Albinism: Genetics

William S Oetting, University of Minnesota, Minneapolis, USA

Published online: December 2011

DOI: 10.1002/9780470015902.a0006081.pub2

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 albinism-related 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.
close
 References
    Chi A, Valencia JC, Hu ZZ et al. (2006) Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. Journal of Proteome Research 5: 3135–3144.
    Cooksey CJ, Garratt PJ, Land EJ et al. (1997) Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. Journal of Biological Chemistry 272: 226–235.
    Cruz-Inigo AE, Ladizinski B and Sethi A (2011) Albinism in Africa: stigma, slaughter and awareness campaigns. Dermatologic Clinics 29: 79–87.
    Cullinane AR, Curry JA, Carmona-Rivera C et al. (2011) A BLOC-1 mutation screen reveals that PLDN is mutated in Hermansky–Pudlak Syndrome type 9. American Journal of Human Genetics 88: 778–787.
    Dessinioti C, Stratigos AJ, Rigopoulos D and Katsambas AD (2009) A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Experimental Dermatology 18: 741–749.
    Giebel LB, Tripathi RK, Strunk KM et al. (1991) Tyrosinase gene mutations associated with type IB (yellow) oculocutaneous albinism. American Journal of Human Genetics 48: 1159–1167
    Haefemeyer JW and Knuth JL (1991) Albinism. Journal of Ophthalmic Nursing and Technology 10: 55–62.
    Halaban R, Svedine S, Cheng E et al. (2000) Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proceedings of the National Academy of Sciences of the USA 97: 5889–5894.
    Han J, Kraft P, Nan H et al. (2008) A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genetics 4(5): e1000074. PMID: 18483556.
    Hoyle DJ, Rodriguez-Fernandez IA and Dell'angelica EC (2011) Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation. Pigment Cell and Melanoma Research 24: 275–281.
    Huizing M, Anikster Y and Gahl WA (2001) Hermansky–Pudlak syndrome and Chediak–Higashi syndrome: disorders of vesicle formation and trafficking. Thrombosis and Haemostasis 86: 233–245.
    Inagaki K, Suzuki T, Shimizu H et al. (2004) Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. American Journal of Human Genetics 74: 466–471.
    Ito S and Wakamatsu K (2008) Chemistry of mixed melanogenesis – pivotal roles of dopaquinone. Photochemistry and Photobiology 84: 582–592.
    King RA, Mentink MM and Oetting WS (1991) Non-random distribution of missense mutations within the human tyrosinase gene in Type 1 (tyrosinase-related) oculocutaneous albinism. Molecular Biology and Medicine 8: 19–29.
    book King RA, Oetting WS, Summers CG, Creel DJ and Hearing VJ (2007) "Abnormalities of pigmentation". In: Rimoin DL, Connor JM, Pyeritz RE and Korf BR (eds) Principles and Practice of Medical Genetics, 5th edn, pp. 3380–3427. Edinburgh: Churchill Livingstone.
    King RA, Pietsch J, Fryer JP et al. (2003) Tyrosinase gene mutations in oculocutaneous albinism (OCA1): definition of the phenotype. Human Genetics 113: 502–513.
    Newton JM, Cohen-Barak O, Hagiwara N et al. (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, x OCA4. American Journal of Human Genetics 69: 981–988.
    book Nordlund JJ, Boissy RE, Hearing VJ et al. (2006) The Pigmentary System: Physiology and Pathophysiology, 2nd edn. Oxford, UK: Blackwell.
    Oetting WS, Fryer JP, Shriram S and King RA (2003) Oculocutaneous albinism type 1: the last 100 years. Pigment Cell Research 16: 307–311.
    Rundshagen U, Zuhlke C, Opitz S, Schwinger E and Kasmann-Kellner B (2004) Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4. Human Mutation 23: 106–110.
    Sarangarajan R and Boissy RE (2001) Tyrp1 and oculocutaneous albinism type 3. Pigment Cell Research 14: 437–444.
    Scherer D and Kumar R (2010) Genetics of pigmentation in skin cancer – a review. Mutation Research 705: 141–153.
    Sturm RA, Teasdale RD and Box NF (2001) Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 277: 49–62.
    Sulem P, Gudbjartsson DF, Stacey SN et al. (2007) Genetic determinants of hair, eye and skin pigmentation in Europeans. Nature Genetics 39: 1443–1452.
    Summers CG (1996) Vision in albinism. Transactions of the American Ophthalmological Society 94: 1095–1155.
    Summers CG (2009) Albinism: classification, clinical characteristics, and recent findings. Optometry & Vision Science 86: 659–662.
    Tibber MS, Becker D and Jeffery G (2007) Levels of transient gap junctions between the retinal pigment epithelium and the neuroblastic retina are influenced by catecholamines and correlate with patterns of cell production. Journal of Comparative Neurology 503: 128–134.
    Toyofuku K, Wada I, Spritz RA and Hearing VJ (2001) The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochemical Journal 355: 259–269.
    Tripathi RK, Strunk KM, Giebel LB, Weleber RG and Spritz RA (1992) Tyrosinase gene mutations in Type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. American Journal of Medical Genetics 43: 865–871.
    Valenzuela RK, Henderson MS, Walsh MH et al. (2010) Predicting phenotype from genotype: normal pigmentation. Journal of Forensic Science 55: 315–322.
    Zhang KH, Li Z, Lei J et al. (2011) Oculocutaneous albinism type 3 (OCA3): analysis of two novel mutations in TYRP1 gene in two Chinese patients. Cell Biochemistry and Biophysics [Epub ahead of print].
 Further Reading
    book Lamoreux ML, Delmas V, Larue L and Bennett D (2010) The Colors of Mice: A Model Genetic Network. New York: Wiley, 297 p.
    book Willys KS (1979) The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction. New York: Springer-Verlag.
 Web links
    ePath The Albinism Database http://www.cbc.umn.edu/tad

Related Sub-Topics:

Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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