INDEX

Chapter 4: Genomics

The last ten years of the 20^th century constituted "The Decade of the Brain". The Human Genome Project began in 1990 and produced a nearly complete working draft of the genome by the year 2000. The time now seems ripe to begin a 21^st century unification of genomics and neuroscience with one goal being to understand how only about 22-25,000 human genes contribute to the structure and function of an organ containing a trillion neurons with 10¹⁵ estimated connections. The full-scale application of genomics and bioinformatics technologies to brain research could lead to a new kind of systems neuroscience akin to the reconceptualization of "systems biology" in the genome era. Neurogenomics is the study of how the genome as a whole contributes to the evolution, development, structure and function of the nervous system. It includes investigations of how genome products (transcriptomes and proteomes) vary in time and space. Neurogenomics differs markedly from the application of genome sciences to other systems, particularly in the spatial category, because anatomy and connectivity are paramount to our understanding of function in the nervous system. Neurogenomics focuses on the contributions of genome-based research efforts in uncovering the molecular pathways and processes that underlie psychiatric and neurodegenerative disorders in the mammalian CNS. Although it has long been thought that many diseases of the CNS in humans had a genetic component, the polygenic nature of these conditions made identification of specific genes challenging. The virtual completion of the human and mouse genome projects combined with advances in transgenic mouse technologies now affords the possibility of integrating often-times quite disparate fields of research to provide unique insights into the molecular basis of aberrant CNS function. Neurogenomics areas include:

• Model organisms of psychiatric disorders

• Network genetics and applications to behavioral phenotypes; see under Functional Neurogenomics

• Genetics of neurodegenerative disorders

• Gene expression atlases of the brain; see under Generation of gene expression atlases of the CNS

• Genome-wide screens for genetic risk factors for human psychiatric disorders; see under Genetic variations: SNPs and CNVs

• Comparative Neurogenomics