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Developmental and temporal characteristics of clonal sperm mosaicism.
Yang, Xiaoxu; Breuss, Martin W; Xu, Xin; Antaki, Danny; James, Kiely N; Stanley, Valentina; Ball, Laurel L; George, Renee D; Wirth, Sara A; Cao, Beibei; Nguyen, An; McEvoy-Venneri, Jennifer; Chai, Guoliang; Nahas, Shareef; Van Der Kraan, Lucitia; Ding, Yan; Sebat, Jonathan; Gleeson, Joseph G.
Afiliação
  • Yang X; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Breuss MW; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Xu X; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Antaki D; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • James KN; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Stanley V; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Ball LL; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • George RD; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Wirth SA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Cao B; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Nguyen A; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • McEvoy-Venneri J; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Chai G; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Nahas S; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Van Der Kraan L; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Ding Y; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
  • Sebat J; Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA
  • Gleeson JG; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA. Electronic address: jogleeson@health.ucsd.edu.
Cell ; 184(18): 4772-4783.e15, 2021 09 02.
Article em En | MEDLINE | ID: mdl-34388390
ABSTRACT
Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of clonal mosaic mutations in male gonads by sequencing ejaculated sperm. Through 300× whole-genome sequencing of blood and sperm from healthy men, we find each ejaculate carries on average 33.3 ± 12.1 (mean ± SD) clonal mosaic variants, nearly all of which are detected in serial sampling, with the majority absent from sampled somal tissues. Their temporal stability and mutational signature suggest origins during embryonic development from a largely immutable stem cell niche. Clonal mosaicism likely contributes a transmissible, predicted pathogenic exonic variant for 1 in 15 men, representing a life-long threat of transmission for these individuals and a significant burden on human population health.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espermatozoides / Crescimento e Desenvolvimento / Mosaicismo Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espermatozoides / Crescimento e Desenvolvimento / Mosaicismo Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article