Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Genomic Variant Associated with Sun Sensitivity Identified

Published: Friday, November 22, 2013
Last Updated: Friday, November 22, 2013
Bookmark and Share
NIH-funded work finds genetic switch for pigmentation trait in non-coding, regulatory region of newly associated gene.

Researchers have identified a genomic variant strongly associated with sensitivity to the sun, brown hair, blue eyes – and freckles. In the study of Icelanders the researchers uncovered an intricate pathway involving the interspersed DNA sequence, or non-coding region, of a gene that is among a few dozen that are associated with human pigmentation traits.  The study by an international team including researchers from the National Institutes of Health was reported in the Nov. 21, 2013, online edition of the journal Cell.

It is more common to find people with ancestors from geographic locations farther from the equator, such as Iceland, who have less pigment in their skin, hair and eyes. People with reduced pigment are more sensitive to the sun, but can more easily draw upon sunlight to generate vitamin D3, a nutrient essential for healthy bones.

The researchers, including scientists from the National Human Genome Research Institute (NHGRI), a part of NIH, analyzed data from a genome-wide association study (GWAS) of 2,230 Icelanders. A GWAS compares hundreds of thousands of common differences across individuals’ DNA to see if any of those variants are associated with a known trait.

“Genes involved in skin pigmentation also have important roles in human health and disease,” said NHGRI Scientific Director Dan Kastner, M.D., Ph.D. “This study explains a complex molecular pathway that may also contribute insights into skin diseases, such as melanoma, which is caused by the interaction of genetic susceptibility with environmental factors.”

The GWAS led the researchers to focus on the interferon regulatory factor 4 (IRF4) gene, previously associated with immunity. IRF4 makes a protein that spurs production of interferons, proteins that fight off viruses or harmful bacteria. The researchers noted from genomic databases that the IRF4 gene is expressed at high levels only in lymphocytes, a type of white blood cell important in the immune system, and in melanocytes, specialized skin cells that make the pigment melanin. The new study established an association between the IRF4 gene and the pigmentation trait.

The Icelandic GWAS yielded millions of variants among individuals in the study. The researchers narrowed their study to 16,280 variants located in the region around the IRF4gene. Next, they used an automated fine-mapping process to explore the set of variants in IRF4 in 95,085 people from Iceland. A silicon chip used in the automated process enables a large number of variants to be included in the analysis.

The data revealed that a variant in a non-coding, enhancer region that regulates the IRF4 gene is associated with the combined trait of sunlight sensitivity, brown hair, blue eyes and freckles. The finding places IRF4 among more than 30 genes now associated with pigmentation, including a gene variant previously found in people with freckles and red hair.

Part of the research team, including the NHGRI co-authors, studied the IRF4’s role in the pigment-related regulatory pathway. They demonstrated through cell-culture studies and tests in mice and zebrafish that two transcription factors — proteins that turn genes on or off — interact in the gene pathway with IRF4, ultimately activating expression of an enzyme called tyrosinase. One of the pathway transcription factors, MITF, is known as the melanocyte master regulator. It activates expression of IRF4, but only in the presence of the TFAP2A transcription factor. A greater expression of tyrosinase yields a higher production of the pigment melanin in melanocytes.

“This non-coding sequence harboring the variant displayed many hallmarks of having a function and being involved in gene regulation within melanocyte populations,” said Andy McCallion, Ph.D., a co-author at Johns Hopkins University, Baltimore, and collaborator with the NHGRI group.

The newly discovered variant acts like a dimmer switch. When the switch in the IRF4 enhancer is in the on position, ample pigment is made. Melanin pigment gets transferred from melanocytes to keratinocytes, a type of skin cell near the surface of the skin, and protects the skin from UV radiation in sunlight. If the switch is turned down, as is the case when it contains the discovered variant, the pathway is less effective, resulting in reduced expression of tyrosinase and melanin production. The exact mechanism that generates freckling is not yet known, but Dr. Pavan suggests that epigenetic variation—a layer of instructions in addition to sequence variation—may play a role in the freckling trait.

More research is needed to determine the mechanism by which IRF4 is involved in how melanocytes respond to UV damage, which can induce freckling and is linked to melanoma, the type of skin cancer associated with the highest mortality.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Lucentis Effective for Proliferative Diabetic Retinopathy
NIH-funded clinical trial marks first major advance in therapy in 40 years.
Tuesday, November 24, 2015
Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Researchers Identify Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Saturday, October 31, 2015
Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Friday, October 23, 2015
Charting Genetic Variation Across the Globe
An international team of scientists has created the world’s largest catalog of human genetic differences in populations around the globe.
Tuesday, October 20, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
$21M Invested in Research Hubs in Developing Countries
The National Institutes of Health and other U.S. and Canadian partners are investing $20.9 million dollars over five years to establish seven regional research and training centers in low- and middle-income countries (LMICs).
Friday, October 09, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
NIH Announces High-Risk, High-Reward Research Awardees
NIH to fund 78 awards to support highly innovative biomedical research.
Wednesday, October 07, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos