What Happens to Individual Samples?

What happens to individual samples in CIRCA?

How CIRCA works: a summary

Patients with extraordinary clinical presentations and strong family histories are continually being recruited to take part in CIRCA’s research.

Targeted sequencing or diagnostic whole genome sequencing is performed through the Immunopathology lab at the Children's Hospital at Westmead and Genome.One. The function of a patient’s immune cells is assessed by affiliated research groups, which have cutting edge expertise in bioinformatics, molecular genetics and cellular immunology, and the capacity to develop mouse models of disease using the CRISPR/Cas9 platform.

The role of whole genome sequencing in CIRCA’s research

Candidate families for sequencing are presented by their consulting immunologists and screened on the basis of strict criteria, including extensive phenotyping and sequencing of a panel of known genes.

CIRCA is working closely with Genome.One to obtain genomic information from consenting individuals with immune disease. Genome.One, a wholly owned subsidiary of the Garvan Institute of Medical Research, is the southern hemisphere’s only clinical diagnostic service using whole genome sequencing (WGS) to obtain genomic diagnoses.

Potential disease causing genes will be identified using WGS, which will be performed and analysed by Genome.One. Where known disease-causing mutations are not found, the sequence will be interrogated for novel mutations.

Next steps: Defining new molecular pathologies

Every individual’s genome contains large numbers of genetic variations, so understanding which of a patients’ gene mutations actually causes disease requires in-depth analysis in experimental systems.

Following genetic analysis, consulting clinicians, geneticists and research scientists collaborate to identify candidate gene variations and perform functional studies. These include in vitro human cell assays and establishment of mouse models with orthologous mutations, to test the functional consequences of the genetic variations observed. This experimental work has the power to confirm which genetic variations are causative of disease, and through what mechanism.