Fig. 1

Graphical abstract of the study. a Schematic overview of the workflow of our analysis. 99 individuals with the wellderly phenotype were sequenced three times with Illumina HiSeq X (HSX, Apr. 2016), Illumina HiSeq (MOL, Feb. 2011), and Complete Genomics (CG, Apr. 2011). The resulting sequencing data were processed with three different bioinformatic pipelines. For CG, the in-house software cgatools (v. 1.6.0) with the Complete Genomics Analysis pipeline (v. 2.0.22) was used. At the same time, both Illumina cohorts were aligned and called with Isaac Alignment Software and Isaac Variant Caller. In our current study, we analyzed the resulting vcf-files. We also reprocessed the MOL and HSX cohorts with the GATK pipeline for germline short variant discovery (SNP + indel). b We evaluated the concordance of called variants between different setups by intersecting the respective vcf-files. The average number of concordant variants for different intersections was calculated and reported. Furthermore, we investigated the concordance in introns, exons, intergenic regions, repeat elements annotated with the RepeatMasker software, and bins with varying GC content. Concordance was assessed with the Jaccard distance. c We applied the MAF 5% and HWE 5% filters and kept the variants with MAF < 0.05 and HWE < 0.05. We then determined the distribution of these rare variants