Extended Data Fig. 4: Identification of functional variants associated with skin pigmentation near OCA2.
(a) SNP rs6497271 is in a melanocyte-specific enhancer. Blue tracks indicate DNase-Seq, ATAC-Seq, and ChIP-Seq data from melanocytes; orange tracks indicate ChIP-Seq data from melanoma (501-mel) cells; green tracks indicate DNase-Seq data from ENCODE cell lines. E1-E4, enhancers. The plotted region is chr15: 28,335,146-28,385,146 (hg19). (b) MPRA and LRA reveals that rs4778242 significantly affects the enhancer activity of E1 in MNT-1 and WM88 cells. MPRA (n = 3), LRA (n = 9). (c) MPRA showed that rs6497271 affects the enhancer activity of E2 in MNT-1 and WM88 cells (n = 3). (d) MPRA shows that rs7495989 affects the enhancer activity of E3 in MNT-1 and WM88 cells (n = 3). (e) MPRA and LRA reveals that rs4778141 affects the enhancer activity of E4 in MNT-1 and WM88 cells. MPRA (n = 3), LRA (MNT-1, n = 9; WM88, n = 6). (f) rs6497271 overlaps transcription factor binding sites. Left panel shows rs6497271 disrupts the binding motif of LEF1 and SOX10. Right panel shows that rs6497271 overlaps ChIP-seq peaks from Cistrome database103. LRA data are presented as mean ± SEM, tested with two-tailed paired t-tests. MPRA p-values are estimated with a random effects model for mpralm and paired t-tests with multiple testing adjustments. For MPRA boxplots, central lines are median, with boxes extending from the 25th to the 75th percentiles. Whiskers further extend by ±1.5 times the interquartile range from the limits of each box.
