Genetic Strategies to Detect Genes Involved in Alcoholism and Alcohol-Related Traits

By Dick, Danielle M.; Foroud, Tatiana | Alcohol Research, January 1, 2002 | Go to article overview

Genetic Strategies to Detect Genes Involved in Alcoholism and Alcohol-Related Traits


Dick, Danielle M., Foroud, Tatiana, Alcohol Research


Researchers are using a variety of sophisticated approaches to identify genes that contribute to the development of alcoholism in humans or influence other alcohol-related traits. These strategies include linkage approaches, which can identify broad chromosomal regions that are likely to contain genes predisposing to the disorder, and association approaches, which test the association between a particular marker allele and a specific outcome. Animal studies using diverse strategies can also help identify genes or DNA regions that influence alcohol-related traits in humans. The results of these analyses are likely to have implications for fields such as genetic counseling, gene therapy, and pharmacogenetics. KEY WORDS: genetic theory of AODU (alcohol and other drug use); genetic linkage; genetic correlation analysis; genetic screening method; genome; genetic trait; QTL (quantitative trait locus) mapping; mutation; AOD dependence potential; alcoholic beverage; DNA

Alcoholism is one of the most common and costly health problems in the United States. Substantial evidence from family, twin, and adoption studies suggests that genetic factors play a role both in normal patterns of alcohol use and in alcohol use disorders (i.e., alcohol abuse and dependence). It is estimated that approximately 50 to 60 percent of the variance in alcohol dependence can be attributed to genetic factors (McGue 1999). Researchers are currently attempting to identify the specific genes involved in patterns of alcohol use and alcohol dependence. These efforts are complicated by the complex nature of alcoholism and its development. Thus, although studies have convincingly demonstrated that genes play a role in the development of alcoholism, the same studies have also provided strong evidence for the importance of environmental factors. The genetic and environmental factors likely interact to result in disease development (for a more detailed discussion of those interactions, see the article in this issue by Heath and Nelson, pp. 193-201).

Despite these complexities, new developments in genetic technologies are enhancing scientists' understanding of alcoholism. Several of these advances are described throughout this issue. This overview provides an introduction to some of the strategies currently being used to search for genes involved in alcoholism. It also discusses the implications of such basic genetic research for applied clinical practice.

THE HUMAN GENOME

In most cells of the human body, the genetic information is contained in 46 microscopic structures in the nucleus, called the chromosomes. The first 22 chromosomes are present in pairs, and the 23rd pair consists of either 2 X chromosomes (female) or an X and Y chromosome (male) (see figure 1A). The chromosomes are inherited from the parents, with each parent providing 1 set of 23 chromosomes. These chromosomes contain a large molecule called deoxyribonucleic acid (DNA) (see figure 1B). The DNA consists of four building blocks called nucleotides that are arranged in a specific order. This sequence of nucleotides encodes the genetic information necessary for the organism to develop and function. The DNA segments that determine those characteristics of an individual that are inherited from one generation to the next are called genes. Large areas of the DNA, however, do not appear to contain genes. Some of these regions help regulate the activity (i.e., expression) of genes; for other DNA segments the function is still unknown. Nevertheless, these "noncoding" DNA regions can provide important tools for the study of the genome, as described next.

Many variations in the DNA exist among the genes and noncoding DNA regions of different individuals. Such variants of a DNA sequence are called alleles. A DNA region for which several alleles exist is said to be polymorphic-that is, it exists in many forms. The identification of these variants has revolutionized the study of genetics because it allows researchers to study the inheritance of the alleles and to associate specific alleles with the presence of certain diseases. …

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