THE range of tests performed on embryos before they are implanted in the womb could be vastly increased by a new method for amplifying the DNA of a single cell.
Hundreds of different tests could be run on each embryo, making it possible to simultaneously check for a large number of genetic defects, or even traits that the parents might desire, such as tissue that was compatible with a sick sibling. At the same time, clinics could confirm that there had been no mix-up involving sperm or eggs from other couples.
The use of the new amplification method for pre-implantation genetic diagnosis (PGD) has been evaluated by Alan Handyside of the London Bridge Fertility Centre. He plans to apply for permission to start using the method in the UK in around six months.
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PGD is increasingly being used to screen test-tube embryos for genetic faults such as sickle-cell disease (New 杏吧原创, 12 June, p 6). But PGD is still expensive and technically difficult. Only one or two cells can be taken from an early embryo without harming it. The relevant piece of DNA in a single cell is then copied again and again, using a modified version of the PCR technique that is prone to errors.
The whole process must be carried out in special clean rooms because a single stray cell can affect the result. Amplifying more than one piece of the genome at the same time so that you can run more than one test is extremely difficult and can take up to two days of round-the-clock work.
If embryologists could start by making millions of copies of all the DNA in a cell 鈥� amplifying the whole genome, in other words 鈥� diagnosis would be much easier. After the crucial first amplification step, there would be no need for clean rooms: with millions of copies of a genome one stray cell won鈥檛 matter. And there would be plenty of material on which to run the tests.
Various methods of whole genome amplification have been tried before, but they all have too high an error rate for PGD. Now a technique developed by Molecular Staging of Connecticut and Amersham Biosciences in Sweden could change all that.
Handyside鈥檚 team used a kit supplied by Molecular Staging to analyse cells taken from embryos that had already been screened for cystic fibrosis, using current PGD methods. As well as confirming the results, they were able to run 20 additional tests, including looking at the sequences used for DNA fingerprinting and at the HLA genes that determine whether tissue from a fetus could be transplanted into a sibling. The team has submitted a paper to the journal Molecular Human Reproduction.
The method stills need refining. For instance, in 1 of the 11 embryonic cells the team has tested so far, some pieces of DNA were missing after the amplification process. Even so, Handyside says it will still be more accurate than existing methods.
Molecular Staging is also working on improving the technique. It has cut the time taken to amplify a genome from the 16 hours to just 1 hour. That is crucial because PGD tests have to be completed within two or three days, before the embryo is too old to implant.
The uses to which PGD can be put are restricted in most European countries. But elsewhere, including the US, it is used for sex selection. The latest technique could also, in theory, make it easier to select embryos with other desired traits, including one day physical characteristics such as eye colour. But as most couples have fewer than 10 embryos to choose from, the scope for doing anything beyond screening out embryos with defects is very limited.