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What is Genome Sequencing?

A brief introduction to sequencing

Sequencing may appear to be a very challenging in-depth technology, but here we will break it down into steps and discuss the application of each step.

All living things have a unique code which is made up of RNA or DNA containing nucleotide bases. Sequencing is a technique that helps us to determine this unique code. See step 1.15 for further information on DNA and RNA.

Sanger sequencing was the first technique discovered by Frederick Sanger in the 1970s. This technique used radiolabelled partially digested fragments to discover the unique bases and was known as the chain termination method. However, this method was time consuming and very expensive to determine small fragments of DNA.

The Human Genome Project (HGP) has led to changes that have dramatically changed our approach to disease diagnosis, and together with the development of sequencing-by-synthesis techniques (otherwise known as next-generation sequencing or NGS technologies) the cost and time to sequence has decreased considerably. The HGP enabled clinicians to find mutations within the DNA code which we now use to test for genetic disorders and for personalised medicine. Today, we can sequence the whole genome of a human in 1-2 days and it is expected that this will continue to decrease in time and cost.

This is an additional video, hosted on YouTube.

At the beginning of the 21st century NGS methodologies became available and the development and improvement of these methods have been continuous. These are high-throughput sequencing platforms. Nowadays there are multiple NGS platforms available (see the videos explaining the Illumina and Oxford Nanopore Technologies), and a variety of techniques and sequencing strategies. We will address the details of NGS later in our course series.

Since the COVID-19 pandemic began, the COG-UK Consortium has used NGS and viral Whole Genome Sequencing (WGS) technologies to find the unique code of the SARS-CoV-2 RNA genomes. Although there are different sequencing methods that can be used, WGS has helped us to understand many different aspects about the virus in rapid time: it’s epidemiology and transmission, how the interventions and treatment are working and the biological understanding of the virus. Sequencing the human DNA from a large cohort of people who have been infected with the virus has allowed us to determine the genetic changes over time and understand how this translates into patient health and genetic evolution of the virus during the pandemic. See Step 1.18 for a more specific focus on SARS-CoV-2 sequencing.

This is an additional video, hosted on YouTube.

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The Power of Genomics to Understand the COVID-19 Pandemic

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