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

Breuss, M. W., Antaki, D., George, R. D., Kleiber, M., James, K. N., Ball, L. L., Hong, O., Mitra, I., Yang, X., Wirth, S. A., Gu, J., Garcia, C. A. B., Gujral, M., Brandler, W. M., Musaev, D., Nguyen, A., McEvoy-Venneri, J., Knox, R., Sticca, E., Botello, M. C. C., Uribe Fenner, J., Perez, M. C., Arranz, M., Moffitt, A. B., Wang, Z., Hervas, A., Devinsky, O., Gymrek, M., Sebat, J., Gleeson, J. G. (December 2019) Autism risk in offspring can be assessed through quantification of male sperm mosaicism. Nat Med, 26 (1). pp. 143-150. ISSN 1078-8956

URL: https://www.ncbi.nlm.nih.gov/pubmed/31873310
DOI: 10.1038/s41591-019-0711-0

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.

Item Type: Paper
Subjects: diseases & disorders > mental disorders > personality disorders > autism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > de novo mutation
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Depositing User: Adrian Gomez
Date: 23 December 2019
Date Deposited: 09 Jan 2020 17:28
Last Modified: 14 Feb 2020 19:05
Related URLs:
URI: https://repository.cshl.edu/id/eprint/38888

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