Figure 1. IBD mapping of founder mutations in recurrent regions of LOH.

This diagram illustrates the principles underlying our method. A founder mutation (red star on the schematic diagram of chromosomes) spreads through a population within a chromosome fragment (in red) inherited from the ancestral founder (A). Due to crossing-overs (dashed lines) between homologous chromosomes at meiosis, this chromosome fragment is shortened over generations, such that mutation carriers (indicated in red) eventually harbor only a short identical by descent (IBD) haplotype around the mutant gene (B). In addition, the wild-type counterpart of germline mutations is frequently lost by LOH in tumors, such that the founder mutation typically lies within a minimal region of LOH (C). As a result, the founder mutation is located within a haplotype conserved in each mutation carrier (peak IBD score), in the minimal region of LOH (D).