Bioinformatics for Geneticists: A Bioinformatics Primer for the Analysis of Genetic Data

579 Pages·2007·8.75 MB·English

by  Michael R. Barnes

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Bioinformatics for Geneticists
Second Edition
A bioinformatics primer for the analysis of
genetic data
Michael R. Barnes
Bioinformatics, GlaxoSmithKline Pharmaceuticals,
Harlow, Essex, UK
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Bioinformatics for Geneticists
Second Edition
i
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ii
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Bioinformatics for Geneticists
Second Edition
A bioinformatics primer for the analysis of
genetic data
Michael R. Barnes
Bioinformatics, GlaxoSmithKline Pharmaceuticals,
Harlow, Essex, UK
iii
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Bioinformaticsforgeneticists:abioinformaticsprimerfortheanalysisofgeneticdata/[editedby]Michael
Barnes.–2nded.
p. ; cm.
Includesbibliographicalreferencesandindex.
ISBN-13:978-0-470-02619-9 (cloth:alk.paper)
ISBN-13:978-0-470-02620-5 (pbk.:alk.paper)
1.Genetics–Dataprocessing.2.Bioinformatics.I.Barnes,MichaelR.
[DNLM:1.ComputationalBiology–methods.2.Genomics–methods.3.
Databases,Genetic.4.Software.QU26.5B61472007]
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Contents
Foreword xi
Preface xv
Contributors xvii
Glossary xix
SECTION I AN INTRODUCTION TO BIOINFORMATICS FOR
THE GENETICIST 1
1 Bioinformatics challenges for the geneticist 3
MichaelR.Barnes
1.1 Introduction 3
1.2 Theroleofbioinformaticsingeneticsresearch 4
1.3 Geneticsinthepost-genomeera 5
1.4 Conclusions 12
References 15
2 Managing and manipulating genetic data 17
KarlW.BromanandSimonC.Heath
2.1 Introduction 17
2.2 Basicprinciples 18
2.3 Dataentryandstorage 20
2.4 Datamanipulation 21
2.5 Examplesofcode 22
2.6 Resources 30
2.7 Summary 31
References 31
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vi CONTENTS
SECTION II MASTERING GENES, GENOMES AND GENETIC
VARIATION DATA 33
3 The HapMap – A haplotype map of the human genome 35
EllenM.BrownandBryanJ.Barratt
3.1 Introduction 35
3.2 Accessingthedata 38
3.3 ApplicationofHapMapdatainassociationstudies 42
3.4 Futureperspectives 54
References 54
4 Assembling a view of the human genome 59
ColinA.M.Semple
4.1 Introduction 59
4.2 Genomicsequenceassembly 60
4.3 Annotationfromadistance:thegeneralities 64
4.4 Annotationupcloseandpersonal:thespecifics 70
4.5 Annotation:thenextgeneration 78
References 80
5 Finding, delineating and analysing genes 85
ChristopherSouthanandMichaelR.Barnes
5.1 Introduction 85
5.2 Whylearntopredictandanalysegenesinthecompletegenomeera? 86
5.3 Theevidencecascadeforgeneproducts 88
5.4 Dealingwiththecomplexitiesofgenemodels 95
5.5 Locatingknowngenesinthehumangenome 97
5.6 Genomeportalinspection 100
5.7 Analysingnovelgenes 101
5.8 Conclusionsandprospects 102
References 103
6 Comparative genomics 105
MartinS.TaylorandRichardR.Copley
6.1 Introduction 105
6.2 Thegenomiclandscape 106
6.3 Concepts 109
6.4 Practicalities 113
6.5 Technology 118
6.6 Applications 132
6.7 Challengesandfuturedirections 137
6.8 Conclusion 138
References 139
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CONTENTS vii
SECTION III BIOINFORMATICS FOR GENETIC STUDY DESIGN
AND ANALYSIS 145
7 Identifying mutations in single gene disorders 147
DavidP.Kelsell,DianaBlaydonandCharlesA.Mein
7.1 Introduction 147
7.2 Clinicalascertainment 147
7.3 Genome-widemappingofmonogenicdiseases 148
7.4 Thenatureofmutationinmonogenicdiseases 152
7.5 Consideringepigeneticeffectsinmendeliantraits 160
7.6 Summary 162
References 162
8 From Genome Scan to Culprit Gene 165
IanC.Gray
8.1 Introduction 165
8.2 Theoreticalandpracticalconsiderations 166
8.3 Astepwiseapproachtolocusrefinementandcandidategeneidentification 176
8.4 Conclusion 180
8.5 AlistofthesoftwaretoolsandWeblinksmentionedinthischapter 181
References 182
9 Integrating Genetics, Genomics and Epigenomics to Identify
Disease Genes 185
MichaelR.Barnes
9.1 Introduction 185
9.2 Dealingwiththe(draft)humangenomesequence 186
9.3 Progressinglociofinterestwithgenomicinformation 187
9.4 InsilicocharacterizationoftheIBD5locus–acasestudy 191
9.5 Drawingtogetherbiologicalrationale–hypothesisbuilding 209
9.6 Identificationofpotentiallyfunctionalpolymorphisms 211
9.7 Conclusions 212
References 213
10 Tools for statistical genetics 217
ArunaBansal,CharlotteVignalandRalphMcGinnis
10.1 Introduction 217
10.2 Linkageanalysis 217
10.3 Associationanalysis 223
10.4 Linkagedisequilibrium 229
10.5 Quantitativetraitlocus(QTL)mappinginexperimentalcrosses 235
10.6 Closingremarks 239
References 241