Constrained gene analysis As we have previously described, genes associated with high risk of cancer in childhood show highly significant constraint. 24 This also holds true for genes associated with high WT risk, in which only 8% of expected pLoF occur in adult populations; markedly different from other genes (t-test; genes associated with monoallelic risk of WT vs all other genes, loss-of-function observed versus expected upper fraction (LOEUF) score 20.5% vs 95.3%, p<0.001) ( figure 4A ).
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Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort.
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