Genomics

The term genomics refers to the study of an organism's entire genome. Each organism contains a genome that contains biological information that maintains the organism. Traditionally, individual genes have been investigated, but genomics differs because it encompasses the study of the entire genome. Genomics is a relatively new field with plenty of room for exploration. Newer technologies have made genomics and systems biology (the linking of molecular pathways to describe overall functioning of the organism) not only possible but a must for scientific advancement.

The human genome is made up of deoxyribonucleic acid (DNA) composed of subunits known as nucleotides. There are two main parts to the human genome: the nuclear genome and the mitochondrial genome. The nuclear genome contains roughly 35,000 genes split into 24 chromosomes. The mitochondrial genome consists of only 37 genes that are contained within the mitochondrial organelle. On its own, the genome is unable to release the biological information to the cell. Coordinated activity of enzymes and proteins in biochemical reactions is necessary for genome expression.

The initial product of genome expression is the transcriptome, which is maintained via a process known as transcription. Transcription copies individual genes into RNA molecules. Following transcription, a process known as translation produces the proteome (the cellular complement of proteins) that specifies the reactions that the cell is capable of. The RNA and proteins are important because, although the genes must be present to make a protein, if the gene does not make the protein, biochemical reactions of the gene will not be carried out.

One specific area of genomics that is extremely pertinent to obesity research is the field of nutritional genomics. Nutritional genomics refers to the study of the relationships between the nutrients that are consumed, the health consequences of these nutrients, and the genome of that particular organism. Nutritional genomics can be subcategorized into two main subfields: nutrigenomics and nutrigenetics. Nutrigenomics refers to the study of the effect of the nutrients on the genome, while nutrigenetics refers to the study of the effect of genetic variations on the interactions between nutrition and health. Practically, nutrigenetics, is used to study the impact of genetic variation on dietary requirements, while nutrigenomics is used to study the effect of diet on gene function. Nutrigenomics can be utilized to determine the effects that nutrients have not only on the genome, but also on the transcriptome and the proteome.

The primary technology used in nutrigenomics is the microarray. A microarray is an assay that is used to determine which genes are expressed in a sample. They can assess thousands of genes in a single experiment; therefore, the process is often known as gene expression profiling. Although not quantitative, a microarray allows for determination of a qualitative “yes or no” in terms of expression within the genome or transcriptome. Proteome investigations are primarily conducted via two-dimensional gel electrophoresis or liquid chromatography-mass spectrometry.

These technologies can be used with different interventions to determine what sets of genes are activated by the intervention. For example, one could examine the differences in gene expression in human [Page 328]adipocytes when comparing groups of various calorie levels, dietary macronutrient percentages, or specific bioactive compounds to a placebo. Or it may be combined with a nutrigenetic approach. One example of this type of research was conducted by Burg and colleagues using a mouse model. A group of mice was treated with a drug designed to alter lipid metabolism. The goal was to determine the difference between normal individuals who do not absorb dietary sterols and those with sitosterolemia, a disorder in which dietary sterols are hyperabsorbed leading to hypercholesterolemia. A microarray analyzed differences in mRNA expression profiling a new gene was found. In fact, humans share the gene that produces two proteins and is responsible for removing dietary sterols from the tissues. In those with sitosterolemia, however, a mutation in this gene exists and sterols are therefore not properly transported.

...