by Sanger Sequencing Industry The Original DNA Sequencing Method
Frederick Sanger, a British biochemist, developed the first widely used method of DNA sequencing in 1977, known as the Sanger method or Sanger sequencing. This breakthrough allowed scientists to determine the precise order of nucleotides in DNA for the first time. The Sanger method works by selectively incorporating chain-terminating dideoxynucleotides during in vitro DNA replication, generating a population of truncated extension products that terminate at every position in the DNA sequence. These products are then separated by gel electrophoresis based on their size, enabling identification of the terminal nucleotide. Though laborious, the Sanger method dominated DNA sequencing for over 20 years and revolutionized genetics. It enabled determination of whole genome sequences for various organisms and laid the groundwork for modern genomic research.
Global Impact and Applications of Sanger Sequencing Industry
Sanger Sequencing took off globally, becoming indispensable for myriad applications. It allowed completion of the first draft human genome sequence in 2001. Sanger sequencing still remains the gold standard for validating variations identified by new sequencing technologies. Clinically, it enabled discovery of genes associated with hereditary diseases and prenatal testing for conditions like cystic fibrosis. Forensically, Sanger sequencing helped establish paternity testing and identify crime suspects or victims. Anthropologically, it furthered studies of human evolution by sequencing Neanderthal and extinct hominin genomes. Regulatory agencies also rely on Sanger sequencing for confirming genetically modified organism constructs. Agriculture utilizes it for crop improvement through marker-assisted breeding. Overall, the accessibility, accuracy and reproducibility of Sanger sequencing cemented its status as the backbone of modern molecular biology and genetics research worldwide.
Moving Towards High-Throughput Platforms
While Sanger sequencing was highly successful, its low throughput limited larger genome-scale projects. Newer platforms subsequently arose to achieve higher sequencing throughput and bring down costs. In 2005, 454 pyrosequencing was commercialized as the first next-generation sequencing technology, allowing massively parallel DNA sequencing of multiple samples simultaneously. It found widespread applicability in sequencing microbial and small eukaryotic genomes. Further advancements followed rapidly, such as the Illumina platform utilizing sequencing by synthesis chemistry in 2006. These platforms enabled sequencing of entire human genomes within a day for under $1000. Technologies such as PacBio and Oxford Nanopore sequencing also emerged, capable of generating long reads and detecting epigenetic modifications. Propelled by Moore’s law, newer platforms continue advancing sequencing capacities at an astonishing pace. However, Sanger sequencing remains pivotal and complementary for applications requiring long reads, accuracy and absolute quantification.
Sustaining the Legacy of Sanger Sequencing
While massively parallel sequencing now dominates genomic research, Sanger sequencing sustains an indispensable role. It serves as a gold standard reference for benchmarking and validation of new platforms. Regulatory agencies mandate Sanger validation of variants identified through clinical whole genome or exome sequencing. Numerous initiatives also leverage Sanger sequencing for targeted resequencing efforts. For example, the 1000 Genomes Project performs low-coverage whole genome sequencing with newer platforms, followed by Sanger validation of variants. Similarly, the Exome Aggregation Consortium (ExAC) aggregates exome sequencing data from various disease-specific studies, validating with Sanger sequencing. Other projects focusing on antibiotic resistance, crop genomes, and forensic databases also utilize updated Sanger sequencing. Automation and multiplexing continue enhancing Sanger sequencing efficiency and output. Overall, as newer technologies emerge, Sanger sequencing ensures continuity of accurate, scalable genomic information – a testament to its groundbreaking nature and enduring legacy.
Frederick Sanger’s development of DNA chain-termination sequencing revolutionized biology and laid the foundations for modern genetics. The accessibility and reproducibility of the Sanger method drove its global proliferation and applications across diverse fields. While massively parallel platforms now fuel genome-scale projects, Sanger sequencing remains vital for reference, validation and targeted resequencing efforts. It sustained the Human Genome Project and enables clinical diagnostics, forensics and precision medicine. Forty years since its inception, Sanger sequencing continues substantiating genomic discoveries – a remarkable achievement and fitting tribute to one of the most influential scientific developments of the 20th century.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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