Josh Tycko


Systematic discovery of protein functions in human cells to understand gene regulation and enable gene therapy


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Josh Tycko


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Department of Neurobiology


Harvard Medical School




Josh Tycko


Systematic discovery of protein functions in human cells to understand gene regulation and enable gene therapy



Department of Neurobiology


Harvard Medical School



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


Journal article


V. Bajpai, T. Swigut, Jaaved Mohammed, Josh Tycko, S. Naqvi, M. Arreola, Tayne C. Kim, Neha Arora, J. Pritchard, M. Bassik, J. Wysocka
bioRxiv, 2021

Semantic Scholar DOI
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APA
Bajpai, V., Swigut, T., Mohammed, J., Tycko, J., Naqvi, S., Arreola, M., … Wysocka, J. (2021). A genome-wide genetic screen uncovers novel determinants of human pigmentation. BioRxiv.

Chicago/Turabian
Bajpai, V., T. Swigut, Jaaved Mohammed, Josh Tycko, S. Naqvi, M. Arreola, Tayne C. Kim, et al. “A Genome-Wide Genetic Screen Uncovers Novel Determinants of Human Pigmentation.” bioRxiv (2021).

MLA
Bajpai, V., et al. “A Genome-Wide Genetic Screen Uncovers Novel Determinants of Human Pigmentation.” BioRxiv, 2021.


Abstract

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 transcriptomes from diversely pigmented individuals reveals that the majority of genes discovered in our screen are upregulated in dark skin melanocytes, in agreement with their melanin-promoting function and potential contribution to skin color variation. This association is further buttressed by the significant skin color heritability enrichment in the vicinity of these genes. Taken together, our study presents a novel approach to assay pigmentation and uncovers a plethora of melanogenesis regulators, with broad implications for human variation, cell biology and medicine. One Sentence Summary Genetic screen uncovers genes involved in human melanogenesis, many of which are differentially expressed in individuals of diverse skin color.


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