Genome sequencing how does it work

In addition, the ability to sequence the genome more rapidly and cost-effectively creates vast potential for diagnostics and therapies. Although routine DNA sequencing in the doctor's office is still many years away, some large medical centers have begun to use sequencing to detect and treat some diseases.

In cancer, for example, physicians are increasingly able to use sequence data to identify the particular type of cancer a patient has. This enables the physician to make better choices for treatments. Other researchers are studying its use in screening newborns for disease and disease risk.

Another National Institutes of Health program examines how gene activity is controlled in different tissues and the role of gene regulation in disease. Ongoing and planned large-scale projects use DNA sequencing to examine the development of common and complex diseases, such as heart disease and diabetes, and in inherited diseases that cause physical malformations, developmental delay and metabolic diseases.

Comparing the genome sequences of different types of animals and organisms, such as chimpanzees and yeast, can also provide insights into the biology of development and evolution. PulseNet is actively validating next-generation sequencing NGS technology as well as developing, evaluating, and implementing the tools needed to analyze the data.

In , CDC began using whole genome sequencing to detect outbreaks caused by the deadly bacteria Listeria. Since then, this method has allowed scientists to:. Learn more about how the Listeria Whole Genome Sequencing Project has improved the detection and investigation of foodborne outbreaks.

CDC is quickly expanding the use of whole genome sequencing in state laboratories, and scientists will soon begin using whole genome sequencing for outbreak investigations of other foodborne pathogens, such as Campylobacter , Shiga toxin-producing E.

These activities are critical to launching whole genome sequencing in public health laboratories and improving surveillance for foodborne disease outbreaks and trends in foodborne infections and antibiotic resistance.

With modernization, CDC and its public health partners can continue to successfully detect, respond, and stop infectious diseases. What are genome variations? Regardless of the approach to the genome as a whole, the actual process of DNA sequencing is the same.

Sequencing employs a technique known as electrophoresis to separate pieces of DNA that differ in length by only one base. Electrodes are placed at either end of the gel and an electrical current is applied, causing the DNA molecules to move through the gel. Smaller molecules move through the gel more rapidly, so the DNA molecules become separated into different bands according to their size. Until the late s, electrophoresis gels were always read by a person. Each piece of DNA was attached to a radioactive label, and an X-ray picture was made of the gel to make the positions of the DNA bands visible.

Painstakingly analyzing the rows and columns of bands on the gel, a person could determine the sequence of the DNA. But this process was slow, tedious, and fraught with error. Today's large-scale sequencing projects would be impossible without automatic sequencing machines, which became commercially available in the late s and have made DNA sequencing much quicker and more reliable. In one year, a person can produce a finished sequence of 20, to 50, bases; a machine can produce a rough draft of a sequence that long in just a few hours.

Most automatic sequencing machines have a design based closely on the original, manual sequencing process. To run the machine, a technician pours gel into the space between two glass plates set less than half a millimeter two-hundredths of an inch apart. As the DNA pieces move through the gel, the sequencing machine reads the order of DNA bases and stores this information in its computer memory.

But just like the slab-gel machines, capillary machines read the base sequence as DNA moves through the gel. Figure 5: Anatomy of whole-genome assembly. In whole-genome assembly, the BAC fragments red line segments and the reads from five individuals black line segments are combined to produce a contig and a consensus sequence green line.

The contigs are connected into scaffolds, shown in red, by pairing end sequences, which are also called mates. If there is a gap between consecutive contigs, it has a known size. Next, the scaffolds are mapped to the genome gray line using sequence tagged site STS information, represented by blue stars. Figure 6: How to sequence DNA. This step produces a mixture of newly synthesized DNA strands that differ in length by a single nucleotide.

C The DNA mixture is separated by electrophoresis. D The electropherogram results show peaks representing the color and signal intensity of each DNA band. From these data, the sequence of the newly synthesized DNA strand is determined, as shown above the peaks.

Dennis, C. Used with permission. Panel B shows nine newly synthesized DNA strands. Each of the strands differs in length by a single nucleotide and is labeled at the 3' end with a fluorescently-labeled ddNTP base. Panel C shows the electrophoresis results.

The DNA strands have been separated by size and appear as columns of colored bands. Panel D shows the electropherogram results, which are a series of colored peaks, with red representing T, black representing G, blue representing C, and green representing A. Shown above the peaks is the DNA sequence. From Rough Draft to Final Form. During this phase, the researchers filled in gaps and resolved DNA sequences in ambiguous areas that were not solved during the shotgun phase.

The final form of the human genome contained 2. Furthermore, the IHGSC reduced the number of gaps by fold; only gaps out of , gaps remained. The remaining gaps were associated with technically challenging chromosomal regions. Although the earlier draft publications had predicted as many as 40, protein-encoding genes, the finishing phase reduced this estimate to between 20, and 25, protein-encoding genes. Future challenges identified by the IHGSC during this phase included the identification of polymorphisms as a platform for understanding genetic links to human disease , the identification of functional elements within the genome genes, proteins, elements involved in gene regulation , and structural elements , and the identification of gene and protein "modules" that act in concert with one another.

From Digital Information to Molecular Medicine. One particularly striking finding of the Human Genome Project research is that the human nucleotide sequence is nearly identical However, a single nucleotide change in a single gene can be responsible for causing human disease. Because of this, our knowledge of the human genome sequence has also contributed immensely to our understanding of the molecular mechanisms underlying a multitude of human diseases.

Furthermore, a merging of cytogenetic approaches with the human genome sequence will continue to propel our understanding of human disease to an entirely new level.

Thus, although it was met with skepticism at its inception, the Human Genome Project will certainly be heralded as one of the most important scientific endeavors of our time. Within a span of only 13 years, an amalgam of public and private researchers was able to successfully complete the Human Genome Project. Although these scientists used a number of different methods in their work, they nonetheless obtained the same results.

In doing so, the researchers not only silenced their critics, but they also beat their own estimated project timeline by two entire years. Perhaps even more importantly, these scientists inspired an ongoing revolution in our fight against human disease and provided a new vision of the future of medicine-although that future has yet to be fully realized. References and Recommended Reading Hood, L. The digital code of DNA. Nature , — link to article Venter, J. Article History Close.

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