Extended Data Fig. 5: Identification of functional variants near MITF related to skin pigmentation in the San.
(a) A Plot showing functional Di-SNP rs111969762 is in a melanocyte-specific regulatory region. Blue tracks indicate DNase-Seq, ATAC-Seq, and ChIP-Seq from melanocytes; orange tracks indicate ChIP-Seq from melanoma (501-mel) cells; green tracks indicate DNase-Seq from ENCODE cell lines. E1-E2, enhancers. (b) MPRA showed that rs111969762 affects enhancer activity in WM88 cells (n = 3). (c) MPRA shows that rs7430957 impacts enhancer activity in WM88 cells (n = 3). (d) LRA shows that rs7430957 does not significantly alter the activity of the E2 enhancer near MITF. P values were estimated by two-tailed paired t-tests, MNT-1(n = 6), WM88 (n = 11). Data were presented as mean ± SEM. ns p > 0.05. (e) rs111969762 overlaps transcription factor binding sites. Left panel showed rs6497271 disrupts the binding motif of FOXP3. Right panel showed that rs111969762 overlaps ChIP-seq peaks from the Cistrome database103. MPRA p-values were 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.
