Genetics and stem cells

Gene test 'predicts 448 child diseases'

Scientists have created “a genetic test that allows couples to be checked for incurable inherited diseases before they think about starting a family”, the Daily Mail has reported.

The research behind this story is a genetics study that has combined relevant scientific methods to allow potential parents’ DNA to be screened for 448 serious genetic conditions. The results point to a feasible screening test that could indicate the risk that a couple’s offspring will inherit a serious genetic disease. However, this was established in a research setting and there is further work to be done. For example, the list of diseases assessed needs refining, the testing process needs automating and appropriate reporting and counselling methods still have to be developed. Most importantly, the test itself requires testing in a real-world setting.

Furthermore, there are a number of ethical, legal and social implications that would need to be carefully and sensitively considered before this type of multi-purpose genetic screening can be implemented. Crucially, any system in which the test is offered would need to provide supportive counselling for couples alongside the test, enabling them to make sense of the results and make informed decisions based on them.

Where did the story come from?

The study was carried out by researchers from the National Centre for Genome Resources in Santa Fe, Children’s Mercy Hospital in Kansas City, the Illumina Inc genetic testing company and Life Technologies, a biotechnology company. The study was published in the peer-reviewed medical journal Science Translational Medicine, and received funding from the Beyond Batten Disease Foundation, the US National Institutes of Health, Illumina Inc., Life Technologies and British Airways PLC.

Newspapers have covered this complex research well and have highlighted the important ethical implications of it, which will need further discussion and consideration before such testing becomes widely accepted.

What kind of research was this?

The researchers say that although single gene disorders are individually rare, collectively they account for about 20% of infant mortality and about 10% of hospitalisations in children. The researchers report that there have been reductions in the incidences of some diseases such as cystic fibrosis and Tay-Sachs disease since preconception screening and genetic counselling has been offered to couples in the US.

The researchers in this study developed a method to screen couples for a range of genes that might cause severe recessive childhood disorders in their children if they were to conceive. Recessive genetic disorders occur when a person carries two faulty copies of a particular gene – one inherited from each parent. If a person possesses only one faulty copy of a gene they will not be affected by a recessive condition, but will be a “carrier”. If two carriers of a particular faulty gene have a child there will be:

  • a one-in-four chance that their child will inherit two copies of the recessive gene and therefore have the related condition
  • a one-in-two chance that their child will only inherit a single faulty gene and therefore be unaffected, but a carrier
  • a one-in-four chance that their child will not inherit any copies of the faulty gene, and therefore will not be affected or a carrier

The researchers report that 1,138 of the genes that cause recessive diseases have been identified, but that preconception testing in the USA is recommended only for five of them, including cystic fibrosis and Tay-Sachs disease.

What did the research involve?

Existing techniques are already used to detect the genetic mutations that cause a number of diseases, but separate tests would usually be carried out for each individual disease. Carrying out multiple tests in this way would be time-consuming and costly.

In this study, the researchers investigated whether they could develop a single screening process for a large number of mutations that cause childhood genetic conditions by using genome sequencing techniques in a cost-effective and scalable way.

The methods of this research are complex. The particular methods they applied are called “target enrichment” and “next-generation sequencing”, processes that involve several different laboratory and analytical steps.

The detection of mutations must be carried out very carefully as the results are intended to be used to inform potential parents about the likelihood of a genetic disorder in their future children. Any tests for mutations must be accurate and in particular should have low “false positive” rates, i.e. should be unlikely to suggest potential health problems in instances when such a risk did not actually exist. The researchers considered the following three points to be very important in developing a comprehensive pre-conception screening test:

  • Any resulting test had to be cost-effective, i.e. the benefit from using it should be worth the cost of it. The researchers were aiming for a test that would cost less than US$1 per condition tested for.
  • A broad range of coverage was necessary, i.e. many different diseases.
  • Diseases that were severe and which had strong evidence for mutations causing the disease were selected; the researchers felt that they should prioritise conditions for which prior knowledge would change the way couples planned their family or antenatal, prenatal or postnatal care. They identified which diseases to screen for by reviewing the medical literature to identify important conditions that matched their criteria.

They screen tested for the following different groups of conditions:

  • eight cardiac (heart) conditions
  • 45 severe cutaneous conditions (of the skin, hair etc)
  • 46 developmental problems
  • 15 endocrine disorders
  • 3 gastroenterological conditions
  • 15 hematological (blood) disorders
  • 3 hepatic (liver) conditions
  • 29 immunological conditions
  • 142 metabolic conditions
  • 122 neurological conditions
  • 12 eye disorders
  • 25 kidney conditions
  • 8 respiratory disorders
  • 28 skeletal disorders.

The researchers were able to make use of methods that targeted and amplified particular sequences in DNA samples that were known to be associated with the recessive disease genes, along with advanced DNA sequencing techniques. They designed their test to “read” the DNA many times over to improve the accuracy in detecting the mutations. The researchers also explain their rationale for selecting particular methods over others when detecting mutations in the samples.

The authors had blood and DNA samples available for use in their screening tests. They applied and refined their methods using these samples to ensure that their test was cheap (less than US$1 per condition) and that it could detect the different types of mutation that are important in recessive diseases. Their test was able to label each person’s DNA sample as either “heterozygous” (having one copy of the mutation) or “homozygous” (having two copies of the mutation) for each of the 448 mutations.

The researchers then went on to report the average “carrier burden” in 104 DNA samples (i.e. what proportion of the samples were carrying mutations for any of these diseases).

What were the basic results?

The researchers say they were able to develop a cost-effective, accurate and scalable screening test for 448 different severe childhood diseases.

They used this to investigate the average number of mutations in DNA samples from 104 people, and report that roughly three mutations were being carried in each person. There did not appear to be any differences in this rate between people from different ethnic groups or genders. They say that, overall, the test cost about US$378 for all the diseases, which is lower than their target price of US$1 per disease.

How did the researchers interpret the results?

The researchers are optimistic about their results, saying that they have described a technology platform for comprehensive pre-conception carrier screening for 448 recessive childhood diseases. They say that combining this technology with genetic counselling could reduce the incidence of severe recessive paediatric diseases and may help to improve the diagnosis of these disorders in newborns.


This is a well-conducted genetic study that has used accepted methods in this field to devise large-scale testing of DNA samples to screen for numerous mutations that are known to be responsible for important inherited diseases.

The wide-ranging screening test developed here appears to be relatively low cost, at less than US$400 per test. However, counselling, consultation, interpreting results and managing databases of the results are likely to be important additional costs if such tests are introduced. The researchers say that it is most likely that their testing method will be adopted by IVF clinics and medical genetics clinics, where testing is already common and where counselling systems are already in place.

While this study has established that this is a technically feasible screening test in a research setting, there are several further steps to take, including refining the list of diseases assessed, automating the testing process and developing software and reporting mechanisms. Finally, the screening test itself needs testing in a real-world setting.

The implications of screening, particularly genetic screening, also need consideration in a wider context as a number of ethical, legal and social dilemmas arise from it. For example, while the test may indicate the likelihood that a couple’s children will have a particular condition, it may not necessarily indicate how mildly or severely their condition might affect them.

Certain countries do offer preconception screening to high-risk populations, but only for specific diseases such as Tay-Sachs disease among individuals of Ashkenazi descent. Another key consideration would be whether this type of screening test would be offered to everyone considering a family or just to selected couples.

NHS Attribution