Freckles

Freckles are a common sight at the end of summer. Clusters of tan or light brown spots that seem to come and go with the seasons for some, and be a permanent feature for others. The birth of a freckle is actually a surprisingly complex process that is part of the skin's protective mechanism against UV radiation. In response to UV light, Melanin is produced in the skin to guard against DNA-damage. In parts of the world with high levels of UV, a large amount of Melanin in skin and hair is protective. However, in parts of the world with low levels of UV, melanin is kept low in order to capture more sunlight, which helps the body produce vitamin-D.

Melanin is produced in the skin by a special type of cell called a melanocyte. Freckles appear when small areas of overactive melanocytes produce a large amount of melanin relative to their surroundings. Melanin occurs in two forms - pheomelanin and eumelanin. Pheomelanin is the reddish form that accumulates in freckles and is what gives color to red hair. When it is hit with UV rays, pheomelanin is converted to eumelanin which is the dark brown or black form which absorbs and protects against UV radiation and is what gives rise to a tan. Reduced ability to convert pheomelanin to eumelanin is one of the reasons why people with red hair tend to burn more easily in the sun!

What role does genetics play?

There does not appear to be one single genetic variant that governs the appearance of freckles, rather there seem to be multiple genetic variants that increase the likelihood of their appearance. The gene most commonly associated with freckles is the ‘melanocortin 1 receptor’ (MC1R). This gene acts as receptor for different substances in the melanocyte environment and appears to switch the melanocyte from producing reddish melanin to a darker brown form. Several variants have been identified related to this gene such as rs12931267 for which the G allele is associated with increased freckle probability over the C allele.

The rs1805008 variant for the T allele is associated with increased freckle probability over C.

Another variant, rs619865, is associated with freckling, potentially by causing a decrease in the amount of MC1R receptor. Individuals with an ‘A’ at rs619865 have more freckling, on average, than those with the G variant.

Another gene associated with freckling is IRF4 which controls the production of TYR - a crucial enzyme involved in melanin production. The rs12203592 variant is associated with IRF4 expression with the T allele associated with increased freckling compared to the C allele.

Overall, freckling is a highly heritable trait which is influenced by many genetic variants. While we have a good understanding of the role of many of the genes defined above in melanin production, we are still barely scratching the surface of this trait. As a result, it is still very challenging to predict something even as seemingly simple as freckling based on genetics alone.