Extended Data Fig. 1: Gene expression patterns across whole blood samples.
From: Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
We used a total of 1,061 whole blood samples from our controls cohorts and rare disease samples. a, Density plot representing the proportion of annotated junctions covered per gene. Those are a subset of genes for which at least one junction is covered with at least five uniquely mapped reads across at least 20% of the samples. On average (blue dashed line) 86%, (median of 100%—red dashed line) of junctions fulfil those criteria. b, Percentage of genes from disease genes panels in which at least one junction is covered with at least five uniquely mapped reads in at least 20% of samples. We observe that about 50% of genes from OMIM, Neurology, Musculoskeletal, Ophthalmology or Hematology panels are fulfilling this criteria. c, Tolerance to different types of mutations (from ExAC) in function of the expression status in a single versus multiple tissues (two-sided Wilcoxon test, Pvalue ≤ 2 × 10−16). Analysis performed on 620 individuals from GTEx v.7 across 22 tissues. Boxplots represent median value, with lower and upper hinges corresponding to the 25th and 75th percentiles, and lower and upper whiskers extend from the hinge to the smallest and largest value at most 1.5× interquartile range of the hinge, respectively. Genes that are expressed in multiple tissues tend to be more sensitive to missense and LoF mutations. d, Number of LoF intolerant genes stratified by expression level in blood. We considered genes with pLI score ≥ 0.9 as LoF intolerant.
