A genomic sequencing test aims to identify changes (variants) in any of the large number of genes in your genome that may affect your health.
Genomic sequencing tests - whole exome sequencing
Patients involved in the Melbourne Genomics clinical projects have had different types of genomic sequencing tests performed, depending on their condition.
Most patients have had a test called whole exome sequencing.
We each have about 23,000 genes in our entire genome. Your exome is only about one per cent of your genome – but this is the part most important for health. A whole exome sequencing test aims to identify changes (variants) in your exome that may help diagnose or treat your medical condition.
Some of Melbourne Genomics' clinical projects performed gene panel tests. These involve looking for changes in a specific list of genes. An example is a comprehensive cancer panel which may include 300 to 400 different genes.
There are other types of genomic tests, such as whole genome sequencing, where the whole genetic code (not just the exons) is sequenced.
You can download our infographic, which explains more about genomic tests.
How are genomic tests performed?
How are samples for the test collected?
A DNA sample is required for a genomic sequencing test. DNA can be obtained from a number of body tissues, but the most common way is from a blood sample. The sample is sent to a pathology laboratory where the DNA can be ‘extracted’ or taken from the sample.
What is genomic sequencing?
Genomic sequencing is a process where DNA is examined and the DNA code is ‘written out’ into a letter code and saved in a computer file as genomic data. The sequencing is done by laboratories that specialise in genomic sequencing (for instance, Alliance members Victorian Clinical Genetic Services (VCGS) the Australian Genome Research Facility and Peter MacCallum Cancer Centre Molecular Pathology laboratory.)
How are gene changes or variants identified?
Computer programs are used to analyse genomic data. The computer scans this data for differences (variants) between the sequence of the person being tested and a reference sequence.
This list of variants is filtered further using computing methods, then examined to see if any identified variant might have an impact on health or might explain a person's medical condition.
The first step is to establish whether a variant or change in a gene will stop it working properly. To do this, a scientist considers each variant using large databases or scientific papers.
Then a team of experts, including medical laboratory scientists, bioinformaticians (computer specialists who deal with biological data), doctors and geneticists, match the list of variants which may impair gene function against a person’s health and family medical history. This is how they determine if a particular variant is likely to be the underlying cause of a genetic disease. Or, in other cases, whether a variant might affect how a person might respond to particular treatments.
For more on genomic testing, see our Community resources section.
What are additional findings?
‘Additional’ or ‘secondary’ findings are changes in genes unrelated to the patient’s current health condition but have medical value for future care.
We use the term additional findings to describe the intentional search of patient’s genome for specific gene changes associated with medically actionable, serious conditions. Studies have also shown that patients prefer the term ‘additional findings’.
Gene changes that experts can look for include, for instance:
- Inherited cancer genes, such as the BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer
- Inherited cardiac genes known to cause conditions like dilated cardiomyopathy or increased cholesterol, among other conditions
Whether to search the genome for such findings and how to provide them to patients are topics of debate among experts. There are both ethical and resource implications to consider.
A number of studies internationally are investigating the impact that additional findings can have on patients’ health outcomes. But the way in which additional findings are offered (the ‘model of care’) also requires careful consideration, as this will impact uptake, costs and possibly also outcomes.
The United States is currently the only country where testing for additional findings is embedded in usual clinical care. Searching for additional findings for a set list of serious, treatable conditions is recommended by the American College of Medical Genetics. The college recommends that this testing is done at the same time as genomic sequencing for a patient’s current health condition. European and Canadian guidelines do not actively promote the search for additional findings, but nor do they preclude it.
As part of our 2016 to 2020 phase of work, Melbourne Genomics undertook a proof-of-concept study to better understand the implications of offering additional findings to patients in Victoria. In our proof-of-concept, we evaluated a model of care in which adults were offered re-analysis of their genome for additional findings after diagnostic genomic testing was complete – a separate instance of genetic counselling, consent and results.
The study aimed to inform how additional findings may be provided in Victoria and to identify what is needed to achieve a feasible, effective additional findings service.