Figure 1.
Individuals with DS exhibit CH. Panels A and B are from the initial cohort of disomic and trisomic samples; panels C-I are from the larger validation cohort of individuals with T21. (A) Number of discovered variants per person separated by genotype into disomic (D21) and trisomic (T21) samples. (B) Percent of individuals of each genotype that contain only clonal expansions without identified oncogenic mutations (No Onc) or contain clonal expansions that carry oncogenic mutations (Onc). (C) Total number of mutations per sample for individuals with T21 that contain no detected oncogenic mutations or contain at least 1 detected oncogenic mutation (but all have CH). (D) Within the cohort with T21, individuals are categorized as having no detectable CH (blue), detectable expansions (CH) without the presence of oncogenic mutations (red), or detectable CH with at least 1 oncogenic mutation (purple). (E) Independent error-corrected amplicon sequencing shows similar patterns of observed mutations for typical individuals. In the Young et al9 study, the median VAF for the rarest mutation was 0.0044 (range, 0.0007-0.0395); in the Liggett et al7 study, the median VAF for the rarest mutation was 0.0011 (range, 0.0002-0.0072). For the Young et al9 study, median age was 68 years (range, 63-76 years); for the Liggett et al7 study, the median age was 54 years (range, 0-89 years). (F) The number of oncogenic mutations detected within the trisomic cohort for the top 5 most commonly mutated genes. (G) To estimate the over- or underrepresentation of observed oncogenic mutations, the ratio of probed oncogenic mutations to the entire probed region for a gene was compared with the ratio of observed oncogenic mutations to all observed mutations (Fisher’s exact test). (H) VAF of discovered oncogenic variants. The x-axis shows equally spaced age-ranked individuals from youngest to oldest (left to right), with brackets distinguishing ages in 5-year increments. (I) For those individuals with T21, some showed multiple putative clonal expansions. The x-axis indicates the number of expansions per individual. *P < .05; ***P < .001.

Individuals with DS exhibit CH. Panels A and B are from the initial cohort of disomic and trisomic samples; panels C-I are from the larger validation cohort of individuals with T21. (A) Number of discovered variants per person separated by genotype into disomic (D21) and trisomic (T21) samples. (B) Percent of individuals of each genotype that contain only clonal expansions without identified oncogenic mutations (No Onc) or contain clonal expansions that carry oncogenic mutations (Onc). (C) Total number of mutations per sample for individuals with T21 that contain no detected oncogenic mutations or contain at least 1 detected oncogenic mutation (but all have CH). (D) Within the cohort with T21, individuals are categorized as having no detectable CH (blue), detectable expansions (CH) without the presence of oncogenic mutations (red), or detectable CH with at least 1 oncogenic mutation (purple). (E) Independent error-corrected amplicon sequencing shows similar patterns of observed mutations for typical individuals. In the Young et al9  study, the median VAF for the rarest mutation was 0.0044 (range, 0.0007-0.0395); in the Liggett et al7  study, the median VAF for the rarest mutation was 0.0011 (range, 0.0002-0.0072). For the Young et al9  study, median age was 68 years (range, 63-76 years); for the Liggett et al7  study, the median age was 54 years (range, 0-89 years). (F) The number of oncogenic mutations detected within the trisomic cohort for the top 5 most commonly mutated genes. (G) To estimate the over- or underrepresentation of observed oncogenic mutations, the ratio of probed oncogenic mutations to the entire probed region for a gene was compared with the ratio of observed oncogenic mutations to all observed mutations (Fisher’s exact test). (H) VAF of discovered oncogenic variants. The x-axis shows equally spaced age-ranked individuals from youngest to oldest (left to right), with brackets distinguishing ages in 5-year increments. (I) For those individuals with T21, some showed multiple putative clonal expansions. The x-axis indicates the number of expansions per individual. *P < .05; ***P < .001.

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