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Autism risk in offspring can be assessed through quantification of male sperm mosaicism.
Breuss, Martin W; Antaki, Danny; George, Renee D; Kleiber, Morgan; James, Kiely N; Ball, Laurel L; Hong, Oanh; Mitra, Ileena; Yang, Xiaoxu; Wirth, Sara A; Gu, Jing; Garcia, Camila A B; Gujral, Madhusudan; Brandler, William M; Musaev, Damir; Nguyen, An; McEvoy-Venneri, Jennifer; Knox, Renatta; Sticca, Evan; Botello, Martha Cristina Cancino; Uribe Fenner, Javiera; Pérez, Maria Cárcel; Arranz, Maria; Moffitt, Andrea B; Wang, Zihua; Hervás, Amaia; Devinsky, Orrin; Gymrek, Melissa; Sebat, Jonathan; Gleeson, Joseph G.
Afiliación
  • Breuss MW; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Antaki D; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • George RD; Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
  • Kleiber M; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • James KN; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Ball LL; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Hong O; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Mitra I; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Yang X; Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
  • Wirth SA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Gu J; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Garcia CAB; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Gujral M; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Brandler WM; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Musaev D; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Nguyen A; Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
  • McEvoy-Venneri J; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Knox R; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Sticca E; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Botello MCC; Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Uribe Fenner J; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.
  • Pérez MC; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Arranz M; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Moffitt AB; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Wang Z; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Hervás A; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Devinsky O; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Gymrek M; Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
  • Sebat J; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.
  • Gleeson JG; Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
Nat Med ; 26(1): 143-150, 2020 01.
Article en En | MEDLINE | ID: mdl-31873310
ABSTRACT
De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno Autístico / Espermatozoides / Predisposición Genética a la Enfermedad / Mosaicismo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Trastorno Autístico / Espermatozoides / Predisposición Genética a la Enfermedad / Mosaicismo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos