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An Indian-origin researcher in Oklahoma, Vivek Bajpai along with his team has identified 135 new melanin genes associated with pigmentation.
According to the study published in the journal Science, the skin, hair and eye color of more than eight billion humans is determined by the light-absorbing pigment known as melanin.
Melanin is produced within special structures called melanosomes.
Melanosomes are found inside melanin-producing pigment cells called melanocytes.
Although all humans have the same number of melanocytes, the amount of melanin they produce differs and gives rise to the variation in human skin color, the researchers said.
“To understand what actually causes different amounts of melanin to be produced, we used a technology called CRISPR-Cas9 to genetically engineer cells,” said Bajpai, PhD, lead author and an assistant professor at the University of Oklahoma.
“Using CRISPR, we systematically removed more than 20,000 genes from hundreds of millions of melanocytes and observed the impact on melanin production,” he added.
To identify which genes influence melanin production, cells that lost melanin during the gene removal process needed to be separated from millions of other cells that did not.
Using in vitro cell cultures, Bajpai developed a novel method to achieve this goal that detects and quantifies the melanin-producing activity of melanocytes.
“Using a process called side-scatter of flow cytometry, we were able to separate cells with more or less melanin. These separated cells were then analyzed to determine the identity of melanin-modifying genes. We identified both new and previously known genes that play important roles in regulating melanin production in humans,” he said.
The researchers found 169 functionally diverse genes that impacted melanin production, and of those, 135 were not previously associated with pigmentation.
They further identified the function of two newly discovered genes — KLF6 and COMMD3.
According to the study, the DNA-binding protein KLF6 led to a loss of melanin production in humans and animals, confirming the role KLF6 plays in melanin production in other species as well, while the COMMD3 protein regulated melanin synthesis by controlling the acidity of melanosomes.
“By understanding what regulates melanin, we can help protect lighter-skinned people from melanoma, or skin cancer,” Bajpai stated.
“By targeting these new melanin genes, we could also develop melanin-modifying drugs for vitiligo and other pigmentation diseases,” he added.
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