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SUMMARY:Allele specific expression analysis using high throughput DNA sequ
 encing - Plagnol\, V (University College London)
DTSTART:20100716T090000Z
DTEND:20100716T093000Z
UID:TALK25512@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Over the recent years\, genome-wide association studies provid
 ed new insights into the genetic architecture of multiple complex multi-fa
 ctorial disorders. A natural next step to follow-up these findings at the 
 molecular level is to correlate disease associated variants with quantitat
 ive gene expression RNA data. A widely used approach to achieve that goal 
 consists of measuring RNA expression level in large samples of unrelated i
 ndividuals with available genotype data. However\, the large sample size r
 equirement for this design may be impractical when dealing with tissue typ
 es or cell lines that are difficult to obtain in large quantities\, for ex
 ample brain tissues or induced pluripotent stem cell lines. A dual approac
 h to answer the same question that is less limited by sample size requirem
 ent is allele specific expression (ASE). ASE correlates genetic factors wi
 th uneven RNA gene expression of both haplotypes for nearby genes. Informa
 tive measurements are made within rather than between individual and are t
 herefore unaffected by the between individual noise not explained by genet
 ic factors. This elegant and powerful design maximizes the per sample info
 rmation. Here\, we show how the combination of high throughput DNA sequenc
 ing and sequence capture provides a powerful tool for quantitative ASE ana
 lysis for up to 200 target genes typically selected from genome-wide assoc
 iation analysis. The key challenge to increase the accuracy of this approa
 ch is a better understanding of the experimental and in silico biases gene
 rated by high troughput DNA/RNA sequencing.
LOCATION:Seminar Room 1\, Newton Institute
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