Authors
Martin W Breuss, Danny Antaki, Renee D George, Morgan Kleiber, Kiely N James, Laurel L Ball, Oanh Hong, Ileena Mitra, Xiaoxu Yang, Sara A Wirth, Jing Gu, Camila AB Garcia, Madhusudan Gujral, William M Brandler, Damir Musaev, An Nguyen, Jennifer McEvoy-Venneri, Renatta Knox, Evan Sticca, Martha Cristina Cancino Botello, Javiera Uribe Fenner, Maria Cárcel Pérez, Maria Arranz, Andrea B Moffitt, Zihua Wang, Amaia Hervás, Orrin Devinsky, Melissa Gymrek, Jonathan Sebat, Joseph G Gleeson
Publication date
2020/1
Journal
Nature Medicine
Volume
26
Issue
1
Pages
143-150
Publisher
Nature Publishing Group US
Description
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 …
Total citations
20202021202220232024202124139
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