BrainCloud: Data from Human Postmortem Brain Across the Lifespan

This study explores the temporal dynamics and genetic control of transcription and DNA methylation in the human dorsolateral prefrontal cortex in postmortem tissue. This study examines 269 subjects for gene expression (version 1) and 108 subjects for DNA methylation (version 2). The subjects are normal controls without neuropathological and neuropsychiatric diagnosis and range in age from fetal weeks 14-20 through old age (>80). We discover fast changes in gene expression occurring during early brain development. Later in life, the changes are considerably slower. Many genes reverse pattern of expression between fetal and early postnatal development. We identify thousands of strong associations of SNPs with gene expression. We examine DNA methylation in ~14,500 genes at ~27,000 CpG loci focused on 5' promoter regions. The fastest changes in DNA methylation also occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes. DNA for genotyping was obtained from the cerebella and applied to either Illumina 650K or 1 million BeadArrays - only genotypes common to both platforms are analyzed here. Genotypes were called using BeadExpress software. Doi: 10.1038/nature10524 Nature, 478:519-524, 2011; doi:10.1016/j.ajhg.2011.12.020, AJHG 90, 1-13, Feb 10, 2012. The methylation data can be downloaded at: BrainCloud.]]>
Postmortem human brains from the NIMH Brain Tissue Collection in the Clinical Brain Disorders Branch (NIMH, CBDB) were obtained at autopsy primarily from the Offices of the Chief Medical Examiner of the District of Columbia, and of the Commonwealth of Virginia, Northern District, all with informed consent from the legal next of kin (protocol #90-M-0142 approved by the NIMH/NIH Institutional Review Board). Additional postmortem fetal, infant, child, and adolescent brain tissue samples were provided by the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders (BTB: www.BTBank.org) under contracts NO1-HD-4-3368 and NO1-HD-4-3383. Toxicological analysis was performed on every case. Subjects with evidence of macro- or microscopic neuropathology, drug use, alcohol abuse, or psychiatric illness were excluded. SNPs were removed if the call rate was <98% (mean call rate for this study >99%), if not in HWE (p<0.001) in Cauc or AA, or not polymorphic (MAF<0.01). The total number of SNPs remaining in the analysis was 605,371.]]>