Embryo gene mapping technique

30 October 2008

A new genetic testing methodology for pre-implantation genetic diagnosis (PGD) has been developed by scientists at the Bridge Centre in London (see the Times and the BBC news articles). According to media reports, this new methodology known as karyomapping has been hailed as a breakthrough technique which has the potential to test embryos produced via in vitro fertilisation (IVF) for almost any known genetic disorder. Currently, embryos that are produced by IVF can be screened for some chromosomal defects such as aneuploidies (known as pre-implantation genetic screening). If there is a known family history of a specific genetic disease such as cystic fibrosis, it is possible to perform prenatal genetic diagnosis (PGD) to select embryos without the condition for implantation, subject to the granting of a licence by the Human Fertilisation and Embryology Authority (HFEA). Such licences are granted on a case-by-case basis, although decisions in principle to permit licensing for specific conditions are sometimes taken; for example, adult onset hereditary forms of cancer (see previous news).

According to the news reports, the advantage of this methodology is that it can be used to screen a far wider range of genetic conditions as well as multiple genetic traits, and produces results in a shorter time period (BBC news). The technique involves the analysis of single nucleotide polymorphisms (SNPs) in DNA from parents and embryos to produce a ‘karyomap’ showing which parts of the embryo’s chromosomes have been inherited from which parent. In other words, it allows the origin of specific chromosomal segments to be identified and consequently also allows tracing of chromosomal segments that might be associated with a particular disease or phenotype. Thus far, the methodology used in producing karyomaps sounds remarkably similar to pre-implantation genetic haplotyping (PGH), which is used to identify haplotypes associated with familial disease regions (see previous news). However, a karyomap reportedly allows the identification of multiple genetic variations and aneuploidies, in addition to single gene defects.

Despite wide media coverage, the scientific basis or clinical utility of this technique is currently unclear. The divergence from (and purported superiority over) PGH remains uncertain, as there have been no scientific publications describing the details of the new methodology, and no clear explanation of how exactly multiple genetic traits are identified.

The Bridge Centre is currently undertaking clinical trials prior to applying for a licence from the HFEA for the use of the technique, and the possibility of being able to test rapidly for a wide range of different mutations associated with genetic forms of disease is exciting. However, proposals that it may be used as a “MoT” for embryos or for the production of “designer babies” are distinctly premature. Although this technique may be able to identify some genetic variants associated with physical traits or susceptibility to common diseases, the effect or risk of these individual variants on multi-factorial developmental or pathological processes could be very small, and potentially entirely non-pathogenic variants (such as copy number changes) could be found. It would not be feasible to select embryos on this basis, nor would the HFEA be likely to grant a licence for screening without a proven medical benefit.

In addition, IVF is a specialised procedure typically only undertaken where normal fertility is impaired, and may be coupled with PGD to prevent the conception of embryos with inherited forms of serious genetic diseases, the genetic basis of which is generally already known. Moreover, the process entails small but significant risks to the health of the mother and often fails to result in an established pregnancy. Together with the expense of the test (£1500), these factors mean that it is unlikely to become a routine procedure for couples who do not require IVF, but possibly as a potential additional technique to help select the most viable embryos for implantation where a couple is already undergoing IVF. However, a thorough evaluation of the clinical validity and utility of the test will be required before it can be offered even for this purpose.