Acquired 6pLOHs in AA patients that target the HLA locus. (A) Typical CNAG outputs in SNP array analysis showing CNN-LOH (purple line) that appears as significant dissociation in allele-specific copy number graphs (red and green lines) from the baseline with normal total copy numbers (tCN; top panel). As a result of an allelic conversion, the affected segment causes LOH (* indicates 1; bottom panel). The “acquired” origin of these lesions is indicated by the retention of substantial numbers of heterozygous SNP calls (green bars below the chromatogram) that would otherwise mostly disappear. (B) The breakpoints of 6pLOHs found in a total of 28 AA cases, all involving the HLA locus in common. In more than half of cases (indicated by arrowheads in panel B), the exact location of the breakpoint was difficult to uniquely determine, where dissociation of the allele-specific copy number graphs continuously tapered along the 6p arm, indicating the presence of multiple 6pLOH(+) clones with common missing alleles (C). Indeed, the breakpoint containing regions are separated into multiple segments having significantly different copy numbers in the circular binary segmentation model, as indicated by solid lines with P values. Note that the most telomeric breakpoint is located within (case 24) or centromeric to (case 23) the HLA locus in each case. (D) A skewed distribution of the logarithm of P values in AA cases compared with normal persons. The P values were calculated in the Mann-Whitney U test, with which the difference in the mean allele-specific copy numbers between 6p and other chromosomal regions was evaluated (see “Analysis of genomic copy numbers and detection of 6pLOH”). A total of > 250 values are plotted as 250.