Such discordance, for the most part not yet understood in detail, is grounded in complex interactions of genes with stochastic SKI-606 cost and environmental factors

that influence brain development, maturation, and function. That said, genomes carry enormous biological influence: the remarkable similarities of basic brain structure and function within species are testimony to the central significance of the genetic blueprint. A recent demonstration that human pluripotent stem cells in vitro (extremely distant from a natural developmental environment) can give rise to cerebral organoids with discrete recognizable brain structures and significant features of a cerebral cortex (Lancaster et al., 2013) serves as a remarkable reminder

of the information contained in genomes—even if the resulting organoids are only pale simulacra of a human brain. Genetic information is particularly important to neurobiologists studying brain disease because the human brain is, both for Selleck Vorinostat ethical and practical reasons, generally inviolable. Scientists studying the biology of cancer or immunologic diseases, for example, can have direct access to diseased tissues obtained from surgical specimens or blood. The resulting cells can be examined for somatic mutations, epigenetic marks, patterns of gene expression, and other molecular indicia. In contrast, for the most part, the human brain can only be examined indirectly in life. Thus, when disorders of the CNS have a significant hereditary component of risk, the ability to obtain molecular clues from genetic analysis may create the most effective current opportunities for scientific investigation. The utility of genetic insights is particularly salient in brain

disorders that affect evolutionarily recent brain circuits and regions or that for other reasons have been difficult to model in animals. These include common else psychiatric disorders such as autism, schizophrenia, bipolar disorder, and major depression as well as late-onset versions of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. In the case of the psychiatric disorders, the relative lack of neuropathology that can be analyzed in postmortem tissue makes genetic information even more valuable as a source of molecular clues to pathogenesis. Psychiatric disorders have long been recognized to cluster in families even though they do not segregate in simple, Mendelian fashion. Twin and adoption studies demonstrated that familiality resulted from heredity, thus suggesting that information about the molecular basis of these serious and disabling disorders is hidden in DNA sequence variation.