Investigating the role of genetics in disease predisposition
Research type
Research Study
Full title
Pathogenic variants and clonal dynamics in gonads and their role in disease predisposition.
IRAS ID
273194
Contact name
Raheleh Rahbari
Contact email
Sponsor organisation
Wellcome Sanger Institute
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
The impact of mutation accumulation in testes and ovaries is more important than in any other tissue in our body. This is due to the fact that, any alterations in the genomes of these tissues can affect both the individual, by causing diseases such as cancer, and their child by potentially predisposing them to diseases such as cancer. Despite this, not much is known about how mutations accumulate and what proportion of the sperm and eggs may carry disease causing mutations. This has hampered efforts to take preventative action, identify and screen “high-risk” individuals and develop treatments.
The aim of this study is to ascertain which DNA errors in the sperm/eggs of parents underpin disease predisposition in their children. We also wish to identify what factors may increase the proportion of disease carrying sperm/eggs in testes/ovaries. The answer to the latter question will enable us to estimate, the risk of having a child with a disease predisposition syndrome. This is especially very important for families who already have a child with cancer predisposition syndrome such as Li-Fraumeni and are concern about the risks for future pregnancies.
We wish to study healthy and cancerous testes and ovaries collected from individuals of differing ages with consent for use in research. These samples will be sourced from NHS pathology departments and/or tissue banks and sequenced to identify which mutations arise in these tissues. We also wish to collect blood or saliva samples from children diagnosed with disease predisposition syndromes and/or cancer and their family members (mother, father, siblings) and collect semen samples from their fathers. We will also ask family members to complete a questionnaire. We may also include the wider family in the study.
state-of-the-art sequencing methods will be applied to all of the samples to identify the prevalence of disease-causing mutations.
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
20/EE/0075
Date of REC Opinion
13 May 2020
REC opinion
Further Information Favourable Opinion