What is whole genome sequencing? A guide for families

If your child or a family member has been offered whole genome sequencing, you may have heard it described as "the biggest genetic test there is".

That is broadly true. But what does it actually involve, what can it show, and what can it not show?

This guide explains it in plain English.

Quick answer: whole genome sequencing (often shortened to WGS) reads almost all of a person's DNA in one test. In the NHS in England, it is offered to some people with suspected rare genetic conditions, usually through a genetics team, and often alongside samples from both parents. Results can take weeks or months. It can find a genetic diagnosis, find nothing, or find a change that is not yet understood.

First, what is a genome?

Your genome is the full set of instructions in your DNA. It includes around 20,000 genes, plus the stretches of DNA in between them.

A rare genetic condition can happen when there is a change in one of those instructions. If you are new to this, our guide to what a rare genetic disease is covers the basics.

How is whole genome sequencing different from other genetic tests?

There are several types of genetic test. They differ in how much DNA they look at.

• Single gene tests look at one gene, when the team already has a strong idea of the cause.

• Gene panels look at a group of genes linked to a particular condition or set of symptoms.

• Exome sequencing looks at the parts of genes that carry instructions for making proteins. This is a small part of the genome, but it is where many known disease-causing changes are found.

• Whole genome sequencing reads almost all of the DNA, including the parts between genes.

Even though the whole genome is read, the lab usually starts by analysing the genes most likely to be linked to the person's symptoms. This is sometimes called a "virtual panel". The data is usually kept, so it may be possible to look at it again in future.

Whole genome sequencing can also pick up some types of change that other tests can miss, such as larger rearrangements of DNA. It is not perfect, though. Some conditions are caused by changes it does not detect well, so other tests are still sometimes needed.

Who can have whole genome sequencing on the NHS?

In England, genetic testing is provided through the NHS Genomic Medicine Service. A national list, called the National Genomic Test Directory, sets out which tests are available and who is eligible for each one.

Whole genome sequencing is offered for a number of rare conditions and situations on that list. Your doctor or genetics team decides whether it is the right test, and you need to be referred.

Arrangements in Scotland, Wales and Northern Ireland are organised separately, so ask your team what applies where you live.

What does the test involve?

For the person being tested, it is usually a blood sample.

For children with a suspected rare condition, samples are often taken from both parents too. This is sometimes called trio testing. Comparing the child's DNA with both parents' DNA helps the lab work out which changes are new and which are inherited, and which ones are more likely to matter.

Before the test, a member of the team will talk you through consent. This usually includes:

• what the test is looking for

• the types of result that could come back

• whether results could affect other family members

• whether you would like your data to be used for research, which is optional

It is a good moment to ask questions. Our guide to preparing for a genetics appointment includes questions families often find useful.

How long do results take?

The NHS says results can take weeks or months.

Whole genome sequencing usually takes longer than smaller tests, because there is much more data to analyse. It is worth asking your team roughly how long to expect, and how you will get the results.

What can the results show?

Broadly, there are three kinds of result.

A genetic diagnosis

The test finds a change that explains the person's condition. This can help families understand what is happening and connect with others who have the same condition. Sometimes it can also change the care a team offers.

Nothing found

The test does not find a change that explains the condition. This does not always mean the condition is not genetic. It may be caused by a change that current tests cannot detect, or by a gene that has not yet been linked to a condition.

Because the data is kept, it may be possible for it to be looked at again in future as knowledge grows. It is worth asking whether and when that might happen.

An uncertain result

The test finds a change, but it is not yet known whether it causes a condition. This is often called a variant of uncertain significance. It can be frustrating, and it is worth asking your team what it means for your family now and whether it may be reviewed in future.

Occasionally, testing can reveal something unexpected, such as information about how family members are related. It is worth asking your team before the test what kinds of unexpected result could come back and how they would be shared.

How often does it find an answer?

It varies a lot.

These figures describe a large group of people. They cannot tell you what testing will show for any one person.

In a large NHS research project, the 100,000 Genomes Project, a pilot study published in 2021 found a genetic diagnosis for around 1 in 4 people with rare diseases. The rate was higher for some groups of conditions, including intellectual disability, hearing conditions and vision conditions, and lower for others.

Your genetics team is the best person to ask what testing might find in your family's situation.

Why is everyone talking about the cost?

Reading a whole human genome used to be enormously expensive. The Human Genome Project, which produced the first human genome, took 13 years and cost around $3 billion.

Costs have fallen sharply since then.

• A UK study published in 2019 costed whole genome sequencing for rare disease at about £7,050 per family of three (a child and both parents). The materials used in the sequencing step made up around 70% of that cost.

• In 2024, US company Ultima Genomics launched machines it said could sequence a genome for around $100 in materials.

That headline figure covers the sequencing step only. A test that families receive also involves preparing samples, storing and analysing huge amounts of data, and specialist scientists and clinicians interpreting the results. Those costs do not fall in the same way.

Even so, cheaper sequencing matters. Over time, it could make it more affordable to offer genome sequencing to more people, earlier, and to look at existing data again as knowledge grows.

Sequencing newborn babies

One example of where this could go is the Generation Study, run by Genomics England with the NHS. It aims to sequence the genomes of 100,000 newborn babies, to look for more than 200 rare genetic conditions that usually start in early childhood and where early treatment or care can make a difference.

It is a research study offered in some hospitals in England. Taking part is optional, and it is separate from the standard newborn blood spot test.

What to remember

• Whole genome sequencing reads almost all of a person's DNA in one test.

• On the NHS, you need to be referred, and eligibility is set nationally.

• For children, both parents are often tested too.

• Results can take weeks or months.

• A result can be a diagnosis, nothing found, or uncertain. "Nothing found" does not always mean the condition is not genetic.

• The data is usually kept, so it may be possible to look at it again in future.

How Rarevia can help

Waiting for genetic results can take months, and life does not pause in the meantime.

Rarevia is being built so families can say or write what is happening, in their own words, and keep it organised in one place. Whenever you need it, before an appointment or at any other time, a summary of how things are, recent updates and your questions are ready to share.

If you would like a lighter way to keep the story together while you wait, join the waitlist and help shape Rarevia as it is built.

Sources and further reading

This article draws on guidance from NHS England, the NHS and NHS England's Genomics Education Programme, published research from the 100,000 Genomes Project, a UK study on the costs of genome sequencing, and reporting on sequencing costs. It is general information, not medical advice. Your care team can tell you what applies to you.

• NHS England: NHS Genomic Medicine Service

• NHS England: National genomic test directories

• NHS: Genetic and genomic testing

• NHS England Genomics Education Programme: Whole genome sequencing

• 100,000 Genomes Project Pilot Investigators: 100,000 Genomes pilot on rare-disease diagnosis in health care, New England Journal of Medicine, 2021

• Schwarze and colleagues: The complete costs of genome sequencing, Genetics in Medicine, 2019

• STAT News: Ultima Genomics launching DNA sequencers that can read a genome for $100, January 2024

• Genomics England: The Generation Study