genomics genomics genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. a genome is an organism's complete set of dna, including all of its genes as well as its hierarchical, three-dimensional structural configuration. in contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. genes may direct the production of proteins with the assistance of enzymes and messenger molecules. in turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. genomics also involves the sequencing and analysis of genomes through uses of high throughput dna sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain. part of a series ongenetics key components chromosome dna rna genome heredity mutation nucleotide variation outline index history and topics introduction history evolution (molecular) population genetics mendelian inheritance quantitative genetics molecular genetics research geneticist dna sequencing genetic engineering genomics ( template) medical genetics branches of genetics personalized medicine personalized medicine category the field also includes studies of intragenomic (within the genome) phenomena such as epistasis (effect of one gene on another), pleiotropy (one gene affecting more than one trait), heterosis (hybrid vigour), and other interactions between loci and alleles within the genome. history etymology from the greek γεν gen, "gene" (gamma, epsilon, nu, epsilon) meaning "become, create, creation, birth", and subsequent variants: genealogy, genesis, genetics, genic, genomere, genotype, genus etc. while the word genome (from the german genom, attributed to hans winkler) was in use in english as early as 1926, the term genomics was coined by tom roderick, a geneticist at the jackson laboratory (bar harbor, maine), over beers with jim womack, tom shows and stephen o’brien at a meeting held in maryland on the mapping of the human genome in 1986. first as the name for a new journal and then as a whole new science discipline. early sequencing efforts following rosalind franklin's confirmation of the helical structure of dna, james d. watson and francis crick's publication of the structure of dna in 1953 and fred sanger's publication of the amino acid sequence of insulin in 1955, nucleic acid sequencing became a major target of early molecular biologists. in 1964, robert w. holley and colleagues published the first nucleic acid sequence ever determined, the ribonucleotide sequence of alanine transfer rna. extending this work, marshall nirenberg and philip leder revealed the triplet nature of the genetic code and were able to determine the sequences of 54 out of 64 codons in their experiments. in 1972, walter fiers and his team at the laboratory of molecular biology of the university of ghent (ghent, belgium) were the first to determine the sequence of a gene: the gene for bacteriophage ms2 coat protein. fiers' group expanded on their ms2 coat protein work, determining the complete nucleotide-sequence of bacteriophage ms2-rna (whose genome encodes just four genes in 3569 base pairs ) and simian virus 40 in 1976 and 1978, respectively. dna-sequencing technology developed frederick sangerwalter gilbertfrederick sanger and walter gilbert shared half of the 1980 nobel prize in chemistry for independently developing methods for the sequencing of dna. in addition to his seminal work on the amino acid sequence of insulin, frederick sanger and his colleagues played a key role in the development of dna sequencing techniques that enabled the establishment of comprehensive genome sequencing projects. in 1975, he and alan coulson published a sequencing procedure using dna polymerase with radiolabelled nucleotides that he called the plus and minus technique. this involved two closely related methods that generated short oligonucleotides with defined 3' termini. these could be fractionated by electrophoresis on a polyacrylamide gel (called polyacrylamide gel electrophoresis) and visualised using autoradiography. the procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still very laborious. nevertheless, in 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded bacteriophage φx174, completing the first fully sequenced dna-based genome. the refinement of the plus and minus method resulted in the chain-termination, or sanger method (see below), which formed the basis of the techniques of dna sequencing, genome mapping, data storage, and bioinformatic analysis most widely used in the following quarter-century of research. in the same year walter gilbert and allan maxam of harvard university independently developed the maxam-gilbert method (also known as the chemical method) of dna sequencing, involving the preferential cleavage of dna at known bases, a less efficient method. for their groundbreaking work in the sequencing of nucleic acids, gilbert and sanger shared half the 1980 nobel prize in chemistry with paul berg (recombinant dna). complete genomes the advent of these technologies resulted in a rapid intensification in the scope and speed of completion of genome sequencing projects. the first complete genome sequence of a eukaryotic organelle, the human mitochondrion (16,568 bp, about 16.6 kb ), was reported in 1981, and the first chloroplast genomes followed in 1986. in 1992, the first eukaryotic chromosome, chromosome iii of brewer's yeast saccharomyces cerevisiae (315 kb) was sequenced. the first free-living organism to be sequenced was that of haemophilus influenzae (1.8 mb ) in 1995. the following year a consortium of researchers from laboratories across north america, europe, and japan announced the completion of the first complete genome sequence of a eukaryote, s. cerevisiae (12.1 mb), and since then genomes have continued being sequenced at an exponentially growing pace. as of october 2011, the complete sequences are available for: 2,719 viruses, 1,115 archaea and bacteria, and 36 eukaryotes, of which about half are fungi. the number of genome projects has increased as technological improvements continue to lower the cost of sequencing. (a) exponential growth of genome sequence databases since 1995. (b) the cost in us dollars (usd) to sequence one million bases. (c) the cost in usd to sequence a 3,000 mb (human-sized) genome on a log-transformed scale. most of the microorganisms whose genomes have been completely sequenced are problematic pathogens, such as haemophilus influenzae, which has resulted in a pronounced bias in their phylogenetic distribution compared to the breadth of microbial diversity. of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. yeast (saccharomyces cerevisiae) has long been an important model organism for the eukaryotic cell, while the fruit fly drosophila melanogaster has been a very important tool (notably in early pre-molecular genetics). the worm caenorhabditis elegans is an often used simple model for multicellular organisms. the zebrafish brachydanio rerio is used for many developmental studies on the molecular level, and the plant arabidopsis thaliana is a model organism for flowering plants. the japanese pufferfish (takifugu rubripes) and the spotted green pufferfish (tetraodon nigroviridis) are interesting because of their small and compact genomes, which contain very little noncoding dna compared to most species. the mammals dog (canis familiaris), brown rat (rattus norvegicus), mouse (mus musculus), and chimpanzee (pan troglodytes) are all important model animals in medical research. a rough draft of the human genome was completed by the human genome project in early 2001, creating much fanfare. this project, completed in 2003, sequenced the entire genome for one specific person, and by 2007 this sequence was declared "finished" (less than one error in 20,000 bases and all chromosomes assembled). in the years since then, the genomes of many other individuals have been sequenced, partly under the auspices of the 1000 genomes project, which announced the sequencing of 1,092 genomes in october 2012. completion of this project was made possible by the development of dramatically more efficient sequencing technologies and required the commitment of significant bioinformatics resources from a large international collaboration. the continued analysis of human genomic data has profound political and social repercussions for human societies. the "omics" revolution general schema showing the relationships of the genome, transcriptome, proteome, and metabolome (lipidome). the english-language neologism omics informally refers to a field of study in biology ending in -omics, such as genomics, proteomics or metabolomics. the related suffix -ome is used to address the objects of study of such fields, such as the genome, proteome or metabolome respectively. the suffix -ome as used in molecular biology refers to a totality of some sort; similarly omics has come to refer generally to the study of large, comprehensive biological data sets. while the growth in the use of the term has led some scientists (jonathan eisen, among others) to claim that it has been oversold, it reflects the change in orientation towards the quantitative analysis of complete or near-complete assortment of all the constituents of a system. in the study of symbioses, for example, researchers which were once limited to the study of a single gene product can now simultaneously compare the total complement of several types of biological molecules. genome analysis after an organism has been selected, genome projects involve three components: the sequencing of dna, the assembly of that sequence to create a representation of the original chromosome, and the annotation and analysis of that representation. overview of a genome project. first, the genome must be selected, which involves several factors including cost and relevance. second, the sequence is generated and assembled at a given sequencing center (such as bgi or doe jgi). third, the genome sequence is annotated at several levels: dna, protein, gene pathways, or comparatively. sequencing historically, sequencing was done in sequencing centers, centralized facilities (ranging from large independent institutions such as joint genome institute which sequence dozens of terabases a year, to local molecular biology core facilities) which contain research laboratories with the costly instrumentation and technical support necessary. as sequencing technology continues to improve, however, a new generation of effective fast turnaround benchtop sequencers has come within reach of the average academic laboratory. on the whole, genome sequencing approaches fall into two broad categories, shotgun and high-throughput (or next-generation) sequencing. shotgun sequencing an abi prism 3100 genetic analyzer. such capillary sequencers automated early large-scale genome sequencing efforts. shotgun sequencing is a sequencing method designed for analysis of dna sequences longer than 1000 base pairs, up to and including entire chromosomes. it is named by analogy with the rapidly expanding, quasi-random firing pattern of a shotgun. since gel electrophoresis sequencing can only be used for fairly short sequences (100 to 1000 base pairs), longer dna sequences must be broken into random small segments which are then sequenced to obtain reads. multiple overlapping reads for the target dna are obtained by performing several rounds of this fragmentation and sequencing. computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence. shotgun sequencing is a random sampling process, requiring over-sampling to ensure a given nucleotide is represented in the reconstructed sequence; the average number of reads by which a genome is over-sampled is referred to as coverage. for much of its history, the technology underlying shotgun sequencing was the classical chain-termination method or 'sanger method', which is based on the selective incorporation of chain-terminating dideoxynucleotides by dna polymerase during in vitro dna replication. recently, shotgun sequencing has been supplanted by high-throughput sequencing methods, especially for large-scale, automated genome analyses. however, the sanger method remains in wide use, primarily for smaller-scale projects and for obtaining especially long contiguous dna sequence reads (>500 nucleotides). chain-termination methods require a single-stranded dna template, a dna primer, a dna polymerase, normal deoxynucleosidetriphosphates (dntps), and modified nucleotides (dideoxyntps) that terminate dna strand elongation. these chain-terminating nucleotides lack a 3'-oh group required for the formation of a phosphodiester bond between two nucleotides, causing dna polymerase to cease extension of dna when a ddntp is incorporated. the ddntps may be radioactively or fluorescently labelled for detection in dna sequencers. typically, these machines can sequence up to 96 dna samples in a single batch (run) in up to 48 runs a day. high-throughput sequencing the high demand for low-cost sequencing has driven the development of high-throughput sequencing technologies that parallelize the sequencing process, producing thousands or millions of