Human-specific tandem repeat expansion and differential gene expression during primate evolution

Short tandem repeats (STRs) and variable number tandem repeats (VNTRs) are among the most mutable regions of our genome but are frequently underascertained in studies of disease and evolution. Using a combination of long-read sequence data (PacBio) and linked reads (10x Genomics) from a collection of humans and three nonhuman primates, we present a sequence-based evolutionary framework for ∼20,000 phased STRs and VNTRs. We identify 1,584 tandem repeats that are specifically expanded in the human lineage, and demonstrate their biological relevance in association with gene expression, RNA splicing, and genetic instability.