VHL UK Ireland has granted £20,000 to Professor William Drake Consultant Physician/Professor of Clinical Endocrinology at St Bartholomew’s Hospital.
Some snippets taken from the project description.
Saturation genome editing (SGE)is a method that allows us to assay thousands of genetic variants in their endogenous genomic context. SGE was used previously to assay 3,893 SNVs in BRCA1 for functional effects at the mRNA and protein level in human HAP1 cells2. “Function scores” derived for each variant were highly accurate at distinguishing established pathogenic variants, indicating SGE data can aid clinical variant interpretation. Watch this YouTube video about SGE used for BRCA1.
Using SGE on VHL variants to produce a systematic genotype-phenotype map of VHL would prove useful for adjudicating which variants are pathogenic. Furthermore, by using multiple assays to study all possible coding variants, we will gain insights into how disruption of the gene’s distinct molecular functions correlates with clinical presentation.
This Grant Award was made possible from the fundraising by Charles White in 2020
This project was successfully completed in July 2024 with the publication of results in Nature Saturation genome editing maps the functional spectrum of pathogenic VHL alleles. This was announced in a press release from the Crick Institute. Learn more