Image-guided cardiovascular functional genomics: finding the needle in the haystack. Society of Nuclear Cardiology

摘要

The vast amount of information generated by the Human Genome Project has resulted in burgeoning genomic and pharmacogenomic associations but has increased the difficulty in identifying the genetic variant responsible for the clinical association. For example, information gained from the HapMap project facilitates efficient and cost-effective genotyping of a gene via a "tagSNP" approach, where one does not need to genotype all existing single-nucleotide polymorphisms (SNPs) because genotypes at many polymorphic sites are strongly linked and therefore form linkage disequilibrium (or LD) blocks. Consequently, one can genotype individual SNPs that "tag" or track with many others, providing maximum coverage per genotyping cost. However, the bulk sampling of the method makes it incapable of' predicting which of the many linked SNPs has functional relevance. The field of functional genomics, or the use of bioinformatic, molecular, and physiologic tools to assess the functional relevance of candidate SNPs, is therefore emerging. Paralleling the emergence of functional genomics are dramatic advancements in noninvasive imaging reflected by continued improvements in current imaging approaches such as single photon emission computed tomography, positron emission tomography (PET), and magnetic resonance imaging, as well as the introduction of new technologies such as hybrid imaging that can be performed in both small animals and human beings. Furthermore, there has been the rapid development of targeted as well as activatable contrast agents permitting imaging of biologically relevant processes with a high degree of sensitivity and specificity. As a consequence, noninvasive imaging is well positioned to play a central role in identifying functionally relevant gene variants. The study by Tuun-anen et al,1 published in this issue of the Journal, represents an important first step in this regard.