Investigation of genetic variants regulating the expression of metabotropic glutamate receptor, subtype 5 (GRM5) mRNA in human brain MEETING ABSTRACT Open Access Investigation of genetic variants regulating the expression of metabotropic glutamate receptor, subtype 5 (GRM5) mRNA in human brain Jian Wang1,3, David Saffen1,2,3* From 2011 International Conference on Molecular Neurodegeneration Shanghai, China. 22-24 September 2011 Background The metabotropic glutamate receptor, subtype 5 (GRM5) regulates cell excitability and neurotransmission and has been suggested to play a modifying role in sev- eral neuropsychiatric and neurodegenerative disorders, including Parkinson’s disease (PD). The observation that GRM5 inhibitors ameliorate symptoms and slow the degradation of nigrostriatal dopamine neurons in rodent models of PD suggests that low expression of GRM5 may also reduce symptoms in human patients and, pos- sibly, slow the development of the disease. The goal of the present study is quantify common variation of GRM5 mRNA expression in human brain and identify haplotypes or combinations of genotypes that correlate with mRNA expression. Haplotypes and genotype com- binations that predict mRNA expression should be use- ful as markers in genetic association studies aimed at detecting possible contributions of GRM5 to PD and other disorders. Methods Sixty-three independent frozen sections of prefrontal cortex (Han Chinese; Brodmann area 46) were obtained from the China Brain Bank Center (Wuhan). Genomic DNA and total RNA were isolated using standard proce- dures. A common SNP, rs566277 (heterozygosity = 0.42), located within the 3’-untranslated region of GRM5 mRNA was chosen as a molecular marker to distinguish mRNAs derived from each autosomal allele. SNaPShot©- based AEI assays were carried out as previously described [Lim J et al., Molecular Psychiatry, 2007]. Analysis of population distributions of log2AEI ratios was carried out using a mathematical model developed in-house.