Researchers at Johns Hopkins University investigated how genetic and epigenetic regulation combine to control gene expression in catastrophic antiphospholipid syndrome (CAPS), a rare but severe thromboinflammatory disease. Their work focuses on Complement Receptor 1 (CR1), a key regulator of immune complex clearance, and seeks to understand why CR1 expression is profoundly reduced in affected patients.
In this study, the authors integrated genetic findings with DNA methylation profiling to dissect mechanisms underlying CR1 downregulation. Using duet evoC 6-base sequencing, they directly measured 5mC levels across the CR1 locus, enabling precise mapping of promoter hypermethylation and its relationship to gene expression changes, alongside known genetic variants.
The researchers demonstrated that CR1 downregulation arises through two distinct but converging mechanisms: rare germline variants that disrupt CR1 transcription, and promoter hypermethylation that epigenetically silences CR1. Together, these findings show how genetic and epigenetic information provide complementary insight into disease biology.
This work illustrates the value of single‑molecule multiomic analysis for uncovering mechanisms of gene regulation that would otherwise remain hidden, highlighting how combined genetic and DNA methylation data can link regulatory state to functional gene expression in human disease.
