A Genetic Legacy
by Lauren Stancheck
Remember....Research is the key to your cure!"
When a Dutch orphan, Ariaantje Adriaanse, set sail for South Africa in 1688, chances are she offered more than her hand in marriage.
Now, more than 300 years and thousands of descendants later, scientists have uncovered her likely genetic legacy — a disease that has spread exponentially throughout the South African population.
|Scientists Peter Meissner at the University of Cape Town and Harry Dailey at the University of Georgia have identified the gene mutation that causes variegate porphryia.|
|Ariaantje Adriaanse, the Dutch orphan who likely carried the porphyria gene to South Africa, journeyed for four months from the Netherlands to Table Bay aboard the China — a ship similar to the one depicted here from the same period. In this painting, the Griffioen, a type of ship called an eastindiaman, docks at the foot of Table Mountain, off Cape of Good Hope. Pen painting by Cornelius Pietersz. de Mooij (?-1676).|
In the 1950s a British doctor noticed South Africa’s high incidence of a disease called variegate porphyria (poor-FEAR-ee-ah). Using family Bibles to trace lineages, he discovered its genetic nature. Since then scientists have found that variegate porphyria is the second most common inherited disease in South Africa.
Several kinds of porphyria have been found in humans, each with its own telltale combination of symptoms. For example, patients with variegate porphyria experience light sensitivity, easily broken skin, and occasional and unpredictable acute attacks involving intense abdominal pain. Various medications, chemicals and even sunlight can trigger these attacks.
Scientists like Peter Meissner at the University of Cape Town (UCT) study the disease and its symptoms to better understand how it affects the South African population. Researchers have learned that heme, the iron-rich molecule that transfers oxygen from the blood to cells, plays a key role in the disease.
Half a world away, Harry Dailey, a UGA professor of microbiology, biochemistry, and molecular biology and director of UGA’s new Biomedical and Health Sciences Institute, is studying the body’s assembly line-like production of heme.
Dailey drew the South Africans’ attention with his research on PPO — which stands for protoporphyrinogen oxidase — one of the enzymes required to make heme. A defect in PPO is the key element in the onset of porphyria.
Producing heme requires eight different enzymes. When any one of these enzymes malfunctions, heme precursors, called porphyrins, build up in the blood. This increase in porphyrins results in porphyria.
The human body makes the heme molecules it needs like an assembly line — enzymes add each piece sequentially to create the finished product.
“So anything that affects one part of the assembly line will have an impact on the other part of the assembly line,” Dailey said.
Science has yet to understand how the overproduction of porphyrins causes the skin sensitivity and abdominal pains.
“The actual symptoms are, as far as one can tell, really not directly related to the compound heme itself,” Dailey said.
Porphyria is divided into seven types, depending on which enzyme is malfunctioning. For example, PPO functions at the sixth step in the heme assembly line. Defective PPO results in variegate porphyria, the type most common in South Africa.
Dailey’s lab was the first to purify the PPO enzyme. For this reason, Meissner arranged to do post-doctoral studies in his lab, creating the foundation for a future partnership. Then UCT invited Dailey to South Africa to share laboratory techniques. Two years later, Meissner, now director of the internationally recognized Porphyria Research Unit at UCT and the leading researcher on porphyria in South Africa, again settled temporarily at the University of Georgia to work on another project — identifying the mutation responsible for variegate porphyria.
Together, Meissner and Dailey first found the normal PPO gene, or the chain of molecules within DNA that acts as a code to make PPO. They then sequenced the gene, or determined the order of the molecules in the gene, using the enzyme Dailey’s lab had already copied.
“We had strong clues about what we were looking for and we had samples from patients,” Meissner said. “My Cape Town lab was sequencing DNA from a patient named Lusinda and so was Harry’s lab, because you can get sequence errors. So we both ran the sequences to compare results.”
To determine the mutation — or change in the DNA sequence — they compared the normal PPO sequence to that of a person with the disease. The researchers specifically compared the function of the normal and mutant PPO enzymes and found that the mutant PPO results in variegate porphyria.
In order to even begin this process, the researchers needed cells containing the mutation. Because variegate porphyria is a dominant inherited trait, an individual only needs one copy of the mutant gene to develop the disease.
Wednesday, August 13, 2014
A Genetic Legacy Part 1
Bright Ideas! This is a place for kids to learn from others with EPP, to share their own tips and tricks on things like what to wear...
Happy Thanksgiving everyone 2017
EXCITING ANNOUNCEMENT!! You can now receive FREE genetic testing (DNA) and counseling for acute porphyria. DNA can tell a person if the...
4. The Pain Scale Is Useless to Us There’s that pain scale, numbered one through ten, with increasingly dour expressions on the faces...