Each year, Genome.gov publishes statistics for Dna Sequencing Costs in both chart and table format. This post is updated with those costs. Original tables from 2010 can be found here.
This table represents the current DNA Sequencing Costs in US$. Charts for presentations or other materials can be found at the Genome website.
|Date||Cost per Mb of DNA Sequence||Cost per Genome|
In 1953, two researchers, namely James Watson and Francis Crick, discovered the basic structure of DNA. DNA is basically a long molecule that stores coded instructions for the cell. All cells are in some way encoded in the DNA- the DNA provides a basic blueprint that is responsible for the creation and functioning of cells. The information contained in it dictates which cells should grow and when a particular cell should die and how cells should be structured into creating various body parts. For example, the DNA is responsible for determining the quality of our hair, the color and the abundance, or the lack of it. We resemble our parents because our bodies have been formulated by the DNA guiding the process, the DNA that we inherit from them.
DNA and Nucleotides
DNA stands for Deoxyribonucleic acid. It is present in almost all organisms and it stores long term information that is used to construct an organic body.
DNA comprises of a long molecule analogous to a chain, while the links of the chain are called Nucleotides. There are four different nucleotides in the DNA, namely adenine, guanine, cytosine and thymine. They are also called as “A”, “G”, “C” and “T”.
DNA Sequencing entails several techniques and methods that are used to determine the sequence of the aforementioned nucleotide bases in a DNA molecule.
Understanding of DNA sequences has become an integral part of biological research. However, it has been an uphill battle for scientists and researchers to develop and share the core idea of DNA sequencing. But DNA sequencing has come a long way since the 1970s, when the first techniques were introduced.
The Need for DNA Sequencing
The process of DNA sequencing translates the DNA of a specific organism into a format that is decipherable by researchers and scientists. DNA sequencing has given a massive boost to numerous fields such as forensic biology, biotechnology and more. By mapping the basic sequence of nucleotides, DNA sequencing has allowed scientists to better understand genes and their role in the creation of the human body.
Forensic biology uses DNA sequences to identify the organism which it is unique to. Although identifying an individual is less accurate currently, but as the processes evolves further, direct comparisons of large DNA segments, and maybe even genomes, will be more practical and viable and will allow precise identification of an individual. Scientists will be able to isolate the genes responsible for genetic diseases like Cystic Fibrosis, Alzheimer’s disease, myotonic dystrophy, etc., which are caused by the inability of genes to work properly.
Agriculture has been helped immensely by DNA sequencing. It has allowed scientists to make plants more resistant to insects and pests, by understanding their genes. Likewise, the same technique has been utilized to increase the productivity and quality of the milk, as well as the meat, produced by livestock.
The DNA Structure
DNA structure resembles to that of a double helix and is composed of three components – alternating sugars, phosphates and one of the four bases.
When a cell divides and the DNA is to be replicated, the double helix is divided, and enzymes called polymerases use each of the two halves as the template for a new opposing strand. Polymerase causes the hydroxyl group at the end to react and link together to form the link of the chain. DNA sequencing relies on the process of DNA duplication.
DNA sequencing attempts to understand the order of bases along the strand. The process of DNA sequencing can be terminated in precise locations and the bases can be isolated where it stops.
The Maxam-Gilbert technique relies on the cleaving of nucleotides by chemical and is most efficient with small nucleotide polymers. This technique was developed by Maxam-Gilbert in 1976-1977 and was published two years after the enlightening papers on Plus-Minus sequencing by Sanger and Coulson. Unlike in Sanger’s initial method, which required that each read start be cloned for the synthesis of single-stranded DNA, this method used the purified DNA directly, which made it very popular.
Although due to the advancements in chain termination methodology, the Maxam-Gilbert method has become redundant. It was made obsolete due to it being less ergonomically feasible. It is also considered unsafe because of the extensive use of toxic chemicals.
The simplest way to do chain sequencing is to manipulate the chemistry of the molecule. Instead of catering to DNA with normal nucleotides, it’s possible to synthesize one in absence of the hydroxyl group, which is essential for the polymerase that adds to the next base. This technique is also known as Sanger method and is named after the discoverer Fredrick Sanger.
The archetypal chain reaction requires a DNA template, DNA polymerase, normal dexoynucleotide (dNTP) and modified deoxynucleotides (ddNTP). The strand synthesis is carried out four times separately, which involves the reaction with ddNTP. This terminates the reaction due to the lack of hydroxyl that is essential for the formation of bond between two nucleotides. The result is four discrete families of polynucleotides.
The polyacrylamide gel electrophoresis is used to denature the DNA to obtain the newly synthesized strands from the given template. High voltage is utilized to heat up the gel to 60 degree centigrade and this makes sure that the two strands don’t re-associate. Autoradiography helps in determining the strands as they are radio labeled.
Dye-terminator sequencing involves labeling of the chain terminating ddNTPs, which allows the sequencing in single reaction, instead of four parallel reactions. In this process, each of the ddNTP is labeled with a fluorescent dyes, which emit light in different wavelengths.
Owing to it is convenience and speed, dye terminator sequencing is the preferred in automated sequencing. Its limitations include anomalies in the incorporation of dye-labeled chain terminators into DNA fragments, which can result in abnormal readings in electronic DNA sequence trace chromatography after the capillary electrophoresis.
DNA sequencing, in time, may allow us to manipulate the process of evolution. Diseases will vanish, and the human race will be stronger, smarter and better than ever before.
As recently reported by Genome.gov, DNA Sequencing costs have dramatically dropped over the past 10 years for most large-scale programs. The cost base chart below is taken directly from the site and represents the cost per megabase, or per genome, of a given sequential analysis.
|Date||Cost per Mb of DNA Sequence||Cost per Genome|
|September-2001||$ 5,292.39||$ 95,263,072|
|March-2002||$ 3,898.64||$ 70,175,437|
|September-2002||$ 3,413.80||$ 61,448,422|
|March-2003||$ 2,986.20||$ 53,751,684|
|October-2003||$ 2,230.98||$ 40,157,554|
|January-2004||$ 1,598.91||$ 28,780,376|
|April-2004||$ 1,135.70||$ 20,442,576|
|July-2004||$ 1,107.46||$ 19,934,346|
|October-2004||$ 1,028.85||$ 18,519,312|
|January-2005||$ 974.16||$ 17,534,970|
|April-2005||$ 897.76||$ 16,159,699|
|July-2005||$ 898.90||$ 16,180,224|
|October-2005||$ 766.73||$ 13,801,124|
|January-2006||$ 699.20||$ 12,585,659|
|April-2006||$ 651.81||$ 11,732,535|
|July-2006||$ 636.41||$ 11,455,315|
|October-2006||$ 581.92||$ 10,474,556|
|January-2007||$ 522.71||$ 9,408,739|
|April-2007||$ 502.61||$ 9,047,003|
|July-2007||$ 495.96||$ 8,927,342|
|October-2007||$ 397.09||$ 7,147,571|
|January-2008||$ 102.13||$ 3,063,820|
|April-2008||$ 15.03||$ 1,352,982|
|July-2008||$ 8.36||$ 752,080|
|October-2008||$ 3.81||$ 342,502|
|January-2009||$ 2.59||$ 232,735|
|April-2009||$ 1.72||$ 154,714|
|July-2009||$ 1.20||$ 108,065|
|October-2009||$ 0.78||$ 70,333|
|January-2010||$ 0.52||$ 46,774|
|April-2010||$ 0.35||$ 31,512|
|July-2010||$ 0.35||$ 31,125|
|October-2010||$ 0.32||$ 29,092|
In order to present a proper model of DNA, this three-dimensional representation will allow you to zoom in and out as well as rotate and segregate various sections of the DNA model.
You can select to view only certain elements, such as Oxygen, Hydrogen, Phosphorus, Nitrogen and Carbon. You can also drill down into the Bases or the sugar-phosphate backbone.
By presenting the DNA in 3d you have full control over all the aspects of the object.
As DNA Analysis has become more prevalent and necessary in modern time, so have methods of sequencing.
Genome.gov holds programs and grants for those with the most rewarding possible future methods of DNA Sequencing. Below are a few that have some great potential.
Microfluidic DNA Sequencing
A single molecule detection method leveraging droplet-based microfluidics. This should limit the amount of reagent required to sequence DNA to less than several milliliters, while still retaining the ability to amplify the template that thereby enables us to use relatively inexpensive and robust detection. The method is simple and does not require enzymes.
Ultra-high throughput polony genome sequencing, generating raw data to re-sequence the human genome in one week. The goal of the method is to increase the polony sequencing read length using a cyclic ligation strategy that involves enzymatic cleavage, and increase read density by using different clonal amplification strategies.
Millikan Sequencing by Nucleotide
This novel sequencing-by-synthesis approach measures the increased charge as nucleotides are added to DNA templates attached to a tethered bead. Opposing electrical, hydrodynamic and entropic forces will be used to measure the bead displacement, which is a function of the length of DNA attached to the bead. The much lower per-bead copy number required compared to the 454 system should enable amplification options other than emulsion PCR, such as bridge PCR, making initial sample preparation easier and cheaper.
Single-Molecule DNA Sequencing with Engineered Nanopores
In nanopore strand sequencing, a single strand of DNA moves through a narrow pore and the bases are identified as they pass a reading head. Here, we focus on the remaining tasks required to put into practice strand sequencing with the ±-hemolysin (±HL) protein nanopore. Nanopore sequencing is a rapid real-time technology; it does not require the time-consuming cyclic addition of reagents. After implementing a chip with 106 pores, we expect nanopore sequencing to achieve a 15-minute genome by 2014 with a very short sample preparation time. In addition, nanopore sequencing will be able to identify modified bases and to sequence RNA directly. The latest goal is to refine base recognition by using ±HL nanopores, engineered by conventional mutagenesis, unnatural amino acid mutagenesis and targeted chemical modification, to produce DNA reading heads fit for real-time sequencing.
Direct Real-time Single Molecule DNA Sequencing
Direct real-time sequencing of single DNA molecules from genomic DNA at the speed and accuracy of the natural DNA polymerases using native nucleotides. Unlike the difficult to engineer man-made nanostructures used in nanopore sequencing to distinguish the 4 base types in close proximity and constant fluctuation, DNA polymerases have precise atomic-resolution 3D structures and can synthesize very long DNA molecules with high fidelity and velocity. The strategy is to engineer sensors onto the surface of the polymerase by protein engineering to monitor the subtle yet distinct conformational changes accompanying the incorporation of each base type.
Tunnel Junction for Reading All Four Bases with High Discrimination
Distinct tunneling signals can be generated for all four nucleosides (and 5-methyldeoxycytidine) using one pair of tunneling electrodes functionalized with a simple reagent containing a hydrogen-bond donor and a hydrogen bond acceptor. The goals of this proposal are to extend the measurements to nucleotides in aqueous electrolyte, and then to small oligomers.
Single Molecule Sequencing by Nanopore-induced Photon Emission (SM-SNIPE)
Nanopore induced photon emission (SNIPE), utilizes optical detection rather than the more ubiquitous electrical detection. Dramatically increase the throughput, speed and accuracy of SNIPE. Develop and optimize our proprietary DNA conversion approach, Circular DNA conversion (CDC).
Modeling Macromolecular Transport for Sequencing Technologies
In Nanopore-based electrophoretic experiments, translocation of single molecules of DNA is monitored as they pass through protein channels and solid-state nanopores under an external electric field. This proposed method deals with a fundamental understanding of the behavior of DNA in nanopore environments under the influence of electrical and hydrodynamic forces.
Base-selective Heavy Atom Labels for Electron Microscopy-based DNA Sequencing
Since efficient electron scattering to a detector is highly dependent on atomic number (Z), it is possible to label single stranded DNA (ssDNA) with heavy atoms. To test the limits of this trend, this method proposes a multipronged approach to selectively prepared metal-DNA base pair complexes, focusing on the selective labeling of DNA bases and the development of an appropriate assay to evaluate our success.
Certainly one of the most important events was the discovery of the DNA Double-helix in 1953.
DNA Sequencing sprung to life in 1972, when Frederick Sanger at the University of Cambridge, in England began work on the genome sequence using a variation of the recombinant DNA method. The full DNA sequence of a viral genome was completed by Sanger in 1977. However, Sanger's technique of DNA sequencing was inefficient and no serious work beyond this attempt was even considered, due to the vast resources needed to compute a single genome. At the same time, Maxam and Gilbert publish their own "DNA sequencing by chemical degradation" which became an important method of sequencing for many years thereafter.
During the bulk of the 80's little work was done on furthering the science of sequential analysis, but by 1992, most of the computer technology and lab equipment was in place to allow large companies to sequence up to 100,000 base pair DNA strands - but the cost was very high for any sequencing. While progress was not at a standstill it was clear that no massive work could be done without tremendous effort.
The Human Genome Project began in the late 90's as an attempt to sequence what was considered the ultimate achievement, the human genome. Engineers and scientists worldwide gathered to create new methods in the field. Their goals were twofold: to reduce the overall pricetag associated with performing sequencing and to improve the speed and reliability of these techniques.
We now have numerous sites that can sequence to the 100 million base pair and even higher and at a drastically reduced cost over the older methods used in the early 1990's.