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Figure 3 The Rationale of Genetic Genomics
The ultimate determinant of biologic phenotype is the pattern of cellular protein expression (i.e., the proteome). The proteome is in turn determined largely by transcription within the cell (i.e., the transcriptome). Microarray technology permits a comprehensive and quantitative description of the transcriptome. Traditional approaches to understanding disease pathogenesis have attempted to correlate genetic variants with gross phenotype. Instead, genetic correlations can be made with messenger RNA expression patterns as measured by arrays. These intermediate phenotypes are termed "expression quantitative traits" (eQTs). The combination of the systematic power of arrays to measure transcription and the power of genetic analysis to identify causality has proved to be powerful. The genetic determinants of gene expression, termed "expression quantitative trait loci" (eQTL), represent cis and trans regulatory elements in which variations cause alterations in cells’ gene expression patterns. Identification of variants in these regulatory elements, termed "master-switches," not only identifies key molecular protagonists in health and disease per se, but also implicates downstream pathways with therapeutic implications.
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