1. Berdanier, Carolyn D.

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By Naima Moustaid-Moussa and Carolyn D. Berdanier


Published by Marcel Dekker, New York, NY. July 2004.


This new book by our Editorial Advisory Board member Carolyn Berdanier, PhD, and her colleague Naima Moustaid-Moussa, PhD, is one of the best of the new offerings on the "-omics" that we hear so much about today. The book describes the use of proteomics and genomics in nutrition research. These terms refer to some of the latest techniques being used in nutrition research which makes it possible to assess the response at the whole cell or whole organ or whole body level to a nutritional variable. The investigator is now able to ask whether this response is at the level of gene expression by assessing whether a large array of genes are activated or suppressed. For example, the investigator might want to know whether fat feeding suppresses carbohydrate metabolism. He/she might examine all the genes known to encode all the enzymes and proteins known to be involved in carbohydrate metabolism. This might be 200 genes or perhaps as many as 1,000 genes. Using a technique called the microarray, the investigator extracts the genetic material from an organ or cell or tissue of interest and, using specific pieces of DNA to identify the genes of interest, the investigator is able to answer his/her question. In addition, he/she might find that more than the suspect genes are responding and in which direction (increased or decreased transcription). When this genetic information is then used with quantitative estimates of the amounts of gene products produced under these dietary conditions, the investigator develops a fuller understanding of the total metabolic response to a dietary variable.


Other uses of these techniques include determining how obesity, diabetes, or heart disease develops under fixed conditions from the genetic perspective. At this point, this use is limited to animal models for these degenerative conditions. But in the near future, one can envision a use for early diagnosis of the disease; early enough to provide preventative measures to delay the expression of the genotype for disease. Similarly, there may be uses of both genomic and proteomic technologies to segregate people with differing needs for the essential nutrients or for differing tolerances of the macronutrients. As they develop, these possible applications will help us design diets that will maximize the genetic potential for health and minimize that for disease.


In genomics there is a technique called quantitative linkage analysis. Quantitative linkage analysis uses a genome-wide scan to find areas of the genome that are more prominent than other areas and that are linked to the appearance of a certain phenotype such as obesity or diabetes. Using a genome-wide scan does not require any knowledge about specific gene functions and can identify chromosomal regions accounting for a quantitatively assessed trait such as body weight. This is called a QTL or a quantitative trait loci technique and is particularly useful in identifying those genes involved in a polygenic disease where more than 1 gene is involved in the development of a particular trait. Polygenic diseases, such as diabesity, for example, can be examined in this way. It assumes that the disease or condition is not due to a single mutation but due to an interaction between several genes and perhaps environmental factors such as overeating, underactivity, and so forth. Multiple genes contribute to a complex trait, thus, the term polygenic trait. They can be assessed quantitatively, and thus, the trait-controlling genes or loci are called QTLs. QTLs can be mapped. That is, their position on one or more chromosomes can be determined.


Typically, chromosomal mapping is initiated by crossing 2 different genotypes that show contrasting phenotypic features. For example, one strain might be very lean and another strain moderately fat. The resulting F1 progeny are then intercrossed (brother-sister mating) or back-crossed to one of the parental strains. This produces F2 progeny. For obvious reasons, this mapping can only be done on short-lived species such as mice. The F2 progeny segregate with some very lean, some fat, and some in between. They do not segregate like the grandparental or parental generation. This is due to recombination events within the genome. The phenotypic segregation then allows the investigator to examine the DNA to find differences and similarities between the mice and how this relates to their phenotypic characteristics. Through a process of refining and re-refining the mapping position, the actual allelic variants can be found and sequenced. Again, QTL can be used, and indeed, some research on the usefulness of this technique has shown some traits in humans that can predict, for example, lipoprotein disorders and possibly associated heart disease.


Sometimes investigators discover an aberrant gene but do not know how it is expressed. Here is where proteomic analysis comes in. The investigator can compare a normal individual with a normal gene with an abnormal individual, but instead of isolating and segregating the genes, the investigator segregates suspect proteins. Using 2-dimensional protein separations of specific cells or cell fractions, the investigator examines the array of individual proteins. Those that show up with different physical characteristics are identified, isolated, and sequenced. This is the technique of proteomics. It allows for the study of these aberrant proteins and for the study of how aberrant proteins function within the body's milieu.


Altogether then, genomic analysis and proteomic analysis provide new power to learn how bodies function and what happens when they malfunction. This is an exciting time for nutrition science!


Carolyn D. Berdanier


University of Georgia



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