A genome-wide genetic screen uncovers novel determinants of human pigmentation

@article{Bajpai2021AGG,
  title={A genome-wide genetic screen uncovers novel determinants of human pigmentation},
  author={Vivek K. Bajpai and Tomek Swigut and Jaaved Mohammed and Josh Tycko and Sahin Naqvi and Martin Arreola and Tayne C. Kim and Neha Arora and Jonathan K. Pritchard and Michael C. Bassik and Joanna Wysocka},
  journal={bioRxiv},
  year={2021}
}
The skin color is one of the most diverse human traits and is determined by the quantity, type and distribution of melanin. Here, we leverage light scattering properties of melanin to conduct a genome-wide CRISPR-Cas9 screen for novel regulators of melanogenesis. We identify functionally diverse genes converging on melanosome biogenesis, endosomal transport and transcriptional/posttranscriptional gene regulation, most of which represent novel associations with pigmentation. A survey of… 
View via Publisher
biorxiv.org

References

SHOWING 1-10 OF 34 REFERENCES

The Genetics of Human Skin and Hair Pigmentation.

The responsible polymorphisms within these pigmentation genes appear at different population frequencies, can be used as ancestry-informative markers, and provide insight into the evolutionary selective forces that have acted to create this human diversity.

Genome-Wide siRNA-Based Functional Genomics of Pigmentation Identifies Novel Genes and Pathways That Impact Melanogenesis in Human Cells

The power of RNAi-based functional genomics to identify novel genes, pathways, and pharmacologic agents that impact a biological phenotype and operate outside of preconceived mechanistic relationships is illustrated.

A curated gene list for expanding the horizons of pigmentation biology

A comprehensive, cross‐species list of 650 genes involved in pigmentation phenotypes that was compiled with extensive manual curation of genes annotated in OMIM, MGI, ZFIN, and GO provides a valuable tool that can be used to expand the knowledge of complex, pigmentation‐associated pathways.

Shades of complexity: New perspectives on the evolution and genetic architecture of human skin.

Examining how the knowledge of pigmentation genetics has shifted in the last decade can better appreciate how far humans have come in understanding human diversity and the still long road ahead for understanding many complex human traits.

Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

A novel method of removing melanin that includes in-solution digestion and immobilized metal affinity chromatography (IMAC) is reported, which has allowed this work to characterize melanosome proteomes at various developmental stages by tandem mass spectrometry.

Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas

A comprehensive view of changes in advanced melanoma relative to normal melanocytes is provided and new targets that can be used in assessing prognosis, staging, and therapy of melanoma patients are revealed.

Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas.

A comprehensive view of changes in advanced melanoma relative to normal melanocytes is provided and new targets that can be used in assessing prognosis, staging, and therapy of melanoma patients are revealed.

GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background

UK Biobank GWAS results for three molecular traits—urate, IGF-1, and testosterone—with better-understood biology than most other complex traits are described, with strong enrichment of signal in putative core gene sets, even while most of the SNP-based heritability is driven by a massively polygenic background.

Melanocytes and their diseases.

Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues, and vitiligo is reviewed as a representative of an acquired hypopigmentation disorder.

Partitioning heritability by functional annotation using genome-wide association summary statistics

A new method is introduced, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers, which is computationally tractable at very large sample sizes and leverages genome-wide information.