Embryo screeners turn to crime scenes for clues

日期:2019-03-02 07:07:08 作者:崔癀茕 阅读:

By Linda Geddes 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. 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 Guy’s 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 Guy’s 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. 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. PGH is also attracting international interest. Karen Sermon of the Centre for Medical Genetics at Brussels Free University, Belgium, used Renwick’s 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,