Whole Genome Sequencing

The purpose of genetic testing is to determine whether there is a gene responsible for your symptoms, or to provide a diagnosis to an unknown condition. This can have benefits such as increased treatment options, reproductive options and the offer of cascade testing to family members at risk.

A genetic diagnosis can also confirm a diagnosis from clinical examination and help a clinician predict disease progression.

In some cases, particularly in cancer diagnoses, a genetic diagnosis can make patients eligible for trials or research studies into medication that is not yet available routinely. The benefit is very specific to the condition you have and what is found within your results and your clinical team are available to give you advice on this.

The purpose of genetic testing is to locate a genetic cause for you/your child’s condition, this often leads to a genetic diagnosis and may have an impact on how the condition is treated and managed. If you as a parent, have also had Whole Genome Sequencing with your child, then we hope to find some information on if the gene has been inherited and to determine if there are other family members at risk, who may also benefit from testing. All genetic changes start somewhere, and in some cases are not inherited from parents. Any further queries about inheritance can be discussed with your clinical team when the results are returned to you.

There is a small chance. This testing is the most extensive genetic testing currently available. We are sequencing 3.2 billion letters of your DNA code, and then analysing certain regions. The regions that the scientists analyse are determined by the clinical information provided by your clinician. In some rare cases genes outside of these regions can be accidentally analysed due to the various algorithms that are used to help interpret the data. These are very rare situations but it is possible that while we are testing you, we may pick up something additional and unrelated to your condition. If these are found then it will be fed back to you either by your clinical team or the genetics department, and they will be able to advise you on what exactly this means.

No, your DNA will not be given to or accessible by the police. This will not be used against you in criminal situations.

We inherit 50% of our DNA from our biological mother, and 50% of our DNA from our biological father. Our children inherit 50% of our DNA. There are also different ways in which specific genetic conditions can be inherited, which may increase or decrease your child’s possibility of inheriting the causative genetic variant.

We therefore strongly encourage anyone having genetic testing to discuss this with their family members, as any results can potentially be relevant to them. This can be further discussed with your referring clinician or clinical genetics team.

No you do not have to share your results with family members. However, we would encourage you and can help you to contact any family members in a way that does not personally identify you. The genetics department has a lot of experience in facilitating sharing of results within complex family relationships.

This testing only looks into your DNA that is extracted from a blood sample, and the analysis is focused on the regions of your genome that relate to the reason you have been referred. We do not look at any other clinical levels in your blood such as proteins or hormones, therefore, if there is something unusual in your blood count, this would not be identified through genetic testing. If you have any clinical concerns or symptoms these need to be discussed with your clinical team or GP. For matters such as brain tumours etc, these are detected by imaging and other tests that will not be visible from a genetic test.

The 100,000 Genomes Project was a research project managed by the UK Government that aimed to sequence 100,000 genomes from NHS patients and this data was shared with researchers to improve knowledge of the cause, treatment and care of diseases. Whole Genome Sequencing is a diagnostic NHS test that uses the same method of testing, and is offered to patients for a range of different clinical indications. There have been some advances in the machines, technology and genetic knowledge since the 100,000 Genomes Project was launched in 2012.

If you have previously had a negative 100,000 Genomes Project result, in some cases your clinician may refer you for Whole Genome Sequencing due to the advances in scientific understanding, or due to changes in your clinical features or diseases progression. For more information on the 100,000 genomes project please visit https://www.genomicsengland.co.uk/initiatives/100000-genomes-project

In theory, yes this would be possible. However, our genome is very large (3.2 billion nucleotide pairs of code), so we focus our analysis on smaller sections of your genome that are related to your clinical symptoms.

Other reasons that we do not look at your whole genome are due to the ethics that surround genetic testing. More information can be found here: http://www.rcplondon.ac.uk/projects/outputs/consent-and-confidentiality-genomic-medicine

Saliva is a permissible sample type, however, saliva often does not yield a DNA concentration that is sufficient for Whole Genome Sequencing. We can try with saliva but it is important to understand that if it does not pass quality controls tests (ie DNA concentration) then you would need to provide a blood sample. If the patient is having other blood tests or surgery etc the sample could be taken at that time.

Due to the complexity of Whole Genome Sequencing (WGS), different parts of the test need to be performed by different specialist laboratories. The entire process must be done robustly to guarantee the highest accuracy of results.

After your blood sample was taken, it was sent to the Genomic Laboratory at Guy’s Hospital in London for DNA to be extracted. It was then forwarded securely to a laboratory in Birmingham where the DNA was prepared for sequencing. Following this, the sample was sent to Illumina in Cambridge where your DNA was sequenced. This process enables the unique order of your DNA to be determined and can take approximately 6 – 10 weeks to be completed.

The DNA sequence is then returned to the South East Genomic Laboratory Hub for analysis. This procedure involves ‘filtering’ the genetic changes (variants) identified in your DNA against a very large repository of genes, some of which have been associated with your symptoms or clinical circumstances. A clinical scientist examines each of the variants in detail to determine the likelihood that one or more variants may be genetically responsible for your symptoms. For each person who has been tested, there might be anywhere between a handful to 20 – 30 gene variants to evaluate. This work is then checked by a different scientist to ensure that nothing has been missed. If one or more variants of interest have been identified, the findings will be discussed with the Genomics team and a clinical geneticist might also be consulted. Subsequently a test report is prepared, checked and sent to the referring clinician (your specialist doctor).

The first check usually takes 2 – 4 weeks to be completed while the second may take another 1 – 2 weeks. Team discussion of the results and the reporting process may each take another week. Within the overall process, the majority of the waiting time occurs between the time we receive the ‘raw’ data from Cambridge and the case being prepared for the first check. We receive a very large number of DNA samples for analysis which at present exceeds our capacity to turn around results in a short time.