Genome-wide profiling of heritable and de novo STR variations

Abstract

Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases, population genetics applications, and forensic casework. However, it has proven problematic to genotype STRs from high-throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based method for robustly genotyping and phasing STRs from Illumina sequencing data, and we report a genome-wide analysis and validation of de novo STR mutations. HipSTR is freely available at https://hipstr-tool.github.io/HipSTR.

Figure 1. Performance of variant callers in STR regions

The accuracy of each tool’s calls is shown as a function of sensitivity for the Marshfield STR panel. Solid and dashed lines denote tools run using default settings and settings optimized for STR genotyping, respectively.

Figure 2. Experimental validation of de novo STR mutations

The top panel depicts the number of repeats HipSTR identified in each family member for four STRs with a predicted de novo mutation (novel allele in bold). The bottom three panels illustrate the number of clones with repeat sizes predicted (red) or not predicted (gray) by HipSTR during Sanger sequencing of these same individuals.