Identification of Cis-regulatory Elements for Gene Expressed in Human Brain
2006 Seed Grant
Chunyu Liu, Ph.D.
The University of Chicago
Aberrant gene expression is a possible cause of some complex diseases including bipolar disorder and schizophrenia. However, regulation mechanisms of gene expression, especially in the brain, remain unknown for most genes. Dr. Liu’s lab proposes to use genetic methods to map regulatory elements of gene expression in the human brain.
They will genotype about 500.,000 tag SNPs (Single Nucleotide Polymorphisms) across the human genome in 196 Caucasian individuals from two Stanley and Harvard brain collections. Prefrontal cortex regions of these 196 brain samples have already been analyzed for gene expression using different microarray platforms. Gene expression data will be available before this study begins. They will use gene expression level as a quantitative trait to perform genotype-phenotype.ccrrelatlon analysis. They will look for trans-acting regulatory elements for every gene that shows variable levels of gene.expresslon in the samples. SNPs around each variably expressed gene and its 100Kb flanking regions will be evaluated for correlation between SNP genotypes/haplotypes and gene expression. They will also look for cis-acting, regulatory elements for those variably expressed genes. They will use appropriate statistical methods to approach multiple testing and potential population stratification problems. For selected genes with novel cis-acting elements in putative promoterregions, expression data will be verified using real-time PCR. DNA genotype data will be released to the Stanley Institute according to its policies.
This study will identify gene expression regulatory elernents and genetic variants that affect gene expression in human brains. To our knowledge, it is the first effort trying to fine map expression control elements in human neurons. Combining these findings with SNP genotype-disease association(from the other studies) will enhance our understanding of the molecular-etiology of the major psychiatric diseases, including bipolar and schizophrenia. This could lead to development of new diagnoses and treatments.