Fig. 1

Targeted HaploSeq experimental design. a Outline of the Targeted HaploSeq protocol. Briefly, crosslinked chromatin is digested using restriction enzyme(s) of choice. The digested chromatin ends are biotinylated and ligated in a spatially proximal manner, enabling formation of signature artificial fragments—where spatially proximal distinct chromatin segments are combined into a single fragment. Target-specific oligonucleotide probes are then used to capture and enrich for user-defined proximity-ligated artificial fragments, to create a targeted HaploSeq library. This library is sequenced and used to generate locus-spanning haplotypes. b Illustration of oligonucleotide probe design: A browser shot of the 3.5 Mb MHC region illustrating location of probes near HindIII cut sites. The inset shows probe targets near HLA-A gene. Specifically, we tiled 120 nt probes (blue) at 4X density across non-repetitive segments around HindIII cut sites. In addition, we also targeted exonic regions of the MHC locus, as depicted in yellow