Raheleh Rahbari

Keywords postzygotic mosaicism early embryonic mutations whole-genome sequencing trio sequencing germline mutation rare disease genetics Main text Most heritable mutations arise in adult germ cells throughout aging and gametogenesis and are known as germline de novo mutations (DNMs).1,2 However, mutations can also arise as early as the first zygotic cell division. These are termed postzygotic mutations (PZMs).1,3,4,5 Depending on developmental timing, PZMs can be classified into two categories.

Abstract Our immune system contains multiple checkpoints to prevent the activation of self-reactive lymphocytes. How some lymphocytes escape these constraints to cause autoimmune disease remains poorly understood. A long-standing hypothesis posits that somatic mutations in immune-regulatory genes may enable self-reactive lymphocytes to bypass tolerance checkpoints1–3, but testing this has been challenging due to technical limitations.