BIOINFORMATICS FOR GENETICISTS
CONTENTS SECTION I AN INTRODUCTION TO BIOINFORMATICS FOR THE GENETICIST CHAPTER INTRODUCTION: THE ROLE OF GENETIC BIOINFORMATICS INTRODUCTION KNOWLEDGE MANAGEMENT AND EXPANSION DATA MANAGEMENT AND MINING GENETIC STUDY DESIGNS PHYSICAL LOCUS ANALYSIS SELECTING CANDIDATE GENES FOR ANALYSIS PROGRESSING FROM CANDIDATE GENE TO DISEASE-SUSCEPTIBILITY GENE COMPARATIVE GENETICS AND GENOMICS 1 10 CONCLUSIONS REFERENCES INTERNET RESOURCES FOR THE GENETICIST SUB-DIVISION OF BIOLOGICAL DATA ON THE INTERNET SEARCHING THE INTERNET FOR GENETIC INFORMATION WHICH WEB SEARCH ENGINE? SEARCH SYNTAX: THE MATHEMATICS OF SEARCH ENGINE USE BOOLEAN SEARCHING SEARCHING SCIENTI?C LITERATURE — GETTING TO ‘STATE OF THE ART’ SEARCHING FULL-TEXT JOURNALS SEARCHING THE HEART OF THE BIOLOGICAL INTERNET — SEQUENCES AND GENOMIC DATA 2 10 NUCLEOTIDE AND PROTEIN SEQUENCE DATABASES 2 11 BIOLOGICAL SEQUENCE DATABASES — PRIMARY AND SECONDARY 2 12 CONCLUSIONS GENETICS IN THE POST-GENOME ERA — THE ROLE OF BIOINFORMATICS CHAPTER HUMAN GENETIC VARIATION: DATABASES AND CONCEPTS FORMS AND MECHANISMS OF GENETIC VARIATION DATABASES OF HUMAN GENETIC VARIATION SNP DATABASES MUTATION DATABASES GENETIC MARKER AND MICROSATELLITE DATABASES NON-NUCLEAR AND SOMATIC MUTATION DATABASES TOOLS FOR SNP AND MUTATION VISUALIZATION — THE GENOMIC CONTEXT TOOLS FOR SNP AND MUTATION VISUALIZATION — THE GENE CONTEXT 3 10 CONCLUSIONS FINDING, DELINEATING AND ANALYSING GENES THE EVIDENCE CASCADE FOR GENE PRODUCTS SHORTCOMINGS OF THE STANDARD GENE MODEL LOCATING KNOWN GENES ON THE GOLDEN PATH GENE PORTAL INSPECTION LOCATING GENES WHICH ARE NOT PRESENT IN THE GOLDEN PATH ANALYSING A NOVEL GENE COMPREHENSIVE DATABASE SEARCHING CONCLUSIONS AND PROSPECTS SECTION II THE IMPACT OF COMPLETE GENOME SEQUENCES ON GENETICS ASSEMBLING A VIEW OF THE HUMAN GENOME GENOMIC SEQUENCE ASSEMBLY ANNOTATION FROM A DISTANCE: THE GENERALITIES ANNOTATION UP CLOSE AND PERSONAL: THE SPECI?CS ANNOTATION: THE NEXT GENERATION ACKNOWLEDGEMENTS MOUSE AND RAT GENOME INFORMATICS THE MODEL ORGANISM DATABASES FOR MOUSE AND RAT MOUSE GENETIC AND PHYSICAL MAPS RAT GENETIC AND PHYSICAL MAPS GENOME SEQUENCE RESOURCES COMPARATIVE GENOMICS FROM GENOTYPE TO PHENOTYPE FUNCTIONAL GENOMICS RODENT DISEASE MODELS 6 10 SUMMARY ACKNOWLEDGEMENTS REFERENCES GENETIC AND PHYSICAL MAP RESOURCES — AN INTEGRATED VIEW GENETIC MAPS PHYSICAL MAPS PHYSICAL CONTIG MAPS THE ROLE OF PHYSICAL AND GENETIC MAPS IN DRAFT SEQUENCE CURATION THE HUMAN GENOME SEQUENCE — THE ULTIMATE PHYSICAL MAP? QC OF GENOMIC DNA — RESOLUTION OF MARKER ORDER AND GAP SIZES TOOLS AND DATABASES FOR MAP ANALYSIS AND INTEGRATION CONCLUSIONS SECTION III BIOINFORMATICS FOR GENETIC STUDY DESIGN FROM LINKAGE PEAK TO CULPRIT GENE: FOLLOWING UP LINKAGE ANALYSIS OF COMPLEX PHENOTYPES WITH POPULATION-BASED ASSOCIATION STUDIES THEORETICAL AND PRACTICAL CONSIDERATIONS A PRACTICAL APPROACH TO LOCUS RE?NEMENT AND CANDIDATE GENE IDENTI?CATION CONCLUSION GENETIC STUDIES FROM GENOMIC SEQUENCE DE?NING THE LOCUS CASE STUDY 1: IDENTI?CATION AND EXTRACTION OF A GENOMIC SEQUENCE BETWEEN TWO MARKERS CASE STUDY 2: CHECKING THE INTEGRITY OF A GENOMIC SEQUENCE BETWEEN TWO MARKERS CASE STUDY 3: DE?NITION OF KNOWN AND NOVEL GENES ACROSS A GENOMIC REGION CASE STUDY 4: CANDIDATE GENE SELECTION — BUILDING BIOLOGICAL RATIONALE AROUND GENES CASE STUDY 5: KNOWN AND NOVEL MARKER IDENTI?CATION CASE STUDY 6: GENETIC/PHYSICAL LOCUS CHARACTERIZATION AND MARKER PANEL DESIGN SNP DISCOVERY AND PCR-BASED ASSAY DESIGN: FROM IN SILICO DATA TO THE LABORATORY EXPERIMENT 10 1 INTRODUCTION 10 2 SNP IDENTI?CATION 10 3 PCR PRIMER DESIGN 10 4 BROADER PCR ASSAY DESIGN ISSUES 10 5 PRIMER SELECTION 10 6 PROBLEMS RELATED TO SNP ASSAY VALIDATION 10 7 CONCLUSION TOOLS FOR STATISTICAL ANALYSIS OF GENETIC DATA 11 1 INTRODUCTION 11 2 LINKAGE ANALYSIS 11 3 ASSOCIATION ANALYSIS 11 4 HAPLOTYPE RECONSTRUCTION 11 5 LINKAGE DISEQUILIBRIUM 11 6 QUANTITATIVE TRAIT LOCUS (QTL) MAPPING IN EXPERIMENTAL CROSSES SECTION IV BIOLOGICAL SEQUENCE ANALYSIS AND CHARACTERIZATION PREDICTIVE FUNCTIONAL ANALYSIS OF POLYMORPHISMS: AN OVERVIEW PRINCIPLES OF PREDICTIVE FUNCTIONAL ANALYSIS OF POLYMORPHISMS THE ANATOMY OF PROMOTER REGIONS AND REGULATORY ELEMENTS THE ANATOMY OF GENES PSEUDOGENES AND REGULATORY MRNA ANALYSIS OF NOVEL REGULATORY ELEMENTS AND MOTIFS IN NUCLEOTIDE SEQUENCES FUNCTIONAL ANALYSIS ON NON-SYNONYMOUS CODING POLYMORPHISMS A NOTE OF CAUTION ON THE PRIORITIZATION OF IN SILICO PREDICTIONS FOR FURTHER LABORATORY INVESTIGATION FUNCTIONAL IN SILICO ANALYSIS OF NON-CODING SNPS GENERAL STRUCTURE OF CHROMATIN-ASSOCIATED DNA GENERAL FUNCTIONS OF REGULATORY REGIONS TRANSCRIPTION FACTOR BINDING SITES (TF-SITES) STRUCTURAL ELEMENTS ORGANIZATIONAL PRINCIPLES OF REGULATORY REGIONS RNA PROCESSING SNPS IN REGULATORY REGIONS EVALUATION OF NON-CODING SNPS 13 10 SNPS AND REGULATORY NETWORKS 13 11 SNPS MAY AFFECT THE EXPRESSION OF A GENE ONLY IN SPECI?C TISSUES 13 12 IN SILICO DETECTION AND EVALUATION OF REGULATORY SNPS 13 13 GETTING PROMOTER SEQUENCES 13 14 IDENTI?CATION OF RELEVANT REGULATORY ELEMENTS 13 15 ESTIMATION OF FUNCTIONAL CONSEQUENCES OF REGULATORY SNPS 13 16 CONCLUSION AMINO ACID PROPERTIES AND CONSEQUENCES OF SUBSTITUTIONS PROTEIN FEATURES RELEVANT TO AMINO ACID BEHAVIOUR AMINO ACID CLASSI?CATIONS PROPERTIES OF THE AMINO ACIDS AMINO ACID QUICK REFERENCE STUDIES OF HOW MUTATIONS AFFECT FUNCTION A SUMMARY OF THE THOUGHT PROCESS SECTION V GENETICS/GENOMICS INTERFACES GENE EXPRESSION INFORMATICS AND ANALYSIS TECHNOLOGIES FOR THE MEASUREMENT OF GENE EXPRESSION THE CANCER GENOME ANATOMY PROJECT (CGAP) PROCESSING OF SAGE DATA INTEGRATION OF BIOLOGICAL DATABASES FOR THE CONSTRUCTION OF THE HTM THE HUMAN TRANSCRIPTOME MAP REGIONS OF INCREASED GENE EXPRESSION (RIDGES) DISCUSSION PROTEOMIC INFORMATICS PROTEOMIC INFORMATICS EXPERIMENTAL WORK?OW: CLASSICAL PROTEOMICS PROTEIN INTERACTION NETWORKS BUILDING PROTEIN INTERACTION NETWORKS FALSE NEGATIVES AND FALSE POSITIVES ANALYSING INTERACTION NETWORKS CELL PATHWAYS PREDICTION OF PROTEIN NETWORKS 16 10 ASSESSMENT AND VALIDATION OF PREDICTIONS 16 11 EXPLOITING PROTEIN NETWORKS 16 12 DEDUCING PREDICTION RULES FROM NETWORKS 16 13 CONCLUSION CONCLUDING REMARKS: FINAL THOUGHTS AND FUTURE TRENDS 17 1 HOW MANY GENES? 17 2 MAPPING THE GENOME AND GAINING A VIEW OF THE FULL DEPTH OF HUMAN VARIATION 17 3 HOLISTIC ANALYSIS OF COMPLEX TRAITS 17 4 A ?NAL WORD ON BIOINFORMATICS