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18 Feb 2021

Explainer – SARS-CoV-2 genomics

What is a genome?

A genome is an organism’s complete genetic code. 

Our human genome is all the genetic information in our body, making us who we are. Similarly, a bacterial or viral genome is all the genetic material of that organism.

A genome can be made up of DNA or RNA. 

In a human, DNA builds and maintains our body, and RNA is a messenger that tells our DNA to do jobs in our body, like carrying oxygen.

RNA is more unstable than DNA and can change rapidly.

Many viral genomes are made up of RNA and SARS-CoV-2 is one of them.

What is genomic sequencing?

A genome sequence is a list of what’s in our DNA and RNA – known as the nucleotides (A (adenine), C (cytosine), G (guanine), and either T (thymine) for DNA genomes or uracil (U) for RNA genomes).

It’s like a barcode.

Genomic sequencing is the process of identifying everything in that barcode.

SARS-CoV-2, for example, has 30,000 RNA nucleotides in its genetic code.

Pathogens like viruses change over time.

Through genomic sequencing, we can see how those pathogens are changing and spreading each time one of its strands change.

What is mutation? 

A genetic mutation is a permanent change in the genetic code of an organism.

Mutations can result from errors when the virus is replicating (making a copy of itself) or due to damage to the genome (for example, exposure to radiation or chemicals). 

Many mutations have no effect on the virus or any disease the virus may cause. 

But some mutations may change characteristics, such as increasing or decreasing how easily the virus is transmitted or the severity of the disease. 

What do mutations tell us?

Once a mutation occurs in the genome of a virus, it makes copies of itself inside the body. 

If it gets transmitted another person, it does so in its mutated form.

Sequences that share the same patterns of mutations are said to be highly genomically related. They have an ‘ancestor’ in common.

If viruses from different people are highly genomically related, it is more likely the virus has been acquired from within the same transmission network.

For example, highly genomically related viruses may have been transmitted directly between members of the same household, or spread indirectly between people in the same workplace. 

In contrast, sequences with very different patterns of mutations are said to be not closely related. 

This occurs, for example, with returned travellers who acquired COVID-19 in different countries. 

What are genomic clusters? What do they tell us?

A cluster is a group of people with an illness who have things in common which suggests they might have acquired it from each other, from a common source or due to a common cause. Traditionally, clusters were based on epidemiological or clinical information, such as where a person lives, or characteristics of their illness. 

However, clusters can also be defined based on characteristics of the pathogen (virus or bacteria) causing the illness. Whole genome sequencing is the highest resolution technology available to identify and determine clusters in this way.

For COVID-19, genomic clusters are groups of sequences that are more genomically related to each other than they are to any other sequences in the analysis. This means that that the people infected with a virus from a particular genomic cluster are more likely to have acquired COVID-19 from other people infected with a virus from within that genomic cluster, than from other people whose viral sequence is not within that genomic cluster.  

Genomic clusters can vary greatly in size and duration, depending on how quickly the virus is spreading, and accumulating mutations, within a population or setting. 

What can genomic sequencing tell us about where or from whom a person acquired COVID-19?

Genomic sequencing can identify groups of people who are more likely to have acquired COVID-19 from each other or from within the same network of transmission.

When combined with epidemiological data, genomic sequencing can help identify the possible source of a virus for a given case or group of cases. It can also rule out a likely source of COVID-19 for a given person, as people with very different sequences are unlikely to have transmitted it to each other.

Genomic relationships can be particularly useful to:

  • Identify possible sources of infection for further investigation, where contact tracing hasn’t identified any likely sources of infection (an unknown source or “mystery” case), or
  • Determine the more likely source of infection where contact tracing has identified more than one possible source.

It is important to note that genomic sequencing alone cannot determine if two people directly transmitted the virus to each other, or what direction transmission may have occurred in. 

In Victoria, the Microbiological Diagnostic Unit Public Health Laboratory at the Doherty Institute and the Victorian Department of Health work closely to ensure genomic and epidemiological information are integrated to help answer these questions and inform our public health actions.

What are variants of concern?

In this context, a “variant” refers to a set of viruses with the same or similar patterns of mutations. Some of these variants are thought to potentially behave differently compared to other virus strains present around the world. Some are thought to be more transmissible (i.e. spread more easily between people), or might cause more severe infection than others - these are labelled as ‘variants of concern’. Data will be gathered in the coming months to confirm whether these variants are significantly more transmissible or cause more severe disease.

Many countries where these variants are not yet present are trying to monitor the COVID-19 infections in their country, and trying to prevent these variants being introduced, or becoming widespread. In Australia and many other countries, genomic sequencing is being used to identify variants of concern (for example, in travellers returning from overseas), so that public health authorities can put measures in place to prevent any spread into the community.

 

Follow this link to access the Doherty Institute's fortnightly genome sequencing and genomic clustering to SARS-CoV-2 in Victoria reports.

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