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