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Allele specific expression design using short read DNA sequencing and application to the genetics of autoimmune disorders

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If you have a question about this talk, please contact Florian Markowetz .

The widespread use of genome-wide association studies has enabled the identification of a large number of disease associated genetic variants, in particular for autoimmune disease like type 1 diabetes and celiac disease. A key challenge is the design of functional assays to understand the molecular role of these risk alleles. Taking RNA as a first step, the typical expression quantitative trait locus (eQTL) experiment correlates gene expression with genotypes in large collections of samples. This design is not practical for samples that are difficult to collect on a large scale such as brain tissue or activated T cells. An alternative to measuring expression differences across individuals is to compare the relative expression of both chromosomes within the same individual. This is the principle of the allele specific expression (ASE) design. Here, I describe how high throughput DNA sequencing can improve the accuracy of ASE assays. However, this process is challenging owing to the multiple biases associated with the sequencing step. Bioinformatic tools and statistical methods need to be constructed to account for these difficulties. I then apply this approach to analyze a set of autoimmune genes.

Hosted by Ana-Teresa Maia

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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