Albinism (OCA2) in Amerindians

Abstract

Homozygosity for a mutation in the P locus mapped to the human chromosome 15q11.2-12 results in tyrosinase-positive albinism (OCA2). This type of albinism has a worldwide distribution, with a prevalence of about 1 in 36,000 among European-Americans in the United States. It has a moderate to relatively high prevalence values (1 in 28 to 1 in 6,500) in various Amerindian populations in the southwestern United States, southern Mexico, eastern Panama, and southern Brazil. The wide distribution of the gene for OCA2 in Amerindian populations, and its relatively high frequency in several of these populations, are enigmatic because of the detrimental nature of OCA2 in the presence of certain environmental conditions. The relative Darwinian fitness of individuals with this inborn error of metabolism would have been reduced in early nomadic huntinggathering populations because of their poor visual acuity and sensitivity to the sun. Nevertheless, specific situations allowed OCA2 to increase in frequency in certain Amerindian populations at various different times in history. The present objectives are to review the literature on albinism (OCA2) in Amerindians, and propose hypotheses for the variable frequencies of the OCA2 gene in Amerindian populations, which include chance processes (founder effect, bottleneck effect, and genetic drift) in small populations, natural selection, cultural selection, and the interaction of situations that led to the increase of the frequency of the albino gene in some generations. Special emphasis is placed on those Amerindian populations with a relatively high frequency of the OCA2 gene that have been best-studied, namely, the Cuna population of eastern Panama and the Hopi population in the southwestern US. Hypothetical scripts are presented for the present relatively high frequencies of the OCA2 gene in these populations. A hypothetical script is also presented, showing how a mutant gene could have reached a relatively high frequency in a small endogamous early Mayan population and then been spread by migrating groups to other geographical regions, following the rapid increase in size of that population. Comprehensive molecular studies of OCA2 genes in Amerindian populations could yield information on the possible origin of the albino gene present in many of these populations, in addition to the gene flow that occurred among some of them in past generations. The results of these studies could lead to more informed hypotheses concerning the wide distribution of OCA2 in

Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene

“…If, as very often, children of albinos who are obligate heterozygotes have lighter skin than the full-coloured parent, we are not aware of any such advantage for OCA2 heterozygotes. The same conclusion about the absence of heterozygote advantage at the P locus was drawn in Amerindian populations with OCA2 albinism (Woolf 2005), particularly among the Navajo, which present a 122.5-kb deletion of the P gene (Yi et al 2003).…”

“…An intense negative cultural selection against San Blas Cuna albinos, culminating in infanticide, and almost complete marriage discrimination against albino males, has been documented. On the contrary, albinos were not ostracised or looked upon as being inferior among the Hopi and Zuni Indians, and they married full-coloured individuals and had healthy offspring (Woolf 2005). Hopi males with albinism were traditionally allowed to remain in the villages, thereby avoiding bright sunlight and its detrimental effects on them, and ''had ample opportunity to engage in sexual activity'' (Hedrick 2003).…”

“…These kings were polygamists, with 80-100 wives and 200-300 children, who were obligate heterozygotes; on the other hand, in the Bamileke tribe, marriages tended to occur within the same clan or town (Puri et al 1997) with a high endogamic rate of around 95% (Spedini et al 1999). A hypothetical scenario would be that the founder effect was the cause of the initial high proportion of albinos in this small endogamous population, which was then spread by migrating groups to other geographic regions followed by the rapid increase in size of that population (Woolf 2005). This scenario could be possible because (1) Balengou had less than 5,000 inhabitants around 1900, (2) albinism occurs most frequently in the Bamileke group [70% (190/ 273 registered albinos) even if the 2.7-kb deletion was less common: 55% (94/170 alleles) than in other ethnic groups (Aquaron 1990;Aquaron and Berge-Lefranc 2002)], (3) the Bamileke population are the predominant ethnic group in Cameroon with approximately 2 million in a population of 10 million with a high fecundity rate (Puri et al 1997), (4) they are located mainly in the west province but for economic reasons also in the two main cities of Cameroon: Yaounde, the administrative capital, and Douala, the economic port where they represent, respectively, 20 and 40% of the population (Marguerat 1975).…”

Variants of the melanocortin 1 receptor gene (MC1R) and P gene as indicators of the population origin of an individual

“…In addition, to date, several potential functions, such as a membrane transporter of a substrate [26] and a sorter of tyrosinase to the melanosome [27], have been proposed for the P protein. Mutations in the P gene are associated with oculocutaneous albinism type II (OCA2), which is the most common type of human albinism [28][29][30][31], and phenotypic variations in human iris color [32,33].…”

Was skin cancer a selective force for black pigmentation in early hominin evolution?

“…The age-related incidence and mortality from skin cancer, both historically and in contemporary albinos, have been modulated by many factors, including lifestyle, occupation and varying degrees of awareness, preventive measures and medical intervention [91]. In these cultural respects, the lethal impact of skin cancer would have been more severe in naked, pale-skinned and outdoor living hominins, dwelling in a habitat with the highest levels of year-round UVB radiation-in open and arid equatorial savannah.…”