NEW_MUTS: New Mutations and Male Germline Development
Research type
Research Study
Full title
Detection of new (de novo) mutations in human Testes and Sperm and male germline development (NEW_MUTS)
IRAS ID
209766
Contact name
Anne E Goriely
Contact email
Sponsor organisation
University of Oxford
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Genetic diseases happen when mistakes, known as ‘mutations’, arise in our DNA code. When these mistakes occur in the DNA of eggs or sperm, they can be transmitted to the next-generation and cause disease in newborns. The situation in which a misprint has arisen during the copying of the DNA code, is termed a “new mutation” and affects ~1:250 births.
Although it is usually assumed that new mutations occur randomly, we know now that most new mutations found in a child actually originated during the production of sperm in the father’s testis. Understanding the process by which these new mutations occur is intimately linked to the way the testis develops and how sperm production is controlled over time. We want to investigate new mutations by studying the tissues (testis and sperm) where these new mutations originate.
We have previously shown that some mutations can be ‘selfish’. These selfish mutations hijack the way sperm is produced to their own advantage and become more abundant in sperm as men get older. Although so far we have only demonstrated this effect for rare disease mutations, we think it may be more common than currently recognised. In this project, we want to use state-of-the-art technologies to establish how the testis develops and regulates sperm production over time and identify new mutations in order to understand why some diseases arise.We have developed methods to quantify newly-arising mutations in human sperm and testes and we now wish to build on these discoveries to address the following questions: (1) how many and what type of new mutations are present in sperm and testes? (2) how does paternal ageing influence their frequency? (3) to which extent does the way sperm production is controlled over time influence the occurrence of new mutations? (4) what is the influence of environmental factors (such as mutagens/chemotherapy agents) on the male germline?
REC name
North East - Newcastle & North Tyneside 1 Research Ethics Committee
REC reference
22/NE/0025
Date of REC Opinion
15 Feb 2022
REC opinion
Further Information Favourable Opinion