Both GluR5 and GluR6 subunit precursor RNAs undergo RNA secondary-structure-dependent adenosine-to-inosine editing, which generates a glutamine-to-arginine amino acid coding change that affects glutamate receptor function (Seeburg et al. 1998; Seeburg & Hartner 2003). GRIK1 is comprised of 18 exons spanning 403kb and maps to chromosome 21q22.11. The HapMap dataset indicates that the gene contains at least 8 haplotype blocks in Europeans. The GRIK1 transcript undergoes alternative splicing to encode two known isoforms of human GluR5. One isoform (GluR5-1d; accession number NM-000830) includes exons 1-17, while the second isoform (EAA3a; accession number U16125) includes exons 1-8, 10-16 and 18. These alternatively spliced sites reflect potential functional polymorphic variation that could influence receptor assembly and intracellular trafficking of kainate receptors. Because GRIK1 spans too great a region to tag it fully, we focused on variation in the 3’-half of the gene, including the differentially spliced exons 9, 17, and 18, which have potential functional significance for the receptor.
