Foreword |
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xi | |
Preface |
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xv | |
Contributors |
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xvii | |
Glossary |
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xix | |
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SECTION I AN INTRODUCTION TO BIOINFORMATICS FOR THE GENETICIST |
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1 | (32) |
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Bioinformatics challenges for the geneticist |
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3 | (14) |
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3 | (1) |
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The role of bioinformatics in genetics research |
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4 | (1) |
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Genetics in the post-genome era |
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5 | (7) |
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12 | (5) |
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15 | (2) |
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Managing and manipulating genetic data |
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17 | (16) |
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17 | (1) |
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18 | (2) |
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20 | (1) |
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21 | (1) |
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22 | (8) |
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30 | (1) |
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31 | (2) |
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31 | (2) |
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SECTION II MASTERING GENES, GENOMES AND GENETIC VARIATION DATA |
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33 | (112) |
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The HapMap -- A haplotype map of the human genome |
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35 | (24) |
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35 | (3) |
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38 | (4) |
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Application of HapMap data in association studies |
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42 | (12) |
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54 | (5) |
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54 | (5) |
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Assembling a view of the human genome |
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59 | (26) |
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59 | (1) |
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Genomic sequence assembly |
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60 | (4) |
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Annotation from a distance: the generalities |
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64 | (6) |
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Annotation up close and personal: the specifics |
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70 | (8) |
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Annotation: the next generation |
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78 | (7) |
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80 | (5) |
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Finding, delineating and analysing genes |
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85 | (20) |
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85 | (1) |
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Why learn to predict and analyse genes in the complete genome era? |
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86 | (2) |
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The evidence cascade for gene products |
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88 | (7) |
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Dealing with the complexities of gene models |
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95 | (2) |
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Locating known genes in the human genome |
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97 | (3) |
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100 | (1) |
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101 | (1) |
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Conclusions and prospects |
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102 | (3) |
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103 | (2) |
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105 | (40) |
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105 | (1) |
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106 | (3) |
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109 | (4) |
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113 | (5) |
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118 | (14) |
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132 | (5) |
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Challenges and future directions |
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137 | (1) |
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138 | (7) |
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139 | (6) |
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SECTION III BIOINFORMATICS FOR GENETIC STUDY DESIGN AND ANALYSIS |
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145 | (102) |
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Identifying mutations in single gene disorders |
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147 | (18) |
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147 | (1) |
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147 | (1) |
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Genome-wide mapping of monogenic diseases |
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148 | (4) |
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The nature of mutation in monogenic diseases |
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152 | (8) |
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Considering epigenetic effects in mendelian traits |
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160 | (2) |
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162 | (3) |
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162 | (3) |
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From Genome Scan to Culprit Gene |
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165 | (20) |
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165 | (1) |
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Theoretical and practical considerations |
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166 | (10) |
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A stepwise approach to locus refinement and candidate gene identification |
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176 | (4) |
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180 | (1) |
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A list of the software tools and Web links mentioned in this chapter |
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181 | (4) |
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182 | (3) |
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Integrating Genetics, Genomics and Epigenomics to Identify Disease Genes |
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185 | (32) |
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185 | (1) |
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Dealing with the (draft) human genome sequence |
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186 | (1) |
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Progressing loci of interest with genomic information |
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187 | (4) |
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In silico characterization of the IBD5 locus -- a case study |
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191 | (18) |
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Drawing together biological rationale -- hypothesis building |
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209 | (2) |
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Identification of potentially functional polymorphisms |
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211 | (1) |
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212 | (5) |
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213 | (4) |
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Tools for statistical genetics |
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217 | (30) |
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217 | (1) |
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217 | (6) |
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223 | (6) |
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229 | (6) |
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Quantitative trait locus (QTL) mapping in experimental crosses |
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235 | (4) |
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239 | (8) |
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241 | (6) |
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SECTION IV MOVING FROM ASSOCIATED GENES TO DISEASE ALLELES |
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247 | (122) |
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Predictive functional analysis of polymorphisms: An overview |
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249 | (32) |
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249 | (3) |
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Principles of predictive functional analysis of polymorphisms |
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252 | (4) |
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The anatomy of promoter regions and regulatory elements |
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256 | (2) |
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258 | (8) |
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Pseudogenes and regulatory mRNA |
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266 | (1) |
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Analysis of novel regulatory elements and motifs in nucleotide sequences |
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266 | (2) |
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Functional analysis of non-synonymous coding polymorphisms |
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268 | (5) |
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Integrated tools for functional analysis of genetic variation |
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273 | (2) |
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A note of caution on the prioritization of in silico predictions for further laboratory investigation |
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275 | (1) |
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275 | (6) |
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276 | (5) |
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Functional in silico analysis of gene regulatory polymorphism |
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281 | (30) |
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281 | (1) |
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Predicting regulatory regions |
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282 | (6) |
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Modelling and predicting transcription factor-binding sites |
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288 | (7) |
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Predicting regulatory elements for splicing regulation |
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295 | (5) |
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Evaluating the functional importance of regulatory polymorphisms |
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300 | (11) |
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302 | (9) |
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Amino-acid properties and consequences of substitutions |
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311 | (32) |
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311 | (1) |
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Protein features relevant to amino-acid behaviour |
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312 | (4) |
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Amino-acid classifications |
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316 | (2) |
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Properties of the amino acids |
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318 | (3) |
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Amino-acid quick reference |
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321 | (13) |
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Studies of how mutations affect function |
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334 | (5) |
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A summary of the thought process |
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339 | (4) |
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340 | (3) |
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Non-coding RNA bioinformatics |
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343 | (26) |
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343 | (1) |
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The non-coding (nc) RNA universe |
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344 | (5) |
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Computational analysis of ncRNA |
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349 | (7) |
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ncRNA variation in disease |
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356 | (6) |
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Assessing the impact of variation in ncRNA |
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362 | (1) |
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Data resources to support small ncRNA analysis |
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363 | (1) |
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363 | (6) |
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364 | (5) |
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SECTION V ANALYSIS AT THE GENETIC AND GENOMIC DATA INTERFACE |
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369 | (160) |
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371 | (18) |
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371 | (2) |
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Principles of the application of microarray technology |
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373 | (4) |
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Complementary approaches to microarray analysis |
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377 | (1) |
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Differences between data repository and research database |
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377 | (1) |
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Descriptions of freely available research database packages |
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377 | (12) |
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385 | (4) |
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Combining quantitative trait and gene-expression data |
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389 | (24) |
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Introduction: the genetic regulation of endophenotypes |
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389 | (1) |
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Transcript abundance as a complex phenotype |
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390 | (4) |
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Scaling up genetic analysis and mapping models for microarrays |
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394 | (3) |
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Genetic correlation analysis |
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397 | (3) |
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400 | (3) |
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Using expression QTLs to identify candidate genes for the regulation of complex phenotypes |
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403 | (5) |
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408 | (5) |
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408 | (5) |
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Bioinformatics and cancer genetics |
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413 | (34) |
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413 | (1) |
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414 | (1) |
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Approaches to studying cancer genetics |
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415 | (3) |
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General resources for cancer genetics |
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418 | (2) |
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Cancer genes and mutations |
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420 | (5) |
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Copy number alterations in cancer |
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425 | (6) |
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Loss of heterozygosity in cancer |
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431 | (1) |
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Gene-expression data in cancer |
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432 | (3) |
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Multiplatform gene target identification |
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435 | (3) |
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The epigenetics of cancer |
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438 | (1) |
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438 | (1) |
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439 | (8) |
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439 | (8) |
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Needle in a haystack? Dealing with 500 000 SNP genome scans |
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447 | (48) |
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447 | (2) |
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Genome scan analysis issues |
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449 | (10) |
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Ultra-high-density genome-scanning technologies |
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459 | (10) |
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Bioinformatics for genome scan analysis |
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469 | (20) |
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489 | (6) |
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490 | (5) |
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A bioinformatics perspective on genetics in drug discovery and development |
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495 | (34) |
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495 | (3) |
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498 | (10) |
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508 | (17) |
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Conclusions: toward `personalized medicine' |
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525 | (4) |
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525 | (4) |
Appendix I |
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529 | (2) |
Appendix II |
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531 | (6) |
Index |
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537 | |