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U of A BENG 500-11 - Lecture Notes

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BENG 500-11CSCE 510-3INTRODUCTION TO COMPUTATIONAL BIOLOGYGENOME PROJECTSSOME GENOME SIZESSIGNIFICANCE OF GENOME SEQUENCINGCURRENT/POTENTIAL APPLICATIONSCHALLENGESEXAMPLEA UNEXPECTED RESULTAFTER HUMAN GENOME COMPLETIONNEW CHALLENGEBENG 500BENG 500--1111CSCE 510CSCE 510--33INTRODUCTION TO COMPUTATIONAL BIOLOGYINTRODUCTION TO COMPUTATIONAL BIOLOGYMolecular Biology OverviewMolecular Biology OverviewJin-Woo KimDepartment of Biological and Agricultural EngineeringThe University of Arkansas – Fayetteville1/28/2003BACKGROUND BACKGROUND ––EXPECTEDEXPECTED• Molecular Biology – Not required, but an interest in learning some basic molecular biology is mandatory.EMPHASESEMPHASES• Understanding important problems in molecular biologyo Biological Significances of Genome Sequence o Overview – Molecular BiologyREADING ASSIGNMENTREADING ASSIGNMENT• Chapter 1 – “Fundamental Concepts of Bioinformatics”• Genomics and Its Impact on Medicine and Society: A 2001 Primer http://www.ornl.gov/hgmis/publicat/primer2001/index.htmlA Brief History of Life on EarthA Brief History of Life on EarthEarth formedFirst Life – Prokaryotes dominatedEukaryotes aroseMulticellular eukaryotes arose4.5 billion years ago3.5 billion years ago1.5 billion years ago0.5 billion years ago0.2 billion years ago Plants and animals (‘Dinosaurs’)Upright apesEarly human ancestors4 million years ago2 million years agoA Characteristic ofEvolutionEvolution“A long, slow starting period, followed by ever-increasing speed”LIFE ON EARTHLIFE ON EARTHTotal = 107 –108Species104 –105species1 – 10% Known106–107SpeciesAnimals and Plants >90%105–106 Species0.1 – 1% KnownHISTORY OF MODERN GENETICS IN ONE SLIDEHISTORY OF MODERN GENETICS IN ONE SLIDEMendelMendelFirst Revealed the Discreteness of Geneswith Pea Plant Breeding ExperimentsWatson & CrickWatson & CrickFirst Report on DNA1944195319031905Existence of Sex ChromosomeStevens & WilsonStevens & Wilson2001Human Genome Project CompletedDNA Structure – Complementary Double Helix198519831978MaxamMaxamand Gilbertand GilbertSmithSmithMullisMullisFirst DNA SequencingRestriction Enzyme DiscoveryPolymerase Chain ReactionGENOME PROJECTSGENOME PROJECTS1990Human GenomeProject Starts19951stComplete Genome-FluYeastE. Coli K-12Archaeon1997Mouse2002Fruit Fly20001998Worm2001Human2003RatFuguCiona…Genome Sequencing Completed (so far)Genome Sequencing Completed (so far)113Total16898Number Number ––Sequence CompletedSequence CompletedEukaryotaProkaryotaArchaeaDomainDomainOnOn--Going Genome ProjectsGoing Genome Projects317Prokaryota218NumberNumber––OnOn--GoingGoingEukaryotaDomainDomainSOME GENOME SIZESSOME GENOME SIZES3.1 billion137 million97 million12 million4.6 million9750Number of Base PairsNumber of Base PairsInternational Collaboration/CeleraMultiple GroupsSanger/Washington UniversityInternational CollaborationUniversity of WisconsinTIGRSourceSourceHIVE. Coli K-12S. Cerevisiae (yeast)H. Sapiens (human)Drosophila M. (fruit fly)C. Elegans (worm)GenomeGenomeSIGNIFICANCE OF GENOME SEQUENCINGSIGNIFICANCE OF GENOME SEQUENCINGMay allow us to answer the following questions …• Disease Diagnosis“What variants in our DNA make us susceptible to specific diseases?”• Evolution“What genes were crucial for the evolution of new species?”“Are we more like mice or like cats?”• Gene Expression“What gene expression patterns differentiate lung cells from liver cells?”• Protein Folding“Can we predict protein structure?”“Can we computationally design proteins with desirable properties?”Need tools (computational) to answer the following questions …• What do two sequence/genomes have in common?• Where are the genes in this genome?• Can diseases be characterized by patterns of gene activity?• What does the protein encoded by a given gene look like? What does it do?Development of HighDevelopment of High--Throughput TechnologiesThroughput Technologies••DNA Sequencing TechnologyDNA Sequencing Technology••MicroarraysMicroarrays––Gene ExpressionGene Expression••HighHigh--Throughput Throughput ChrystallographyChrystallography––Structural GenomicsStructural GenomicsThe developed technologies will greatly benefit the research in The developed technologies will greatly benefit the research in the the field of molecular biology.field of molecular biology.CURRENT/POTENTIAL APPLICATIONSCURRENT/POTENTIAL APPLICATIONSMolecular Medicine• Improve diagnosis of disease • Detect genetic predispositions to disease• Create drugs based on molecular information • Use gene therapy and control systems as drugs • Design "custom drugs" based on individual genetic profiles Microbial Genomics• Rapidly detect and treat pathogens (disease-causing microbes) in clinical practice • Develop new energy sources (biofuels) • Monitor environments to detect pollutants • Protect citizenry from biological and chemical warfare • Clean up toxic waste safely and efficiently Risk Assessment• Evaluate the health risks faced by individuals who may be exposed to radiation (including low levels in industrial areas) and to cancer-causing chemicals and toxinsBioarchaeology, Anthropology, Evolution, and Human Migration• Study migration of different population groups based on maternal genetic inheritance • Study mutations on the Y chromosome to trace lineage and migration of males • Compare breakpoints in the evolution of mutations with ages of populations and historical eventsDNA Identification• Identify potential suspects whose DNA may match evidence left at crime scenes • Exonerate persons wrongly accused of crimes • Identify crime, catastrophe, and other victims • Establish paternity and other family relationships • Identify endangered and protected species as an aid to wildlife officials (could be used for prosecuting poachers) • Detect bacteria and other organisms that may pollute air, water, soil, and food • Match organ donors with recipients in transplant programs • Determine pedigree for seed or livestock breeds • Authenticate consumables such as caviar and wine Agriculture, Livestock Breeding, and Bioprocessing• Grow disease-, insect-, and drought-resistant crops • Breed healthier, more productive, disease-resistant farm animals • Grow more nutritious produce • Develop biopesticidesCHALLENGESCHALLENGESFunctional Annotation of Genes Should Meet Two Conflicting ObjecFunctional Annotation of Genes Should Meet Two


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