Editing Freckle (section)

==Biology==
The formation of freckles is caused by exposure to [[sunlight]]. The exposure to UV-B radiation activates melanocytes to increase melanin production, which can cause freckles to become darker and more visible. This means that one may have never developed freckles before, but after extended exposure to sunlight, they may suddenly appear.

Freckles are predominantly found on the face, although they may appear on any skin exposed to the sun, such as arms or shoulders. Heavily distributed concentrations of melanin may cause freckles to multiply and cover an entire area of skin, such as the face.  Freckles are rare on [[infant]]s, and more commonly found on [[child]]ren before [[puberty]].
Upon exposure to the sun, freckles will reappear if they have been altered with [[Cream (pharmaceutical)|creams]] or [[laser]]s and not protected from the sun, but do fade with age in some cases.

Freckles are not a skin disorder, but people with freckles generally have a lower concentration of photo-protective melanin, and are therefore more susceptible to the harmful effects of UV radiation. It is suggested that people whose skin tends to freckle should avoid overexposure to sun and use [[sunscreen]].<ref name="Hanson">{{cite journal  |title=Sunscreen enhancement of UV-induced reactive oxygen species in the skin |doi=10.1016/j.freeradbiomed.2006.06.011| journal=Free Radical Biology and Medicine |volume=41 |issue=8 |pages=1205–12 |year=2006 |pmid=17015167 |author1=Hanson|first1=K. M|last2=Gratton|first2=E|last3=Bardeen|first3=C. J}}</ref><ref name=Garland>{{cite journal |vauthors=Garland C, Garland F, Gorham E |title=Could sunscreens increase melanoma risk? |journal=Am J Public Health |volume=82 |issue=4 |pages=614–5 |year=1992 |pmid=1546792 |doi=10.2105/AJPH.82.4.614 |pmc=1694089}}</ref>

===Genetics===
[[File:Man with freckles.jpg|thumb|Man with freckles]]
The presence of freckles is related to rare alleles of the [[Melanocortin 1 receptor|MC1R]] gene, though it does not differentiate whether an individual will have freckles if they have one or even two copies of this gene. Also, individuals with no copies of the MC1R do sometimes display freckles. Even so, individuals with a high number of freckling sites have one or more of variants of the MC1R gene. Of the variants of the MC1R gene Arg151Cys, Arg160Trp, and Asp294His are the most common in the freckled subjects.<ref name="Flanagan, N. 2000">{{cite journal | author = Flanagan N. | year = 2000 | title = Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation  | journal = Human Molecular Genetics | volume = 9 | issue = 17| pages = 2531–2537 | doi=10.1093/hmg/9.17.2531|display-authors=etal | pmid=11030758}}</ref><ref name="Bastiaens, M. 2001">{{cite journal | author = Bastiaens M. | year = 2001 | title = The melanocortin-1-receptor gene is the major freckle gene | journal = Human Molecular Genetics | volume = 10 | issue = 16| pages = 1701–1708 | doi=10.1093/hmg/10.16.1701|display-authors=etal}}</ref><ref>{{cite journal | year = 2001 | title = Melanocortin-1 Receptor Genotype is a Risk Factor for Basal and Squamous Cell Carcinoma | url = | journal = Journal of Investigative Dermatology | volume = 116 | issue = 2| pages = 224–229 | doi=10.1046/j.1523-1747.2001.01224.x | pmid=11179997| author1 = Box | first1 = N. F | last2 = Duffy | first2 = D. L | last3 = Irving | first3 = R. E | last4 = Russell | first4 = A | last5 = Chen | first5 = W | last6 = Griffyths | first6 = L. R | last7 = Parsons | first7 = P. G | last8 = Green | first8 = A. C | last9 = Sturm | first9 = R. A }}</ref>  The MC1R gene is also associated with red hair more strongly than with freckles. Most red-haired individuals have two variants of the MC1R gene and almost all have one.<ref name="Bastiaens, M. 2001"/>  The variants that cause red hair are the same that cause freckling.<ref name="Flanagan, N. 2000"/>  Freckling can also be found in areas, such as Japan, where red hair is not seen. These individuals have the variant Val92Met which is also found in [[White people|Caucasians]], although it has minimal effects on their pigmentation. The R162Q allele has a disputed involvement in freckling.<ref>{{cite journal | year = 2012 | title = Association of melanocortin 1 receptor gene (MC1R) polymorphisms with skin reflectance and freckles in Japanese| journal = Journal of Human Genetics | volume = 57 | issue = 11| pages = 700–708 | doi=10.1038/jhg.2012.96| last1 = Yamaguchi| first1 = Kyoko| last2 = Watanabe| first2 = Chiaki| last3 = Kawaguchi| first3 = Akira| last4 = Sato| first4 = Takehiro| last5 = Naka| first5 = Izumi| last6 = Shindo| first6 = Misaki| last7 = Moromizato| first7 = Keiichi| last8 = Aoki| first8 = Kenichi| last9 = Ishida| first9 = Hajime| last10 = Kimura| first10 = Ryosuke}}</ref>

The variants of the MC1R gene that are linked with freckles started to emerge in the human genotype when humans started to leave Africa. The variant Val92Met arose somewhere between 250,000 and 100,000 years ago, long enough for this gene to be carried by humans into central Asia. Arg160Trp is estimated to have arisen around 80,000 years ago while Arg151Cys and Asp294His have been estimated to arise around 30,000 years ago. The wide variation of the MC1R gene exists in people of European descent because of the lack of strong environmental pressures on the gene.<ref name="Harding, R. M. 2000">{{cite journal | last = Harding |first=R. M. | year = 2000 | title = Evidence for variable selective pressures at MC1R | journal = American Journal of Human Genetics | volume = 66 | issue = 4| pages = 1351–1361 | doi=10.1086/302863|display-authors=etal | pmid=10733465 | pmc=1288200}}</ref>  The original allele of MC1R is coded for [[dark skin]] with a high melanin content in the cells. The high melanin content is [[Ultraviolet light and cancer|protective]] in areas of high [[UV light]] exposure.<ref name="Harding, R. M. 2000"/>  The need was less as humans moved into higher latitudes where incoming sunlight has lower UV light content.  The adaptation of lighter skin is needed so that individuals in higher latitudes can still [[Health effects of sun exposure|absorb enough UV]] for the production of vitamin D.<ref name="Harding, R. M. 2000"/>  Freckled individuals tend to tan less and have very light skin, which would have helped the individuals that expressed these genes absorb vitamin D.