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Chunk #48 — Results — Candidate regulators of ethanol-responsive networks

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Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.
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Similar to the Chr 7 trans-band, the regulatory hotspot on Chr 11 was linked to trans-bands from multiple networks, ErGeN3 and ErGeN10 (Table 2). Two strong candidate genes emerged from this region: Gria1 and Ncor1 (Table 3). From a hypothetical functional perspective, both genes are highly intriguing candidates; Gria1, as an ionotropic glutamate receptor and Ncor1 as a transcriptional repressor acting through nuclear receptors and histone deacetylation. In our expression data, both genes were significantly ethanol-responsive, however, Ncor1's response was stronger than Gria1's. Furthermore, while the baseline expression of Gria1 was primarily regulated by a highly significant cis eQTL, regulation of Ncor1 was modulated by a suggestive cis and trans eQTL, the latter of which coincided with the Chr 7 trans-band. Reanalysis of Ncor1's expression using a two-locus model revealed a significant interaction between the Chr 11 and Chr 7 eQTL (data not shown).