On page 53, Dr. Moalem mentions Albinism as an example when talking about the role that melanocytes play for determining skin color. First, explain what melanin is and the role it plays in determining skin color. What are the two forms that melanin comes in?
Next, going along with the main theme of the novel that many genetic diseases are adaptations that were once selective advantages in the past, research how albinism came to be prevalent in the world, relating to Big Idea number 1, "The process of evolution drives the diversity and unity of life."Also, explain what albinism is and research the different types of albinism. What are the inheritance patterns of each type?
Lastly, do this problem. If a man's father has Oculocutaneous Albinism type 1, and the man marries a woman who has Oculucutaneous Albinism type 1, what are the genotypic and phenotypic ratios of their children? (Jeremy Bush jbush3@students.d125.org)
Melanin is a natural pigment that is found in most organisms (but not spiders) that is a derivative of the amino acid Tyrosine (symbolized Tyr or Y). Melanin is the primary pigment responsible for skin and hair color, and there are two principal types of melanin: eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids; and pheomelanin, the form of melanin that is a polymer of benzothiazine. Eumelanin is largely responsible for the different shades of brown seen in peoples’ skin, while pheomelanin is largely responsible for freckles and red hair, as it is of a red-brown color.
ReplyDeleteThe process by which melanin is produced, and thus the process by which skin color comes to be, is called melanogenesis. Melanogenesis occurs in melanocytes, cells located in the bottom-most layer of the epidermis, as well as in the uvea of the eyes, the meninges, the bones, and the heart. When exposed to ultraviolet-b (UVB) radiation, melanocytes are induced to begin producing melanin, as the DNA within the melanocytes acts as a photoreceptor. Overall, the point of melanogenesis is to protect the melanocytes from the harmful sunlight that could damage the cells; melanin, being dark in pigmentation, absorbs the dangerous radiation before it can penetrate to the levels of the melanocytes.
The pathway for melanogensis is an extremely complicated pathway mediated by multiple control agents, according to www.genome.jp. The most important of these control agents is the MC1 receptor (MC1R), which, when activated, activates cyclic AMP (cAMP) and its response-element binding protein (CERB). This, in turn, causes an increase in the concentration of microphthalmia-associated transcription factor (MITF), which stimulates phosphorylation of tyrosine by tyrosinase (in healthy individuals; albinism will be discussed further on). MITF is instrumental, along with certain DNA methyl markers and environmental factors, in causing melanoma (skin cancer).
(for a complicated flow chart, see http://www.genome.jp/kegg/pathway/hsa/hsa04916.html)
Differing colors of skin among individuals is a result of the number of eumelanin and pheomelanin cells contained in the person’s epidermis. Albinos, those who have no skin color, lack the enzyme tyrosinase, which is used in non-albinos to phosphorylate the amino acid tyrosine into melanin molecules during melanogenesis. Without this enzyme, melanin cannot be formed; the lack of skin color attributed to albino mammals is rather that of a lack of melanin. As such, albinos are extremely susceptible to sunburn.
(all the above information was gleaned from several online sources, including Encyclopedia Britannica and the National Institute of Health)
As Dr. Moalem describes on page 57, albinism likely arose as a mutation in the human genome, specifically in the genes that code of apolipoprotein E (ApoE4). ApoE4 is a protein that “cranks up” cholesterol levels in the body to account for limited sunlight. That sunlight is necessary to convert folate into Vitamin D, an vitamin essential for allowing the intestines to absorb certain chemicals and compounds, such as calcium and phosphate. Cholesterol can be converted into Vitamin D by the human body; therefore, in a region that gets little sunlight, high cholesterol levels account for the discrepancy.
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ReplyDeleteApoE4 is very common among Africans and Northern Europeans, which may give some insight into the evolutionary history of albinism. As the primary evidence of albinism is a lack of pigment, it follows that albinos would not be able to convert folate to Vitamin D in the normal manner, and would thus be at an increased need for ApoE4. As it turns out, according to StewartSynopsis, albinism and sickle cell anemia seem to have similar evolutionary backgrounds: both provide some level of protection against malaria, which is hyperendemic to Africa. It has been noted that mosquitoes are “less likely to alight and draw blood from” a white person in comparison to a dark person, likely because of the ocular stimulation the mosquito receives from a darker skinned person in comparison to a lighter skinned person.
As with any mutation, albinism likely began as a variation in the gene pool of the African people. As malaria struck down many dark skinned Africans, those with the mutation that caused albinism were able to survive in greater numbers, reproduce, and pass along their mutation. With malaria acting as the selective pressure, the genes for albinism were passed along from generation from generation, allowing albinism to live on. As Africa has been noted by anthropologists as the starting point of human beings (from a scientific vantage point), these albinos likely then migrated to Europe and the rest of the world (likely in the Pangaeic world), spreading albinism to the rest of the world. There, albinism may not have been a distinct advantage, but neither did it decrease fitness, and thus the genes lived on.
There are multiple types of albinism, according to www.albinism.org, a website organized by the National Organization for Albinism and Hypopigmentation. There are two main types of albinism: Ocular Albinism (OA), which affects mainly the eyes; and Oculocutaneous Albinism (OCA), which affects both the eyes and the skin. There are four types of OCA, each of which arises via a mutation that affects a different enzyme or protein.
Ocular Albinism follows a sex-linked inheritance pattern, while Oculocutaneous Albinism follows an autosomal recessive inheritance pattern, meaning that a male with a single copy of the defective OA gene will have Ocular Albinism, but a woman needs two copies in order to have the disease (women have two X-chromosomes; having a single copy of the defective gene leads to the woman being a carrier for the disease). Ocular Albinism arises from a defect in the GPR143 gene, which is especially important in the pigmentation of the eye. As OCA-1 is the most common type of OCA, I will focus on the genetics of that alone. OCA-1 arises from a mutation in the TYR gene, which codes for the enzyme tyrosinase. The TYR gene is located on autosomal chromosome 11 on the q-arm, from locus 14 to locus 21 (full location: 11q11-q14). The TYR gene is located between base pairs 88,911,039 and 89,028,926, constituting 117,877 base pairs in total. Over 100 different mitotic mutations have been discovered to affect this gene, causing OCA-1.
(the above information regarding the genetics of the different types of albinism taken completely from the National Institute of Health)
Because OCA-1 is an autosomal recessive disease, an individual with the disease will have a homozygous dominant genotype. For the sake of this exercise, I will use a lower case ‘a’ to represent the allele that causes OCA-1. If a man’s phenotype is OCA-1 positive, his genotype is ‘aa’. If a woman’s phenotype is OCA-1 positive, then she too has a genotype of ‘aa’. If the two were to have a child, the ratios for the child would be 100% OCA-1 positive and 100% ‘aa’ genotype, as both parents can pass only the recessive allele onto their offspring. As such, the children will receive a single recessive allele from each parent, resulting in a homozygous recessive genotype, which would cause OCA-1.
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ReplyDelete(Justin Millman, jmillma4@students.d125.org)