Articles
Register for New Test for Both Genetic and Chromosomal Abnormalities in Embryos
ESHRE XXV, Amsterdam
June 29 - July 1, 2009
New test that can detect both genetic and chromosomal abnormalities in
embryos is ready for clinical trials
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 a news briefing at the 25th annual meeting of the European Society of
Human Reproduction and Embryology in Amsterdam 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 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.
Mr Harton said: “This demonstrates that karyomapping, following genome-wide
analysis of a single cell biopsied from embryos at the blastocyst stage, can
provide highly accurate analysis for cystic fibrosis, combined with the
detection of chromosomal aneuploidy. Now that vitrification [an improved method
of embryo freezing] has improved embryo survival after thawing, it should be
possible to vitrify embryos at the blastocyst stage, either before or after
biopsy, and analyse the embryos for virtually any genetic disease and screen for
aneuploidy of all 23 pairs of chromosomes simultaneously. This approach could
make PGD by karyomapping less expensive than conventional single disease PGD
because fewer embryos will be biopsied, more embryos will be chromosomally
normal following growth to the blastocyst stage, and there is no need to custom
develop tests for each disease or couple interested in PGD.”
Prof Handyside concluded: “These tests have helped us to learn everything we can
before we start to treat actual patients. I am confident that we will be
offering a clinical trial to patients using karyomapping some time this year.”
