Journal Article


Derek W Morris
Aiden P Corvin
Michael Gill
Richard Anney
Matthew Hill
Emma M Quinn



gene expression regulation ankyrins bipolar disorder allelic imbalance regulatory elements transcriptional genetic predisposition to disease genetics cacna1c protein human polymorphism single nucleotide ank3 protein human calcium channels l type humans

Evidence for cis-acting regulation of ANK3 and CACNA1C gene expression. (2010)

Abstract Genome-wide association studies (GWAS) have identified Ankyrin-G (ANK3) and the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) as susceptibility genes for bipolar disorder. Available biological information on these genes suggests a potential molecular mechanism involving ion channel dysfunction. The associated single nucleotide polymorphisms (SNPs) at ANK3 (rs10994336) and CACNA1C (rs1006737) are both intronic with no obvious impact on gene function. We investigated whether, instead of affecting protein function, these risk variants might impact on gene regulation affecting expression. We have done this by testing for allelic expression imbalance (AEI) to identify cis-acting regulatory polymorphisms. We identified evidence of cis-acting variation at both loci in HapMap Caucasian Europeans from Utah (CEU) lymphoblastoid cell lines. There was considerable evidence of AEI at ANK3 with more than half of all heterozygous samples (21 out of 34) for marker SNP rs3750800 showing AEI and a small number of samples showing near monoallelic expression. The AEI at either gene could not be attributed to the GWAS-associated SNPs. These data indicate that there is genetic variation local to both genes affecting their expression, but that this variation is not responsible for increasing risk of bipolar disorder.
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Full list of authors on original publication

Derek W Morris, Aiden P Corvin, Michael Gill, Richard Anney, Matthew Hill, Emma M Quinn

Experts in our system

Derek Morris
Trinity College Dublin
Total Publications: 168
Aiden Corvin
Trinity College Dublin
Total Publications: 218
Michael Gill
Trinity College Dublin
Total Publications: 294
Richard Anney
Trinity College Dublin
Total Publications: 40
Matthew Hill
Trinity College Dublin
Total Publications: 10