In utero exposure to maternal smoking is associated with DNA methylation alterations and reduced neuronal content in the developing fetal brain.

Background: Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco.

Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression.

Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations.

MethylomeDB: a database of DNA methylation profiles of the brain.

MethylomeDB (http://epigenomics.columbia.edu/methylomedb/index.

Role of CpG context and content in evolutionary signatures of brain DNA methylation.

DNA methylation is essential in brain function and behavior; therefore, understanding the role of DNA methylation in brain-based disorders begins with the study of DNA methylation profiles in normal brain. Determining the patterns and scale of methylation conservation and alteration in an evolutionary context enables the design of focused but effective methylation studies of disease states. We applied an enzymatic-based approach, Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS), which utilizes second-generation sequencing technology to provide an unbiased representation of genome-wide DNA methylation profiles of human and mouse brains.

Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns.

Abnormalities of genomic methylation patterns are lethal or cause disease, but the cues that normally designate CpG dinucleotides for methylation are poorly understood. We have developed a new method of methylation profiling that has single-CpG resolution and can address the methylation status of repeated sequences. We have used this method to determine the methylation status of >275 million CpG sites in human and mouse DNA from breast and brain tissues.