Genomic landscape of 133 melanocytes from human skin

This supplemental dataset is part of our study to better understand the genetic landscape of normal skin at single-cell resolution. We performed DNA and RNA sequencing of 133 clones of normal human melanocytes (150 cells/clone on average). A manuscript describing these analyses is in preparation. To accompany our forthcoming manuscript, here, we include a summary of the 133 clones from this study. Each page of the pdf corresponds to an individual melanocyte clone and is structured similarly as follows:

Panel A shows cellular and tissue images, where available, alongside information describing clone size, cell morphology, and anatomic location of the donor tissue.

Panel B shows the variant allele fraction of raw calls relative to their validation status. Variants were validated as somatic mutations or assumed to be amplification artifacts (i.e. invalidated) based on their patterns in the DNA and RNA sequencing data (see accompanying manuscript for a full description). Note that validated variants are more likely to have a variant allele fraction of ~0.5, consistent with a true heterozygous variant. Potentially pathogenic mutations are highlighted in orange and pathogenic mutations are highlighted in red.

Panel C shows copy number alterations called from DNA and RNA sequencing data (red = gain; blue = loss) alongside any identified regions of allelic dropout (blue = mono-allelic dropout; black = bi-allelic dropout). The fraction of each clone with allelic dropout is indicated. As expected, deletions coincided with mono-allelic dropout, and thus we also report the portion of the genome with allelic dropout “excluding deletions” – this is an indicator of our sensitivity to detect mutations.

Panel D shows the CDKN2A variant status. Initially, we assumed melanocytes must be null for CDKN2A to have the ability to clonally expand, therefore mutations were engineered with the intent to spur cell division. However, this assumption proved not to hold true and so subsequent melanocytes were not genetically altered. Consequently, only 5 clones, all from the beginning of the study, were engineered to be deficient for the CDKN2A gene.