SysGen Seminar – Juliet French – 26th May, 2017


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Andrew Siebel

T: +61 3 8344 0707

Juliet French

QIMR Berghofer Medical Research Institute

Friday 26th May
FW Jones Theatre, 3rd Floor, Medical Building, The University of Melbourne

Post-GWAS: From Genetic Association to Target Gene

One of the strongest breast cancer associations identified to date via GWAS is with SNP rs614367 at the 11q13 locus. To determine the candidate causal variant(s) underlying this association, we analysed 4,405 variants in 220,000 cases and controls from the Breast Cancer Association Consortium (BCAC) and identified two independent association signals for estrogen-receptor-positive tumors that map to a distal enhancer. We have previously shown that this enhancer regulates the CCND1 gene. In addition to CCND1, this enhancer regulates two novel estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2 that we identified by RNA CaptureSeq. We provide evidence that the risk-associated SNPs are associated with allelic imbalance of CUPID1 and reduced chromatin looping between the enhancer and the CUPID1/2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone receptor-positive breast tumors and play a role in modulating double strand break (DSB) repair pathway choice. These data reveal a novel mechanism for the involvement of this region in breast cancer.

Dr Juliet French is Head of the Functional Genetics Laboratory at QIMR Berghofer. She conducted her PhD and post-doctoral studies at UQ with a research focus on mechanisms of gene regulation. Her research group is aimed at understanding how genetic variants in non-coding regions of the genome influence cancer risk and progression. A major interest of her laboratory is the functional follow-up of breast cancer risk loci identified by Genome Wide Association Studies (GWAS). GWAS have identified 170 loci associated with breast cancer. Fine-mapping of these loci has shown that the putative causative variants at these loci are rarely in gene coding regions. Instead, that the majority of these variants fall in regulatory elements in DNA that often lie at distant physical sites to the genes that they regulate. In this presentation, Dr French will describe the different strategies her laboratory is using to identify the target genes of GWAS loci including RNA CaptureSeq and chromosome conformation capture-based technologies.

Enquiries: Andrew Siebel (