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Genetics: Genetic testing

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Having a genetic test is a very personal decision and the decision to proceed with testing will depend on a variety of factors and life experiences.

Key points

  • Genetic testing is just one part of the genetic counselling process.
  • Not everyone who attends genetic services can be offered a test.
  • Due to their technical complexity, some tests can take many months to complete and will not always identify the underlying genetic cause of an illness.
  • The decision to undergo testing rests with the individual.
  • The decision should be made on the basis of informed consent.
  • The nurses role is to ensure the individual has access to and understands the information related to testing and is supported during and after the decision making process.
  • Special considerations apply in relation to testing of children.

A typical question that you might hear:
Should I have a genetic test, should I have a baby?

Should I have a genetics test….?
Sometimes new information or a diagnosis will motivate an individual to seek further genetic information and testing. Others may postpone seeking information about themselves or their family history until their personal circumstances change (e.g. prior to getting married or when planning a family). Occasionally, an individual is too frightened to seek out information because they may have witnessed the affect of a diagnosis on the life of a family member, or are still coming to terms with their own diagnosis.

Simply asking for a test and taking a blood sample for testing is not a procedure that should be hurried or entered into lightly. A new diagnosis in a family can lead to demands for testing to take place quickly and immediately and deciding to have a test at times of great anxiety and distress can lead to regret in the future. Conversely, there can be pressure from within a family not to have a test.

Genetic counselling explores the complex emotions that motivate an individual to seek information and testing. Information is provided by the genetics team in a balanced non-directive manner so that the individual is supported to make a decision that is right for them. (See Genetic Counselling - what it does and doesn’t do)

Individuals consider genetic testing for:

  • Themselves - To remove uncertainty about their health
  • To give them life and health-related choices (including choices in pregnancy)
  • Others - To provide information that can be used by the wider family

Previous experiences, knowledge and understanding
Having direct experience of a condition can alter the perceptions of an individual or family in many ways in terms of how they deal with disability, testing and reproductive decisions. If the condition is felt not to have had a negative impact upon the life of an individual then having a test may not be as important as it is for those with no prior experience. However, even within the same family decision making can vary from person to person and conflict can arise if one member of the family is seen to take a different course of action.

The effect (signs and symptoms) of a condition may vary within a family (see Family history and risk assessment: My grandfather has some signs of ‘X’ [condition], but my father didn’t. How has it skipped a generation?) Just because one member is “mildly affected” does not mean that everyone in the family will also be affected in the same way. It is important that an individual has a complete understanding of the condition in order to make an informed decision.

Screening is a process of identifying apparently healthy people who may be at increased risk of a disease or condition. Once identified, individuals are offered information, further tests and appropriate treatment to reduce their risk and/or any complications arising from the disease or condition.

There are a number of screening tests offered to women during the antenatal period and to new parents for their newborn baby. A summary of the current and pending antenatal and newborn screening tests available in the UK are available here.

Should I have a baby….?
Couples seeking information pre-conceptually can explore what options will be available to them in pregnancy. An increased risk of having a baby with a genetic condition may deter couples from getting pregnant or encourage them to investigate alternatives (e.g. pre-implantation genetic diagnosis, egg/sperm donation or adoption).

Genetic testing is not available to all families (see Genetic testing: Why can’t I have a test?) and testing in pregnancy requires careful planning. An early referral to the genetics service is essential and, supporting couples at times of uncertainty can require the involvement and coordination of a multidisciplinary team appropriate to the diagnosis (e.g. genetics, obstetrics, fetal medicine, cardiology). Invasive testing during pregnancy (amniocentesis and chorionic villus sampling CVS) can carry a risk of miscarriage that may be unacceptable for some and the decision to terminate an affected pregnancy raises personal, moral and ethical issues. However, testing can also provide couples with information that allows them to make decisions on how they want a pregnancy to be managed or to prepare for having an affected child.

Having choices and options can be very difficult. For some individuals testing in pregnancy or choosing to terminate a pregnancy can cause enormous feelings of guilt and may be perceived as making a judgement about the quality of life of another affected family member. Families can stop communicating and it isn’t uncommon for pregnant women not to reveal that a pregnancy is ongoing until after testing has been completed as they do not wish to disclose that they are considering a termination.

Practice Point
Anyone considering a test should be given the opportunity to discuss this further with a GP, midwife or member of a regional genetics team.

A typical question that you might hear:
Why can’t I have a (genetic) test?

Genetic testing occurs in regional genetic laboratories. Some genetic tests will only be undertaken if the individual being tested has been seen by either a geneticist or genetic counsellor. This ensures that testing is appropriate and the individual is making a fully informed decision aware of the implications for themselves and their family.

For many conditions the primary diagnosis will be a clinical one. Molecular confirmation (genetic testing) is not always necessary or possible. Often individuals seeking genetic testing are surprised to learn that there is no test available for them. There are a variety of reasons for this.

Unknown genetic basis
It would be easy to assume that with the ‘completion’ of the Human Genome Project (HGP) came the information that would allow us to say ‘we know all of the genes that cause disease’. This may be literally true - the HGP has provided the sequence of code that makes up the human genome and from this, scientists have been able to identify the majority of genes present. However, the function of a large proportion of the 22,000+ genes remains unknown and there are still a large number of inherited (‘single gene’) conditions where the gene(s) involved have not yet been determined. The OMIM (Online Mendelian Inheritance in Man) database currently lists around 1700 “Mendelian phenotypes / regions of the genome where the molecular basis is currently unknown” (OMIM).

Practice Point - Testing in the future
It is important to remember that although genetic testing for a condition may not currently be available, this may change. Genetic science continues to move our understanding forward identifying new genes, linking alterations in the genome to specific conditions and in the development of new technologies to improve testing methods. The genetic service will often keep samples (with permission from the individual/family) in anticipation of these developments. DNA, once extracted from blood or other tissue, is very stable when stored correctly. It is not unusual for families to get answers many years after initial referral. Making a diagnosis, even many years later, can help the family to come to terms with the condition, explain it to others, and make more informed medical and reproductive decisions.

Known genetics basis but…
Testing is unavailable
Even when changes to a specific gene have been associated with an inherited condition a test may not be available. Sometimes, the clinical diagnosis may well be sufficient and confirmation through a molecular test may not be necessary or would not provide any further information that would alter the care or decision making of the individual. Many metabolic conditions are only diagnosed with a biochemical test.

Genetic testing in the UK is available though the NHS for a specific set of conditions where the utility and validity of the testing has been reviewed and approved. Not all genetic tests are available through the NHS accredited laboratories. For some conditions that are not included on the UK ‘list’, a patient sample may be sent for testing to a specialist research laboratory in the UK or oversees. This is more common for rare diseases.

  • Clinical Utility: How likely the test is to significantly improve patient outcomes
  • Clinical validity: The accuracy with which a test can predict the presence or absence of the phenotype or clinical disease.

Affected family member needs to be tested first
For some conditions it is important that the person who is being tested for the condition has been affected by it. For example, if a person presents with a strong family history of breast cancer, you may want to think about testing for a high-risk predisposition gene, e.g. BRCA1. Wherever possible, the individual that should be tested first should be a family member that has been affected with breast cancer. [Post-mortem samples can be used]. If an unaffected, family member is tested first, interpretation can be difficult. If no mutation is found in the BRCA gene it would not be clear whether this is because:

  1. there is no mutation to be found because this particular gene is not associated with the cancer in this family
  2. the individual does not carry the gene change present in other family members and is therefore not at risk of this inherited form of breast cancer
  3. due to limitations in the test, the method used is unable to detect the gene change present in the family

Limited information
Sometimes only limited family history information is available (e.g. hearsay information regarding the diagnosis of another family member). If this cannot be confirmed/verified then testing may not be appropriate.

Where a condition has a number of subtypes there may be many genes that could be tested. Additional information may be required in order to narrow down that list before testing can begin. For example there are more than 20 genes associated with a group of progressive peripheral neuropathies collectively referred to as Charcot-Marie-Tooth disease and more than 10 associated with Long QT syndrome (an inherited arrhythmia). Disease characteristics and inheritance pattern (if family history information is available) can help to identifying the possible subtype involved.

Genetic testing during pregnancy is time limited. The offer of prenatal testing for many conditions requires that the gene change(s) in the family is already known. Testing can then be targeted at the specific changes, enabling a quicker turn around time.

Common conditions
Most conditions (e.g. asthma and type II diabetes) are caused by a combination of genetic and environmental factors. Researchers are still learning about the multiple gene variants and environmental factors that are involved in each condition; the combinations that can increase an individual’s susceptibility to a disease and the extent of the contribution that each gene makes to the outcome. Whilst it is possible to test for some of the currently known variants of some common conditions (and testing is available through commercial companies) insufficient is known for testing to be offered within the NHS as the clinical validity of the tests are currently often low.

A typical question that you might hear:
It’s only a blood test, why does it take so long?

As part of the counselling and decision making process the anticipated time frame for receiving a test result will be discussed. It can take months or even years for a genetic test result to become available. For patients, families and some health care staff this length of time may seem excessive especially when the test often only requires a small blood/tissue sample to be provided and fictional characters on TV shows always seem to receive DNA test results within the day!!

It is important that individuals and families understand their own situation and the impact that waiting for a test result might have.

Standards and reporting times for UK accredited (NHS) diagnostic laboratories are nationally defined.
The time frame will depend on whether the test is to:
- confirm a diagnosis and identify a new change(s)
- confirm a mutation already known to be present within the family

A combination of NHS and research laboratories may be involved in processing and testing the sample and some maybe located outside of the UK.

The testing process has many stages
Once a sample is received by the laboratory, it is processed depending on the type(s) of test requested. Where a microscopic review of the number and structure of an individual’s chromosomes is required, cells from the sample will be cultured over a number of days to provide sufficient genetic material. For a detailed (molecular) analysis of the DNA code of a specific gene the genetic material will be extracted from the sample (e.g. blood).

For some conditions the underlying genetic change is well understood and may only require a single /small number of tests to confirm the diagnosis. For example, Down syndrome is due to three copies (trisomy) of chromosome 21. Testing strategies reflect this and look for the presence of an entire or partial additional chromosome 21. Fragile X syndrome (the most common genetic cause of learning difficulties in boys) is usually caused by a specific type of alteration in a gene (FMR1) on the X chromosome. Therefore testing for fragile X syndrome concentrates on this gene mutation.

The majority of conditions are due to very small, discrete changes to the DNA code of a gene. Often a variety of techniques are used in an attempt to pinpoint the change(s) and confirm that each is disease causing. Due to the limitations of current testing methods, the laboratories generally focus on regions of each gene that from experience are more likely to contain identifiable disease causing mutations (see Genetic testing: Understanding a negative test).

Where a sub-set of mutations are found more frequently, the information can be used to target initial mutation screening methods. For example there are well over 1000 different mutations identified within the CFTR gene that can cause cystic fibrosis (CF). However, within the Caucasian population there are around 30 ‘common’ mutations that are found in the majority of individuals with CF. When a person affected with cystic fibrosis has a genetic test their DNA is screened for the most common mutations in the first instant. If this does not identify two genetic mutations (cystic fibrosis is an autosomal recessive condition requiring alterations in both copies of the gene), the DNA would then be analysed for rarer changes. The sample would usually be sent to a national specialist genetic laboratory for this further stage of testing.

Results for some tests, particularly prenatal, are staged. Only when each stage is complete can the next stage be started. For example, when testing for the X-linked condition Duchenne muscular dystrophy, the first test performed is fetal sexing. Molecular testing is then performed only on male (XY) samples and not on female (XX) samples.

Some conditions can result from a change in one of many genes. Even when clinical information can be used to narrow down the list of potential genes involved, it may be that many/all of the ‘candidates’ have to be tested before a change is identified. This can be very time consuming.

At any point in the testing process there may be issues that prolong testing.

  • Technical problems with the equipment or sample (e.g. insufficient material obtained from the sample to complete the test)
  • Unexplained findings may result in further tests

Interpretation of test results
Once any changes to the genetic code are identified, they are reviewed thoroughly before the findings are reported back to the clinician and patient. Careful interpretation is required including a review of the relevant medical literature for previously reported gene changes. This helps the laboratory staff to determine whether a genetic mutation is likely to cause the condition present.

Sometimes changes to the genetic code of a gene can have unknown clinical significance (i.e. it is unclear whether the change is sufficient to cause disease). In these instances the presence of the change in multiple affected family members and an absence in unaffected relatives can provide weight to the change being causative. However, this may not be so clear cut when the condition involved is one that is not completely penetrant (i.e. clinical symptoms are not always present in individuals who have a disease-causing change). See Family history and risk assessment: My grandfather has some signs of X’ [condition], but my father didn’t. How has it skipped a generation?

Additional tests may be performed by the laboratory staff to try and determine the effect of the gene change on the cells and tissues.

Testing does not always identify a disease causing mutation. For some individuals / families the testing process might take many years as they wait for new information about the genetic basis of their condition.

Understanding the meaning of a ‘positive or negative’ test

In addition to managing expectations prior to testing, healthcare professionals involved in the process also need to ensure that the individual understands the test result. Misinterpretation can have knock-on consequences for the individual and potentially other family members.

A typical question that you might hear:
I’ve been told it’s a positive result for my genetic test. That sounds OK, doesn’t it?

Clear communication is a skill. Often a positive result is interpreted as a cause to be optimistic and conversely a negative result suggests a less optimistic, more pessimistic outcome. Our choice of words and the way we explain their meaning is key to ensuring that we are accurately understood.

With genetic testing, a positive result is one where the disease causing gene change has been identified (confirming the diagnosis, risk or carrier status of an individual). A negative result means that a disease causing gene change has not been found. It is important that the reasons for a negative result and the implications of this information are understood.

A typical comment that you might hear:
I don’t have [condition] because I’ve had a (genetic) test and it was negative - they couldn’t find anything.

Known gene change (mutation) in the family
Where the specific gene change (or both changes in an autosomal recessive condition), have already been identified in a family, testing of other family members will target the known change(s). If the individual in question has undergone a pre-symptomatic genetic test and the known changes are not present, the negative test result would indicate that the person is not at risk of developing the condition. (NB see also I’ve had a negative (genetic) test, so I’m no longer at risk of getting [condition]? below)

Importantly, robust counselling by the genetic team would have covered the possibility of residual risk i.e. the likelihood that the individual does have the condition due to i) a false-negative result (because of limitations in the testing methodology), ii) the presence of a new de novo mutation that would not have been picked up under the testing conditions used iii) non-paternity (if relevant to the inheritance pattern of the condition).

Uncertain diagnosis
In cases where the diagnosis is doubtful (e.g. the individual has only some symptoms suggestive of a condition or syndrome), then a negative result may contribute additional evidence against the diagnosis.

Limitations of knowledge and/or testing methods
However, when the clinical evidence is strong not finding a change does not rule out the diagnosis. This is particular important concept for the patient/family to understand. This is particularly true for example, with conditions or syndromes where the clinical features can be highly variable and the clinical diagnosis is not easy to make.

There are still a large number of inherited (‘single gene’) conditions where the gene(s) involved have not yet been determined and so our ability to test is currently limited to those that we know about. Often a genetic condition can result from a change in one of a number of genes (all involved in the same or associated biological process). Even when all/many of the genes involved in a particular condition have been identified, it may be that genetic testing is only available for a subset (e.g. the most commonly involved genes).

Genes vary in size from a few hundred nucleotide bases (‘letters of the genetic code’) to more than one million. The DMD gene associated with the Duchenne and Becker types of muscular dystrophy is around 2.4 million nucleotide bases long. There are many types of change that can disrupt the sequence of a gene and cause disease (see the first article in this series Genetics to genomics: from peas to personalised healthcare for more information). It can be as simple as a single letter change in the genetic code…the problem is finding that change! Testing methods currently focus on the segments of a gene sequence that provide most of the information for the gene’s product - the exons (see figure below). From experience, exons tend to contain the majority of disease causing changes. Science is still trying to understand the significance of sequences between exons which are referred to as introns. Generally these regions are not included in genetic tests as they can be very large and it is often not possible to say what the consequence of a code change would be (i.e. whether it is disease causing).

So for the individual in this question, two reasons why they may have tested negative are that their disease causing mutation is:

  • located on a different (untested) gene, or
  • located in a region of the gene that wasn’t included in the testing method.

A typical comment that you might hear:
I’ve had a negative (genetic) test, so I’m no longer at risk of getting [condition]?

Genetic tests are available for some familial (inherited) forms of common conditions. Examples include breast cancer, bowel cancer and familial hypercholesterolaemia. For some conditions (e.g. inherited breast cancer) the presence of a gene change does not always lead to cancer - incomplete penetrance (see Family history and risk assessment: My grandfather has some signs of X’ [condition], but my father didn’t. How has it skipped a generation? for a definition). Instead, the gene change increases the likelihood (‘risk’) of developing the condition.

Where a test for a known gene change (present in other members of the family) is found to be negative the individual will no longer be at risk of this form of the condition. However, this does not mean that they will never develop the condition. They have reduced their ‘family risk’, but will continue to be being at population risk for the common type of disease. This is a particularly important concept for the individual to understand particularly when there are screening programmes available for the general population that they should access.

Case Scenario:
I’ve had a negative (genetic) test, so I’m no longer at risk of getting breast cancer

Sandra Brown, aged 29 has a significant family history of breast and ovarian cancer. Her mother Sheila developed breast cancer at 40, and her maternal aunt (Fiona Russell) at 43. Her maternal grandmother (Yvonne Barker) was diagnosed with advanced breast cancer at 38 and died 4 months post diagnosis. Her maternal great aunt (Gladys Michael) was diagnosed with ovarian cancer at 42 and died within 3 months of diagnosis. In addition, her great maternal grandmother (Phoebe Johnson) developed breast cancer at 39 and died at the age of 40.

Previously, because Fiona’s was relatively young when diagnosed with breast cancer, her oncologist inquired about her family history. He identified a significant (high risk) history and referred her to the clinical genetics service. The cancers in the other family members were verified and she was counselled for the possibility of being a BRCA 1 (breast cancer 1) or BRCA 2 (breast cancer 2) gene change carrier. Fiona underwent genetic testing for BRCA 1 & 2, and a change was identified in her BRCA 1 gene, confirming the suspicion that her breast cancer was inherited. Due to her own history, Sandra’s mother Sheila suspected she might also carry this gene change and requested referral to genetics for testing as she was concerned about the risk to her two daughters. Following counselling, she was found to carry the BRCA 1 gene change.

Sandra then requested referral to her local clinical genetics service for a predictive test for the gene change found in her mother and aunt, and was counselled for this. She subsequently tested negative, and assumed that she was no longer at risk of breast cancer as she did not carry the familial gene change, and that she would therefore not require breast screening in future. However, when discussing her breast cancer risk and screening needs, she was informed that her risk had significantly reduced, but she was now at the population risk of approximately 10%. As a result, she would still need to attend for screening 3 yearly on the NHS National Breast Screening Programme when she turned 50.


These questions were written by staff at the NHS Genetics Education and Development Centre

Key Points:
BRCA genes are inherited with an autosomal dominant pattern of inheritance (see Family history and risk assessment: Understanding the likelihood of a condition occurring more than once in a family). Sandra had a 50% (1 in 2) risk of having inherited her mother’s gene change.

A negative BRCA 1 or BRCA 2 gene test result in women does not imply a 0% lifetime risk of breast cancer, but rather a population risk (~10%).
It is important for women who test negative for familial BRCA gene changes to attend for breast screening when reaching 50 years of age.


The NHS National Genetics Education and Development Centre provides support for health professionals to learn more about genetics and its relevance to professional practice. A series of fact sheets ‘Understanding Modes of Inheritance’ will be available shortly.

NHS Evidence - a source of information on genetic conditions for staff working in non-genetic disciplines

The UK Genetic Testing Network (UKGTN) advises on genetic testing across the whole of the UK. A list of genetic tests (and the laboratories that offer testing) is available form their website

Information on prenatal and newborn screening programmes in the UK is available from the NHS National Screening Committee’s UK Screening Portal

Genetic Testing of Children- A report from the Clinical Genetics Society.

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