Scientists have devised “a blood test that could predict an unborn baby's risk of numerous disorders”, the Daily Mail has reported. The newspaper said a tiny sample of the mother's blood can be used to piece together the child's entire genetic code and search for conditions such as Down's syndrome and autism.
At present, genetic tests for unborn babies rely on invasive methods, requiring a sample to be taken of the placenta or the amniotic fluid surrounding the foetus in the womb. This research aimed to develop an alternative technique that can analyse fragments of foetal DNA in the mother’s blood and potentially avoid the need for invasive testing. However, this is still a research technique and is not yet ready for practical use. It is important to note that the researchers still needed to use some information from invasive placenta sampling to carry out their analyses.
Overall, this interesting study brings us one step closer to the possibility of non-invasive foetal genetic testing. However, much more development and testing of this prototype method will be needed before it could replace existing methods.
The study was carried out by researchers from the Chinese University of Hong Kong and Sequenom Inc from the USA. The study was funded by the Hong Kong Research Grants Council, Sequenom, the Chinese University of Hong Kong and the Government of the Hong Kong Special Administrative Region, China.
The study was published in the peer-reviewed journal Science Translational Medicine.
The study was reported in the Daily Mail and The Daily Telegraph. Both papers importantly highlighted some of the risks associated with invasive testing and the ethical issues surrounding prenatal testing. Although other studies have tested a similar technique to detect conditions such as Down’s syndrome, in which an individual carries an extra chromosome, the current study only looked for changes within the genetic sequences of chromosomes. It is not clear whether this particular technique is suitable for detecting this type of chromosomal genetic change. The Mail also mentioned autism, but the causes of autism are not clear, so genetic testing for this condition is unlikely to be useful at the moment. The Mail also noted the high cost of such a test, which they estimate would cost £125,000 for each baby.
This laboratory study aimed to develop ways to look at the genetic make-up of a foetus using a blood sample from its mother.
Looking at the genetic make-up of a foetus currently requires the use of invasive techniques, taking a sample of the amniotic fluid surrounding a foetus or a tissue sample from the placenta. In 1997, it was discovered that some of the foetus’ DNA circulates in the mother’s blood stream. If researchers could develop a way to distinguish this from the mother’s own DNA, this could allow non-invasive genetic testing of the foetus. The current study aimed to do this.
The researchers took blood samples from a pregnant woman and her partner who were attending a genetic clinic for prenatal diagnosis of beta thalassemia, a blood condition caused by carrying two mutated forms of the beta-globin gene. The mother and father each carried one mutated copy of the beta-globin gene. Their baby would have a one in four chance of inheriting both these mutated copies of the gene and, therefore, being affected by beta thalassemia (carrying only a single copy of the mutated gene does not usually lead to any symptoms). As well as providing blood samples for the study, the family also received conventional genetic testing using a sample of placental tissue, which researchers also used in their analysis.
The key to the research was to be able to distinguish between the mother’s DNA in her bloodstream and the fragments of DNA in her blood that came from the foetus. This was mainly done by checking the DNA samples from the blood for genetic information that could only have been inherited from the father, therefore indicating that it had come from the foetus.
To do this, the researchers determined the genetic sequence of specific sites in DNA extracted from the mother’s and father’s blood samples, as well as from the foetal DNA found within the placental tissue.
They then used information about the father’s and mother’s DNA sequence to identify those DNA sequences in the mother’s blood sample that must have belonged to the foetus. They could verify their findings using foetal DNA from placental tissue, and use information from this DNA to help their analysis in other ways. They then used computer programs to identify overlaps between the foetal DNA fragments identified in the maternal blood sample, similar to re-constructing a book from overlapping fragments of sentences.
They used their methods to see whether they could determine from DNA from the maternal blood sample whether the foetus had inherited the beta-globin gene mutations from the parents.
The purpose of the research was firstly to be able to distinguish between the maternal and foetal DNA from the maternal blood sample and to see if the foetus’ entire DNA sequence was present. The second objective was to determine the test’s ability to detect beta thalassemia in the foetus.
The researchers found that foetal DNA in the mother’s blood stream broke down into predictably sized fragments, and that these fragments differed in size from those from the mother. The researchers also found that these fragments together covered most of the foetus’ DNA.
The researchers also looked specifically at sites in the maternal blood sample DNA where the father had carried two identical copies of a sequence that differed from the mother’s genetic sequence. For about 94% of these sites, they could identify foetal DNA because it carried a sequence inherited from the father.
In terms of diagnosis, the prediction from the maternal blood sample agreed with the results of conventional invasive sampling. The foetus had inherited the father’s beta-globin gene mutation, but not the mother’s mutation. This meant that the foetus would not be affected by the condition.
The researchers concluded that their results mean it is feasible to test for genetic disorders in a foetus using a non-invasive maternal blood sample.
This study has shown that it should be possible to test foetal DNA using maternal blood samples. However, there are some points to note:
Overall, this interesting study brings us closer to the possibility of non-invasive foetal genetic testing. However, much more development and testing of this method will be needed before it could replace existing ones.