Study Of Malaysian Tribe Could Help Find East Asian Skin Color Genes

Genetic investigation of a Malaysian tribe may tell scientists why East Asians have light skin but lower skin cancer rates than Europeans, according to a team of international researchers. Understanding the differences could lead to a better way to protect people from skin cancer.

While the genetics of skin color is largely unknown, past research using zebrafish by Penn State College of Medicine's Keith Cheng, M.D., Ph.D., identified the gene in Europeans that differs from West Africans and contributes to a lighter skin color. Mutations in the genes SLC24A5 and SLC45A2 are largely responsible for European pigmentation, showing only single amino acid differences between Europeans and West Africans. Each version of a gene is called an allele.

While East Asians -- Chinese, Japanese and Korean -- also are light skinned, these European alleles are not present, suggesting that while both groups' lighter skin color evolved to allow for better creation of vitamin D in northern climates, they did so in a different way. This difference also affects skin cancer rates. Europeans have 10 to 20 times higher rates of melanoma than Africans. However, despite also having lighter skin, East Asians have the same melanoma rates as Africans. The reason for this difference can only be explained when the gene mutations for both groups are found.

"By finding the differences, we have the potential to find ways to make people with the European ancestry genes less susceptible to skin cancer," said Cheng, professor of pathology.

This is a challenge, because to find the unidentified mutations, researchers must study a population that includes a blend of original African ancestry and East Asian ancestry, with little European contribution.

The Senoi, one of three indigenous tribes from Peninsular Malaysia, meet this condition. The Senoi are believed to include ancestry of a dark-skinned tribe called the Negrito, and a regional Mongoloid population of Indo-China, such as the Proto-Malay. Since the skin color of the Senoi is darker than that of Northeast Asians, researchers will be able to focus on finding the primary genetic mutation of light skin color in Asians without seeing further skin lightening mutations.

Khai C. Ang, Ph.D., postdoctoral fellow in the Cheng lab, visited the Senoi, developed a positive relationship with them, and was able to collect 371 blood samples. Characterization of the Senoi's skin color was recently reported in PLoS ONE.

"As the world is becoming globalized, populations are becoming increasingly mixed," Ang said. "Time is running out and it will become increasingly difficult to establish how East Asian skin colors evolved."

The researchers will now map genes in the DNA using the collected samples to identify which might be responsible for the skin color of East Asians. In the Cheng lab, the candidate genes and mutations can then be tested in zebrafish for verification.

"Skin color has been tied to human welfare in modern history," Cheng said. "It is important for us as a species to realize that our skin color is determined by only a small number of minute changes in our DNA -- changes that have nothing to do with the value of human beings."

View the Original article

Discovery Of Molecule In Immune System That Could Help Treat Melanoma

5 (1 votes)

Researchers from Brigham and Women's Hospital (BWH) have made a groundbreaking discovery that will shape the future of melanoma therapy. The team, led by Thomas S. Kupper, MD, chair of the BWH Department of Dermatology, and Rahul Purwar, PhD, found that high expression of a cell-signaling molecule, known as interleukin-9, in immune cells inhibits melanoma growth.

Their findings were published online in Nature Medicine.

After observing mice without genes responsible for development of an immune cell called T helper cell 17 (TH17), researchers found that these mice had significant resistance to melanoma tumor growth, suggesting that blockade of the TH17 cell pathway favored tumor inhibition. The researchers also noticed that the mice expressed high amounts of interleukin-9.

"These were unexpected results, which led us to examine a possible contribution of interleukin-9 to cancer growth suppression." said Purwar.

The researchers next treated melanoma-bearing mice with T helper cell 9 (TH9), an immune cell that produces interleukin-9. They saw that these mice also had a profound resistance to melanoma growth. This is the first reported finding showing an anti-tumor effect of TH9 cells.

Moreover, the researchers were able to detect TH9 cells in both normal human blood and skin, specifically in skin-resident memory T cells and memory T cells in peripheral blood mononuclear cells. In contrast, TH9 cells were either absent or present at very low levels in human melanoma. This new finding paves the way for future studies that will assess the role of interleukin-9 and TH9 cells in human cancer therapy.

"Immunotherapy of cancer is coming of age, and there have been exciting recent results in patients with melanoma treated with drugs that stimulate the immune system," said Kupper. "We hope that our results will also translate to the treatment of melanoma patients, but much work still needs to be done."

According to the researchers, other cell-signaling molecules have been used in treating melanoma; however, this study is the first to investigate the role of interleukin-9 in melanoma tumor immunity.

Melanoma is the most dangerous form of skin cancer. The National Cancer Institute estimates that in 2012, there will be more than 76,000 new cases of melanoma in the United States and 9,180 deaths. Melanoma is curable if recognized and treated early.

View the Original article