Essential gene map aids rare disease understanding

The results from this study could be a useful new resource to help researchers identify mutations responsible for rare childhood diseases.

“When you sequence a person’s genome it’s not always one mutation that stands out as altering a gene’s function,” says Terry Meehan, Coordinator of Mouse Informatics at EMBL-EBI. “We currently don’t have a handle on which genes are important for development and which have a minor impact.”

Identifying which genes are linked to a rare disease is one of the most difficult challenges geneticists face. The low prevalence of these diseases within the population makes it difficult to research and fully understand their causes. However, huge advances in the diagnosis of rare diseases are now being made thanks to innovations in sequencing technology.

This research, published in Nature Communications, compares knockout mice viability and phenotyping data from the International Mouse Phenotyping Consortium (IMPC) with human cell lines provided by the Broad Institute’s Project Achilles to create categories indicating how crucial a gene is to producing viable life.

The researchers also identified new mutations likely responsible for rare childhood diseases by comparing their data with unsolved cases of genetic disorders identified in the 100,000 Genomes Project and the Deciphering Developmental Disorders (DDD) datasets.

“Of particular interest for application to healthcare, we demonstrate that the set of genes that are essential for organism development is particularly associated with known human developmental disorders,” says Damian Smedley, Reader in Computational Genomics at Queen Mary University of London. “This provides candidates for undiscovered causative genes for these conditions.”