What Is Functional Genomics?

Understanding the function of genes and other parts of the genome is known as functional genomics.

Functional genomics is a field of molecular biology that is attempting to make use of the vast wealth of data produced by genome sequencing projects to describe genome function. Functional genomics uses high-throuput techniques like DNA microarrays, proteomics, metabolomics and mutation analysis to describe the function and interactions of genes.

Because of the large quantity of data and the desire to be able to find patterns and predict gene functions and interactions bioinformatics is crucial to this type of analysis. Comparative genomic analyses can also held determine gene function.

Molecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA and protein synthesis and learning how these interactions are regulated.

Genome projects are scientific endeavours that aim to map the genome of a living being or of a species (be it an animal, a plant, a fungus, a bacterium, an archaean, a protist or a virus), that is, the complete set of genes caried by this living being or virus. The Human Genome Project was such a project. Some have argued that the era of genomics is one of the more fundamental advances in human history.

Many organisms have genome projects that have either completed or will complete in the 21st century, including: Homo sapiens Humans, Mus musculus Laboratory mouse, Rattus norvegicus Laboratory rat, Chimp, Gallus gallus Chicken, Macropus eugenii Kangaroo, Felis domesticus Cat, Canis lupis Dog, Drosophila melanogaster Fruit fly, Saccharomyces cerevisiae Yeast, Neurospora crassa A type of mold, Arabidopsis thaliana Mustard weed, Oryza sativa Rice, Triticum spp Wheat, Zea mays Maize (or corn), Escherichia coli bacterium E.coli, SARS virus, Arbacia punctulata the purple-spined sea urchin, Caenorhabditis elegans a nematode worm, Brachydanio rerio Zebrafish, Xenopus laevis The African clawed toad, Oryzias latipes A medakafish, Takifugu rubipres A pufferfish.

Genomics is the study of an organism's genome and the use of the genes. It deals with the systematic use of genome information, associated with other data, to provide answers in biology, medicine, and industry.

Genomics has the potential of offering new therapeutic methods for the treatment of some diseases, as well as new diagnostic methods. Other applications are in the food and agriculture sectors. The major tools and methods related to genomics are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function.

Genomics appeared in the 1980s and took off in the 1990s with the initiation of genome projects for several species. The related field of genetics is the study of genes and their role in inheritance.

The first genome to be sequenced in its entirety was that of bacteriophage FX174 (5,368 kb) in 1980. The first free-living organism to be sequenced was that of Haemophilus influenzae (1.8Mb) in 1995, and since then genomes are being sequenced at a rapid pace. A rough draft of the human genome was completed by the Human Genome Project in early 2001 amid much fanfare.

Comparison of genomes has resulted in some surprising biological discoveries. If a particular DNA sequence or pattern is present among many members of a clade, that sequence is said to have been conserved among the species. Evolutionary conservation of a DNA sequence may imply that it confers a relative selective advantage to the organisms that possess it. Conservation also suggests that sequence has functional significance. It may be a protein coding sequence or regulatory region. Experimental investigation of some of these sequences has shown that some are transcribed into small RNA molecules, although the functions of these RNAs were not immediately apparent.

There are as many definitions of functional genomics as there are enterprising scientists trying to bend a fashionable term to fit their science! Perhaps a good operating definition is 'any approach which is informed by knowledge of the genome'. The major components of a functional genomics approach are: bioinformatics - the extraction of biological utility from genomic sequence, and the reconciliation of multiple datasets microarrays - the global assessment of how the expression of all genes in the genome varies under changing conditions proteomics - the study of the total protein complement expressed by a particular cell under particular conditions reverse genetics - deducing the function of novel genes by mutating them and studying the mutant phenotype.

The identification of similar sequences (including many genes) in two distantly related organisms, but not in other members of one of the clades, has led to the theory that these sequences were acquired by horizontal gene transfer. This phenomenon is most prominent in thermophilic bacteria, where it seems that genes were transferred from Archaea to Eubacteria. It has also been noticed that bacterial genes exist in eukaryotic nuclear genomes and that these genes generally encode mitochondrial and plastid proteins, giving support to the endosymbiotic theory of the origin of these organelles.

Structural genomics or structural bioinformatics refers to the analysis of macromolecular structure particularly proteins, using computational tools and theoretical frameworks. One of the goals of structural genomics is the extension of idea of genomics, to obtain accurate three-dimensional structural models for all known protein families, protein domains or protein folds. Structural alignment is a tool of structural genomics.

Functional genomics refers to the development and application of global (genome-wide or system-wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics. It is characterized by high-throughput or large-scale experimental methodologies combined with statistical or computational analysis of the results.

In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). This includes both the genes and the non-coding sequences.

More precisely, the genome of an organism is a complete DNA sequence of one set of chromosomes; for example, one of the two sets that a diploid individual carries in every somatic cell. When people say that the genome of a sexually reproducing species has been "sequenced," typically they are referring to a determination of the sequences of one set of autosomes and one of each type of sex chromosome, which together represent both of the possible sexes. Even in species that exist in only one sex, what is described as "a genome sequence" may be a composite from the chromosomes of various individuals. In general use, the phrase genetic makeup is sometimes used conversationally to mean the genome of a particular individual or organism. The study of the global properties of genomes of related organisms is usually referred to as genomics, which distinguishes it from genetics which generally studies the properties of single genes or groups of genes.

Most biological entities more complex than a virus sometimes or always carry additional genetic material besides that which resides in their chromosomes. In some contexts, such as sequencing the genome of a pathogenic microbe, "genome" is meant to include this auxiliary material, which is carried in plasmids. In such circumstances then, "genome" describes all of the genes and non-coding DNA that have the potential to be present.

In vertebrates such as humans, however, "genome" carries the typical connotation of only chromosomal DNA. So although human mitochondria contain genes, these genes are not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome, often referred to as the "mitochondrial genome".

Note that a genome does not capture the genetic diversity or the genetic polymorphism of a species. For example, the human genome sequence in principle could be determined from just half the DNA of one cell from one individual. To learn what variations in DNA underlie particular traits or diseases requires comparisons across individuals. This point explains the common usage of "genome" (which parallels a common usage of "gene") to refer not to any particular DNA sequence, but to a whole family of sequences that share a biological context.

Although this concept may seem counter intuitive, it is the same concept that says there is no particular shape that is the shape of a cheetah. Cheetahs vary, and so do the sequences of their genomes. Yet both the individual animals and their sequences share commonalities, so one can learn something about cheetahs and "cheetah-ness" from a single example of either.

Genomes are more than the sum of an organism's genes and have traits that may be measured and studied without reference to the details of any particular genes and their products. Researchers compare traits such as chromosome number, chromosome size, gene order, codon usage bias, and G-C content to determine what mechanisms could have produced the great variety of genomes that exist today.

Duplications play a major role in shaping the genome. Duplications may range from extension of short tandem repeats, to duplication of a cluster of genes, and all the way to duplications of entire chromosomes or even entire genomes. Such duplications are probably fundamental to the creation of genetic novelty.

Horizontal gene transfer is invoked to explain how there is often extreme similarity between small portions of the genomes of two organisms that are otherwise very distantly related. Horizontal gene transfer seems to be common among many microbes. Also, eukaryotic cells seem to have experienced a transfer of some genetic material from their chloroplast and mitochondrial genomes to their nuclear chromosomes.

Functional genomics as a means of assessing phenotype differs from more classical approaches primarily with respect to the scale and automation of biological investigations. A classical investigation of gene expression might examine how the expression of a single gene varies with the development of an organism in vivo. Modern functional genomics approaches, however, would examine how 1,000 to 10,000 genes are expressed as a function of development.

A DNA microarray (also DNA chip or gene chip in common speech) is a piece of glass or plastic on which pieces of DNA have been affixed in a microscopic array. Scientists use such chips to screen a biological sample for the presence of many genetic sequences at once. The affixed DNA segments are known as probes. Thousands of identical probe molecules are affixed at each point in the array to make the chips effective detectors.

Although the name GeneChip is a trademark of Affymetrix, microarray users generally use this term, or, simply, chip, to refer to any microarray, not just those sold by Affymetrix. While Affymetrix arrays use short oligonucleotide probes of 25 bases or less, many microarrays use PCR products, genomic DNAs, BACs, plasmids, or longer oligos (35 to 70 bases). Microarrays may be made by any number of technologies including printing with fine-pointed pins onto glass slides, photolithography using pre-made masks, photolithography using dynamic micromirror devices, or ink-jet printers[1] (http://genomebiology.com/2004/5/8/R58). The use of microarrays for expression profiling was first published in 1995 (Science) and the first complete eukaryotic genome (Saccharomyces cerevisiae) on a microarray was published in 1997 (Science).

Typically arrays are used to detect the presence of mRNAs that may have been transcribed from different genes and which encode different proteins. The RNA is extracted from many cells, ideally from a single cell type, then converted to cDNA or cRNA. The copies may be "amplified" in concentration by rtPCR. Fluorescent tags are enzymatically incorporated into the newly synthesized strands or can be chemically attached to the new strands of DNA or RNA. A cDNA or cRNA molecule that contains a sequence complementary to one of the single-stranded probe sequences will hybridize, or stick, via base pairing (more at DNA) to the spot at which the complementary probes are affixed. The spot will then fluoresce (or glow) when examined using a microarray scanner.

Proteomics is the large-scale study of proteins, particularly their structures and functions. This term was coined to make an analogy with genomics, and is often viewed as the "next step", but proteomics is much more complicated than genomics. Most importantly, while the genome is a rather constant entity, the proteome is constantly changing through its biochemical interactions with the genome and the environment. One organism will have radically different protein expression in different parts of its body, in different stages of its life cycle and in different environmental conditions.

The entirety of proteins in existence in an organism throughout its life cycle, or on a smaller scale the entirety of proteins found in a particular cell type under a particular type of stimulation, are referred to as the proteome of the organism or cell type respectively.

With completion of a rough draft of the human genome, many researchers are now looking at how genes and proteins interact to form other proteins. A surprising finding of the Human Genome Project is that there are far fewer genes that code for proteins in the human genome than there are proteins in the human proteome (~22,000 genes vs ~200,000 proteins). The large increase in protein diversity is thought to be due to alternative splicing and post-translational modification of proteins.

Genes are material entities that parents pass to offspring during reproduction. These entities encode information essential for the construction and regulation of polypeptides, proteins and other molecules that determine the growth and functioning of the organism.

The word "gene" is shared by many disciplines, including classical genetics, molecular genetics, evolutionary biology and population genetics. Because each discipline models the biology of life differently, the material entity that supports the gene in one discipline is not the same as in the other.

Following the discovery that DNA is the genetic material, and with the growth of biotechnology and the project to sequence the human genome, the common usage of the word "gene" has increasingly reflected its meaning in molecular biology. In the molecular-biological sense, genes are the segments of DNA which cells transcribe into RNA and translate, at least in part, into proteins.

In common speech, "gene" is often used to refer to the hereditary cause of a trait, disease or condition—as in "the gene for obesity." Speaking more precisely, a biologist might refer to an allele or a mutation that has been implicated in or is associated with obesity. This is because biologists know that many factors other than genes decide whether a person is obese or not: prenatal environment, upbringing, culture and the availability of food, for example.

Moreover, it is very unlikely that variations within a single gene—or single genetic locus—fully determine one's genetic predisposition for obesity. These aspects of inheritance—the interplay between genes and environment, the influence of many genes—appear to be the norm with regard to many and perhaps most ("complex" or "multifactoral") traits. The term phenotype refers to the characteristics that result from this interplay (see genotype-phenotype distinction).