Figure 2. LINE-1 Retrotransposition in a Boy with Hemophilia A.

Panel A shows the family pedigree. The solid orange square denotes the affected boy, and the other symbols indicate unaffected family members. The boy’s mother is not a carrier of the insertion in exon 14 of F8 (the gene encoding factor VIII). In Panel B, the precursor LINE-1 element isolated from the mother’s DNA is shown above the insertion. The precursor was a full-length LINE-1 in chromosome 22. The smaller pathogenic insertion was identical in sequence to a portion of the precursor LINE-1. The brown arrow at the 5′ end of the precursor element denotes the transcription start site from the LINE-1 internal promoter. TSD denotes target-site duplication, and the light-gray box next to TSD indicates genomic DNA. The diagram in Panel A is adapted from Kazazian et al.,²⁶ and the diagram in Panel B is adapted from Dombroski et al.¹¹