Molecular genetics 

The transformation of the LOD score (an acronym for log of the odds ratio), from obscurity as a footnote in medical genetics, to celebrity as multiple choice test item in professional examinations in psychiatry, epitomizes the invasion of genetics, and particularly molecular genetics into psychiatric research. Moreover, like other celebrities caught up in fast moving fields, LOD scores are likely to return to their humble origins within a few years. As molecular genetic approaches to mental health move away from simply identifying genes and DNA sequence variants towards functional studies of increasing complexity, newcomers to the field have to master an expanding literature that covers diverse fields: from quantitative genetics to cell biology, from LOD scores to epigenetics. This chapter takes on the task of making the reader sufficiently familiar with the broad range of subjects now required to follow the progress of psychiatric genetics in the primary literature. A number of achievements have to be highlighted. Foremost among these is the completion of the human genome project. Announced annually from 2001 and thereby begging the question as to what constitutes completion, the human genome project is now an essential biological resource. As expected, the ability to sequence whole genomes has transformed the way genetics is carried out, perhaps most egregiously with the rise of bioinformatics as a core discipline: discovery now takes place using the internet rather than the laboratory. Anyone with an interest in human biology should look at the frequently updated information at http://www.ensembl.org or http://genome.ucsc.edu. Without the human genome two other critical developments would have been impossible: the ability to analyse the expression of every gene in the genome and the ability to analyse (theoretically at least) every sequence variant. Both developments also depend on miniaturization technologies that enable the manufacture and interrogation of initially thousands and then millions of segments of DNA. In addition, results from the International Haplotype Map (HapMap) project, which catalogues common variation in the human genome have been crucial in making it possible to take apart the genetic basis of common, complex disorders such as depression, schizophrenia, and anxiety. Few disciplines are more burdened with jargon than molecular genetics. This is partly due to the proliferation of molecular techniques, but it is also partly intrinsic to the subject; the only unifying principle is evolution, which often operates in a very ad hoc fashion. Biological solutions to the problems posed by selection result in the adaptation of existing structures to new uses, rather than to the invention of purpose-built systems. Consequently there are few general lessons to be learnt and the novice simply has to become adept at recognizing the acronyms and neologisms that decorate the literature. The material in this chapter aims to equip the reader with the necessary terminology. It begins with the structure and function of DNA, an essential starting place for a number of reasons.