The Generation Study is a research study run by Genomics England in partnership with NHS England. It is investigating whether whole genome sequencing (the sequencing of DNA) can be used as a way of screening newborn babies for a larger number of childhood-onset genetic conditions than the 9 conditions currently being screened for through the UK’s conventional newborn blood spot screening programme.
Over 200 conditions that are caused by changes to specific genes have been selected for screening as part of the study. The conditions include primary immunodeficiencies that are linked to over 100 different genes (see the summary table below).
The research study is sequencing and analysing the genomes (the complete set of genetic instructions in your DNA) of 100,000 newborn babies in England, with parents’ consent. The evidence generated could help to demonstrate how screening for a larger number of conditions could contribute to timely diagnoses, earlier access to care and treatment pathways, and better outcomes for babies and their families. Parents of babies participating in the study will continue to be offered the standard newborn blood spot test as well.
Why have only certain conditions been chosen?
Although there are thousands of conditions that could be detected through whole genome sequencing, the study is only screening for a specific set of conditions, genes and genetic variants.
Genomics England, through stakeholder engagement, developed four principles for selecting the genetic conditions and variants to be screened for.
- There is strong evidence that the genetic variant(s) causes the condition and can be reliably detected.
- A high proportion of individuals who have the genetic variant(s) would be expected to have symptoms that would have a debilitating impact on quality of life if left undiagnosed.
- Early or pre-symptomatic intervention for the condition has been shown to lead to substantially improved outcomes in children, compared to intervention after the onset of symptoms.
- Conditions screened for are only those for which the interventions are equitably accessible for all.
Where and when will the study take place?
The study has started, with recruitment taking place in stages in NHS sites throughout England, starting with five NHS trusts and increasing to 25–40 trusts over time. The sites have been chosen based on birth volume, the diversity of people who use the hospital and the maternity department performance. The study is expected to run until March 2025.
Parents attending maternity services in participating NHS trusts will be informed about the study when their pregnancy reaches 20 weeks. They will be given information to help them decide whether or not to participate in the study.
When a ‘condition suspected’ result is given, further tests will be undertaken to confirm the diagnosis. If the result is ‘no condition is suspected’, then this is not a ‘clean bill of health’ for the baby because not all genetic conditions are being screened for.
Our involvement at Immunodeficiency UK
Immunodeficiency UK has worked with Genomics England on the information sheets that parents will receive once a suspected condition has been detected but before confirmatory testing has been done. We have been named as the support organisation for parents/carers who receive a ‘condition suspected’ result. In addition, we have worked with Genetic Alliance UK providing feedback on the impact evaluation study.
More information
You can find out more about the study by following the links below:
- A short film about the study: https://youtu.be/7gizK7_HSXk
The G Word podcast:
Read more about genomics and immunodeficiency at Genomics and immunodeficiency – Immunodeficiency UK.
Summary of PID conditions that are being screened for
| Condition screened for | Number of genes that will be screened for |
| Adenosine deaminase 2 deficiency | 1 |
| Agammaglobulinaemia | 9 |
| Autoimmune polyendocrinopathy syndrome | 1 |
| Bare lymphocyte syndrome | 4 |
| Chediak-Higashi Syndrome | 1 |
| Chronic granulomatous disorder | 5 |
| Complement deficiency | 14 |
| DOCK8 Deficiency | 1 |
| Ectodermal dysplasia and immunodeficiency 2 | 1 |
| Familial Haemophagocytic lymphohistiocytosis | 4 |
| Griscelli Syndrome | 1 |
| Hepatic venoocclusive disease with immunodeficiency | 1 |
| Hereditary angioedema | 1 |
| Hermansky-Pudlak syndrome | 2 |
| Immune dysregulation | 4 |
| Immunodeficiency | 22 |
| Immunodeficiency-centromeric instability-facial anomalies syndrome | 4 |
| Immunodeficiency with hyper-IgM | 2 |
| Immunodeficiency with lymphoproliferation and autoimmunity | 2 |
| Leukocyte adhesion deficiency | 2 |
| LIG4 Syndrome | 1 |
| Nijmegen breakage syndrome | 1 |
| OAS1 associated polymorphic autoinflammatory immunodeficiency | 1 |
| Otofaciocervical syndrome | 1 |
| Periodic fever syndrome | 1 |
| Properdin deficiency | 1 |
| PSTPIP1 related inflammatory disease | 1 |
| Severe combined immunodeficiencies (SCID) | 16 |
| Specific granule deficiency | 2 |
| Wiskott Aldrich syndrome | 1 |
| X-linked immunodysregulation, polyendocrinopathy, and enteropathy | 1 |
Posted August 2024
