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 up take of tryptophan. Tryptophan is the precursor for serotonin, which is imp licated in the regulation of mood. The gene maps to chromosome 21q22.3, a r egion implicated in bipolar disorder I (BPI) in genetic linkage studies. AB CG1 is thus a suitable candidate gene for study in BPI. 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 s ingle 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. Eig ht of the SNPs, the two VNTRs, the GCC repeat and two known microsatellite markers within the gene were tested for association with BPI in a sample of 110 parent-offspring trios using the Extended Transmission Disequilibrium Test (ETDT). No alleles or haplotypes were significantly preferentially tra nsmitted from parents to affected offspring. However, the trend for prefere ntial 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 therefo re warrants attempts at replication. Marker-to-marker linkage disequilibriu rn (LD) showed that strong LD was present over relatively short distances o f 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 trait s.