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?Alternative Splicing QTL
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By gbaute, Section Biology Posted on Fri Apr 30th, 2010 at 11:54:02 PM PST
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Alternative splicing (AS) is a essential form of gene regulation effecting up to 95% of genes in some eukaryotes, key players in its control are poorly understood. A large component of this unknown is the contribution of cis (signals on the RNA) and trans (mostly protein machinery) regulation. This experiment would identify the contribution of both as well as which regions in the genome are responsible.
This experimental layout could be used for any species with AS but I think drosophila, which has very prevalent AS would be a good choice. Two divergent strains with different AS patterns will be crossed and then back-crossed to make a QTL population. Illuminia runs for each line (depending on funding could be 25-250 lines) will essentially do both parts of the experiment at once, it will assess transcriptome wide AS patterns and find (by allele specific snps) the contribution of each parent to the genome. QTL analysis will reveal which AS events are associated with which genomic regions. This is very similar to eQTL experiments. If most AS events are associated with the loci that the genes come from then cis control is important for that allele if its from another region then its trans.
This would further our understanding of AS and possibly reveal new mechanisms of its control. A bonus will be assessing how AS may have diverged in these species.
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