Rueckert, Erroll H.Barker, DouglasRuderfer, DouglasBergen, Sarah E.O’Dushlaine, ColmLuce, Catherine J.Sheridan, Steven D.Theriault, Kraig M.Chambert, KimberlyMoran, JenniferPurcell, Shaun M.Madison, Jon MorrowHaggarty, StephenSklar, Pamela2014-03-112013Rueckert, E. H., D. Barker, D. Ruderfer, S. E. Bergen, C. O’Dushlaine, C. J. Luce, S. D. Sheridan, et al. 2013. “Cis-Acting Regulation of Brain-Specific ANK3 Gene Expression by a Genetic Variant Associated with Bipolar Disorder.” Molecular psychiatry 18 (8): 10.1038/mp.2012.104. doi:10.1038/mp.2012.104. http://dx.doi.org/10.1038/mp.2012.104.1359-4184http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879743Several genome-wide association studies (GWAS) for bipolar disorder (BD) have found a strong association of the Ankyrin3 (ANK3) gene. This association spans numerous linked single nucleotide polymorphisms (SNPs) in a ~250 kb genomic region overlapping ANK3. The associated region encompasses predicted regulatory elements as well as two of six validated alternative first exons, which encode distinct protein domains at the N-terminus of the protein also known as ankyrin-G (AnkG). Using RNA Ligase-Mediated Rapid Amplification of cDNA Ends (RLM-RACE) to identify novel transcripts in conjunction with a highly sensitive, exon-specific multiplexed mRNA expression assay, we detected differential regulation of distinct ANK3 transcription start sites (TSSs) and coupling of specific 5’ ends with 3’ mRNA splicing events in post-mortem human brain and human stem cell-derived neural progenitors and neurons. Furthermore, allelic variation at the BD–associated SNP rs1938526 correlated with a significant difference in cerebellar expression of a brain-specific ANK3 transcript. These findings suggest a brain-specific cis-regulatory transcriptional effect of ANK3 may be relevant to BD pathophysiology.en-USAnkyrin-G (AnkG)Axon initial segmentbipolar disorderstem cellshuman neuronsJournal Article2014-03-1110.1038/mp.2012.104