Replication factor C subunit 1, the protein encoded by the RFC1 gene, is the largest of five subunits making up the RFC protein complex. This complex loads the ring-shaped PCNA protein onto the DNA during replication. A repeat expansion of RFC1 was identified as the genetic cause of CANVAS, a syndrome clinically characterized by cerebellar ataxia combined with neuropathy and bilateral vestibular areflexia. In a study recently published in The American Journal of Human Genetics, researchers report how they determined the disease-causing genetic variant, a homozygous intronic AAGGG expansion, by applying specific bioinformatics tools. They first performed genome sequencing in their patients and then used five independent algorithms for analysis of the generated NGS data.

Pathogenic repeat expansions, i.e. genetic variations in which the repeat number is expanded beyond a gene-specific threshold, are underlying various neurogenetic disorders. Identifying such expanded repeat sequences is complex and it is only in the past few years that computational tools have been developed which allow to detect them now also in NGS data. In an independent study, another group of researchers found the identical repeat expansion in RFC1 in patients, using a combination of genome sequencing and linkage analysis