Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

Abstract

Oculocutaneous albinism type 2 (OCA2) is a human autosomal-recessive hypopigmentation disorder associated with pathological mutations of the OCA2 gene. In this study, we investigated a form of OCA in a Polynesian population with an observed phenotype characterized by fair skin, some brown nevi present in the sun-exposed areas and green or blue eyes. Hair presented with a unique red coloration since birth, with tones ranging across individuals from Yellow-Red to Brown-Red, or Auburn. We genetically screened for mutations in the OCA2 and MC1R genes as their products have previously been shown to be associated with red hair/fair skin and OCA2. The SLC45A2 gene was also screened to identify any possible relation to skin color variation. We have identified a novel missense substitution in the OCA2 gene (Gly775Asp) responsible for OCA2 in individuals of Polynesian heritage from Tuvalu. The estimated incidence of this form of OCA2 in the primary study community is believed to occur at one of the highest recorded rates of albinism at approximately 1 per 669 individuals. In addition, we have analyzed four unrelated individuals with albinism who have Polynesian heritage from three other separate communities and found they carry the same OCA2 mutation. We also analyzed an out-group comprising three unrelated individuals with albinism of Melanesian ancestries from two separate communities, one Australian Aboriginal and three Australian Caucasians, and did not detect this mutation. We hypothesize that this mutation may be Polynesian specific and that it originated from a common founder.

Human pigmentation genes under environmental selection

“…This allele has a frequency of 0.26 on the Solomon Islands and is not seen outside of Oceania, so it represents a very recent evolutionary event, with the allele acting in a recessive manner [81]. Similarly, a very high frequency of a population-specific OCA2 mutation causing the expression of a full albinism phenotype has been found in the Polynesian Islands [82]. Both are cases of genetic drift resulting from population founder effects (Box 1).…”

Skin Pigmentation Genetics for the Clinic

“…The novel mutation rs387907171 * C/T occurred at a frequency of 26% in the Solomon Islands but was absent outside Oceania. In contrast, TYRP1 was excluded as being the gene responsible for a form of OCA in a Polynesian population in another study [58] . It is notable that at the same position there is a C93H polymorphism present at 1.1% frequency in the European population [60] , but an association with a pigmentation phenotype is yet to be examined.…”

“…TYRP1 can act to stablise the TYR protein and form heterodimeric complexes within the melanosome [57] . It was found that 95% of OCA3-related mutations result in the generation of premature stop codons or frameshifts producing truncated proteins, red-toned hair, reddish-brown pigmented skin and optical features not as severe as in other forms of OCA [58] . Only 5 mutations have been described so far in TYRP1 [39] .…”

Perspective: Evolution of Human Skin Color: How Low Levels of Vitamin D Drove Natural Selection

“…Many of these genes are focused on melanosome biosynthesis and transport and regulation of melanocytes and melanosomes. For example, the red hair color phenotype is controlled by MC1R, and the most common cause of albinism in Europeans is linked to OCA2 [ 78 ] . Two other important genes for albinism, an autosomal recessive disorder, are SLC45A2 and SLC24A5 [ 78 ] .…”

“…For example, the red hair color phenotype is controlled by MC1R, and the most common cause of albinism in Europeans is linked to OCA2 [ 78 ] . Two other important genes for albinism, an autosomal recessive disorder, are SLC45A2 and SLC24A5 [ 78 ] . Sabeti et al used three different forms of long-range haplotype analysis to determine gene under positive selection in the genome of European individuals [ 79 ] .…”