Demand for accurate, inexpensive, and fast DNA sequencing data has led to the evolution and dominance of a new generation of sequencing technologies. The use of genetic information has the potential to provide individuals and medical professionals with an arsenal of life-impacting information. In addition, different sciences are receiving benefits of sequencing technique, including forensic sciences, molecular biology, biotechnology, genetics, anthropology, and archaeology.

DNA sequencing is expected to revolutionize the conceptual foundation of these fields. However, issues related to public health and safety could pose a challenge to the market growth.

The first method described for DNA sequencing was Sanger's method. However, due to inefficiency of this method, the manufacturers described a breakthrough method for sequencing oligonucleotides via enzymic polymerization.

The enzymic method for DNA sequencing has been used for genomics research as the main tool to generate the fragments necessary for sequencing, regardless of the sequencing strategies. Since completion of the first human genome sequence, demand for a faster and cheaper sequencing method has increased greatly.

This demand has driven the development of second-generation sequencing method or next-generation sequencing (NGS). This method is expected to revolutionize the field of genomics in coming years.

Despite opening a new edge of genomics research, the fundamental shift away from the conventional sequencing to the NGS technologies has left many undiscovered applications and capabilities of these new technologies, especially those in clinical segment. The evolution of new sequencing technologies has raised the demand for commercially available platforms, whose diverse applications are restricting the potential of NGS for clinical research.

The global NGS market is expected to reach USD 10,371.1 million by 2021 from USD 4031.7 million in 2016, at a CAGR of 20.8 percent, states Markets and Markets.

The major drivers for the NGS market include the technological advancements in NGS products, increasing applications of NGS, entry of new market players, and increasing partnerships and collaborations among market players as well as growing incidences of cancer, inherited rare disorders, and pre- and neo-natal disorders.

Constant technological changes and creation of new opportunities are expected to attract new market players to the industry. The current breakthrough in micro fluidics, nanotechnology, imaging, and bioinformatics are expected to provide a novel platform for NGS market.

Technology Update

Recent advances in DNA sequencing technologies, so-called NGS, have brought breakthroughs in deciphering the genetic information in all living species at a large scale and at an affordable level.

With NGS, it is now feasible to sequence large amounts of DNA, for instance, all the pieces of an individual's DNA that provide instructions for making proteins. These pieces, called exons, are thought to make up 1 percent of a person's genome. Together, all the exons in a genome are known as the exome, and the method of sequencing them is known as 
whole-exome sequencing.

However, researchers have found that DNA variations outside the exons can affect gene activity and protein production and lead to genetic disorders - variations that whole-exome sequencing would miss. Another method, called whole-genome sequencing, determines the order of all the nucleotides in an individual's DNA and can determine variations in any part of the genome.

While many more genetic changes can be identified with whole-exome and 
whole-genome sequencing than with select gene sequencing, the significance of much of this information is unknown. Because not all genetic changes affect health, it is difficult to know whether identified variants are involved in the condition of interest.

Sometimes, an identified variant is associated with a different genetic disorder that has not yet been diagnosed (these are called incidental or secondary findings).

In addition to being used in the clinic, whole-exome and whole-genome sequencing are valuable methods for researchers. Continued study of exome and genome sequences can help determine whether new genetic variations 
are associated with health conditions, which will aid disease diagnosis in the future.

Dr Arun Raizada, Senior Consultant and HOD (Biochemistry),  Medanta - The Medicity, Gurgaon
Second Opinion
Error-Free Genomic Data

DNA sequencing, a process of reading precise order of nucleotide bases in a DNA molecule, allows researchers to understand the genetic information that is carried in a particular DNA segment. A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. The first automated DNA sequencer was invented by Lloyd M. Smith (1987) and it was based on Sanger sequencing method.

Several drawbacks of Sanger method and increased demand for fast, inexpensive, and accurate DNA sequencing data have led to the birth and dominance of a new generation of sequencing technologies. Next-generation sequencing, also called parallel sequencing, is a broad term that refers to a set of methods for genomic template preparation, generation of millions to billions of short sequence reads, alignment of sequence reads to a reference sequence and sequence assembly from aligned sequence reads and genetic variant discovery. These newer approaches enable many DNA fragments (sometimes on the order of millions of fragments) to be sequenced at one time and are more cost-efficient and much faster than 
first-generation technologies.

Several emerging technologies show promise of delivering next-generation solutions for fast and affordable genome sequencing. First commercially successful next-generation sequencer was based on pyro-sequencing, which detects light emitted by secondary reactions initiated by the release of pyrophosphate during nucleotide incorporation.

Developments in novel detection methods, miniaturization in instrumentation, microfluidic separation technologies, and an increase in the number of assays-per-run will most likely have the biggest impact on reducing cost over the next several years. The availability of next-generation DNA sequencers and implementation of genome sequence information will enable physicians to take a comprehensive look at a patient's genetic blueprint, or genome, to search for a wide range of variations or changes that increase risk of disease, drive the disease process, and/or affect response to medications and other treatments. Further research and development of single-molecule sequencing will allow researchers to gather nearly error-free genomic data in a timely and inexpensive manner.

Dr Arun Raizada
Senior Consultant and HOD (Biochemistry),
Medanta - The Medicity, Gurgaon


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