Albinism Essay, Research Paper
Physical anthropologists view humans as biological organisms. Coupled withgenetics and biochemistry, scientists can form a more complete picture of human anatomy, both past and present. Physical anthropology looks at human variation and evolution. Variation looks at the biological differences that exist between individuals within a population and at individuals between populations (e.g., body shape, size, and physiological responses). These differences in human biology are measured using a technique called anthropometry 1. In order to explain this diversity, physical anthropologists look to environmental conditions (including culture) and genetics. Taking these factors into account, the anthropologist attempts to formulate an evolutionary explanation for the differences.
Human evolution looks at the bodily changes that have occurred over the years leading up to modern day Homo sapiens. In order to determine the changes that have taken place in human anatomy we rely on paleoanthropology, the study of human fossil remains, and primatology, and the study of other primates 1. Paleoanthropology helps us determine who our ancestors were, and when, how and why they evolved. Primatology allows us to see the similarities and differences between other primates and ourselves and allows us to trace these evolutionary relationships. For example, such a study has determined that humans share approximately 98.6% of their DNA (their genetic code) with gorillas, 98.8% with chimpanzees and 97.6% with orangutans 2.
Approaching human variation from the perspective of the anthropologist leaves a vast field of study before the world of medicine. One of the most fascinating examples of human variation is the found in albinism.
The word “albinism” refers to a group of genetically inherited conditions. People with albinism have little or no pigment in the eyes, skin, and hair (or in some cases in the eyes alone). They have inherited from their parents an altered copy of genes that does not work correctly. The altered gene does not allow the body to make the usual amounts of a pigment called melanin.
Approximately one in 17,000 people have one of the types of albinism. About 18,000 people in the United States are affected 3. Albinism affects people from all races. The parents of most children with albinism have normal hair and eye color for their ethnic background, and do not have a family history of albinism 4.
Melanin is a dark compound that is called a photoprotective pigment. The major role of melanin pigment in the skin is to absorb the ultraviolet (UV) light that comes from the sun so that the skin is not damaged. Sun exposure normally produces a tan, which is an increase in melanin pigment in the skin. Many people with albinism do not have melanin pigment in their skin and do not tan with exposure to the sun. As a result, their skin is sensitive to the sunlight and they develop sunburn. In people with albinism, all other parts of the skin are normal even if there is no melanin in the skin.
Melanin pigment is important in other areas of the body, such as the eye and the brain, but it is not known what the melanin pigment does in these areas. Melanin pigment is present in the retina and the area of the retina called the fovea does not develop correctly if melanin pigment in not present in the retina during development. The other areas of the retina develop normally whether or not melanin pigment is present. The nerve connections between the retina and the brain are also altered if melanin pigment is not present in the retina during development. The iris has melanin pigment and this makes the iris opaque to light (no light goes through an opaque iris). Iris pigment in albinism is reduced, and the iris is translucent to light, but the iris develops and functions normally in albinism.
Melanin forms in a special cell called the melanocyte. This cell is found in the skin, in the hair follicle, and in the iris and retina of the eye. There are many steps in the process of converting the amino acid tyrosine to melanin pigment. Two types of melanin form: black-brown eumelanin and red-blond pheomelanin.
As with most metabolic pathways in our body, the first compound in a pathway is converted to the next compound by the action of an enzyme. For example, in the simple pathway A–>B–>C, the conversion of compound A to B occurs because of the action of Enzyme 1, and the conversion of B to C occurs because of the action of Enzyme 2. The formation of melanin pigment follows a pathway like this, but the pathway is more complex and not all of the steps are known.
Tyrosinase is the major enzyme involved in the formation of melanin pigment. Tyrosinase is responsible for converting tyrosine to DOPA and on to dopaquinone. The dopaquinone then forms black-brown eumelanin or red-yellow pheomelanin. The tyrosinase enzyme is made by the tyrosinase gene on chromosome 11, and alterations (mutations) of this gene can produce one type of albinism because the tyrosinase enzyme made by the altered gene does not work correctly 5.
Two additional enzymes called tyrosinase-related protein 1 or DHICA oxidase and tyrosinase-related protein 2 or dopachrome tautomerase are important in the formation of eumelanin pigment 5. The gene for DHICA oxidase in on chromosome 9 and the gene for dopachrome tautomerase in on chromosome 9. Alterations of the DHICA oxidase gene are associated with a loss of function of this enzyme and this produces on type of albinism. Alterations of the gene for dopachrome tautomerase do not produce albinism.
Three other genes make proteins that are also involved in melanin pigment formation and albinism, but the exact role of these proteins remains unknown. These genes are the P gene on chromosome 15, the Hermansky-Pudlak syndrome gene on chromosome 10, and the ocular albinism gene on the X chromosome 5.
The eye needs melanin pigment to develop normal vision. People with albinism have impairment of vision because the eye does not have a normal amount of melanin pigment during development. The skin needs pigment for protection from sun damage, and people with albinism often sunburn easily. In tropical areas, many people with albinism who do not protect their skin get skin cancers.
There are several less common types of albinism, which involve other problems also, such as mild problems with blood clotting or problems with hearing. Albinism may cause social problems, because people with albinism look different from their families, peers, and other members of their ethnic group.
Growth and development of a child with albinism should be normal and intellectual development is normal 4. Developmental milestones should be achieved at the expected age. General health of a child and an adult with albinism is normal, and the reduction in melanin pigment in the skin, hair and the eyes should have no effect on the brain, the cardiovascular system, the lungs, the gastrointestinal tract, the genitourinary system, the musculoskeletal system, or the immune system. Life span is normal.
Most children with albinism should function in a mainstream classroom environment, provided the school gives specific attention to their special needs for vision. Contact with the school system should begin well before kindergarten, since school systems provide preschool services to children with disabilities. Preschool evaluations allow parents and teachers to form an Individual Education Plan for the child. The use of Braille is not necessary, and, if a trial of Braille is given, children with albinism will read the dots visually 4.
Children with albinism often prefer to read with a head tilt and usually hold the page close to the eyes. Occasionally it can be difficult to get them to use their glasses, as they do not notice significant improvement in their vision when glasses are used. Furthermore, use of glasses or books with large print can be difficult because of peer pressure.
There are two main categories of albinism: “oculocutaneous albinism” or “OCA” which means that melanin pigment is missing in the skin, the hair, and the eyes; and “ocular albinism” or “OA” which means that the melanin pigment is missing mainly in the eyes, and the skin and hair appear normal. OCA is more common than OA 5.
It is usually possible to determine the type of albinism present with a careful history of pigment development and an examination of the skin, hair and eyes. The only type of albinism that has white hair at birth is OCA1. Individuals with other types of OCA will have some hair pigment at birth, although it may be very slight in amount. It can be difficult to tell if the hair is completely white or very lightly pigmented in a very young child, and changes in pigment over time will usually help clarify the OCA type present.
The most accurate test for determining the specific type of albinism is a gene test 5. A small sample of blood is obtained from the affected individual and the parents as a source of DNA, the chemical that carries the ‘genetic code’ of each gene. By a complex process, a genetic laboratory can “sequence” the code of the DNA, to identify the changes (mutations) in the gene that cause albinism in the family. The test is useful only for families that contain individuals with albinism, and cannot be performed practically as a screening test for the general population. None of the tests available are capable of detecting all of the mutations of the genes that cause albinism, and responsible mutations cannot be detected in a small number of individuals and families with albinism. The test can be used to determine if a fetus has albinism. For this purpose a sample would be obtained by amniocentesis, a procedure which involves using a needle to draw fluid from the uterus, at 16 to 18 weeks gestation.
As mentioned, albinism is genetic. It is inherited. It is passed on from one generation to the next in the genes. Genes are contained in the egg and the sperm that combine at conception to start the process of forming a baby. Genes act as blueprints that tell the system how to do its work 6. In the case of albinism, the genes involved are those that tell the eyes or skin how to make melanin pigment.
Each cell in the body has two copies of each gene- one version from the mother and one version from the father. For OCA, the individual with albinism has received an albinism gene from both parents, and both versions of his blueprint for making pigment are incorrect.
If a person carries one normal copy of a gene and one altered or albinism copy of a gene, he or she still has one blueprint that will provide enough information to make pigment. That means that he or she will have normal eye and skin color. For OCA, parents carry an albinism gene with an incorrect version of the blueprint, but they have normal pigmentation, because they still have one normal gene with a normal version of the blueprint 7.
About 1 in 70 people carry a gene for OCA 5. Suppose a man and a woman each carries an altered copy of the same gene and have normal coloration. They each have a normal copy and an albinism copy of the gene, and will pass one of these two copies when they conceive a baby. They each have a 1 in 2 chance of passing on the albinism copy of the gene to their baby. As a result, for each pregnancy there is a 1 in 4 chance (1/2 x 1/2) that their baby will get two copies of the gene for albinism, in which case the baby will have no normal blueprint for making pigment, and will have albinism 4.
The above explanation of the inheritance of albinism does not apply to one type of ocular albinism, called X-linked ocular albinism. For X-linked inheritance, the gene for albinism is located on an X chromosome. Females have two X chromosomes, while males have one X chromosome and one Y chromosome. X-linked ocular albinism appears almost exclusively in males. The gene for it is passed from mothers who carry it to their sons. The mothers have subtle eye changes that an ophthalmologist could identify, but mothers generally have normal vision. For each son born to a mother who carries the gene, there is a one in two chance of having X-linked ocular albinism 4.
One of the two most common types of albinism is tyrosinase related OCA, produced by loss of function of the tyrosinase enzyme in the melanocyte. This results from inherited mutations of the tyrosinase gene. Classical OCA, with a total absence of melanin in the skin, hair and eyes over the lifetime of the affected individual is the most obvious type of OCA1, but there is a wide range of pigmentation associated with tyrosinase gene mutations. The range in phenotypes extends from total absence to near normal cutaneous pigmentation, but the ocular features are always present and help identify an individual as having albinism.
Many different mutations of the tyrosinase gene have been identified in individuals and families with OCA1. Most mutations lead to the production of tyrosinase enzyme that does not work. As a result, the first two critical conversions in the melanin pathway (tyrosine–>dopa–>dopaquinone) are not made and no melanin pigment forms; the pathway is “blocked” at the start. Mutations that produce an inactive enzyme or no enzyme at all are called “null” mutations.
Some tyrosinase gene mutations are not null mutations but are called “leaky” mutations 4. These mutations lead to the production of a tyrosinase enzyme that has a little activity but nowhere near the normal amount of activity (often in the range of 1-10% of normal activity). Leaky mutations and the resultant tyrosinase enzyme allow some melanin to form. The formation of melanin can be very small (the minimal pigment type of OCA) or can range to nearly normal (the type of OCA that was mistakenly called autosomal recessive ocular albinism).
An important distinguishing characteristic of OCA1 is the presence of marked hypopigmentation at birth. Most individuals affected with a type of OCA1 have white hair, milky white skin, and blue eyes at birth. The irides can be very light blue and translucent such that the whole iris appears pink or red in ambient or bright light. During the first and second decade of life, the irides usually become a darker blue and may remain translucent or become lightly pigmented with reduced translucency. The skin remains white or appears to have more color with time. Sun exposure produces erythema and a burn if the skin is has little pigment and is unprotected, but may tan well if cutaneous pigment has developed. Pigmented lesions (nevi, freckles, lentigines) develop in the skin of individuals who have developed pigmented hair and skin.
OCA2 is the other more common form of albinism. The common features of OCA2 include the presence of hair pigment at birth and iris pigment at birth or early in life. Localized (nevi, freckles, and lentigines) skin pigment can develop, often in sun exposed regions of the skin, but tanning is usually absent. It was once thought that the ethnic and constitutional pigment background of an affected individual had a more profound effect on the OCA2 phenotype than on the OCA1 phenotype, but this no longer appears to be the case. Both OCA1B and OCA2 have a broad range of pigmentation that, in part, reflects the genetic background of the affected individual. There may be some accumulation of pigment in the hair with age but this is much less pronounced as that found in OCA1B, and many individuals with OCA2 have the same hair color throughout life. OCA2 is the most common type of OCA in the world, primarily because of the high frequency in equatorial Africa 2.
In Caucasian individuals with OCA2, the amount of pigment present at birth varies from minimal to moderate. The hair can be very lightly pigmented at birth, having a light yellow or blond color or more pigmented with a definite blond, golden blond or even red color. The normal delayed maturation of the pigment system in northern European individuals and lack of long hair can make it difficult to distinguish OCA1 from OCA2 in the first few months of life. The skin is white and does not tan on sun exposure. Iris color is blue-gray or lighted pigmented, and the degree of iris translucency correlates with the amount of pigment present. With time, pigmented nevi and lentigines may develop and pigmented freckles are seen in exposed areas with repeated sun exposure. The hair in Caucasian individuals may slowly turn darker through the first two or more decades of life.
There is a distinctive OCA2 phenotype in African-American and in African individuals 4. The hair is yellow at birth and remains yellow through life, although the color may turn darker. Interestingly, the hair can turn lighter in older individuals, and this probably represents the normal graying with age. The skin is white at birth with little change over time, and no tan develops. Localized pigmented lesions such as pigmented nevi, lentigines and freckles can develop in some individuals. The irides are blue/gray or lightly pigmented.
The history of genetic variations is explained in several theories, the most notable is Darwin s explanation for adaptation and evolutionary divergence. Darwin states that because of the “struggle for existence”, few offspring survive to reproduce 8. Any heritable variation that improves an individual s ability to survive and reproduce will tend to be passed on to the next generation. This is called natural selection.
Adaptation is explained by natural selection. Natural selection results in features that, under particular environmental conditions, bestow an advantage in the competition to survive and reproduce. Each successive step in the evolution of an adaptive feature must itself be adaptive 9. If a form or feature requires any particular step to be disadvantageous, such a form will not exist under constant selection. That is, adaptations are not necessarily predicted to be “perfect”. The probability of a reversal of a complex series of changes is very small 9.
An example of adaptation by natural selection is the retina of the vertebrate eye (in contrast to some other eyes, such as those of some molluscs) is “inside out” relative to an efficient design 10. The vascular tree shadows the photoreceptor cells. Because it is on the “wrong side”, the optic nerve has to go through a hole in the retina, resulting in a blind spot. These features imply that vertebrate retina evolution was processive, not designed in a single creative step.
From its origin in a flat, light-sensitive layer in the dorsal side of the anterior nerve system, development of the vertebrate nerve system (making a tube from a planar surface) resulted in the inverted orientation of the future retina. This retinal “inversion” is not a result of some underappreciated function, because some independently evolved eyes have “noninverted” retinas. Once a pathway of successive adaptations begins, reversals may be competitively disadvantageous (e.g., to completely reorganize the vertebrate retina, a redesign of neural tube development might be required. Again, ancestry apparently constrains the range of variation available to natural selection.
Adaptation is used differently in evolutionary biology than it is in physiological anthropology. Aspects of an organism that suggest its adaptability are the complexity between structure and function and the comparative method of correlating species differences with ecological factors. Direct evidence for adaptation can only come from experimental studies 8.
The problems with adaptive significance and studying diseases such as albinism are many, but not invalidating. The possible problems are an adaptation may not appear to result in better performance with respect to the environment. Adaptation increases relative fitness, not necessarily absolute fitness but better competition with other genotypes 11. A variation of a structure could simply be neutral. These adaptations may not have evolved for purposes for which they now appear to be useful. A trait might not be determined genetically, but be a direct consequence of environment or learning. The same trait might be a simple consequence of chemical or physical “laws”. It is evident that different species may have (neutral) variation for the same adaptive feature merely because of different ancestry; e.g., although a pattern that provides good camouflage is likely to be an adaptive trait, alternative patterns that also provide good camouflage may work just as well 11. Many variations that appear may be “constrained” by the developmental system or the genome (e.g., that tetrapods have 4 limbs may not be an adaptation–why couldn t 6 work just as well?–but this number depends on what is allowed by the developmental mechanisms that pattern the organism and on the ancestry of the genome). Any trait is likely to be anachronistic, since the conditions under which a feature evolved existed in the past.
Adaptation, presents obstacles to validity, however, given the formula for environmental factors, genetic influences, and biological variation, it is evident that albinism falls into this category.
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