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Discoveries in genomics have raised important questions for nutrition researchers: How does genetics determine nutrition needs? And how does diet influence gene expression?

Just one drop of blood, taken at birth. That alone could provide enough information for a doctor to develop an individual, lifelong blueprint for optimal vitamin intake, ensuring the newborn a long, healthy life.

Sound far-fetched? Not so. It's already possible, and many researchers predict that in just 10 years, such a procedure could be standard. That's just one of the potential outcomes of the emerging field called genomics, a new approach for understanding the function of genes in many different organisms.

The field made headline news last summer when scientists from Celera Genomics and the National Human Genome Research Institute announced that they had nearly cracked the human genome code, the set of instructions for all life processes. The breakthrough is reputed to be one of the greatest scientific discoveries yet.

The human genome, or the blueprint of life, contains more than 3.1 billion individual codes, or base pairs, that are represented by the letters A, C, G, and T. The sequence that has been deciphered represents the first step in understanding the specific function of individual genes. And the discovery, says Patrick Stover, an associate professor in the Division of Nutritional Sciences and an expert in the field of nutritional biochemistry, allows us to bear witness to genetic variability. One in a thousand base pairs is different among individuals, establishing genetic variation.

"Now we have the opportunity to understand the role of genes in diseases," Stover says. "We've known for years that of different populations--ethnic or other--some are more susceptible to diseases than others."

With the decoding 99 percent complete, researchers can begin to tell who's at risk--and who's not--for certain illnesses. Doctors can then tailor treatments to those individual patients. What's more, researchers can weigh the importance of genes versus other variables, such as the environment and nutrition.

Stover points to a recent study that showed that among all the contributing factors linked to cancer, genetics accounts for only about 30 percent of the cases. That figure, says Stover, is much lower than people expected, which means that external factors like the environment and nutrition play a major role in preventing and eradicating many diseases. By adjusting those factors, people can achieve a high-quality life.

The Division of Nutritional Sciences at Cornell is at the forefront of exploration and discovery in the genome-related sciences. The efforts will integrate genetics into nutrition research and ultimately lead to a greater understanding of how nutrition and genomics relate to health and disease. According to Stover--an active member of the Cornell Genomics Initiative, a broad interdisciplinary effort that will pave the way for the future of biological research--genome projects around the globe have raised three primary questions for nutrition researchers: How can agricultural scientists improve the food supply through genetic engineering? How does genetics determine nutrition needs? And in turn, how does diet influence gene expression?

Breaking the genetic codes of plant cells has begun to revolutionize agriculture. Scientists are able to manipulate the genes of plants, fruits, and vegetables to change their nutrient content and to create the socalled nutraceuticals. Rice can be made with higher concentrations of vitamin A. Corn of the future will have high levels of folate. Researchers at the Boyce Thompson Institute for Plant Research at Cornell have even genetically altered banana and potato to deliver vaccines.

"It's a way of enhancing the food supply so that we can cure a lot of micronutrient deficiencies without hurting the environment," Stover says. "We don't have to chemically synthesize these products, then add the nutrients later."

Nutritionists and nutrition scientists look ahead to discoveries in genomics that will allow people to optimize their health by eating foods for their particular genetic makeup. Current food labels tell consumers, for example, how much vitamin A and C, calcium, iron, and protein humans need. Yet these daily values were not calculated with genetic diversity in mind.

In 1998 the National Academy of Sciences released the Dietary Reference Intake (DRI) values. These establish not only the amount of a vitamin people need to ingest to prevent disease, but also the upper limit of that intake before there are toxic effects.

"That was an important policy measure--to come up with a limit," Stover explains. "But now we know that the window shifts depending on a person's genotype. For certain subpopulations, the proteins and enzymes that use certain vitamins are different. Because they are different, those people have a different requirement for some vitamins than the rest of the population."

Folic acid deficiency is just one example of variations in nutrient requirements within the population. This common B-vitamin was first discovered in the late 1930s and is recognized as essential to cell proliferation. Chemically, it acts with enzymes as a catalyst for the creation of DNA and proteins, which are necessary for cell division. A lack of folic acid in the body can lead to birth defects in the head and spinal cord. These neural tube defects include spina bifida, a condition in which part of the spinal cord remains outside the body, and anencephaly, in which the skull and brain fail to form completely.

That's why in 1998 the federal government started fortifying grain products with folic acid. The goal was to bring everyone's folic acid content up. But it turns out that folic acid fortification is not necessary to cure neural tube defects for the majority of the population--only for 20 percent. The individuals in this subgroup are genetically predisposed to bear a child with a folate-related birth defect. They have a single base pair change in their DNA, called a polymorphism, which is associated with birth defects.

"It's an example of how people's genotypes can alter their nutritional requirements," says Stover, who uses transgenic mice--the model system for almost all new gene discoveries in mammals--to study the roles of prenatal nutrition and genetics in neural tube defects. "Your genotype can dictate what your optimal folate intake should be."

Scientists can only speculate why particular polymorphisms that lead to increased folate requirements have arisen in populations. Stover notes that the 20 percent of the population who are most likely to have children with neural tube defects like spina bifida also have higher blood levels of homocysteine, an amino acid that promotes blood clotting. In the past, pregnant women with high homocysteine levels were probably least likely to die as a result of bleeding problems during childbirth--a selective advantage for that subpopulation. In addition, those who are most susceptible to neural tube defects have the lowest incidence of colon cancer. It is clear that a single polymorphism can have both positive and negative consequences.

Why are these people less susceptible to colon cancer?" Stover asks. "Now that we know the human genome, we can find out what makes them different and then use the knowledge to help protect the 80 percent who have a higher incidence of colon cancer."

Beyond nutrition, knowing the human genome can also help determine the most effective drug therapies to fight cancer and other diseases.

"Recently, Peter Goodfellow, an executive at SmithKlein Beecham, noted that if you look at drugs on the market, 30 percent have no effect and 30 percent have an adverse effect," Stover says. "That difference occurs because of subtle genetic variations among people. Doctors are starting to screen people for polymorphisms to determine what drug therapies are best.

"Whether it's using drugs or adjusting diet, it doesn't matter. The key is to look at the agents that are most suited for a particular genotype and use that information to give people the best outcome."

And just as individual variations in the genome can influence what drugs or diet are most suitable, the expression of many genes is influenced by external factors, such as what nutrients people ingest.

Stover explains that the DNA in liver cells is the same DNA that's in brain cells and finger cells. But each cell expresses those genes differently. The cell picks and chooses which genes to express to make a liver cell look and act like a liver cell and a brain cell look and act like a brain cell.

"The genes expressed make a cell what it is, but the expression of some genes can be greatly affected by nutrients. Polymorphisms in the genome can tell you what level of nutrients you need, but nutrients can also affect how the genome is expressed."

In other words, we are what we eat.

Stover is interested in how different metabolic pathways interact and affect gene expression. For example, it's been established that a nutritional deficiency in iron can interfere with the metabolism of folate, but the biochemical mechanisms of this effect were not known. Stover and his colleagues have pinpointed for the first time a biochemical mechanism that accounts for this. They have shown that a deficiency in iron affects the expression of the enzyme cytoplasmic serine hydroxymethyltransferase (cSHMT) in some cells. Changes in cSHMT levels, in turn, influence folate metabolism, as well as the expression of genes whose regulation may be influenced by folate metabolism. Because folate metabolism is responsible for making three (A, G, and C) of the four bases of DNA, as well as for methylating DNA, iron nutrition that affects folate metabolism can ultimately influence gene expression.

The discoveries by Stover have important implications for understanding how nutrients interact with the human genotypes and then lead to certain pathologies, such as cancer and cardiovascular disease. The challenge of the future, Stover says, will be to use these and other scientific breakthroughs in the field of genomics to prevent disease and to adapt medical care to a particular genotype.
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Title Annotation:nutritional aspects
Publication:Human Ecology
Geographic Code:1USA
Date:Sep 22, 2000
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