Abstract:
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Multifactorial diseases are caused by mutations in several genes and often involve environmental "triggering" factors. While the identification of genes underlying Mendelian disorders has proven relatively straightforward, the identification of susceptibility genes underlying multifactorial disorders has proven onerous. The recent draft sequence of the human genome revealed fewer than 40,000 genes, many less than expected from the estimated 2 million proteins within the proteome. This finding has sparked a renaissance in proteomics by disease researchers and pharmaceutical companies seeking drug targets. While the fundamental protein expression analytical tools have existed for more than twenty-five years, the more recent field of microarray analysis of mRNA expression has led the development of methodologies for the analysis of gene expression profiles. In this presentation, we shall compare and contrast both technologies and describe an approach for the likelihood-based estimation of variance components, prediction of protein expression levels, testing hypotheses for individual protein expression level differences, and empirically establishing type I error thresholds.
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