Deciphering what genes control how we think and move could be overwhelming with so many influences involved. There is no wizard behind a curtain orchestrating all the connections, like there was in the Wizard of Oz. Instead there is an array of genomic tools up for the task. Assembling the right tools as Frank Middleton, Ph.D., did, in a methodical investigation can help pinpoint cause and effect.
Dr. Middleton, an Associate Professor at SUNY Upstate Medical University, devised an approach that characterized response to a mutated glutamate transporter gene he identified in schizophrenia. Using SNP genotyping arrays to study a five generation pedigree affected by schizophrenia, he found a copy number variant (CNV) in the gene. Using whole-genome sequencing (WGS) on the Illumina HiSeq System, he mapped exactly where the CNV started and ended. This led Dr. Middleton and his Ph.D. student, Parisa Afsharito, to create a custom TruSeq targeted RNA expression (TREx) sequencing assay with about 370 of the best schizophrenia candidate genes. He ran the assay on the MiSeq System to characterize expression changes in neurotransmitter pathways in schizophrenia subjects with the CNV.
In just a few days, he received data on dozens of subjects showing that cells with the CNV changed in a consistent way. He saw specific glutamate neurotransmitter receptors responding to the glutamate transporter gene with the CNV. As it turns out, he identified the same neurotransmitter receptors clinical researchers were targeting with schizophrenia medications. Looks like they’re all on the right road to success—not a yellow brick road—just good science.