Oculocutaneous albinism type 1

from Wikipedia, the free encyclopedia
OCA1 is responsible for many of the most common forms of albinism.

Oculocutaneous albinism type 1 , OCA abbreviated 1, is a form of albinism , based on mutations of TYR - gene (encoding tyrosinase back). Another name for this is tyrosinase-related albinism.

Appearance

Tyrosinase negative OCA 1 (OCA 1A)

The complete failure of the tyrosinase function is called tyrosinase-negative OCA 1 (OCA 1A). The people affected by this have completely inoperative tyrosinase and therefore no melanin whatsoever. Affected people are born with white hair, light skin and a translucent light blue and sometimes pink iris. You don't develop melanin over the course of life. OCA 1A is found in all peoples and in numerous animal species. They also have a severe visual impairment with a visual acuity below 10%.

Tyrosinase positive OCA 1 (OCA 1B)

People with OCA 1B can have yellow hair like Mem Nahadr does. Whether Nahadr's albinism is OCA 1B is unknown.

In tyrosinase positive OCA 1 (OCA 1B), tyrosinase can produce melanin, but not as well as normal. As with OCA 1A, those affected are born without pigmentation of the skin, hair or iris. However, in the course of life they form some melanin. People with OCA 1B can look very different, depending on how well the tyrosinase is still working, and the visual impairment can also be different. The eyes can darken from blue to green or brown over the course of life. The OCA 1B is also called yellow OCA, as the darkening often leads to yellow hair color in those affected. This is attributed to the synthesis of pheomelanin, which is less influenced by OCA 1B than that of eumelanin. In contrast to black eumelanin, pheomelanin is a brown dye.

At least one mutation produces a tyrosinase, the functionality of which depends on the temperature. Therefore, the hair on the body is colorless, but the hair on the head and the hair on the hands are colored.

There are also mutations in the TYR gene that are only expressed in the eyes.

genetics

Oculocutaneous albinism type 1 is caused by mutations in the TYR gene. The TYR gene is located on chromosome 11 (11q14-21), contains five exons and codes for the protein tyrosinase with a length of 529 amino acids.

So far, over 100 different mutations have been discovered in the TYR gene. Some of these mutations produce a functioning tyrosinase, whose maturation in the endoplasmic reticulum is disturbed or to disturb the transport of tyrosinase into the melanosomes. Some of the mutations do not affect the functionality of the tyrosinase, but rather ensure that it is not transported into the endoplasmic reticulum and therefore no melanin is formed.

A mutation was also found that lacked the entire tyrosinase gene. Apart from the symptoms typical for albinism (color, optic nerve junction, eyes), the affected person had no deviations in appearance. For humans it has thus been proven that the tyrosinase gene has no essential functions other than melanin production.

frequency

In Europe, 30-40% of people with albinism have OCA1, making it the most common of all forms of OCA. It is only the second most common form of albinism worldwide. The frequency is 1: 39,000 in Caucasians and 1: 28,000 in Africa.

OCA1 in animals: albino locus (C)

British White Cattle

Mammals

Ocolucutaneous albinism type 1 in humans corresponds to the various mutations of the C locus in mammals. In addition to completely white animals with red eyes, the only ones called albinos, the albino series includes a series of alleles that control the gradual lightening of skin, hair and eyes. Starting from a complete pigmentation, as it is in the wild type (C), first the pheomelanin, then the eumelanin is reduced.

Many rodents, rabbits, mink, cattle and cats have a color type called the Himalaya or Colorpoint. With them, the tyrosinase functions depending on the temperature, so the body is lighter than the cooler ears, tip of the nose, tail and paws.

Color mouse

Complete albino (c) mouse

The gene location of the color mouse is on chromosome 7. There are over 100 different mutations of the tyrosinase locus .

One of the oldest known mutations in the mouse is usually abbreviated with the letter c, leads to complete albinism with red eyes and white fur and is based on a mutation in which only one amino acid in the DNA of the tyrosinase locus was exchanged. Mice with the platinum (c p ) mutation look almost like albino mice but have a slightly darker coat.

The Extreme Dilution (c e ) mutation was first described in 1921 when a mouse of this color was caught in a manger with grain. Mice of this color are white with small black spots and black eyes. As the animals get older, they get darker and a brownish tinge. The color can vary considerably depending on the outside temperature.

The chinchilla (c ch ) and intense chinchilla (c i ) mutations do not affect eumelanin as much as pheomelanin. The black areas of the fur are dark slate gray in chinchilla (c ch ) mice, while they are not noticeably lightened in intensive chinchilla (c i ) mice. The brown pheomelanin is lightened much more strongly in both mutations. In animals with the brown mutation, the black fur does not appear noticeably lighter. Mice with the chinchilla-mottled (c m ) mutation are speckled. They have areas of fur with the typical chinchilla color and lighter areas of fur.

Right: Mouse of the color Himalayan (c h )

The mutation Himalayan (c h ) leads to a temperature-sensitive tyrosinase, so that newborn animals look like complete albinos because of the warmth in the womb and, over time, especially their tails, ears and noses darken because they are a little darker than the body, the one assumes beige color. Animals kept in warm rooms have a lighter coat than animals living in cold rooms.

At least 30 mutations of the tyrosinase locus were observed by irradiation, which are fatal in homozygous form . Some young animals die before birth, others only after birth. The prenatal deaths usually occur before or shortly after the embryo is implanted in the placenta. Further mutations lead to the fact that the survival rate decreases in later phases of life. In all mutations that impair survivability, adjacent gene locations are also impaired in addition to the tyrosinase locus. The tyrosinase itself therefore has no vital function.

Mice with complete albinism were slower to escape from the water, are less active in open spaces, and have poorer results in tests where they are supposed to distinguish black and white.

Mongolian gerbil

Gerbil of the color "dark-tailed white"

There are two mutations of the albino locus in the Mongolian gerbil .

The darker version is called Chinchilla Medium (c chm ) and, if the animal were black without this mutation, has a light brown body. The belly side is slightly lighter than the back and at low temperatures below 15 ° C the rear back is darker than the belly. The nose, ears and feet are dark sepia in color, and the tail is almost black. The scrotum is dark. The claws are dark. The color becomes darker from the body outwards. The eyes are almost black, but glow dark red in bright light. Young animals are initially significantly lighter with a slightly darker tail and only get their dark legs, ears and nose after the first coat change.

The lighter mutation is called “dark-tailed white” (c h ) and leads to animals with pink eyes and dark tails.

If they are also lightened by the P gene , they appear like complete albinos c. It is unclear whether there are complete albinos, as such was only reported once and it could be a question of these double-highlighted animals and not a mutation of their own.

Animals with a black basic color and both mutations "dark-tailed white" and Chinchilla Medium (c h c chm ) on the Albinolocus lie between the two pure-breeding forms in terms of coloration.

Domestic cat

Siamese Cat

Several alleles of the TYR gene are known in cats . The allele c a leads to white fur with blue eyes, the allele c to complete albinism with red eyes, c b causes the typical coloration of the Burmese cat , the allele c s that of the so-called point cats , the most famous representative of which is the Siamese . is.

Ferrets

An albino of the ferret

In the ferret ( Mustela putorius furo ), the domesticated form of the polecat, there is albinism which arises from the fact that exon 4 - i.e. a whole section - of the tyrosinase gene is missing.

Domestic cattle

The color of the white Galloway cattle , the British White Cattle and the White Park Cattle is also created by a temperature-sensitive tyrosinase .

Domestic pig

The pig tyrosinase locus has been mapped on chromosome 9. Complete albinism is not known in pigs. The dirty white color of the Mangalica pig (allele c e ) and the recessively inherited lightening of the color from yellow to white and from red to cream in the Berkshire pig (allele c ch ) are attributed to mutations of the C allele .

Birds

A mutation of the albino locus also leads to a recessive white color in chickens

Three mutations of the tyrosinase gene are known in chickens. All three have completely white plumage, but the eye color varies from completely unpigmented to gray.

fishes

In the Japanese rice fish ( Oryzias latipes ), which is one of the rice fish , the tyrosine focus is abbreviated with i. Several mutations of this gene are known. There are several albino mutants (i1, i4, and i5) in which a transposable element is inserted into the tyrosinase gene and this results in albinism, which corresponds to OCA 1 in humans. In another tyrosinase mutation (i6), OCA1 arises from the fact that part of the gene is missing. Animals with the mutation i1 are completely albinotic, i4 has a low tyrosinase activity and therefore somewhat darker eyes. Albinism is only weak in the i5 mutant.

Tyrosinase function in insects

Tyrosinase not only contributes to the formation of melanin in insects, but also plays an essential role in hardening the cuticle . As a result, individuals without a functioning tyrosinase are not viable and there is no tyrosinase-negative albinism in insects.

literature

  • B. Käsmann-Kellner: Albinism: Much more than just blue eyes. In: Ophthalmologist. 104 (8), 2007, pp. 646-647, doi: 10.1007 / s00347-007-1588-8
  • B. Käsmann-Kellner, B. Seitz: Phenotype of the visual system in oculocutaneous and ocular albinism. In: Ophthalmologist. 104 (8), 2007, pp. 648-661, doi: 10.1007 / s00347-007-1571-4

Web links

Individual evidence

  1. ↑ a b c K. Grønskov, J. Ek, K. Brondum-Nielsen: Oculocutaneous albinism. In: Orphanet J Rare Dis. 2007 Nov 2, 2, 43rd Review, PMID 17980020
  2. ↑ a b c d e f Markus Kaufmann: Albinism: The tyrosinase gene in 78 variations . Inaugural dissertation to obtain a doctorate from the University of Lübeck, in September 2004, DNB 982725965/34
  3. ^ RE Schnur, BT Sellinger, SA Holmes, PA Wick, YO Tatsumura, RA Spritz: Type I oculocutaneous albinism associated with a full-length deletion of the tyrosinase gene. In: Journal of Investigative Dermatology . 1996, Volume 106 (5), pp. 1137-1140, PMID 8618053 .
  4. ↑ a b c d Krista Siebel: Analysis of genetic variants of loci for the coat color and their relationships to the color phenotype and to quantitative performance characteristics in pigs. Institute for Livestock Sciences at Humboldt University Berlin, July 2001 (dissertation), Chapter 2 (summary of the current state of research)
  5. ^ Tyr Gene Detail Mouse Genome Database (MGD) at the Mouse Genome Informatics website, The Jackson Laboratory, Bar Harbor, Maine. World wide web. 21:01, Jun 30, 2009 (CEST).
  6. ^ A b Liane B. Russell, Clyde S. Montgomery, GD Raymer: Analysis of the Albino-Locus Region of the Mouse: IV. Characterization of 34 Deficiencies. In: Genetics. 1982 March ,; 100 (3), pp. 427-453. PMID 7117820
  7. ↑ Takahiko Yokoyama, David W. Silversides, Katrina G. Waymire, Byoung S. Kwon, Takuji Takeuchi, Paul A. Overbeek: Conserved cysteine ​​to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice. In: Nucleic Acids Research . Vol. 18, No. 24, 1990, PMID 2124349
  8. ↑ a b c d e II. The c (Albino) Series of Alleles . In: Willys K. Silvers: The Coat Colors of Mice . Springer Verlag, 1979.
  9. ^ A b c d e F. Petrij, K. van Veen, M. Mettler, V. Brückmann: A second acromelanistic allelomorph at the albino locus of the Mongolian gerbil (Meriones unguiculatus).
  10. ^ A. Schmidt-Küntzel, E. Eizirik, SJ O'Brien, M. Menotti-Raymond: Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci. In: J Hered. 2005 Jul-Aug, 96 (4), pp. 289-301, PMID 15858157 .
  11. ↑ DL Imes, LA Geary, RA Grahn, LA Lyons: Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation. In: Anim Genet. 2006 Apr, 37 (2), pp. 175-178, PMID 16573534
  12. ↑ WM Blaszczyk, C. Distler, G. Dekomien, L. Arning, KP Hoffmann, JT Epplen: Identification of a tyrosinase (TYR) exon 4 deletion in albino ferrets (Mustela putorius furo). In: Anim Genet. 2007 Aug, 38 (4), pp. 421-423, PMID 17655555
  13. ^ Sheila M. Schmutz: Genetics of Coat Color in Cattle: White. Retrieved June 20, 2009.
  14. ↑ Chung-Ming Chang, Jean-Luc Coville, Gérard Coquerelle, David Gourichon, Ahmad Oulmouden, Michèle Tixier-Boichard: Complete association between a retroviral insertion in the tyrosinase gene and the recessive white mutation in chickens. In: BMC Genomics. 2006, 7, p. 19, doi : 10.1186 / 1471-2164-7-19 , PMID 16457736 , PMC 1373650 (free full text).
  15. ↑ Akihiko Koga, Hidehito Inagaki, Yoshitaka Bessho, Hiroshi Hori: Insertion of a novel transposable element in the tyrosinase gene is responsible for an albino mutation in the medaka fish, Oryzias latipes. In: Molecular and General Genetics. MGG, Volume 249, Number 4, July 1995, pp. 400-405, doi: 10.1007 / BF00287101 , PMID 8552044 .
  16. ↑ A. Koga, Y. Wakamatsu, J. Kurosawa, H. Hori: Oculocutaneous albinism in the i6 mutant of the medaka fish is associated with a deletion in the tyrosinase gene. In: Pigment Cell Res. 1999 Aug, 12 (4), pp. 252-258, PMID 10454293
  17. ↑ A. Koga, H. Hori: Albinism due to transposable element insertion in fish. In: Pigment Cell Res. 1997 Dec, 10 (6), pp. 377-381, PMID 9428004 .
  18. ↑ A. Iida, H. Inagaki, M. Suzuki, Y. Wakamatsu, H. Hori, A. Koga: The tyrosinase gene of the i (b) albino mutant of the medaka fish carries a transposable element insertion in the promoter region. In: Pigment Cell Res. 2004 Apr, 17 (2), pp. 158-164, PMID 15016305
  19. ↑ Isao Kuboa, Ikuyo Kinst-Horia, Ken-Ichi Niheia, Frida Soriaa, Midori Takasakia, José S. Calderó and Carlos L. Céspedes: Tyrosinase Inhibitors from Galls of Rhus javanica Leaves and Their Effects on Insects. In: Journal of Nature Research C . 58, 2003, pp. 719–725 ( PDF , free full text). PMID 14577638 .