTAGCCCAT 5' 5' TAATCGGGTA 3‘ the string "attagcccat" is bonded to its complement "atgggctaat".
Protein Molecular Structure a) Protein is a polymer of amino acids. 20 Amino Acids ( Functional Groups) Peptide Bond Formation
Human genome project (1990 - 2003) Goal: to determine the complete sequence of the 3 billion DNA subunits (bases), identify all human genes, and make them accessible for further biological study. Ref: http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml http://www.ddj.com/184410424 (How Perl saved the Human Genome project?) Major Database and Data collection methods: Genbank: (www.ncbi.nih.gov) DNA sequence: shortgun gene sequencing (molecular biology + computation) Protein sequence: ORF finder, theoretical translation, Experimental: Proteolysis +Mass spectrometry Protein structure db: (www.pdb.org) x-ray crystallography, Nuclear Magnetic Resonance(NMR) spectroscopy Protein structure modeling:http://swissmodel.expasy.org//SWISS-MODEL.html Genomewide expression data (RNA): Gene chip (microarray technology) special gene chips: microRNA chip SNP chip Protein-protein interaction (Proteomics): 2D gel, mass spectrometry
Primary Biological information databases • NCBI (Natl Center Biotech Information) - GenBank • http://www.ncbi.nlm.nih.gov/ • EBI (European Bioinformatics Institute) - EMBL • http://www.ebi.ac.uk/ • NIAS, Japan (National Institute of Agrobiological systems) • http://www.dna.affrc.go.jp/ (genebank, DNA and proteins) • KEGG http://www.genome.jp/kegg/pathway.html (pathways database) • ExPASy - SwissProt and TrEMBL: http://www.expasy.org/sprot • Database of annotated proteins • http://swissmodel.expasy.org//SWISS-MODEL.html • Database for predicting protein structure using homology modeling • Prosite: http://kr.expasy.org/prosite • Database of protein active sites • Structure Databases: • PDB (Protein Data Bank): http://www. pdb.org/ • Data base of Protein tertiary structures • SCOP: http://scop.mrc-lmb.cam.ac.uk/scop • CATH: http://www.biochem.ucl.ac.uk/bsm/cath
http://www.ncbi.nlm.nih.gov/ Tools and Tutorial: BLAST, Structure, PubMed, OMIM, Taxbrowser http://www.ncbi.nlm.nih.gov/IEB/ (Information Engineering) http://www.ncbi.nlm.nih.gov/Education/
Significance of the Genomics Revolution • data driven biology – functional genomics – comparative genomics – systems biology • molecular medicine – identification of genetic components of various maladies – diagnosis/prognosis from sequence/expression – gene therapy • pharmacogenomics – developing highly targeted drugs – predicting adverse effects or efficacy on individual basis • toxicogenomics – elucidating which genes are affected by various chemicals