近日，美国加州大学圣地亚哥分校Joseph G. Gleeson、Jonathan Sebat等研究人员合作发现，后代的自闭症风险可通过量化男性精子镶嵌来评估。2019年12月23日，《自然—医学》在线发表了这项成果。

研究人员使用全基因组深层测序技术对精子镶嵌进行了测量，确定了子代中存在且仅在父亲精子中可见的变体，并鉴定了单核苷酸、结构和短串联重复序列的变体。研究人员发现镶嵌症量化可以将因从头突变引起的自闭症谱系障碍的复发风险分层为两种：一大类复发率接近0％的，以及一小部分具有明显更高的可量化风险的，并且研究人员发现了新型镶嵌变异体有可能传播到后代中。因此，这表明精子镶嵌评估将有助于生育遗传咨询。

据介绍，父源染色体上出现的从头突变对已知的自闭症风险贡献最大，并且与受孕时的父亲年龄相关。自闭症谱系障碍的复发风险很大，导致许多家庭减少未来怀孕，但目前的研究尚未考虑评估父母性腺镶嵌症的潜在影响。

附：英文原文

Title: Autism risk in offspring can be assessed through quantification of male sperm mosaicism

Author: 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 A. B. 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 Crcel Prez, Maria Arranz, Andrea B. Moffitt, Zihua Wang, Amaia Hervs, Orrin Devinsky, Melissa Gymrek, Jonathan Sebat, Joseph G. Gleeson

Issue&Volume: 2019-12-23

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.

DOI: 10.1038/s41591-019-0711-0

Source: https://www.nature.com/articles/s41591-019-0711-0