Embryo screeners turn to crime scenes for clues
Linda Geddes, NewScientist.com news service
2006-06-20
Fertility experts have adapted a DNA fingerprinting technique used at crime scenes to create a new way of screening embryos for disease. The technique could vastly increase the number of tests available for genetic diseases and could result in more healthy IVF embryos for implantation in the womb.
Pre-implantation genetic diagnosis (PGD) involves taking a
single cell from an embryo and screening it for disease before it is implanted.
Until now, PGD has largely relied on searching for a specific mutation, such as
the delta F508 mutation implicated in 70% of cystic fibrosis cases.
However, for families who possess one of the hundreds of
other mutations that can also cause the disease, it has been difficult to come
up with a test. Private clinics can create a tailor-made test, but that can be
expensive and time-consuming.
The new technique, termed pre-implantation genetic
haplotyping (PGH), combines two techniques. The first allows the entire genome
to be amplified from a single cell, ensuring there is enough DNA to
test.
Once that has been achieved, a standard DNA fingerprinting
technique is used to identify chromosomes carrying the faulty gene. Embryos
found to be carrying this chromosome can be discarded.
Five pregnancies
So far the researchers who pioneered the technique have
used it on seven couples to screen for cystic fibrosis, Duchenne muscular
dystrophy and hydatidiform mole. The work has resulted in five pregnancies,
which have yet to come to term.
Pamela Renwick and her colleagues at Guys and St
Thomas Hospital in London, UK, begin by taking DNA samples from a family
member already affected with the disease and others who are not.
They search these samples for about 15 short sequences of
DNA from within the disease-causing gene - markers - that distinguish the
high-risk chromosomes from healthy ones. These markers, which do not have to be
actual disease-causing mutations, then provide a fingerprint to search for in
the embryo samples.
We are trying to identify chromosomes which, if
inherited, will cause the child to get the disease, says Alison Lashwood,
nurse consultant in genetics and PGD at Guys and
St Thomas
Hospital, who has been using PGH to screen embryos.
The technique should make it easier to create tests for
diseases that currently cannot be screened for.
Sex selection
It also has implications for X-linked disorders such as
Duchenne muscular dystrophy, in which 50% of boys born to female carriers of the
disease will get it. Because mutations in the dystrophin gene are so variable,
previous screening has involved sex-selection of embryos, so that only female
embryos are implanted.
However, PGH allows healthy male embryos to be identified,
increasing the choice of those available for implantation and potentially
enabling families to screen for a healthy son.
Renwick says: Many more families with mapped single
gene disorders will be able to benefit, providing an alternative to the
testing of fetuses in the womb and termination of pregnancy.
International interest
PGH is also attracting international interest. Karen
Sermon of the Centre for Medical Genetics at Brussels Free University,
Belgium
, used Renwicks technique for the first time on Friday to screen embryos for
spinocerebeller ataxia 7, a genetic disorder that causes loss of coordination
and vision.
In the near future, she plans to develop tests for fragile
X syndrome and cystic fibrosis too. It enables us to generate a large amount
of DNA from a single cell using the same method each time, then screen it in the
same way we currently screen DNA taken from blood, she says.
Alan Handyside of the London Bridge Fertility Centre, who
pioneered the DNA amplification technique in 2004 (see Is
a new era dawning for embryo screening?), welcomes the new development,
but warns that there will still be single-gene disorders for which the technique
does not work.
The challenge is to find seven or eight informative
markers that are close to the gene involved and work out which ones are linked
to the mutant copy, he says. For some genes this is straightforward,
but in others it is more difficult or not possible at all.
The work of Renwick and her colleagues will be presented
at a meeting of the European Society for Human Reproduction and Embryology in
Prague
, the
Czech
Republic
, on Monday.
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