High Throughput Technologies for Single Cell Genetic Analysis

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SELECTBIO

Single cell genetic analysis offers an unprecedented view of the behaviors of cell populations that are masked by the ensemble average. In many cancers, small subpopulations of distinct cell types cause or drive the disease but are difficult to study using conventional biomolecular methods. Using emulsion PCR and RT-PCR, we are able to determine the sequences and frequencies of genetic mutations and changes in gene expression at the single cell level. The microfluidic droplet generators developed by my group facilitate rapid analysis of the thousands of single cells required for meaningful statistical analysis. Specifically, we have developed a method for high-throughput single cell DNA purification and detection of the t(14;18) translocation, an approach for investigating the frequency of rare mutation events within individuals prior to the onset of clinical symptoms, and an assay for telomerase splice variants and expression levels in single cells that are associated with more severe cancer cases. These techniques open cellular behaviors to be quantitatively studied with unprecedented sensitivity in order to develop a greater mechanistic understanding of cellular processes of cancer onset and progression.