Exclusion Testing

Exclusion testing is a reproductive option available to individuals at risk of inheriting Huntington’s disease who wish to have children without knowing their own genetic status. This form of testing is typically used in combination with in vitro fertilisation (IVF) and Preimplantation Genetic Testing (PGT) to reduce the risk of passing Huntington’s disease to the next generation.

Instead of testing embryos for the presence or absence of the Huntington’s gene mutation directly, exclusion testing looks at the gene markers that are inherited alongside the HTT gene within a family. Think of genetic markers as harmless variations in your DNA, which are found in all members of a family or descendants of certain origin and varies between different subgroups within the population. These help scientists locate and track a nearby gene, like the HTT gene, which causes Huntington’s disease when changed.

These markers help figure out if it highly likely that someone has inherited a particular version of the gene, without confirming the gene mutation. This allows the geneticists to identify which embryos are unlikely to have inherited the gene from the affected side of the family—without revealing whether the parent themselves carries the mutation.

Exclusion testing may be an option for:

• People who are at 50% risk of inheriting Huntington’s disease (typically with an affected parent)
• People who do not wish to undergo predictive testing for themselves, but want to reduce the risk to their children
• Couples looking to build a family without passing on the Huntington’s disease gene

IVF is used to create embryos outside the body using the egg and sperm of the prospective parents. A few cells are taken from each embryo at an early stage of development. These cells undergo PGT using exclusion testing, where DNA markers (inherited from the side of the family with Huntington’s disease) are analysed. Embryos that do not appear to have inherited the “high-risk” markers are selected for implantation. The selected embryo is then transferred to the uterus for potential pregnancy. This process allows parents to avoid passing on the Huntington’s disease gene without revealing their own genetic status.