EPFL BioE Talks SERIES "High-Throughput Differentiation of hIPSCs From Hundreds of Individuals to Study Genetic Influences on Gene Expression"


Event details

Date 30.11.2020
Hour 16:0017:00
Speaker Prof. Daniel Gaffney, Wellcome Sanger Institute, Hinxton, Cambridge (UK)
Location Online
Category Conferences - Seminars

The majority of common human trait associated genetic variation appears to alter gene expression rather than protein structure. Despite substantial progress in mapping expression quantitative trait loci (eQTLs), there are significant gaps in our resources to interrogate the function of human noncoding genetic variation. For example, studying genetic variants that change expression only in activated cell states, or those whose function varies across developmental stages remains challenging. I will present two related pieces of work from our group that address some of these challenges using a model system based on human induced pluripotent stem cells (hIPSCs). In the first project, I will discuss using hIPSCs from hundreds of individuals differentiated to macrophages to map "response eQTLs" across scores of stimulated cell states. We show that, even within a single cell type, extensive disease relevant regulatory variation remains undiscovered. In the second project, I will discuss using “pooled” designs, where cell lines from multiple individuals are grown together and profiled using single cell RNA-seq. Here, we profile IPSCs differentiated to using an established dopaminergic protocol, and discover hundreds of disease relevant-associations that are not well captured by existing eQTL data bases, such as GTEx. I will also discuss some of the limitations of this system, such as extensive variation between lines in differentiation outcomes.

Daniel Gaffney earned his PhD in evolutionary genetics from Edinburgh University in 2006 under the supervision of Dr Peter Keightley. His graduate research used computational methods to study variation in the mutation rate and natural selection in noncoding DNA. From 2006 to 2008 he pursued a postdoc with Dr Jacek Majewski in McGill University and Genome Quebec Genome Centre, where he worked on the evolution of transcriptional regulation and alternative splicing in mammals. From 2008 until 2011 he worked on population genetic variation in gene expression and regulation with Dr Jonathan Pritchard at the University of Chicago.
In July 2011 Daniel Gaffney started as a Career Development Fellowship Group Leader at the Wellcome Sanger Institute and was promoted to Group Leader in October 2015. The long-term goal of the group is to understand the molecular and cellular consequences of genetic changes in gene regulatory regions. His research combines statistical genetics with high-throughput experimental techniques in human cells to address these questions. Much of the group’s recent research has been focussed on using human induced pluripotent stem cells (hIPSCs) and cells derived from hIPSCs as model systems to map and characterise human noncoding genetic changes.

Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks

IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 situation, this seminar can be followed via Zoom web-streaming only, following prior one-time registration through the link above.

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