Screening ABCG1, the human homologue of the Drosophila white gene, for polymorphisms and association with bipolar affective disorder.

ABCG1 encodes a transporter protein that may be involved in the cellular uptake of tryptophan. Tryptophan is the precursor for serotonin, which is implicated in the regulation of mood. The gene maps to chromosome 21q22.3, a region implicated in bipolar disorder I (BPI) in genetic linkage studies. ABCG1 is thus a suitable candidate gene for study in BP1. We screened all 15 exons and 700 bases of the 5' flanking region of ABCG1 for mutations, using Denaturing High Performance Liquid Chromatography (DHPLC). A total of 13 single nucleotide polymorphisms (SNPs) were identified. Ten of the SNPs were intronic, two lie within the 5' flanking region and one within the 3' UTR. We identified a GCC repeat within Exon 1 and two novel intronic VNTRs. Eight of the SNPs, the two VNTRs, the GCC repeat and two known microsatellite markers within the gene were tested for association with BP1 in a sample of 110 parent-offspring trios using the Extended Transmission Disequilibrium Test (ETDT). No alleles or haplotypes were significantly preferentially transmitted from parents to affected offspring. However, the trend for preferential transmission of markers in the 3'UTR is in the same direction as in a previous report for association with mood and panic disorders and therefore warrants attempts at replication. Marker-to-marker linkage disequilibrium (LD) showed that strong LD was present over relatively short distances of up to 20 kb and was present for SNPs as well as for polymorphic repeats. The polymorphisms identified in this study will be useful in examining the role of this gene in other neuropsychiatric disorders and behavioural traits.