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Chunk #24 — Methods — Prioritizing positional candidate genes

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Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.
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Candidate regulators for trans-bands were derived by an empiric ranking scheme for genes contained within the support interval of the trans-band. As detailed in Figure S1, this ranking scheme assigned points for gene information within four categories: genetic sequence variation (SNPs), expression genetics (cis eQTL), ethanol regulation and network properties. Positional candidates were scored based on harboring polymorphisms between the B6 and D2 genomes that may alter protein function, which we identified using GeneNetwork's SNP browser. Genes carrying non-synonymous or functional polymorphisms were considered higher priority candidates. We also took into account non-coding polymorphisms whose functional impact may only manifest at the transcript level by further prioritizing interval candidate genes associated with a robust cis eQTL (see above) in either the basal saline or S-score expression datasets. In order to prevent false positive cis eQTLs from being prioritized, probe-sets with cis eQTL were penalized if their binding target region contained a B6/D2 polymorphism. As Affymetrix probe sequences were designed against the B6 genome, probe SNPs primarily reduce binding avidity with D2 transcripts. Therefore, this penalty was only applied to cis