The genetic revolution: Change and challenge for the dietetics profession.

ABSTRACT

Advances in genetics are occurring at a pace that challenges our ability to understand and respond to the implications. Soon we will be able to define more precisely the molecular mechanisms underlying human health and disease; subdivide diseases and conditions (eg, obesity) that are clinically indistinguishable into more distinct entities, thereby improving our ability to choose rational preventive and treatment measures; identify genotypic markers that predict metabolic responses to dietary interventions; stratify the population into groups at higher or lower risk for chronic diseases such as cancer, thus allowing dietary intervention to be appropriately targeted; and develop dietary recommendations that take into account genetically determined taste preferences. Dietetics leaders, teachers, practitioners, and researchers must act now to ensure that dietetics professionals are prepared for practice in this new era. In this article we introduce the Human Genome Project, review the fundamentals of molecular g enetics, discuss genetics and disease risk, and define and give examples of diet-gene interactions. We also discuss issues relevant to dietary counseling of healthy people with genetic susceptibility to chronic disease. To foster the growth of knowledge regarding this new biology among dietitians, The American Dietetic Association should take the following steps: require course work on diet-gene interactions and include human genetics as a topic area on dietetic registration examinations, form a practice group on this topic, develop an Internet-based communication and information hub for dietetics professionals, sponsor a session on human genetics at annual meetings, begin a dialogue regarding a new practice specialty in diet and genetic counseling, and encourage a health care system in which personal counseling on diet-gene interactions is valued and reimbursed. J Am Diet Assoc. 1999;99:1412-1420.

Aclient walks into your office with a packet of information. He explains that he has several relatives who had colon cancer and his physician tested him for inherited susceptibility to cancer. He hands you his laboratory results, which show that he is heterozygous for ABC1 and has a null genotype for XYZ2. He has consulted a genetic counselor, who presented him with information on the probabilities of his being diagnosed with colon cancer. (Here the client pulls out graphs and charts showing both short-term and lifetime probabilities). The genetic counselor referred him to you for counseling on a diet appropriate for his genotype. This diet would include large amounts of certain vegetables, special techniques for cooking meats, and prescription of large doses of a dietary supplement. Although your client is willing to consider dietary changes, he wants to know how much this diet will reduce his risk of getting colon cancer. The genetic revolution has arrived.

Despite the vigorous investigation of environmental causes of disease, it has long been recognized that not all persons exposed to the same risk factors develop the associated disease [1]. For example, although it is well accepted that smoking causes lung cancer, only 10% to 15% of smokers will be diagnosed with the disease [2]. More and more, we are beginning to understand the impact of differential genetic susceptibility in the etiology and pathogenesis of common diseases such as coronary heart disease and cancer. This new biology offers promise of practical means for individualized practice of preventive medicine through risk profiling and provision of information on how to modify the potential results of genetic predisposition [3].

The objective of this article is to present an overview of this new biology as it relates to diet-gene interactions, which is likely to be a major new practice area for dietitians [4]. Specifically, we introduce the Human Genome Project, review basic genetic mechanisms, discuss genetics and disease risk, define diet-gene interactions, and give examples of different types of diet-gene interactions. We also provide a glossary of relevant terms. Words defined in the glossary (Figure 1) appear in boldface type in the text (the first time they are used). We also discuss the implications of diet-gene interactions on the practice of dietetics and suggest steps that can be taken by The American Dietetic Association (ADA) to ensure that dietetics professionals develop competence in this new area in a timely manner.

HUMAN GENOME PROJECT

Advances in genetics are occurring at a pace that challenges our ability to understand and respond to the implications of the data. The flurry of discoveries in human genetics is partially the result of the Human Genome Project [5]. This initiative is an international research program to develop technologies that make it easier, cheaper, and faster to identify specific genes and understand their function. Launched in 1990, the major objective of this 15-year project is to map the entire human genome at the base-pair level, thereby establishing the basic blueprint of a human being. In the United States, the Human Genome Project is carried out by the National Center for Human Genome Research (part of the National Institutes of Health) and the US Department of Energy.

REVIEW OF BASIC GENETIC MECHANISMS

To understand advances in human genetics, it is useful to review the fundamentals of molecular genetics. This review is brief and necessarily simplistic; for more information refer to the texts by Mueller and Young [6] and Alberts et al [7], from which the following overview is largely synthesized.

The genetic material within our cells contains the complete set of instructions for making an organism, called its genome. The human genome is organized into 46 chromosomes. Of these chromosomes, 44 are in 22 pairs (autosomes) in which one chromosome is inherited from the mother and one from the father. In addition, females inherit an X chromosome from each parent, whereas males inherit an X chromosome from the mother and a Y from the father.

Each chromosome contains many genes. A gene is a segment of a chromosome that encodes instructions that allow a cell to produce a specific protein, such as an enzyme or a receptor or carrier protein. The human genome is estimated to contain about 100,000 genes. Each gene is composed of long stretches of DNA that can be divided into 3 separate classes (Figure 2). The parts of a gene that actually provide the specific "instructions" (the coding region) for making a protein are called exons. In most genes, multiple exons are present, but they are separated by noncoding stretches of DNA called introns. In addition to exons and introns, each gene also contains a noncoding region at its beginning (the 5' end) that serves to regulate when, and to what extent, the gene is expressed. This is referred to as the regulatory region of the gene and can be envisioned as a series of on-off switches that respond to signals (eg, proteins and hormones) from within the cell, from neighboring cells, and from more distant parts o f the organism.

Genes are composed of DNA, which exists as 2 paired or complementary strands forming a double helix (Figure 1). Each strand is made up of millions of chemical building blocks called bases. There are 4 different chemical bases in DNA: adenine (A), thymine (T), cytosine (C), and guanine (G). The 4 bases are strung along a repetitive sugar (deoxyribose) phosphate backbone. The 2 strands of DNA are held together by pairing of the chemical bases. Adenine forms hydrogen bonds with thymine and cytosine forms hydrogen bonds with guanine.

Every 3 bases (called a triplet) along a strand of DNA specifies an amino acid to be incorporated into a protein, in what is called the genetic code. For example, a triplet composed of the bases guanine, cytosine, and adenine, in that order, is the genetic triplet code for the amino acid alanine. Certain combinations of bases (eg, TAA), called termination or stop codons, terminate the gene product. Mathematically, the 4 bases could form up to 64 unique triplet codes; however, there are only 20 amino acids. This "redundancy" in the genetic code is called degeneracy.

When a cell is "switched" on to make a protein, the information from a gene is copied, base by base, from DNA into a single new strand of complementary RNA. RNA is different from DNA in 3 ways: RNA is single …