Oculocutaneous albinism type 2

from Wikipedia, the free encyclopedia
People with OCA 2 can have blonde hair like Mem Nahadr does. Whether Nahadr's albinism is OCA 2 is unknown
In some forms of OCA 2, dark nevi appear like this man from Niger has them

The oculocutaneous albinism type 2 (OCA 2) is a form of albinism is also referred to as albinism totalis 2. It is caused by mutations in the P gene, which was named after the homologous pink eye dilution gene in mice.

Appearance

Variants of oculocutaneous albinism type 2

The appearance of people with OCA 2 can vary significantly depending on the mutation. There are mutations that are recessive compared to the wild type, but also mutations with intermediate inheritance. The pheomelanosomes are less affected by mutations in the P gene than the eumelanosomes, so people with OCA 2 often have yellowish, blonde or even brown hair that darkens over the course of their lives. The skin and hair color of people from peoples with dark skin is always lighter than that of their non-albinotic relatives. People from countries with fair skin and hair color such as Scandinavia, on the other hand, often look completely normal. Then only the typical eye defects can lead to the diagnosis. Another phenotype of OCA 2 is also known as the brown OCA (BOCA). This has so far only been described in Africans and African-Americans. Those affected have brown hair, brown or blue-green irises, and light brown skin that tans easily. Visual impairment, eye tremors, and strabismus are also found.

Contribution of the gene to the normal variance in hair and eye color

Black and white: blonde hair and blue eyes in Europeans go back to variants of the OCA2 gene.

In a study of Americans of Northern European descent, it was found that OCA2 was responsible for 74% of the variance in eye color . A mutation in intron 1 of the OCA2 gene leads to blue eyes. In redheads, the gene leads to a significant reduction in the number of nevi . In addition, two variations of the gene explain 85% of the variation in hair color. Mutations in the OCA4 gene are responsible for the light skin color of Asians and Europeans .

Genetics and Physiology of OCA2

The P gene is located on the long arm of chromosome 15 (15q11-13) and encodes a membrane protein of the endoplasmic reticulum.

The P protein, which is responsible for oculocutaneous albinism type 2 (OCA2), has 12 transmembrane domains and is located in the endoplasmic reticulum. In OCA2, a significant part of the tyrosinase remains in the endoplasmic reticulum, where it is synthesized, and tyrosinase is also excreted or broken down from the cell instead of being transported into the melanosomes.

Syndromes

Two syndromes are often associated with OCA 2: Prader-Willi syndrome (PWS) and Angelman syndrome . Both are based on mutation on the long arm of chromosome 15, where the P gene, which is responsible for OCA 2, is located.

frequency

With 50% share of OCA, OCA 2 is the most common form of albinism worldwide and occurs 1: 277 in Hopi Indians. In Europe, approximately 10-20% of patients with OCA have an OCA 2.

OCA2 is the most common form of albinism among black Africans. On average, one out of 36,000 US citizens has an OCA 2; one in 10,000 Americans of African descent is affected; in South Africa it is one in 3,900 black Africans, and in the Igbo of Nigeria it is one in 1,000.

The prevalence among some North American natives is also very high. Among the Navajo, one in 1500 to one in 2000 people has OCA 2.

In Japan, OCA 2 is rarer than OCA 1.

OCA2 in animals: the pink eye series (pink eye P)

In mammals

Left: pink-eye mutation in guinea pigs
Astyanax jordani

The mutations of the pink eye series in mammals correspond to oculocutaneous albinism 2 (OCA2) in humans. Several mutations of this locus lead to phenotypes in which the fur is only lightened, while the eyes contain little or no melanin and therefore appear red or pink. There are also variants that cause sperm abnormalities, but also mutants with lightened fur and normal-colored spots. The variant p m forms a mosaic between wild type and lightening, so it is spotted.

The lightening of the color results from the fact that fewer melanosomes for eumelanin (eumelanosomes) are formed, which are often smaller and clump together. In the melanosomes, the dyes are not so densely packed, so that the melanosomes are not quite as dark. There are fewer of the melanosomes that form pheomelanin, but they are otherwise normal.

Domestic pig

A mutation is known in the Hampshire pig breed that led to red eyes and a lightening of the black color to gray, which has been suspected to be associated with the P locus of the pig.

mouse

The allele p s (p-sterile) of the P locus of the mouse leads homozygously to small body size, nervousness, misaligned teeth, premature old age and sterility of the male animals. The sterility is mainly caused by abnormal sperm, but is sometimes associated with poor libido. There is also a variant with color lightening and infertility in hamsters. The mouse allele p (pink-eye dilution) also influences growth.

With fish

The albinism of the blind cave tetra ( Astyanax jordani ) is due to various mutations that lead to OCA2.

Individual evidence

  1. ↑ a b c d e ALBINISM, OCULOCUTANEOUS, TYPE II; OCA2.  In: Online Mendelian Inheritance in Man . (English).
  2. ↑ David L. Duffy, Grant W. Montgomery, Wei Chen, Zhen Zhen Zhao, Lien Le, Michael R. James, Nicholas K. Hayward, Nicholas G. Martin, Richard A. Sturm: A Three-Single-Nucleotide Polymorphism Haplotype in Intron 1 of OCA2 Explains Most Human Eye-Color Variation. In: Am J Hum Genet. 2007 February; 80 (2), pp. 241-252. PMID 18252222 .
  3. ↑ SN Shekar, DL Duffy, T. Frudakis, RA Sturm, ZZ Zhao, GW Montgomery, NG Martin: Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2. In: Journal of Investigative Dermatology . 2008; 128 (12), pp. 2807-2814. PMID 18528436
  4. ↑ M. Soejima, H. Tachida, T. Ishida, A. Sano, Y. Koda: Evidence for recent positive selection at the human AIM1 locus in a European population. In: Mol Biol Evol. 2006 Jan; 23 (1), pp. 179-188. Epub 2005 Sep 14. PMID 16162863 .
  5. ↑ a b Kun Chen, Prashiela Manga, Seth J. Orlow: Pink-eyed dilution protein controls the processing of tyrosinase. In: MBC. Vol. 13, Issue 6, pp. 1953-1964, June 2002.
  6. ↑ GE Costin, JC Valencia, WD Vieira, ML Lamoreux, VJ Hearing: Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4. In: J Cell Sci. 2003 Aug 1; 116 (Pt 15), pp. 3203-3212. PMID 12829739
  7. ↑ K. Grønskov, J. Ek, K. Brondum-Nielsen: Oculocutaneous albinism. In: Orphanet J Rare Dis. 2007 Nov 2; 2, p. 43. Review. PMID 17980020
  8. ↑ 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)
  9. ^ ME Protas, C. Hersey, D. Kochanek, Y. Zhou, H. Wilkens, WR Jeffery, LI Zon, R. Borowsky, Clifford J. Tabin : Genetic analysis of cavefish reveals molecular convergence in the evolution of albinism. In: Nat Genet. 2006 Jan; 38 (1), pp. 107-111. Epub 2005 Dec 11. PMID 16341223 .