Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder.

The first genome scan conducted in early-onset obsessive-compulsive disorder used a non-parametric analysis to identify a peak in a region of chromosome 9 containing the gene SLC1A1, which codes for the neuronal and epithelial glutamate transporter EAAC1. Interaction between the glutamatergic and serotonergic systems within the striatum suggests EAAC1 as a functional candidate in OCD as well. We determined the genomic organization of SLC1A1 primarily by using primers designed from cDNA sequence to amplify from adaptor-ligated genomic DNA restriction fragments. In order to confirm SLC1A1 as a positional candidate in early-onset OCD, common single nucleotide polymorphisms (SNPs) were identified that enabled mapping of SLC1A1 within the region of the lod score peak. Based on the linkage evidence, the coding region was sequenced in the probands of the seven families included in the genome scan. No evidence was found for a functional mutation, but several SNPs were identified. Capillary electrophoresis SSCP typing of a haplotype consisting of two common SNPs within EAAC1 revealed no significant linkage disequilibrium.