Raheleh Rahbari

Abstract Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles1. Whereas crossovers in humans are well characterized2, the more frequent non-crossovers that lead to gene conversion remain challenging to study. Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, which enables effectively arbitrary sample sizes for analysis from a single male.

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.