Albinism: Genetics

Abstract

Albinism has classically been described as the complete absence of melanin pigment in the skin, hair and eyes throughout the life of the affected individual. Modern molecular analysis has shown that albinism is a much more complex genetic disorder than previously thought, involving many genes with an array of functions, as well as great variation in the phenotype of affected individuals. There are currently 15 genes that have been associated with albinism, including four nonsyndromic forms of oculocutaneous albinism (reduced pigment affects skin, hair and eyes), one nonsyndromic form of ocular albinism (reduced pigment affects eyes only) and ten syndromic disorders that include albinism as part of the phenotype. The gene functions of the nonsyndromic forms are thought to be involved in melanin biosynthesis and many of the genes associated with the syndromic forms are involved in protein trafficking. Common genetic variants within some of these genes are also associated with normal variation in eye, hair and skin colouration.

Key Concepts:

  • All animals make melanin as the chief form of colouration.

  • Melanin is made in specific cells called melanocytes.

  • Albinism is caused by an absence of melanin biosynthesis resulting in several clinical features.

  • There are many different types of albinism.

  • There are several genes associated with albinism.

  • The molecular pathology of albinism is complex and involves different types of mutations.

  • Variation in skin pigmentation involves common polymorphisms in some albinismÔÇÉrelated genes.

  • Albinism can affect interactions between individuals and society.

Keywords: oculocutaneous albinism; tyrosinase; nystagmus; melanin

Figure 1.

Melanin pathway. The initial substrate for melanin biosynthesis is the amino acid tyrosine. The rate‐limiting enzyme is tyrosinase (TYR), which has both tyrosine hydroxylase and dopa oxidase activity. In the presence of sulfhydral‐containing compounds, such as cysteine, pheomelanin is produced through the compound cysteinyldopa. In the absence of sulfhydral groups, black‐brown eumelanin is synthesised. Two other enzymes are involved in the eumelanin pathway, dopachrome tautomerase (TYRP2) and dihydroxyindolecarboxylic acid (DHICA) oxidase (TYRP1).

Figure 2.

Structure of tyrosinase. Tyrosinase is a copper‐containing enzyme and the rate‐limiting enzyme in melanin biosynthesis. This figure shows the coding region of the TYR gene (529 amino acids). The signal peptide is important in protein trafficking and translation on membrane‐bound ribosomes. The boxes shown as CuA and CuB are the two copper binding regions. The circles show the location of cysteine residues and the EGF is an epidermal growth factor‐like region. Arrows indicate the location of possible glycosylation sites. There is also a dileucine motif in the 3′ end of the enzyme that is important in intracellular trafficking of the enzyme to the melanosome.

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Further Reading

Lamoreux ML, Delmas V, Larue L and Bennett D (2010) The Colors of Mice: A Model Genetic Network. New York: Wiley, 297 p.

Willys KS (1979) The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction. New York: Springer‐Verlag.

Web links

The Albinism Database http://www.cbc.umn.edu/tad

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Oetting, William S(Dec 2011) Albinism: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006081.pub2]