genomics

n. (used with a singular verb)
The study of all of the nucleotide sequences, including structural genes, regulatory sequences, and noncoding DNA segments, in the chromosomes of an organism.

Genomics is a recent scientific discipline that strives to define and characterize the complete genetic makeup of an organism. Its primary approaches are to determine the entire sequence and structure of an organism's DNA (its genome) and then to determine how that DNA is arranged into genes. This second goal is accomplished by determining the structure and relative abundance of all messenger RNAs (mRNAs), the middlemen in genetics that encode individual proteins.

From Microorganisms to Human Dna

For many years, genomics has been focused on microorganisms, which have relatively small genomes. However, more recently the field has been energized by the advent of more industrialized, higher-throughput sequencing technologies. By 2001 more than seventy organisms had been completely sequenced, and a working draft of the human genome had been produced. Vigorous efforts have now been initiated to map the mouse genome, and one company already claims to have completed the sequence. From the description of the structure of the genetic material by James Watson and Francis Crick in 1953, it will have taken only about fifty years to determine the complete genetic codes of humans and most of the model organisms that are important in biological research.

Table 1

Latin Name	Common Name	Genome Size
Eukaryotes (haploid genome)
Oryza sativa	Rice	420,000 Kb
Homo sapiens	Human	3,200,000 Kb
Arabidopsis thaliana	Mustard cress	115,428 Kb
Drosophila melanogaster	Fruit fly	137,000 Kb
Caenorhabditis elegans	Roundworm	97,000 Kb
Saccharomyces cerevisiae	Yeast	12,069 Kb
Eubacteria
Haemophilus influenzae	-	1,830 Kb
Escherichia coli	Human colon bacterium	4,639 Kb
Helicobacter pylori	Stomach ulcer bacterium	1,667 Kb
Mycobacterium	Tuberculosis	4,411 Kb
Yersinia pestis	Plague	4,653 Kb
Archaea
Halobacterium	Salt-tolerant archaean	2,014 Kb
Methanobacterium thermoautotrophicum	Methane-producing archaean	1,751 Kb
Kb=one thousand base pairs

Of what value is the knowledge of these genomes? How are they being used within the scientific community? The first fully sequenced genomes included the fruit fly, a worm, and a number of bacteria and yeast. One of the first analyses performed was to simply compare the sequences between organisms, in order to identify what is shared in common and what is different. This allows the very specific comparison of organisms that will enable the refining of phylogenic relationships. This kind of information is also very valuable for asking questions about how organisms have evolved, how they adapt to different circumstances, and what gene products contribute to their survival in various environmental conditions.

Applications

Genomics has brought us to the threshold of a new era in controlling infectious diseases. These studies will likely lead to the development of new disease prevention and treatment strategies for plants, animals, and humans alike. For instance, understanding pathogen genes, their expression, and their interaction will lead to new antibiotics, antiviral agents, and "designer" immunizations. These new DNA-based immunizations are by-products of genomic research and will undoubtedly eventually replace the traditional vaccines made from whole, inactivated microorganisms. This is highly relevant to domesticated animals, where viruses still kill billions of dollars worth of livestock every year.

Understanding the genomes of plants and animals has additional benefits. Gene mapping should allow us to understand the basis for disease resistance, disease susceptibility, weight gain, and determinants of nutritional value. The use of genomic information provides the opportunity to select optimal environments for the healthy growth of plants and animals, to develop disease-resistant strains, and to achieve improved nutritional value such as with the "golden" rice. Success in these species may well provide important insights needed to improve the health of humans.

The Human Genome Project and Future Research

The Human Genome Project reached a major milestone in 2001, with two separate publications of working drafts of the human genome. Although much knowledge has been generated, the sequence is not complete. Neither the actual number of genes nor all their structures have been determined. However, several major lessons have been learned. First the number of genes is estimated to be between 30,000 and 70,000, fewer than previously thought. In addition, it is clear that a very large proportion of our genes are highly similar to those in other organisms, such as the fruit fly and the microscopic worm, C. elegans. The observation that we can build humans with between 30,000 and 70,000 genes and a fruit fly with 15,000 genes suggests that we owe much of the complexity of humans to the fine regulation of genes and not their absolute number.

Genomics has also forced biologists to begin to look at the function of genes in an industrialized mode. This new field of functional genomics takes advantage of a number of new technologies. Since many fly and worm genes are so similar to human genes (homologs), these animals can be used as model systems to study gene function. In these model systems it is possible to mutate (or alter) the structure of every single gene, enabling researchers to determine each gene's function and how several of the genes interact in complex metabolic pathways. Similar efforts using systematic gene mutations are also underway to create DNA "libraries" of two vertebrates, mice and zebrafish, whose genes are surprisingly similar to humans. Once these genomes are fully sequenced and characterized, it will be possible to create animals with disorders that are more precisely like those of humans, allowing for a better understanding of complex diseases and determination of novel and effective therapies.

Genomics allows for the comparison of sequences between individuals, too. These studies can be used as a basis for the understanding and diagnosis of disease, especially of the complex disorders not governed by single genes. Knowledge of the entire human sequence is also the basis of the fields of pharmacogenetics and pharmacogenomics. Pharmacogenomics seeks a broader understanding of how genes influence drug response and toxicity, and the discovery of new disease pathways that can be targeted with tailor-made drugs. Pharmacogenetics is the study of the genetic factors involved in the differential response between patients to the same medicine. Polymorphisms, nucleotide changes that occur in more than 1 percent of the population, are the basis for our individuality but also account for our differential susceptibility to disease and the variable outcome of treatments. Through a variety of research efforts, more than one million polymorphisms have been identified in the human genome. The study of these variants, that occur once every 500 to 1,000 nucleotides in the human genome, should enable pharmacogenetics to define the optimal treatment regimens for subsets of the population, allowing a wider range of patients to be treated and more effective outcomes to be produced with any given drug.

Bibliography

Bloom, Mark V., Greg A. Freyer, and David A. Micklos. Laboratory DNA Science: An Introduction to Recombinant DNA Techniques and Methods of Genome Analysis. Menlo Park, CA: Addison-Wesley, 1996.

Koonin, Eugene V., L. Aravind, and Alexy S. Kondrashov. "The Impact of Comparative Genomics on Our Understanding of Evolution." Cell 101 (2000): 573-576.

O'Brien, Stephen J., et al. "The Promise of Comparative Genomics in Mammals." Science 286 (1999): 458-462, 479-481.

Ye, Xudong, et al. "Engineering the Provitamin A (-Carotene) Biosynthetic Pathway into (Carotenoid-Free) Rice Endosperm." Science 287 (2000): 303-305.

Internet Resources

Celera, Inc. http://www.celera.com.

"Entrez Genomes." National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/Entrez/Genome/main_genomes.html.

—Kenneth W. Culver and Mark A. Labow

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).

(juh-noh-miks)

The field of science that studies the entire DNA sequence of an organism's genome. The goal is to find all the genes within each genome and to use that information to develop improved medicines as well as answer scientific questions. (See also proteomics.)

The science that broadly deals with understanding the genome at the cellular and organism levels.

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