Figure 2. Fine mapping of the consensus AJ N370S founder haplotype region.

Hundreds of GBA-flanking SNPs (±250 kb from GBA) were sequenced in order to identify a conserved N370S founder haplotype. (A) NGS-based homozygosity mapping with 7 unrelated homozygote N370S Gaucher patients (denoted as H₁–H₇) (14 N370S chromosomes) was used to identify a preliminary founder haplotype. (B) A representative linkage-based inference of a familial N370S haplotype (hap_N370S). This linkage analysis was performed for 6 different heteroallelic GBA N370S mutation carrier duos (6 N370S chromosomes from 6 sets of 2 first-degree family members carrying the N370S mutation). The resultant alleles were each compared separately to the haplotype from A until a consensus N370S haplotype was demarcated with a 5′ cutoff. (C) Ultimately, the consensus AJ N370S founder haplotype (composed of 153 SNPs) used for NIPD was constructed from 20 different AJ N370S chromosome sequences. Note that this analysis set a 5′ cutoff for the conserved N370S haplotype, but a 3′ cutoff could not be established. WT denotes a WT allele.