Deep Immunogenetics: New Diagnostic Service for Mosaic Variants in Immune Disorders

October 31, 2024

CeGaT’s new service, Deep Immunogenetics (DIG), is a high-coverage enrichment solution. DIG enables the detection of low-frequency mosaic variants in a broad range of genes associated with immune disorders. It has been designed in close collaboration with the group of Prof. Dr. Stephan Ehl, medical director of the Center for Chronic Immunodeficiency (CCI) in Freiburg, Germany.

Somatic mosaic variants are currently under-recognized as drivers of monogenic immune disorders. With evolving sequencing technologies, it has become apparent that low-grade mosaic variants with frequencies in blood samples of 5% and even less are sufficient to drive autoinflammation and immune dysregulation in affected patients. If present at such low frequencies, mosaic variants often remain undetected in standard next-generation sequencing panels, exome enrichments, and especially genome enrichments. With our new high-coverage enrichment Deep Immunogenetics (DIG), we address this diagnostic challenge and provide a tool for investigating mosaic variants in immune disorders.

With a mean coverage of approximately 1000X, DIG can reliably detect mosaic variants down to a frequency of 5% of sequencing reads and known disease-causing or hotspot variants down to a frequency of 2%. The enrichment contains not only protein-coding regions but also intronic and intergenic variants that are described to be disease-relevant in the HGMD and ClinVar databases.

We offer two gene panels: DIG01 covers monogenic disorders of lymphoproliferation and autoimmunity, such as autoimmune-lymphoproliferative syndrome (ALPS) and differential diagnoses. DIG02 addresses autoinflammatory diseases, including NLRP3 (cryopyrin)-associated periodic syndrome (CAPS) and NOD2-associated Blau syndrome. In addition to these predesigned panels, individual genes and custom gene sets for specific diagnostic queries are available upon request thanks to the large size of the DIG enrichment (337 genes).

Further information on Deep Immunogenetics can be found here.