One of our biggest worries in the field of genome medicine is the use of prenatal genetics tests to justify the abortion of human embryos. Current technologies allow enhanced detection of genetic abnormalities that a few years ago would have been unthinkable.
Array-CGH (Comparative Genomic Hybridisation) is becoming a common method for analysing patients’ genomes. Array-CGH works by taking a reference genome covering the whole human genome sequence, cutting it into thousands of pieces and attaching them to a chip. These pieces are called probes or oligos and are usually on the range of dozens to thousands DNA bases long respectively. A saliva or blood sample is then taken from the patient and his/her DNA chopped into millions of pieces, carried by a suspension with a solvent. The array is then washed with the suspension containing the patient DNA pieces.
DNA is a double chain of nucleotide bases where one chain complements the other. Knowing one chain of the DNA, it is possible to know the other chain. In its natural state, a single DNA chain tends to bind to its complementary chain. Thus, by washing the patient’s suspension with array probes attached to a chip, the patient’s DNA ends up binding to their complementary DNA probe in the array.
Array-CGH can be used to detect whether a a region of the genome is missing or has been duplicated. Probes attached to the chip emit a different color depending on their state of binding. Once the array is washed, most probe spots appear yellow, meaning that most of the reference genome’s probes are bound to the patient’s DNA. If a patient is missing a DNA region big enough to span a probe, the complementary spot in the array appears in red. If several red spots appear in sequential order, these can be mapped to the patient’s genome as missing regions or deletions. The symptoms of the genetic disease depend on the genes that overlap the deletion.
The same happens if the array shows a series of green spots, indicating that a duplicated region of the genome has been found in the DNA of the patient. Because the gene content is also duplicated, this may cause disease as a consequence of the over-expression of genes included in such regions.
Thus we are now able to find deletions or duplications in the genome of a patient beyond the microscopic level. We are all familiar with the features of a patient with Down’s Syndrome. This syndrome is caused because there is an extra copy of chromosome 21 in the affected patient, due to a duplication of one of the two usual copies (trisomy 21). This was discovered in 1959 by the French geneticist Jerome Lejeune.
But it is only recently that we have discovered the importance of structural changes such as deletions and duplications in the evolution of a genome. Before these technologies became widely accessible to hospital practice, many patients with genomic diseases, ie diseases caused by pathogenic deletions or duplications, went undiagnosed because only big chromosomal changes (like trisomy 21) could be detected.
Techniques such as array-CGH now allow the detection of chromosomal changes a thousand times smaller in length. For a price of about US$170 per array a genome can be screened for chromosomal changes. In fact, it seems that most of the genetic changes observed between any two people (in terms of number of DNA bases) are micro-deletions and duplications (called copy number variations).
Next-generation sequencing technologies are fast arriving that will allow base-by-base complete sequencing of the DNA at a price of US$1,000 in 24 hours.
So far there is no remedy for DNA anomalies when they are detected other than the treatment of symptoms. Many prenatal tests are now by default array-CGH tests instead of the traditional microscope chromosomal observation (called a karyotype). We are now able to detect genetic abnormalities before children are born. Thus these marvellous array-CGH techniques may lead to the diagnosis of more and more subtle syndromes and changes that may lead to not-so-severe abnormalities.
In the current climate of laws that regulate abortion, the enhancement of detection techniques for genetic anomalies is creating a situation where parents are faced with abortion for ever less severe results. In such cases, it is necessary to make people aware that many of the results given by such genetic tests are not necessarily conclusive in terms of the prognosis for the born child.
Many so-called diseases might lead parents to decide to have an abortion because it is socially unacceptable for them to have children with a disability or simply because they cannot face the risk. These fears may lead to indiscriminate abortion for mild genetic abnormalities such as polydactyly (having an extra finger or toe) or microcephaly (having a small head).
In a society where we already allow abortion up until birth, for a simple (and, one should note, operable) cleft palate, the consequences of allowing array-CGH diagnostics ante-natally are huge. Once again, we are confronted with the delicate frontier between scientific research and the sensitive realm of ethics and morality. The benefits of array-CGH diagnostics are manifiold. Identifying the causes behind genetic diseases brings us a very large step closer to finding treatments and possibly even cures. But there are some who see “prevention” as better than cures, and certainly more cost-effective — even when “prevention” really means abortion.
But this is eugenics, not therapy. Our society is already using karyotyping to eradicate Down syndrome babies. The chillling reality is that about 94 percent of positive diagnoses end in abortion. What will happen to foetuses who have one of the huge range of genetic abnormalities which will be uncovered by array-CGH?
If Down syndrome, a series of conditions that are amenable to both life and happiness, is considered unacceptable, what then of other “problems”? In a society obsessed with so-called health, the outcome seems predictable. For those of us who are uncomfortable with or disagree with the laws on abortion, do we have to stop using a wonderful diagnostic tool for fear that it will, literally, fall into the wrong hands? Or is this a good moment for declaring a moratorium on ante-natal diagnostics and re-opening the abortion debate?
Manuel and Sophia Corpas write from the UK. Manuel Corpas is a scientist
working in genome research.