15 Jul Unbiased mosaic variant assessment in sperm: a cohort study to test predictability of transmission
Genomic mosaic mutations—present in some but not all cells within a tissue—record the history of embryonic development, environmental exposure, and have a wide range of implications for human health (Biesecker and Spinner, 2013; Paquola et al., 2017). Mosaic mutations are commonly recognized in cancers or localized overgrowth disorders, such as Proteus, CLOVES, and hemimegalencephaly syndromes (Lee et al., 2012; Lindhurst et al., 2011; Goncalves et al., 2018). Increasingly recognized in more complex diseases such as autism spectrum disorder or structural abnormalities (Jamuar et al., 2014; Rodin et al., 2021,) mosaic mutations are typically restricted to the individual in which they arise unless they appear prior to the embryonic separation of somatic and germline lineages or within germ cell progenitors. In these cases, gonadal mosaic mutations (comprising gonad specific and gonosomal) have the potential to transmit to offspring. These will appear as a considerable portion of de novo mutations and may result in miscarriage or a congenital or complex disease—often without phenotypes in the parents (Breuss et al., 2021; Yang et al., 2020).