RRM
2007Rustbelt RNA Meeting
RRM
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Talk abstracts
Abstract:
Schizophrenia (SZ) is a severe neuropsychiatric illness affecting 1% of the adult population, costing the U.S. economy in excess of $60 Billion annually. Decades of SZ study has shown that detectable variations in coding genes are scarce. We hypothesize that a microRNA is a SZ-susceptibility gene. A microRNA (miRNA) regulates its target gene expression by inhibiting translation initiation or degrading the mRNA. By predicting the gene-targeting ratio between the SZ genes as the target pool and the whole genome as the target pool, we identified a miRNA targeting SZ genes twice more frequently than expected. The frequencies for other miRNAs are largely comparable, i.e. the frequency for a miRNA targeting the whole genome as a pool tends to match that of SZ genes as a pool. This miRNA gene, hsa-mir-346, is located in the intron 2 region of a linkage mapped SZ-susceptibility gene, Grid1. Total RNA was extracted from Brodmann's area 46 of the dorsolateral prefrontal cortex from SZ and bipolar patients, as well as normal control subjects. Using real-time PCR, we determined the expression level of the miRNA in the total RNA samples and found that the miRNA expression level is 42% lower (p= 0.02) in SZ patients and 32% lower (p=0.09) in bipolar patients compared to normal subjects. The host gene expression level is roughly colinear with that of the miRNA, but with a lower confidence level. This study demonstrates for the first time that a quantifiable genetic distinction exists between the schizophrenia and the normal subjects and that the etiology of a linkage mapped SZ susceptibility locus involves a miRNA gene which potentially has far-reaching regulatory consequences.
Keywords: schizophrenia, bipolar, microRNA hsa-mir-346, real-time PCR
