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Chapter 3. Genetics and Genomics

Elisabeth B. Binder, M.D., Ph.D.; Joseph F. Cubells, M.D., Ph.D.
DOI: 10.1176/appi.books.9781585623860.407883

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Excerpt

Genetics and genomics have become among the most important tools in modern psychiatric research. Spurred by the completion of the human genome sequence in February 2001, the number of psychiatric genetic studies has increased dramatically in the past two decades (Lander et al. 2001; Venter et al. 2001). The following chapter will attempt to cover the basic methodologies and concepts, and define key terms, currently used in psychiatric genetics and genomics. Our goal is to facilitate interpretation by working physicians and scientists in the field of psychopharmacology of the avalanche of genetic and genomic data that are accumulating in the human neuroscience literature. Throughout this chapter, terms in common use in the genetics and genomics literature will be italicized upon their first use and definition.

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FIGURE 3–1. Patterns of intrapair correlations and source of variance implied.Intrapair correlations around zero imply effects of individual-specific environment. Equal intrapair correlations greater than zero that are equal for monozygotic (MZ) and dizygotic (DZ) twins imply effects of shared environment. Correlations for MZ twins that are twice as great as those for DZ twins imply additive genetic effects. Correlations for MZ twins that are greater than—but not twice as great as—those for DZ twins imply additive genetic effects and shared environment effects. The correlations of less than 1.0 in the last three examples are likely mediated by individual-specific environment effects.

FIGURE 3–2. Chromosomes, genes, and genetic variation.Panel A shows a representation of chromosome 6 (Chr6), which spans 170 megabases of DNA. Panel B shows a zoomed-in representation of the area highlighted in red in panel A. This region contains 31 genes within 2 megabases. Genes can be transcribed from both strands of the DNA. The arrows indicate the direction of transcription and translation of the respective genes. In the region shown, three copy number variants (CNVs) have been identified. All three span several genes. Panel C shows a zoomed-in representation of the gene for FK506 binding protein 5 (FKBP5) highlighted with a red frame in panel B. The gene spans 115 kilobases and is composed of 11 exons (translated into protein). The intervening introns are transcribed into RNA but are spliced out to form the mature mRNA that serves as the template for translation. The transcription start is at exon 1. In this gene, more than 60 SNPs have been genotyped within the HapMap Project. Their positions are indicated by the triangles. Panel D shows sequence examples for three common polymorphisms.Source. Representations from www.hapmap.org.
Table Reference Number
TABLE 3–1. Heritability scores for major psychiatric illnesses, with focus on results of recent meta-analyses

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Genetic epidemiological studies have established that psychiatric disorders are quite complex and are not single-gene disorders. One reason for this complexity is that different patterns of variation within the same gene or genes can lead to similar or identical disease phenotypes. This reason is called
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