Basic Principles Of Molecular Biology And Genomics Introduction

In June 2000, it was announced that both a corporate effort and a government consortium had succeeded in sequencing all of the human genome. This was followed by the publication of that sequence in February 2001 (Lander et al. 2001; Venter et al. 2001). For anyone involved in biology or medicine, these events represented a revolution in the technical and conceptual approach to both research and therapy.

It seems that humans are far less complex than most scientists had previously thought. Rather than having 100,000-150,000 genes, as was once the belief, humans may have only about 30,000 genes. At this point, not all of those genes have an identified function, and it is becoming clear that many gene products have more than one function. Perhaps more importantly, genes that have been identified in a single cell type may have an entirely different function in other cell types. Some other genes may enjoy a brief and transient expression during the process of embryonic development only to play an entirely different role in the adult. Truly understanding those genes and gene products will revolutionize all of science, and this may be especially true for psychiatry.

Consider that prior to identification of the genome, psychiatric genomics has been limited to studies of chromosomal linkage wherein a putative gene for a disorder could be roughly localized to a given region of a chromosome. The burgeoning understanding of the human genome now occurring has led to a rudimentary understanding of genetic variation among humans. In many humans, a single base or single nucleotide is modified, and it is a combination of knowing the entire genetic code and determining aberrations in individuals with disease that will allow the pinpointing of specific genes associated with psychiatric diseases.

New advances and technology are also furthering our understanding of the genome. Microarrays, which permit one to put several genes on a chip, show the ability of a given cell or tissue to activate given genes. Sometimes, during a disease process, inappropriate genes are activated or inactivated. Identification of these genes also helps to shed light on the disease process and on possible therapy. At the same time that rapid advances are being made in understanding the genome, rapid advances in molecular biology are allowing the manipulation of genes and proteins in individual nerve cells. The development of molecular and cellular models for neuropsychiatric disease has also permitted tremendous advancement in our understanding of both biochemical defects and possible new approaches toward ameliorating those defects.

In this chapter, we present information about genetics, genomics, and the genome and explain modern molecular biology and the investigative methods used in that field. We also discuss pathophysiology, as related to neuropsychiatry and molecular strategy, and introduce findings from studies on the cell biology of the neuron that help us to understand both psychopharmacology and the biology of the brain and mind.

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