ABSTRACT
The identification of the genetic and epigenetic factors involved in complex diseases and quantitative traits in humans and nonhumans has not yet met with the hope for success [1-4]. A variety of factors have led to this situation including, but not limited
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to, lack of power, genetic heterogeneity, allelic heterogeneity, sporadic cases, poorly defined phenotypes, and perhaps an overreliance on reverse genetics or positional cloning. Ten years ago, Francis Collins [5] proposed that the future localization of quantitative traits would be via positional candidates. While this was fine in practice, our knowledge of the functions of genes is at best spotty, thus requiring us to expand the list of positional candidate genes. One manner to refine the list of candidate genes is to use objective quasi-genome wide high dimensional biology (HDB) techniques to get a different point of view on the diseased phenotype. It is hypothesized that, by combing linkage with other HDB techniques, investigators will be more successful in identifying genes for diseases and traits than any single approach. The HDB techniques that have been integrated include many combinations of linkage, association studies, expression microarrays, proteomics, comparative genomics, advanced test crosses, metabolomics, mutagenesis studies, online databases, and, most recently, quantitative epigenetic techniques. This combined approach has been successful in identifying the genes for several traits and it is expected that many more will be identified in the future. In this chapter, we review some of the successful techniques for integrating data, as well as make suggestions for conducting future studies. We also make suggestions for improving these types of studies and encourage researches to take a multipronged approach in understanding complex diseases.
