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P locus
P locus
The p locus, also known as pink-eyed dilution (p), is located on chromosome 7 of the mouse genome and is associated with the oculocutaneous albinism II (Oca2) gene. Mutations in this gene affect the size, number, and composition of melanosomes. The Oca2 gene encodes a transmembrane protein that assists in regulating the pH level within the melanosome.50 Wildtype Oca2 produces an intense pigmentation of the hair, but the mutant Oca2p allele reduces the pigmentation of the coat. The eyes of Oca2p mice resemble those of albinos, possessing a pink tint, thus the name. Oca2p alleles reduce both black and brown pigments (eumelanin synthesis), but has only a slight influence on pheomelanin synthesis. The melanin granules within the hair shaft of Oca2p mice are smaller than their normal counterparts.51 Additionally, levels of tyrosinase are reduced within melanosomes of mice possessing the mutant allele.52 The Oca2 gene encodes a melanosomal transmembrane protein which functions as an ion exchange protein that is similar to Na+/ H+ transporters.8 The initial step in melanogenesis requires the acidification of the melanosome,53,54 but further processing requires a rise in pH.55 So, one function of OCA2 is to regulate the pH of the melanosome, which in turn could regulate tyrosinase activity that is dependent on the pH of the surrounding milieu.
The tyrosinase gene is located in the human genome at 11q14.3. As with mice, humans with mutations in the TYR gene experience pigmentation disorders. Specifically, mutations in this gene have been shown to be causative in both type IA oculocutaneous albinism (OCAIA) and type IB oculocutaneous albinism (OCAIB). OCAIA, also known as tyrosinase-negative OCA,33 presents with amelanotic melanocytes in the skin34,35 and subsequent loss of pigmentation in the skin, hair, and eyes. Additionally, patients may also experience ocular phenotypes reducing visual acuity including strabismus and/or nystagmus.36 OCAIB or tyrosinase-positive OCA arises from mutations in the TYR gene that affect the stability and catalytic activity of the tyrosinase enzyme. Thus, tyrosinase can still be detected in these patients
The p locus is located in chromosomal location 15q12-q13 in the human genome. Mutations in the human OCA2 gene have been linked to both OCAII and brown oculocutaneous albinism (BOCA) in the human population. Over 50 different mutations have been reported in the literature within the OCA2 gene,56 ranging from single nucleotide substitutions, to large deletions of entire exons, to complex rearrangements.50,57โ66 Both OCAII and BOCA are tyrosinase-positive, autosomal recessive disorders whereby pigmentation is reduced in skin, hair, and eyes, and patients have characteristic vision deficits associated with albinism, although usually less severe than
those with OCAI.40,67 As opposed to OCAI, patients with OCAII may experience darkening of their hair with age and may be freckled. In affected individuals with African and African American descent, patients may present with yellow hair and blue-gray iris. The BOCA variant of OCA has been observed mostly in African and African American populations and is characterized by light brown hair and skin color and gray irides.40