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Publications of the Week

A Scalable Drosophila Assay for Clinical Interpretation of Human PTEN Variants in Suppression of PI3K/AKT Induced Cellular Proliferation

By September 29, 2021No Comments

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This week we profile a recent publication in PLOS Genetics from the labs of Drs. Esther Verheyen (pictured, top, right) from SFU and Douglas Allan (top, left) from UBC with first authors Payel Ganguly (inset, left) and Landiso Madonsela (inset, right).

Can you provide a brief overview of your lab’s current research focus?

Our labs at UBC and SFU use the fruit fly as a genetically tractable model organism because of its ease of use, and because of the myriad parallels between fruit fly and human gene, cell and organ function. Our labs are interested in signalling pathway function and gene regulation in cell development and growth, with a focus on learning more about how human genes function and why certain mutations cause cancer, as well as developmental and neurological disorders. Our overall goal is to contribute to efforts to make fruit fly models a standard complementary system for increasing a clinician’s confidence that specific gene variants are causing their patient’s disease.

What is the significance of the findings in this publication?

Discovering gene mutations that cause disease is a powerful tool for tackling disease. Gene sequencing is now routine in clinical practice, with the assumption that by identifying gene sequence variants we can identify the cause of disease. However, we all have thousands of gene variants. So, the daunting challenge that clinicians face is to pinpoint which variants are actually causing their patient’s disease so that they can tailor the best therapy. To address this challenge, experimental assays are being developed at an increasing pace to identify which variants disrupt protein function. These efforts have highlighted the need to develop multiple assays per single gene, because every assay has certain drawbacks. Our labs collaborated on this publication to develop methods that exploit the fruit fly as an inexpensive universal assay platform to assay any human gene variant for its function. For this first demonstration of the platform’s power, we determined the clinical relevance of ~100 variants in the common human cancer-causing gene PTEN, using known pathogenic and benign human PTEN variants as a critical calibration step.

If you’d like to mention your funding sources, please list them.

Funding for this publication’s work on establishing our fruit fly platform for clinical interpretation of human gene variants was provided by Simons Foundation Autism Research Initiative and the Natural Sciences and Engineering Council of Canada. Work in the Verheyen lab that uses fruit flies to discover the disease mechanisms of gene variants causing Robinow Syndrome was provided by the Canadian Institutes for Health Research. Funding in the Allan lab that uses fruit flies to discover the disease mechanisms and assess gene variants in overgrowth diseases and in autism and dementia come from the Canadian Institutes of Health Research, Simons Foundation Autism Research Initiative, and the Alzheimer’s Society of Canada, respectively.


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