This study provides the first demonstration that gene specific RNA-seq can detect and quantify unexpected rare splice junctions and shows novel splicing complexity of the GABAB1 gene. Gene specific libraries were used to query whole transcriptome libraries for splice junctions and exon/intron usage changes in prefrontal cortex from alcoholics. Among the 65 GABAB1 splice junctions, about 45 were previously unknown rare junctions. Other studies have also identified rare splice junctions from different genes and organisms (27, 30). Splicing can generate new variants with unique functions, e.g. down-regulating other major splicing variants (7-9, 31-33), controlling transcript intracellular localization (34, 35), or providing novel functions (36, 37). Here, we showed that chronic alcohol abuse alters GABAB1 variant production without altering the overall gene expression. Our results from the GABAB1 gene raise the possibility that chronic alcohol abuse may affect the splicing of other genes in brain and other tissues. This is supported by our preliminary genome wide analysis showing many changes in exons/introns and splice junctions.
