Genomics

█ JULI BERWALD

Genomics is the study of genes and their function in relation to the environment. In contrast to genetics, which focuses on genes and inheritance, the goal of genomics is to understand genes, their products and how, when, and why these products are synthesized.

The genome of every organism is the collection of the genetic information contained in the DNA (deoxyribonucleic acid). DNA is a molecule consisting of long strands of four different molecules called nucleotides: adenine, cytosine, guanine and thymine or A, C, G and T, as they appear in published sequences. The strands of DNA are paired so that A on one strand always corresponds to T on the opposite strand and similarly, C always corresponds to G. These paired strands of DNA are further twisted into the conformation of a double helix. A functional unit of DNA is called a gene. In a gene, the sequence of A, C, G, and T on a strand of DNA specifies the sequence of amino acids that make up a protein. In order for a specific protein to be synthesized, the DNA in a gene is first transcribed to messenger RNA (ribonucleic acid), which is similar to DNA, but single stranded. The messenger RNA is then translated into a sequence of amino acids. In this process, three nucleotides of DNA, for example CGT, are transcribed into three nucleotides of messenger RNA, in this case GCA, which code for one amino acid, in this case alanine. Proteins and products of proteins are fundamentally responsible for all cellular behavior. Protein function is altered by changes in the sequence of amino acids. Genomics investigates how variations in genes affect protein structure and function throughout the life of a cell.

The field of genomics. Although it is a young and evolving field, genomics generally includes at least three key research areas: bioinformatics, proteomics and structural genomics. Masses of DNA sequence data have accumulated though projects like the Human Genome Project, the Mouse Genome Project and over 40 microbial genomes have been sequenced. Not all DNA is made up of genes. In humans, for example, only about 3% of the DNA is actually genes. Some of this non-coding DNA is used by enzymes as markers indicating the beginning and ends of genes. Some of it, the so-called junk DNA, may not have any function at all. Using statistical tools and data-mining techniques, the field of bioinformatics attempts to identify genes in the DNA and to determine the relationships among genes in different individuals. Although the DNA in organisms is essentially constant throughout their lives, the kinds and amounts of proteins that are synthesized at any instant are subject to much variation. The field of proteomics investigates which proteins are expressed at what stages in an organism's life and exactly how and why these proteins are expressed. Translating a sequence of DNA to its corresponding amino acid sequence is only the beginning of understanding the function of a protein. Many amino acid chains are modified after they are synthesized and protein structure changes depending on environmental conditions, e.g. heat, pH or association with other molecules. The study of structural genomics attempts to unravel the molecular structures that result from a sequence of DNA.

Applications of genomics. One of the most promising applications of genomics is improving the ability to fight diseases. Many diseases, such as sickle cell anemia, cystic fibrosis and Huntington's disease, are caused by abnormalities in the sequence of DNA that codes for a specific protein or proteins. Genomics will be able to help in both the diagnosis of these diseases and the treatment of these conditions. It is estimated that only about 500 molecules are actually targeted by drugs currently available. Genomics will hopefully lead to an increase in the number of drug targets used in pharmaceuticals. It may also provide information on the genetic basis for side effects and the effectiveness of treatments that can be used to tailor prescriptions for individuals. Two specific types of gene therapies have been advanced. Somatic cell therapy involves the insertion of therapeutic genes into specific cells in the body. This will hopefully allow those cells to synthesize proteins that they are unable to produce or to turn off genes that are over expressed. Germ line therapy involves the insertion of normal genes into an egg cell, with the hope that the normal gene will be incorporated in to the genome of the offspring and that a genetic disease will not be inherited.

In addition to their importance in medicine, bacteria, viruses and fungi play key roles in agriculture. Because their genomes are small, the genomes of at least 40 species of microorganisms have been sequenced. Understanding the genomics of these organisms has the potential to improve crop yields, decrease damage done by pest species and increase the nutritional value of food. As part of their metabolism, some microorganisms have the ability to break down harmful products and to produce energy as a product. Understanding the gene products involved in these transformations may lead to industrial uses, with the potential for solving different types of environmental problems and providing new energy sources.

Military uses of genomics. Identifying the genes and gene products in the organisms that lead to disease in humans will lead to the development of treatments for these diseases. Characterizing genes responsible for diseases will likely lead to the development of new antibiotics and other drugs used to treat diseases caused by biological warfare. It can also reveal methods for combating drug resistance and preventing the use of this phenomenon by opponents. Genomics should also provide new techniques for identifying biological agents on the battlefield. One of the most promising technologies is the biochip or DNA chip, which is a microarray of molecular probes on a silicon chip that specifically bind to the DNA of biological threats. Once bound, the DNA is then detected using a fluorescent signal. These arrays identify genes that are active in cells, and indicate if a particular immune response is occurring. In the case of a biological attack, this can provide quick, detailed information about the course of the infection to medical personnel.

█ FURHER READING:

ELECTRONIC:

American Medical Association. "Proteomics."< http://www.ama-assn.org/ama/pub/category/3668.html#3 > (April 3, 2003).

Human Genome Project. "From the Genome to the Proteome." < http://www.ornl.gov/TechResources/Human_Genome/project/info.html > (March 14, 2003).

Pharmaceutical Researchers and Manufacturers of America. "Genomics: A Global Resource." < http://genomics.phrma.org/ > (April 3, 2003).

U.S. Department of Energy Joint Genome Institute. "An Introduction to Genomics." < http://www.jgi.doe.gov/education/genomics_1.html > (April 3, 2003).

Weizmann Institute of Science Genome and Informatics. < http://bip.weizmann.ac.il/mb/functional_genomics.html > (April 3, 2003).

SEE ALSO

Pathogen Genomic Sequencing