ABSTRACT
Introduction ..........................................................................................................170 Game Plan for Early Adopters ................................................................. 170 Forewarned is Forearmed: Overview of the Caveats............................... 170 Questions to Consider before Embarking on a Study ............................. 171
Technical Considerations...................................................................................... 172 Overview of SNP Chip Technology......................................................... 172 Lessons from Transcriptomics: Is the Chip Content Trustworthy?......... 174 The Intersection of Technical and Biological Limitations: Variation within Genetic Variation ........................................................... 175 The Intersection of Technical and Biological Limitations: Genomic Peculiarities............................................................................... 176
Biological Considerations..................................................................................... 178 Genes, Environment, and Complexity ..................................................... 178 Linkage Disequilibrium............................................................................ 179
Definitions ....................................................................................... 179 Frequencies and Spacing of Polymorphisms ................................. 179 Correlating a Mapped Marker and a Trait of Interest.................... 180 High LD When Frequencies Match for Derived States of the Mapped Marker and Trait of Interest ........................................................................ 182 The Consequences of Genetic Recombination............................... 183 Population Structure and Admixture .............................................. 185 Correcting for Multiple Comparisons ............................................ 185
Mapping Strategies ................................................................................... 186 Concluding Remarks ............................................................................................ 188 References............................................................................................................. 188
Some scientists quickly embrace new technologies with the desperate hope that a panacea for the unsolvable is at last at hand, but others in the field approach with greater caution. Historically, the pessimists have amassed more credible data and there is good cause to be skeptical. However, for a scientist to avoid the monikers of either Luddite or
naïf,
it is necessary to approach new technology with the intent to both expose the caveats and to engage one’s creativity to overcome these limitations. The objective of this chapter is to provide a practical guide to understanding and, where possible, compensating for the caveats inherent in using microarray technology to facilitate association studies.
