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Chunk #34 — Discussion

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Fine mapping of calcineurin (PPP3CA) gene reveals novel alternative splicing patterns, association of 5'UTR trinucleotide repeat with addiction vulnerability, and differential isoform expression in Alzheimer's disease.
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Messenger RNAs from brain samples can provide evidence for effects of agonal state, effects of acute gene regulation, consequences of illness, death, developmental underrepresentation, developmental overrepresentation, or trait differences, among other features, in the relative levels of expression. Studies that document features of the clinical course and brain handling that could influence mRNA levels and work that uses the “haplotype” (or allele) specific expression approaches employed in the present study provide some of the best current means to control for these issues. Studies of relative expression levels of specific splice variants of the same primary transcript also provide significant control for several of these issues. Nevertheless, replication of these findings in independent samples of brains from different sources will also help solidify the observations made in postmortem RNA.