|
Fig. 2 Haplotype analysis performed on individuals with homozygous repeat expansions in VWA1 (top) compared to similar results for RFC1 (bottom). Shared homozygous SNPs are plotted for 20 Mb segments of chromosome 1 and 4. In both cases, the most significant regions detected span the VWA1 and RFC1 loci where several consecutive SNPs are homozygous in 7/7 or 10/10 individuals respectively. For the VWA1 locus, the five shared SNPs labelled with rsIDs are highly informative, with global 1000 Genomes project allele frequencies <5% (1000G AF). The reciprocal of the allele frequency is plotted on the y-axis to give an idea of the information content for each of the shared SNPs. Within the VWA1 haplotype block we also observed a rare SNV in the 5′-UTR of ANKRD65 (rs758603246), which is heterozygous in 3/7 individuals. The variants appear to be in complete linkage disequilibrium as in the 100KGP all individuals with rs758603246 also have p.G25Rfs*74. Our interpretation is that rs758603246 is a more recent mutation and so is observed only on a subset of p.G25Rfs*74-containing haplotypes.