Extended Data Fig. 5: Sperm mosaicism stratifies recurrence risk for dSV and dSTRΔ variants.
From: Autism risk in offspring can be assessed through quantification of male sperm mosaicism
a-c, Calculated copy number (a, c) and fraction of supporting reads (b) for the 6q16.1 deletion in F01 and The 1p36.32 duplication as indicated. Orange band in a and c: ± 1 SD of the CN using similarly sized regions across the genome (n = 1,000 random regions, see Methods). Plot in b shows the estimated fraction of supporting reads (estimated fraction ± binomial 95% CI; based on the fraction of mutant reads, see Supplementary Data 7). Together, these approaches suggest that these dSVs are not mosaic in paternal sperm. Note that the fraction of supporting reads could not be used for the duplication due to the repetitive elements flanking this SV. d, Copy number variant plot for the duplication in F06 for the Proband (40 × ), Father (200 × both), and the mother (40 × ). Visualization was performed with the CNView36 tool (see Methods). e, Correlation of the number of dSTRΔs with paternal age at birth. Dashed line shows a regression curve (n = 14 trios, adjusted R2 = -0.058, P = 0.598). Adjusted R2, coefficient of determination, and F-statistic nominal P-value are derived from a linear regression model through ordinary least squares. Graph shows individual data points, a regression line, and the 95% CI. f, Number of STR repeat units for non-mosaic dSTRΔs or those that are mosaic. No significant difference can be observed between the two groups (n = 111 non-mosaic variants and n = 15 mosaic variants; two-tailed Mann Whitney test; nominal P = 0.5490). Boxplots show median and quartiles with outliers as well as individual values. g, Detailed analysis of the TCTA repeat numbers in paternal, maternal, and child’s blood at low sequencing depth. Results show a de novo 13 × repeat in the child that is neither present in the father nor the mother. h, Sample reads showing the presence of a 10 × and 13 × allele in the child, a homozygous 10 × allele in the mother, a 10 × and a 12 × allele in the father, and the presence of a mosaic 13 × allele exclusively in paternal sperm.
