ReCAP | Repair capacity and genome diversity in mammals

Summary
Genome evolution is driven by the generation of diversity. In mammals, genome diversification occurs in germline during the specialised division (meiosis) in gametes, when chromosomes recombine and assort into new haploid sets as they are passed from parent to offspring. Recently, the traditional view that genome diversification occurs exclusively in the germline has been challenged by findings that mutations in early embryos may cause predisposition to childhood cancers. We are uniquely placed to explore genome diversification in the germline and early embryos due to our breakthroughs in developing single-cell genomics and reproductive technologies.

Our strategic aim is to uncover the capacity for genetic diversity in the human genome and investigate how DNA repair capacity in adult oocytes and early embryos facilitates genome stability. This will allow us to identify the selective forces that shape the genomic landscape in humans. Based on preliminary data, we hypothesize that repair capacity determines reproductive fitness of mammalian females, and that impaired repair capacity may underlie infertility, miscarriage, and congenital disorders. In Objective 1 we focus on adult oocytes, their survival in the adult ovary and the maintenance of genetic quality as women age. Objective 2 investigates genome diversification and stability in early embryos and putative ‘self-corrective’ mechanisms that restore the genetic quality of embryos. This proposal will shed light on a poorly understood area of enormous socioeconomic and medical importance.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/724718
Start date: 01-07-2017
End date: 30-06-2023
Total budget - Public funding: 1 997 592,92 Euro - 1 997 592,00 Euro
Cordis data

Original description

Genome evolution is driven by the generation of diversity. In mammals, genome diversification occurs in germline during the specialised division (meiosis) in gametes, when chromosomes recombine and assort into new haploid sets as they are passed from parent to offspring. Recently, the traditional view that genome diversification occurs exclusively in the germline has been challenged by findings that mutations in early embryos may cause predisposition to childhood cancers. We are uniquely placed to explore genome diversification in the germline and early embryos due to our breakthroughs in developing single-cell genomics and reproductive technologies.

Our strategic aim is to uncover the capacity for genetic diversity in the human genome and investigate how DNA repair capacity in adult oocytes and early embryos facilitates genome stability. This will allow us to identify the selective forces that shape the genomic landscape in humans. Based on preliminary data, we hypothesize that repair capacity determines reproductive fitness of mammalian females, and that impaired repair capacity may underlie infertility, miscarriage, and congenital disorders. In Objective 1 we focus on adult oocytes, their survival in the adult ovary and the maintenance of genetic quality as women age. Objective 2 investigates genome diversification and stability in early embryos and putative ‘self-corrective’ mechanisms that restore the genetic quality of embryos. This proposal will shed light on a poorly understood area of enormous socioeconomic and medical importance.

Status

SIGNED

Call topic

ERC-2016-COG

Update Date

27-04-2024
Geographical location(s)
Structured mapping
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EU-Programme-Call
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2016
ERC-2016-COG