Extended Data Fig. 8: Cases with protein-null phenotypes.
From: Whole-genome sequencing of patients with rare diseases in a national health system
a, Alignments in the ITGB3 locus for an individual with Glanzmann’s thrombasthenia with a premature stop (blue bar) and a tandem repeat revealed by improperly mapped read pairs. b, Number of improperly mapped read pairs in the ninth intron of ITGB3 in 6,656 samples sequenced by 150-bp reads before (light grey dots) or after (dark grey squares) the data freeze. The patients with Glanzmann’s thrombasthenia with the tandem repeat and with the SVA insertion, and the carrier mother of the latter, are highlighted. c, d, Alignments in the ITGB3 locus for the proband with Glanzmann’s thrombasthenia (c) and his mother (d) with a p.T456P variant for the proband (blue bar) and an insertion revealed by an excess of mapped reads for the ninth intron for the proband and his mother. e, Top, long-read alignments for the PCR-amplified ITGB3 DNA from the proband with Glanzmann’s thrombasthenia covering the element with excess reads. Downstream read element (DRE) starts are represented in the histogram. Bottom (from left to right), the pedigree for the patient with Glanzmann’s thrombasthenia (A, proband; B, mother; C, grandmother) with the flow cytometry measurements of platelet GPIIbIIIa expression indicated as the percentage of normal levels and genotypes; confirmation of the insertion by gel electrophoresis of PCR products covering the insertion; diagram of the inserted SVA retrotransposon element (insSVA). f, Alignments in the RHAG locus of the Rh-null case with a splice donor variant (blue bar) and a tandem duplication revealed by improperly mapped read pairs.
