Importance of prenatal screening

Prenatal diagnosis is commonly used for couples where both parents are known carriers of the same genetic disorder, have a high incidence within their family, or already have a child affected by the disorder. For example, sickle cell disorder is the most common inherited disorder in the UK, affecting between 12,500 and 15,000 people. The UK commenced a universal antenatal screening program in 2004 to identify couples at risk of having a child affected with sickle cell disease. Currently, invasive diagnostic methods are used, such as amniocentesis and chorionic villus sampling, which carry a risk to the foetus.

Existing non-invasive screening approaches for genetic disorders use circulating cell-free foetal DNA (ccffDNA). These disorders are limited to those with particular characteristics that make diagnosis easier, for example, identification of alleles that are paternally inherited by the foetus and not present in the mother. However, many genetic disorders are recessive and current non-invasive tests cannot diagnose these conditions.

The Oxford solution

Researchers at Oxford have developed an improved non-invasive prenatal technique that allows for the diagnosis of single gene recessive disorders where the mother is a carrier of exactly the same mutation in addition to the diagnosis of disorders caused by autosomal dominant mutations or compound heterozygosity. The method only requires a blood sample from the mother, which contains both the maternal and foetal DNA.

The technique measures the frequency of the mutant allele in the maternal blood to determine if the foetus has sickle cell disease and it is validated with software and a dataset which calculates the risk of the foetus to develop the disease. Hence this technology provides pregnant women with key genetic information on their babies without the risks associated with invasive tests.

Key improvement

This platform screening method has potential applications in screening all other single gene disorders including Beta Thalassemia, Cystic Fibrosis, Tay-Sachs syndrome, Spinal Muscular Atrophy (SMA) and Haemophilia (A and B).

Key improvements of this new platform diagnostic test are:

• Low risk to mother and foetus
• A simple, targeted approach
• Reliable and reproducible

Proof of concept experiments have been successful and clinical evaluation has now commenced. Oxford University Innovation would like to speak to any party who specialise in sequencing, screening and diagnosis of diseases.

The technology is subject of a PCT patent application, plus copyright protection for the statistical method and the dataset, and all three pieces of the technology are available to license.