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Inheritance
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Variegata Porphyria (the form prevalent in South Africa) is inherited in an autosomal dominant manner, although other forms of porphyria can be inherited in other ways. |
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Occurrence
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3 in 1,000 in South Africa have Variegata Porphyria |
| Description | a group of disorders caused by a deficiency of an enzyme in the pathway for making heme (a component of hemoglobin)-- this causes a variety of symptoms: sensitivity to light, mental changes which border on insanity, itchy and blistering skin, dark colored urine, abdominal pain and cramping, and hairiness |
Background:
This genetic trait is a peculiar one in existence. Many people have made some wild speculations about it. One such speculation is that one form of poryphria is the disorder that brings us stories of werewolves. Individuals who had porphyria would avoid all sunlight (perhaps they would wait and come out at night), be excessively hairy, and suffer temporary bouts of insanity. With these traits one can see how and where these rumors could have arisen.
It is thought that perhaps Vincent Van Gogh ( Loftus, L. S.; Arnold, W. N. :Vincent van Gogh's illness: acute intermittent porphyria? Brit. Med. J. 303: 1589-1591, 1991) could have suffered from another form of porphyria known as acute intermittent porphyria as well as King George III. Thus, the madness of King George gains new meaning.
For this exercise, a specific form of porphyria will be studied. It is called Variegata Porphyria. Throughout the world incidence of Variegata Porphyria (VP) is extremely rare; however it is relatively common in South Africa. Why is this? Because South Africa is a classic example of the founder effect. Dr. Geoffrey Dean was the first to study VP in South Africa. He traced the pedigrees of many individuals and estimated that in 1972 1 million of the 3 million whites living in South Africa were the descendants of 40 original settlers (Dean, G.: The Porphyrias. A Story of Inheritance and Environment. Philadelphia: J.B. Lippincott (pub.) (2nd ed.) 1972.)
This exercise can be used in an evolution unit to exemplify one of the many evolutionary processes; however skills in basic Mendelian genetics are required such as pedigree analysis and Punnett squares.
Activity:
Two of the founders of the European population in South Africa were Gerrit Jansz and his wife Ariaantje Jacobs. Pedigrees have traced the start of porphyria in South Africa to these two individuals. They had eight children, four of whom suffered from porphyria. A critical question asks which of the parents suffered from porphyria? Gerrit Jansz came from the Netherlands (the only other place in the world where porphyria is relatively common) and we know that Ariaantje's sister had a son with porphyria increasing the likelihood of Ariaantje having porphyria. It could even have been possible for both to have had it (What a coincidence!!!!)
Draw a pedigree of Gerrit and Ariaantje's family. Assume for simplicity that only Gerrit suffered from porphyria and that he was heterozygous (Aa). Determine the genotypes for their eight children. Imagine that all of their children married non-affected individuals, and they each had four children. Determine the probability of Gerrit and Ariaantje's grandchildren having porphyria and assume that the probability expectations were met in reality. How many of Gerrit and Ariaantje's grandchildren suffer from porphyria? (Eight) If all the grandchildren married and had four children, how many of Gerrit and Ariaantje's great grandchildren would suffer from porphyria? (Sixteen)
Activity:
Another interesting fact about porphyria is that individuals who have it do not always suffer from the symptoms. Generally the symptoms are triggered by something in the environment, most commonly alcohol, barbituates, drugs containing estrogen, and exposure to sunlight. This disease shows just how much the environment can influence us. Initiate a discussion with class as to what things in the environment can affect us. Encourage thinking and discussion of ideas. Below are just a few of the possibilities that your students may develop.
(1) Air pollution (PM5 and PM10), cigarette smoke, second hand smoke, and other factors can cause lung disease, lung cancer and other respiratory problems.
(2) Pollution has been linked to cancer and other diseases.
(3) The types of food we eat can lead to heart disease and strokes.
(4) The weather can influence mood. In some areas of the world there are six months of sunlight and six months of darkness. During the six months of darkness, seasonal affective disorder is a major health issue.
For more information visit Online Mendelian Inheritance in Man or the American Porphyria Foundation
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