Temporal Dynamics and Genetic Control of Transcription in the Human Prefrontal Cortex

ABSTRACT: In order to gain a global molecular perspective on how the human genome gives rise to the brain, we explore the temporal dynamics and genetic control of transcription in human dorsolateral prefrontal cortex in an extensive series of brain tissue from fetal development through aging. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half century later in life, this phenomenon is mirrored in aging as well as neurodegeneration. While we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire dataset is freely available (GEO). RNA from 269 human prefrontal cortex samples ranging from fetal development (negative ages) through aging (80 years) were analyzed on custom 2-color microarrays from the National Human Genome Research Institute (NHGRI) microarray core facility using a reference RNA comprised of a pool of all samples. SNP genotype data for these subjects can be found in dbGAP under Study ID *phs000417.v1.p1* http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000417.v1.p1 Both the gene expression and SNP data from this study can be interrogated gene-by-gene with a biologist-friendly stand-alone application available at http://www.libd.org/braincloud . The original publication of this data appeared in the Oct. 27th 2011 volume of Nature: http://www.nature.com/nature/journal/v478/n7370/full/nature10524.html .

ORGANISM(S): Homo sapiens

SUBMITTER: Carlo Colantuoni 

PROVIDER: E-GEOD-30272 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress