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Dr Olivia Fletcher

Team Leader

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Dr Olivia Fletcher leads a team of genetic epidemiologists and molecular biologists working on the Generations Study, the British Breast Cancer Study and other population-based studies. She also took over leadership of the Complex Trait Genetics team from Dr Nick Orr in July 2017. Team: Complex Trait Genetics
Team: Functional Genetic Epidemiology

T 020 7153 5177

Biography

Dr Olivia Fletcher leads a team of genetic epidemiologists and molecular biologists working on the Generations Study, the British Breast Cancer Study and other population-based studies. She is based within the Breast Cancer Now Toby Robins Research Centre at the ICR. She obtained her first degree in Biochemistry at the University of Oxford, her PhD in the laboratory of Gene Structure and Expression at The National Institute of Medical Research, Mill Hill, and an MSc in Medical Statistics at the London School of Hygiene and Tropical Medicine.

Her research interests focus on the identification and characterisation of genetic variants that are associated with breast cancer risk – specifically, low penetrance variants that map to non-coding DNA. To facilitate these studies, Dr Fletcher uses quantitative intermediate phenotypes – for example, female sex hormones, peptide growth factors and their binding proteins. These quantitative intermediate phenotypes can be used as statistically efficient alternatives to traditional case-control studies in the identification of novel genetic variants.

Dr Fletcher has also contributed to developing a more systematic approach to the functional characterisation of genetic risk loci identified, primarily, through genome-wide association studies (GWAS). In collaboration with scientists at the Babraham Institute, Dr Fletcher developed a modified chromosome conformation capture-based method that allows high-resolution analysis of regulatory interactions between risk loci and their target genes. She used this methodology to characterise a series of breast cancer risk variants that map to gene deserts – regions of the genome of several hundred kilobases that lack protein-coding genes. She is now expanding this work to characterise more than 50 risk loci.

Her work is funded by Breast Cancer Now.

Research highlight: 2q35 Risk Locus

Image below: Two-way heatmap of Capture Hi-C (CHi-C) interaction peaks between bait fragments within the 2q35 breast cancer risk locus (capture region) and target fragments either side of the capture region (green) or between two bait fragments within capture region (red) for CHi-C libraries in BT483 breast cancer cells. The genomic locations of the bait fragments are shown on the y-axis. The genomic locations of the target fragments, aligned with GENCODE genes, are shown on the x-axis. The colour intensity of each square represents the statistical significance of the interaction peak from dark green/red (P = 1 x 10-10) to light green/red (P ≤ 0.01). Interaction peaks with a false discovery corrected P value of >0.01 are not shown.

2q35 Risk Locus
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