Research in Progress

Gene Regulation

GRIK2: The Function of a Modifier Gene in HD

Drs. James Gusella and Marcy MacDonald (whose work appears in the first section of Research Frontiers) investigated the relationship between the age of onset of HD and the sequence of the functional region of the GRIK2 (GluR6) gene. This region codes for a subunit of the glutamate receptor in the nerve cells. The glutamate receptor, which is important in many brain functions, binds to the neurotransmitter glutamate (released when the nerve cell’s axon is stimulated).

Previous studies have shown that only 50-60% of the variation in age of onset of Huntington’s disease can be attributed to the length of the CAG repeat region on the Huntington gene. Instead, the nonfunctional allele of the GRIK2 gene, which has trinucleotide (triplet) repeats of TAA (thymine-alanine-alanine, three nucleotides), may be correlated with the age of HD onset.

The researchers sequenced the functional region of the GRIK2 gene in four pairs of patients with similar CAG repeats but different onset ages. They found no variation in the functional sequence that would explain the differential onset ages. Consequently, the difference in onset age might be explained by a difference in GRIK2 gene expression among the various patients or by the effects of a different gene altogether.

This research finding was featured at the 2003 World Congress on Huntington’s Disease. For a listing of all research posters presented, please click here.

Last Modified: 04/12/2007

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