Academic journal article Alcohol Research

Genomic Approaches to the Genetics of Alcoholism

Academic journal article Alcohol Research

Genomic Approaches to the Genetics of Alcoholism

Article excerpt

When studying complex diseases such as alcoholism that develop as a result of numerous genetic and environmental factors, researchers can use the sequence data that have become available both for the human and for animal genomes. For these analyses, investigators are being aided by efforts to identify and characterize functionally relevant DNA sequences in the entire genomic DNA sequence-a process called annotation. Various bioinformatics and annotation tools can help in this enterprise. These include four primary approaches: (1) precomputed, annotated public Web sites that provide a plethora of information; (2) in-house analyses from which users can choose the appropriate analyses for their purposes; (3) Web-based annotation systems that analyze a user's DNA sequence; and (4) private resources that provide access to annotated genomic sequences at cost. In addition to careful study of the DNA sequence for clues about function, expression studies of mRNA levels using gene chips provide information about the activity levels of thousands of genes that may vary in different tissues, different animals and people, or under different environmental conditions. KEY WORDS: genetic theory of AODU (alcohol and other drug use); AOD dependence potential; alcoholic beverage; genome; gene expression; genetic mapping; DNA; mRNA; genetic correlation analysis

Since the 1980s, researchers have attempted to identify genes that underlie various diseases. Initially, these efforts focused mainly on relatively rare genetic diseases-such as cystic fibrosis and Huntington's disease-that because of their simple inheritance patterns were likely to be caused by only one gene. Using family studies to search for certain DNA segments (i.e., markers) that occurred only in people affected by these diseases, researchers successfully identified the underlying genes. More recently, the field of genetics has entered an era in which much of the focus has shifted to the study of more complex disorders-such as cancer, diabetes, hypertension, schizophrenia, and alcoholism-that are believed to develop as a result of a combination of numerous genetic and environmental factors.

The genetic study of complex diseases poses challenges that are not typically associated with single-gene disorders. For example, complex diseases are generally more common than single-gene disorders, tend to involve multiple genes, also include significant environmental factors, and are associated with a variety of characteristics and behaviors, or phenotypes, that are not simple to describe. To separate the multiple genetic and environmental components that underlie these diseases, researchers have developed more sophisticated methodological and statistical techniques. These techniques exploit knowledge about the inheritance of chromosomes, about the reorganization of genetic material that occurs during the generation of eggs and sperm (i.e., recombination), and about the analysis of quantitative traits-characteristics, such as height or intelligence, that vary along a continuum in the population. Based on this knowledge, investigators can identify specific DNA markers that are linked to complex diseases, thereby delineating regions within the genetic material of the cell that are likely to contain genes which contribute to complex phenotypes. These regions are called quantitative trait loci (QTLs). Many different alcohol-related QTLs have been identified in recent years, both through family studies of human populations and through research in model organisms, such as mice, rats, and flies.

Concurrent with the efforts to identify QTLs in alcohol studies, a vast array of bioinformatics resources have become available as the result of projects to decipher the entire genetic information (i.e., the genome) of various organisms. After the March 2000 publication of the genome sequence of the fruit fly Drosophila melanogaster, a draft of the entire DNA sequence of the human genome was completed, and in December 2002, public access to a draft sequence of the complete mouse genome became available (Waterston et al. …

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