New test detects genetic and chromosomal abnormalities in embryos

One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.

They told at the 25th annual meeting of the European Society of Human Reproduction and Embryology that, as a result, they would be able to offer clinical trials to couples seeking fertility treatment later this year.

The researchers based in the USA and the UK have been able to prove that the technique, known as genome-wide karyomapping, was capable of not only detecting diseases caused by a specific gene mutation, in this case cystic fibrosis, but that it was also capable of detecting aneuploidy (an abnormal number of any of the 23 pairs of chromosome) at the same time. This is the first time they have been able to demonstrate that the test can work in cells taken from embryos that have already been diagnosed with the cystic fibrosis gene mutation using conventional preimplantation genetic diagnosis (PGD).

Gary Harton, PGD scientific director of the Genetics & IVF Institute in Fairfax, Virginia (USA) told a news briefing: "Karyomapping is a universal method for analysing the inheritance of genetic defects in the preimplantation embryo without any prior patient or disease specific test development, which often delays patient treatment. For the first time, the inheritance of both single gene defects and chromosomal abnormalities can be detected simultaneously at the single cell level. Unlike other methods, this is achieved entirely by analysing the DNA sequence at over 300,000 locations genome-wide in parents and appropriate family members, often children already affected by a disease, and comparing their sequence with that inherited by the embryo. This can be achieved very rapidly using current microchip technology known as microarray."


With karyomapping it is not necessary to know the exact DNA mutation that is being sought; the scientists just need to take the relevant chunk of DNA from the parent that carries the mutation somewhere along its length, and if it matches a chunk of DNA from the embryo, then they know the embryo has inherited the mutation. As karyomapping involves analysing chromosomes, it also detects the existence of aneuploidy at the same time.



"The range of applications is broad", says Dr Harton


"The range of applications is broad and includes single gene defects, abnormal chromosome number, structural chromosome abnormalities and HLA [human leukocyte antigen] matching in 'saviour sibling' cases," said Mr Harton.

Karyomapping was developed by Professor Alan Handyside of the London Bridge Fertility Gynaecology and Genetics Centre in London (UK), and Mr Harton has been providing samples and DNA information in order to test the method and validate it for use in the clinic.

"The hope is that clinicians will be able to test embryos for specific genetic diseases and know that, with one test, they are transferring chromosomally normal embryos. This will be a step forward from current technology that is mostly limited to choosing one test or the other," explained Prof Handyside.

Karyomapping would also be quicker and cheaper. Currently, developing a PGD test for a single gene defect can take weeks or months, as scientists have to identify the exact patient or disease-specific genetic mutation first before screening for it, which is labour-intensive and costly. By contrast, karyomapping can be carried out without such extended pre-test development; at present, it takes about three days, but Mr Harton and his colleagues believe this could be reduced to 18-24 hours.

In this most recent stage of their research they examined cells from five embryos that had been donated for medical research by a couple who had received successful fertility treatment, including PGD for cystic fibrosis. The embryos had developed to the blastocyst stage, which is about five days after fertilisation. Conventional PGD had already identified which embryos were unaffected, affected or were carriers of the disease. Karyomapping of cells from the donated embryos confirmed these diagnoses, but, in addition, it was able to identify which parent carried the affected chunk of DNA. Karyomapping also revealed two aneuploidies in two embryos, which had not been detected by the earlier PGD.