Genetic background effects in human iPSCs and iPSC-derived cell types (360G-Wellcome-207797_Z_17_Z)


Human induced pluripotent stem cells (iPSC) have emerged as a key model system to study the function of genetic variants, as they provide access to relevant cell types and developmental lineages through cellular differentiation. However, while it has been shown that the genetic background of the donor individual has an effect on molecular phenotypes measured from iPSCs, it is currently not known how much the genetic background influences studies that use iPSCs to model rare disease mutations, making interpretation of results challenging. In this project, I will use CRISPR-Cas9 technology to study specific rare disease mutations in different genetic backgrounds. Specifically, I will focus on loss-of-function mutations causing Kabuki syndrome, a disorder of the epigenetic machinery, and use patient-derived iPSCs together with engineered mutant and control lines to quantify the contribution of the genetic background on the transcriptome and epigenome of the iPSCs as well as neuronal precursor cells derived from them. This project will establish the value of using patient-derived iPSCs over generic iPSC lines with engineered mutations. This information is critical for the design of any subsequent studies in which iPSCs serve as the baseline, such as directed differentiation experiments and therapeutic targeting of the mutation.

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Grant Details

Amount Awarded 99935
Applicant Surname Kilpinen
Approval Committee Science Seeds Advisory Panel
Award Date 2017-05-12T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Seed Award in Science
Internal ID 207797/Z/17/Z
Lead Applicant Dr Helena Kilpinen
Partnership Value 99935
Planned Dates: End Date 2021-12-31T00:00:00+00:00
Planned Dates: Start Date 2018-01-02T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London