For many families, genetic testing may be the first step toward answering confusing health questions, especially in situations where there hasn’t been a diagnosis. Learning more about genetics can help to identify the root causes of a disease, including some rare conditions.
Although it may sometimes feel overwhelming, identifying a genetic cause of a rare disease, or a potential carrier status, can help families find the right medical care to support their journey after diagnosis.
The content in this section may not be applicable in all countries. Genetic testing regulations vary and in some instances may only be carried out at the request of the court, or by a doctor for medical or scientific research purposes.
Every single cell in the human body contains your individual blueprint to life, known as DNA. DNA is the instruction book that tells each cell how to behave, when to switch on/off and which proteins to produce.1
Typically, humans have 46 chromosomes – the structures that make up DNA – with one set of 23 coming from the father and the other set from the mother. Every female has two X chromosomes, while a male has an X and a Y chromosome.1
Each chromosome is made up of genes, the basic building blocks that determine our genotype (the genes you carry) and phenotype (how those genes express themselves, e.g. as eye / hair color or susceptibility to health conditions).2
In this way, our genes and the proteins they encode impact all physical characteristics and functions of the body. However, sometimes a variation or an error in the genes can prevent proteins from working properly or even being created in the first place. When this protein is related to a critical body function(s), it can disrupt normal development and be identified as a genetic disorder.3 It’s important to remember that not all diseases have a genetic cause or an identified related gene.
Genetic testing is used to detect changes in either the chromosomes, genes or proteins. The results of these tests can usually help confirm whether an individual may have, or is a carrier of, a genetic disorder.1 Click here for more information on being a rare disease carrier.1
There are several reasons for having a genetic test:4
There are a number of genetic tests available and the type of test can impact the results. The test a physician suggests will depend on the individual’s symptoms – if present – and which tests the individual has previously undergone, if applicable. For rare diseases, the most commonly used tests are highlighted below. Genetic testing is rapidly changing. Be sure to connect with your doctor for the most up-to-date information.1
|Genetic test||What’s it used for?||How long does it take?||Limitations|
|FISH||To identify small deletions or duplications||Rapid: 24–48 hours
Deletion syndromes: 7–10 days
|Limited to the specific disease/chromosome being studied|
|Karyotype||To identify chromosomal abnormalities or large deletions||1–2 weeks||Cannot identify small deletions|
|Chromosomal microarray||To identify causes of developmental delay / abnormal ultrasound findings||1 week||5% risk of uncertain results|
|Targeted mutation analysis||To identify known mutation(s) in the family or in certain ethnic groups||10–14 days||Limited to the specific mutations being tested|
|Single gene sequencing||To examine a single gene in detail when a specific syndrome is suspected||2–6 weeks||Many labs routinely offer additional deletion/duplication studies that may detect larger changes not detected on sequencing. Does not detect deletions or duplications unless specified by the specific testing lab|
|Multiple gene sequencing||To examine multiple genes in detail where several can cause similar symptoms||4–12 weeks||Many labs routinely offer additional deletion/duplication studies that may detect larger changes not detected on sequencing. Does not detect deletions or duplications unless specified by the specific testing lab|
|Whole exome sequencing||To sequence all coding regions within an individual’s genome when other tests have proved inconclusive||6 months – 1 year||Large amounts of data produced, not all of which are relevant|
|Whole genome sequencing||To sequence an individual’s entire genome when other tests have proved inconclusive||Variable||Research use only; not available clinically. Large amounts of data produced, not all of which are relevant|
Abridged and adapted from: Global Genes (2014) Genetic testing: Is this my path to diagnosis?
Genetic testing is complicated and there are a number of factors to consider during the decision-making process. While results from a test may make the future more certain and help inform health care decisions, there are also financial, social and emotional issues that come into play, e.g. understanding what a genetic test will tell you and exploring how you will feel when you get the results.1,4
Knowing how to access support before, during and after undergoing genetic testing will be important on this part of the journey. Click here for more information on how to talk about family genetic testing and the role of a genetic counselor.
Genetic testing can give you information about the presence of a particular genetic mutation and if it is associated with a known genetic disorder. However, there are still many unknowns, like when or if disease symptoms may develop or the level of severity. Your genetic counselor should be able to explain your results in more detail. There are still a lot of unknown variants that may be associated with a disease, but not yet identified with a specific test. This may lead to an inconclusive result and put you down a path for additional tests and discussions with your genetic counselor and/or health care provider.5
Global Genes introductory toolkit to genetics and genetic testing
Advances in genetic testing are rapidly changing the way patients are being diagnosed and treated and providing new hope to patients with rare, genetic disorders. This toolkit is designed to provide rare disease patients and their families an introduction to genetics and genetic testing. Here, the most frequently used tests are explained in more detail, alongside the likely financial costs and limitations.
Thank you to the following organizations that provided strategic guidance on our genetic testing topics: Global Genes, Permanente Medical Group – Genetic Movement Disorder Clinic, Our Odyssey, One Rare and Remember the Girls.