whole genome sequencing whole genome sequencing whole genome sequencing (wgs), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the dna sequence of an organism's genome at a single time. this entails sequencing all of an organism's chromosomal dna as well as dna contained in the mitochondria and, for plants, in the chloroplast. electropherograms are commonly used to sequence portions of genomes. schematic karyogram of a human, showing an overview of the human genome, with 22 homologous chromosomes, both the female (xx) and male (xy) versions of the sex chromosome (bottom right), as well as the mitochondrial genome (to scale at bottom left).further information: karyotype whole genome sequencing has largely been used as a research tool, but was being introduced to clinics in 2014. in the future of personalized medicine, whole genome sequence data may be an important tool to guide therapeutic intervention. the tool of gene sequencing at snp level is also used to pinpoint functional variants from association studies and improve the knowledge available to researchers interested in evolutionary biology, and hence may lay the foundation for predicting disease susceptibility and drug response. whole genome sequencing should not be confused with dna profiling, which only determines the likelihood that genetic material came from a particular individual or group, and does not contain additional information on genetic relationships, origin or susceptibility to specific diseases. in addition, whole genome sequencing should not be confused with methods that sequence specific subsets of the genome – such methods include whole exome sequencing (1–2% of the genome) or snp genotyping (< 0.1% of the genome). history the first bacterial whole genome to be sequenced was of the bacterium haemophilus influenzae. the worm caenorhabditis elegans was the first animal to have its whole genome sequenced. drosophila melanogaster's whole genome was sequenced in 2000. arabidopsis thaliana was the first plant genome sequenced. the genome of the lab mouse mus musculus was published in 2002. it took 10 years and 50 scientists spanning the globe to sequence the genome of elaeis guineensis (oil palm). this genome was particularly difficult to sequence because it had many repeated sequences which are difficult to organise. the dna sequencing methods used in the 1970s and 1980s were manual; for example, maxam–gilbert sequencing and sanger sequencing. several whole bacteriophage and animal viral genomes were sequenced by these techniques, but the shift to more rapid, automated sequencing methods in the 1990s facilitated the sequencing of the larger bacterial and eukaryotic genomes. the first virus to have its complete genome sequenced was the bacteriophage ms2 by 1976. in 1992, yeast chromosome iii was the first chromosome of any organism to be fully sequenced. the first organism whose entire genome was fully sequenced was haemophilus influenzae in 1995. after it, the genomes of other bacteria and some archaea were first sequenced, largely due to their small genome size. h. influenzae has a genome of 1,830,140 base pairs of dna. in contrast, eukaryotes, both unicellular and multicellular such as amoeba dubia and humans (homo sapiens) respectively, have much larger genomes (see c-value paradox). amoeba dubia has a genome of 700 billion nucleotide pairs spread across thousands of chromosomes. humans contain fewer nucleotide pairs (about 3.2 billion in each germ cell – note the exact size of the human genome is still being revised) than a. dubia, however, their genome size far outweighs the genome size of individual bacteria. the first bacterial and archaeal genomes, including that of h. influenzae, were sequenced by shotgun sequencing. in 1996 the first eukaryotic genome (saccharomyces cerevisiae) was sequenced. s. cerevisiae, a model organism in biology has a genome of only around 12 million nucleotide pairs, and was the first unicellular eukaryote to have its whole genome sequenced. the first multicellular eukaryote, and animal, to have its whole genome sequenced was the nematode worm: caenorhabditis elegans in 1998. eukaryotic genomes are sequenced by several methods including shotgun sequencing of short dna fragments and sequencing of larger dna clones from dna libraries such as bacterial artificial chromosomes (bacs) and yeast artificial chromosomes (yacs). in 1999, the entire dna sequence of human chromosome 22, the shortest human autosome, was published. by the year 2000, the second animal and second invertebrate (yet first insect) genome was sequenced – that of the fruit fly drosophila melanogaster – a popular choice of model organism in experimental research. the first plant genome – that of the model organism arabidopsis thaliana – was also fully sequenced by 2000. by 2001, a draft of the entire human genome sequence was published. the genome of the laboratory mouse mus musculus was completed in 2002. in 2004, the human genome project published an incomplete version of the human genome. in 2008, a group from leiden, the netherlands, reported the sequencing of the first female human genome (marjolein kriek). currently thousands of genomes have been wholly or partially sequenced. experimental details cells used for sequencing almost any biological sample containing a full copy of the dna—even a very small amount of dna or ancient dna—can provide the genetic material necessary for full genome sequencing. such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, plant leaves, or anything else that has dna-containing cells. the genome sequence of a single cell selected from a mixed population of cells can be determined using techniques of single cell genome sequencing. this has important advantages in environmental microbiology in cases where a single cell of a particular microorganism species can be isolated from a mixed population by microscopy on the basis of its morphological or other distinguishing characteristics. in such cases the normally necessary steps of isolation and growth of the organism in culture may be omitted, thus allowing the sequencing of a much greater spectrum of organism genomes. single cell genome sequencing is being tested as a method of preimplantation genetic diagnosis, wherein a cell from the embryo created by in vitro fertilization is taken and analyzed before embryo transfer into the uterus. after implantation, cell-free fetal dna can be taken by simple venipuncture from the mother and used for whole genome sequencing of the fetus. early techniques an abi prism 3100 genetic analyzer. such capillary sequencers automated the early efforts of sequencing genomes. sequencing of nearly an entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing technology. while full genome shotgun sequencing for small (4000–7000 base pair) genomes was already in use in 1979, broader application benefited from pairwise end sequencing, known colloquially as double-barrel shotgun sequencing. as sequencing projects began to take on longer and more complicated genomes, multiple groups began to realize that useful information could be obtained by sequencing both ends of a fragment of dna. although sequencing both ends of the same fragment and keeping track of the paired data was more cumbersome than sequencing a single end of two distinct fragments, the knowledge that the two sequences were oriented in opposite directions and were about the length of a fragment apart from each other was valuable in reconstructing the sequence of the original target fragment. the first published description of the use of paired ends was in 1990 as part of the sequencing of the human hprt locus, although the use of paired ends was limited to closing gaps after the application of a traditional shotgun sequencing approach. the first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991. in 1995 the innovation of using fragments of varying sizes was introduced, and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. the strategy was subsequently adopted by the institute for genomic research (tigr) to sequence the entire genome of the bacterium haemophilus influenzae in 1995, and then by celera genomics to sequence the entire fruit fly genome in 2000, and subsequently the entire human genome. applied biosystems, now called life technologies, manufactured the automated capillary sequencers utilized by both celera genomics and the human genome project. current techniques while capillary sequencing was the first approach to successfully sequence a nearly full human genome, it is still too expensive and takes too long for commercial purposes. since 2005 capillary sequencing has been progressively displaced by high-throughput (formerly "next-generation") sequencing technologies such as illumina dye sequencing, pyrosequencing, and smrt sequencing. all of these technologies continue to employ the basic shotgun strategy, namely, parallelization and template generation via genome fragmentation. other technologies have emerged, including nanopore technology. though the sequencing accuracy of nanopore technology is lower than those above, its read length is on average much longer. this generation of long reads is valuable especially in de novo whole-genome sequencing applications. analysis in principle, full genome sequencing can provide the raw nucleotide sequence of an individual organism's dna at a single point in time. however, further analysis must be performed to provide the biological or medical meaning of this sequence, such as how this knowledge can be used to help prevent disease. methods for analyzing sequencing data are being developed and refined. because sequencing generates a lot of data (for example, there are approximately six billion base pairs in each human diploid genome), its output is stored electronically and requires a large amount of computing power and storage capacity. while analysis of wgs data can be slow, it is possible to speed up this step by using dedicated hardware. commercialization total cost of sequencing a whole human genome as calculated by the nhgri. a number of public and private companies are competing to develop a full genome sequencing platform that is commercially robust for both research and clinical use, including illumina, knome, sequenom, 454 life sciences, pacific biosciences, complete genomics, helicos biosciences, ge global research (general electric), affymetrix, ibm, intelligent bio-systems, life technologies, oxford nanopore technologies, and the beijing genomics institute. these companies are heavily financed and backed by venture capitalists, hedge funds, and investment banks. a commonly-referenced commercial target for sequencing cost until the late 2010s was $1,000 usd, however, the private companies are working to reach a new target of only $100. incentive in october 2006, the x prize foundation, working in collaboration with the j. craig venter science foundation, established the archon x prize for genomics, intending to award $10 million to "the first team that can build a device and use it to sequence 100 human genomes within 10 days or less, with an accuracy of no more than one error in every 1,000,000 bases sequenced, with sequences accurately covering at least 98% of the genome, and at a recurring cost of no more than $1,000 per genome". the archon x prize for genomics was cancelled in 2013, before its official start date. history in 2007, applied biosystems started selling a new type of sequencer called solid system. the technology allowed users to sequence 60 gigabases per run. in june 2009, illumina announced that they were launching their own personal full genome sequencing service at a depth of 30× for $48,000 per genome. in august, the founder of helicos biosciences, stephen quake, stated that using the company's single molecule sequencer he sequenced his own full genome for less than $50,000. in november, complete genomics published a peer-reviewed paper in science demonstrating its ability to sequence a complete human genome for $1,700. in may 2011, illumina lowered its full genome sequencing service to $5,000 per human genome, or $4,000 if ordering 50 or more. helicos biosciences, pacific biosciences, complete genomics, illumina, sequenom, ion torrent systems, halcyon molecular, nabsys, ibm, and ge global appear to all be going head to head in the race to commercialize full genome sequencing. with sequencing costs declining, a number of companies began claiming that their equipment would soon achieve the $1,000 genome: these companies included life technologies in january 2012, oxford nanopore technologies in february 2012, and illumina in february 2014. in 2015, the nhgri estimated the cost of obtaining a whole-genome sequence at around $1,500. in 2016, veritas genetics began selling whole genome sequencing, including a report as to some of the information in the sequencing for $999. in summer 2019 veritas genetics cut the cost for wgs to $599. in 2017, bgi began offering wgs