Detection and molecular characterization of a large deletion at the HFE locus. (A) Summary of mapping PCRs showing location of primer pairs on the chromosome band 6p21.3. indicate a region deleted in the reported case and indicate an unmodified sequence. Positions and directions of the gap PCR primers are shown in grey. Numbering is based on the UCSC human genome assembly. (B,C) Sequencing electrophoretogram of the recombined allele and sequence alignment of the Alu elements (AluSc in 5′, and AluSg in 3′) responsible for the chromosomal alteration. The gray box highlights a 17 bp track of perfect homology that marks the crossover region. The sequence deleted in the new allele is shown in gray. Interestingly, the intervening sequence contains 2 sequence motifs, CCACCA and CCAGC. Both motifs represent truncated versions of the Chi hotspots (consensus sequence: 5′-GCTGGTGG-3′ or its complement, 5′-CCACCAGC) of generalized recombination.^12,13  In particular, CCACCA has been previously reported as a mutational “super-hotspot” common to micro-deletions, micro-insertions, and indels.¹⁴