Genomic ancestry, self-reported "color" and quantitative measures of skin pigmentation in Brazilian admixed siblings

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.     

Technical Note: Comparing von Luschan skin color tiles and modern spectrophotometry for measuring human skin pigmentation

Prior to the introduction of reflectance spectrophotometry into anthropological field research during the 1950s, human skin color was most commonly classified by visual skin color matching using the von Luschan tiles, a set of 36 standardized, opaque glass tiles arranged in a chromatic scale. Our goal was to establish a conversion formula between the tile‐based color matching method and modern reflectance spectrophotometry to make historical and contemporary data comparable. Skin pigmentation measurements were taken on the forehead, inner upper arms, and backs of the hands using both the tiles and a spectrophotometer on 246 participants showing a broad range of skin pigmentation. From these data, a second‐order polynomial conversion formula was derived by jackknife analysis to estimate melanin index (M‐index) based on tile values. This conversion formula provides a means for comparing modern data to von Luschan tile measurements recorded in historical reports. This is particularly important for populations now extinct, extirpated, or admixed for which tile‐based measures of skin pigmentation are the only data available. Am J Phys Anthropol 151:325–330, 2013. © 2013 Wiley Periodicals, Inc.     

A library of action spectra for erythema and pigmentation

The first action spectra for erythema and delayed pigmentation in human skin were determined 90 years ago by Karl Hausser and Wilhelm Vahle in Germany, and since then a number of studies have been undertaken to redefine these action spectra. In this paper we give an overview of the action spectra for erythema and pigmentation that have been published during this 90-yr period, as well as indicating their uncertainties and shortcomings.     

Human skin pigmentation, migration and disease susceptibility

Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D(3). Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D(3) under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples-nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)-are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century.     

Mechanism of skin pigmentation

Melanin is a pigment that plays an important role in providing coloration and protecting human skin from the harmful effects of UV light radiation. Human skin color is determined by the type and amount of melanins that are synthesized and deposited within the melanosomes. In addition, the transfer of these specialized membrane-bound organelles from melanocytes to surrounding keratinocytes also plays a role in dictating human skin color. In order to investigate the principle features of skin pigmentation, the origin, function, and production ability of melanin should be highly understood in terms of biological and pathophysiological aspects. Furthermore, a deep understanding of melanin synthesis will also contribute to cosmetics and drugs development. In this review, the processes of melanin biosynthesis, such as survival, proliferation, and differentiation of melanin cells, as well as the biological regulation of human pigmentation were described.     

Non-invasive measurements of skin pigmentation in situ

Objective in situ measurements of skin pigmentation are needed for accurate documentation of pigmentation disorders, in studies of constitutive and induced skin pigmentation, for testing of the efficacy of pro-pigmentation or de-pigmentation agents, etc. Non-invasive instrumental measurements of skin pigmentation have been used for many decades. All are based on the ability of melanin to attenuate light. However, hemoglobin in dermal capillaries also attenuates light and needs to be accounted for when pigmentation is assessed. The methods under consideration include: (a) single point measurements, in which light reflected from a defined skin area is collected and a pigment index is calculated representing the average pigmentation over the examined area, and (b) imaging methods that attempt to generate a concentration distribution map of melanin pigment for the skin area being imaged. In this article, we describe the potentials and the limitations of the different approaches to both single point and imaging methods.     

Sibling correlations of skin pigmentation during growth

The present study is focused on the analysis of skin color correlations in a sample of 1039 siblings aged 4 to 20 years from the province of Biscay (Basque Country, Spain). Measurements were taken at the upper inner arm and forehead by means of an EEL DS29 Digital Unigalvo reflectance spectrophotometer fitted with filters 601, 605, and 609. The reflectance data were internally standardized according to sex and age of the individuals, and the analysis of the degree of similarity between siblings was based on the calculation of intraclass correlation coefficients. All 3 filters gave fairly high and statistically significant correlations regarding forehead skin color (between 0.28 and 0.45) for all types of siblings under consideration. However, with respect to filter 609 the arm reflectance values did not reveal correlation either between brothers (0.01) or between siblings (0.02), even though it did reveal correlation between sisters (0.29). When other filters or type of sibling were considered (also for arm), all coefficients happened to be statistically significant and relatively high (0.35-0.43). This study confirms that the degree of sibling resemblance with regard to skin pigmentation is influenced by growth factors and that the upper inner arm and the forehead skin patterns change with age in the sense that, during and especially after puberty, the coefficients of correlation are higher for arm reflectance than for forehead reflectance; the forehead is a site that is more influenced by environment.     

A life history perspective on skin cancer and the evolution of skin pigmentation

The ancestral state of human skin pigmentation evolved in response to high ultraviolet radiation (UVR) stress. Some argue that pigmentation evolved to limit folate photolysis, therein limiting neural tube defects. Pigmentation also protects against sunburn which decreases the efficiency of sweating and potentiates skin infection. Pigmentation increases the efficacy of skin as a barrier to infection. Skin cancer has been rejected or minimized as a selective pressure because it is believed to have little or no effect on mortality during reproductive years. This argument ignores evidence of human longevity as a derived life history trait and the adaptive value of investment in offspring and kin, particularly during the post‐reproductive lifespan. Opponents argue that lifespan in prehistoric hunter‐gatherers was too short to be relevant to the evolution of skin pigmentation. This argument is flawed in that it relies on estimates of longevity at birth rather than adolescence. When appropriate estimates are used, it is clear that human longevity has a deep evolutionary history. We use a life history perspective to demonstrate the value of skin pigmentation as an adaptation to skin cancer with the following points: UVR exposure increases dysregulation of gene expression in skin cells leading to immortal cell lines; cutaneous malignant melanoma (CMM) affects individuals throughout reproductive years; and lifespan was longer than has previously been acknowledged, providing the opportunity for kin selection. This hypothesis is not at odds with the folate or barrier hypotheses. We stress that the evolution of skin pigmentation is complex and is an ongoing process. Am J Phys Anthropol 153:1–8, 2014. © 2013 Wiley Periodicals, Inc.     

The relationship between constitutive pigmentation and sensitivity to ultraviolet radiation induced erythema is dose-dependent

The relationship between skin colour and experimental exposure to ultraviolet radiation (UVR) B, with response measured as erythema was studied. Two reflectance methods were used to measure skin colour--tristimulus colorimetry using a Minolta instrument (summarized as the alpha characteristic angle) and the melanin index based on the Diastron reflectance instrument. As expected both measures are highly correlated (0.91). A dose-dependent relationship between skin colour measured as the alpha characteristic angle and UVR was established, with the gradient increasing from 0.99 at 119 mJ to 2.7 at 300 mJ, with the relevant standard errors being 0.39 and 0.47, respectively. Similarly, for the melanin index (where the scale goes in the opposite direction) the gradient differs between -0.49 for 119 mJ and -0.91 for 300 mJ, with the standard errors being 0.14 and 0.17 respectively. The proportion of variation explained is also greater at higher UVR challenge doses. Studies relating UVR sensitivity and pigmentation need to take account of the dose of UVR administered.     

Rapid,quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay

Biomechanics and Modeling in Mechanobiology - Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are...     

Regulation of human skin pigmentation and responses to ultraviolet radiation

Pigmentation of human skin is closely involved in protection against environmental stresses, in particular exposure to ultraviolet (UV) radiation. It is well known that darker skin is significantly more resistant to the damaging effects of UV, such as photocarcinogenesis and photoaging, than is lighter skin. Constitutive skin pigmentation depends on the amount of melanin and its distribution in that tissue. Melanin is significantly photoprotective and epidermal cells in darker skin incur less DNA damage than do those in lighter skin. This review summarizes current understanding of the regulation of constitutive human skin pigmentation and responses to UV radiation, with emphasis on physiological factors that influence those processes. Further research is needed to characterize the role of skin pigmentation to reduce photocarcinogenesis and to develop effective strategies to minimize such risks.