Albinism

INTRODUCTION For my research project I have chosen the genetic disease albinism. There are a few reasons why I chose albinism as my topic. First and foremost, in kindergarten I had a friend who was an albino, and although I have not seen him in over 10 years I am still curious as to what the causes of albinism are. Back then, my mother explained it to me by saying, “that’s just the way his skin is” which is a fine way to explain it to a five year old, but now I find myself wanting to know more. Another reason I am curious about albinism actually extends from my first reason. I often wondered if there was any chance that my kids could possibly be born with it. I know now that it sounds a little bit ridiculous but I would sometimes worry that I wouldn’t be able to take my children to the beach (I knew this because my friend from kindergarten could never come with us when we went in the summer). I also used to wonder whether or not my friend could see the same way I could, since his eyes looked so different from mine. As a result of all of this, I could not turn down the opportunity to research a disease that has held my curiosity for such a long time. PHENOTYPIC CHARACTERISTICS The most prominent phenotypic characteristic of albinism is obviously the lack of skin coloring. Albino skin is whitish in appearance, sometimes seeming to be almost translucent. Similarly, albino hair is also very pale, appearing closer to white than blonde. Albinism makes the skin extremely sensitive to sunlight. Albinos need to be very careful about exposure to the sun as they have a very high risk of burning due to lack of protection from ultraviolet rays, which is normally provided by the pigment melanin (2). Similar to the skin, albino eyes also lack color; the irises usually appear pinkish. People with albinism often have eye problems. First of all, they suffer from severe sensitivity to bright lights. Cases of extreme nearsightedness or farsightedness that cannot be completely corrected with eyeglasses are also common. People with albinism also sometimes demonstrate an involuntary back and forth movement of the eyes called nystagmus. Finally, people with albinism are more likely to develop astigmatism. It is possible to have albinism that affects the eyes without also affecting the skin. This is known as ocular albinism (3). INHERITANCE Albinism is an autosomal recessive disorder. All the children of two affected homozygous affected parents are also affected. This means that two parents who have albinism, and who possess two recessive alleles each for albinism will produce affected children 100% of the time. Being a relatively rare disorder, albinos are often the children of unaffected parents (this is the case with autosomal recessive disorders). Parents who are both heterozygotes (both carriers of the disease but not having it themselves) have a 75% chance of producing a normal, non-affected child. Because albinism is not carried on the sex chromosomes, it is expressed equally in both males and females, and either parent can transmit the disorder. Albinism also affects people of all races equally. Approximately 1 in 17,000 people has one of the types of albinism, which amounts to roughly 18,000 people in the United States (1). GENETIC AND CELLULAR ORIGINS Albinism is located on chromosome 11q 14-21. The gene associated with albinism is called OCA1 (among a few others). OCA1 codes for the protein tyrosinase. This protein is responsible for converting tyrosine into something called DOPA (dihydroxyphenylalanine). DOPA plays an important part in the formation of melanin by next becoming dopaquinone. Dopaquinone then forms black-brown eumelanin or red-yellow pheomelanin. Melanin is a pigment, the absence of which causes albinism (2). Albinism occurs when something causes the OCA1 gene to function improperly. This improper function disrupts the production of tyrosinase. With tyrosinase production malfunctioning, it is impossible for the body to make DOPA and as a result the body is also prevented from making melanin. The absence of melanin causes the lack of color in the skin of people who are affected with albinism (2). MOLECULAR ORIGINS The cDNA sequence for the OCA1 gene is 1607 bases long; 325 Adenine, 466 Cytosine, 439 Guanine, and 377 Thymine. Albinism results from mutations in genes involving the biosynthesis of melanin pigment. The OCA1 gene is not the only gene with which albinism is associated, however (4). There are actually six genes that are now known to be responsible for causing albinism: the tyrosinase gene (TYR), the OCA1, OCA2, and OCA3 genes, the tyrosinase-related TYR1 gene, and the CHS1 gene. The function of only two of the gene products is known; tyrosinase and tyrosinase-related protein-1, both of which are enzymes in the melanin biosynthetic pathway. Frameshift mutations, Nonsense mutations, and Missense mutations in the OCA and TYR genes can all disrupt the biosynthetic pathways that produce melanin and ultimately result in albinism however there are too many of them to list here. Since it is not known what function the other gene (CHS1) listed above carries out, it is not yet known what mutations on it leads to the development of albinism (1,4). While researching, I could locate no evidence of any genetic testing that might be available for detecting albinism. I would imagine that if there were one it would be similar to other genetic tests we have studied. You would have to use specific probes to search the DNA strands for one of the many different mutations which are known to result in albinism, although I would question the efficiency of this method since there are quite a lot of them. It is probably also possible to use RFLP markers to test for the presence of albinism, but again the number of different mutations that cause albinism is high enough that the efficiency of such a test would be greatly in question (1,4,5). CONCLUSION Now that my study of albinism has come to an end, I feel what I can only describe as a sense of closure on a subject that has been (at least in some small part) in my thoughts for the past fifteen years. My knowledge of this disorder has come a long way since my curiosity about my kindergarten friend. Obviously my fear that I would catch the disease from him is long gone, but I wish I could say the same for some other more realistic fears. The mutations that cause albinism (and for that matter many other genetic disorders) remain something of an enigma. We know where they are, but we are still unable to prevent or repair many of them with any great rate of success. I’m sure that greater (or at least better-equipped) minds than mine have wondered what direction research in albinism should take, but in my opinion they should look into a cure for the disorder. Is there some way we can stimulate the OCA and TYR genes into correctly performing their jobs, or maybe introduce melanin directly into those suffering from this disorder? I think that once our scientists and researchers better understand the human genome and it inner workings, the cures for genetic diseases like albinism will follow shortly after. Then maybe my friend from kindergarten can finally come with us to the beach. BibliographyREFERENCES 1. www.cbc.umn.edu/iac 2. www.albinsim.org 3. www.eyeassociates.com/images/albinsim.html 4. www.ncbi.nlm.gov 5. www.genome.wi.mit.edu/SNP/human/index.html

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