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Out of Africa
Research on Rare Genetic Disease
Leads to Ancestral African Culture

By Carla Garnett

On the Front Page...

"In all of us there is a hunger, marrow deep, to know our heritage -- to know who we are and where we have come from. Without this enriching knowledge there is a hollow yearning. No matter what our attainment in life, there is still a vacuum, an emptiness and the most disquieting loneliness." -- Alex Haley

When author Alex Haley revealed his Roots in the late 1970's, everyone in the nation, it seemed, wondered about their own great-great-great grandfolks. As a result, the genealogical quest fever spread, particularly among African Americans. It took Haley more than a decade to trace back several generations, but as most Black people realize, not many of similar heritage will be able to unearth their lineage even that soon. That's because few, if any, reliable records of the centuries-long Atlantic slave trade remain to help in the search. That's what became all too apparent to NIAMS rheumatologist Dr. Paul Plotz in 1992, when "a chance occurrence" pointed his research on a rare muscle disorder to West Africa and "the greatest undocumented migration of modern times."


As Haley pointed out, people have an inherent interest in knowing their heritage. Plotz said our investment in modern science, specifically the Human Genome Project, is poised not only to reveal medical truths about ourselves and our potential for health, but also to help us make that connection to our past.

"This work holds out a promise for the future," he said, during Clinical Center Grand Rounds on May 13. "At the heart of it is the recognition of a deep biological truth: Each chromosome holds within it not just the knowledge of what diseases are in store for us and how to cure or prevent them, but also its whole biological history over endless generations, stretching back almost unimaginably far."

While conducting clinical studies on the rare muscle disease myositis a few years ago, Plotz, who is chief of NIAMS's Arthritis and Rheumatism Branch, and his group were contacted by a physician from Children's Hospital. There was an infant with an enlarged liver, heart failure and abnormal muscle function who had been diagnosed with a rare genetic disease called acid maltase deficiency (AMD, or Pompe Syndrome, as it is more commonly known). After thoroughly reviewing the child's clinical data, the physician had made a connection between the AMD case and NIAMS's myositis work. The baby was African, born to parents working temporarily in the United States. Would Plotz be interested in examining the child? Plotz and his colleagues agreed.

By 1993, two other infants -- both Africans born with AMD -- had been referred to Plotz. Two researchers in his group, pediatrician Dr. Jeffrey Becker and molecular biologist Dr. Nina Raben, beginning to suspect a pattern, foraged the lab's fridge for other stored samples of AMD patients. Hunches paid off. The Children's Hospital infants -- whose parents hailed originally from the Ivory Coast, Ghana and Nigeria -- were all found to have a genetic mutation identical to one found in the cell line of an African American AMD patient.

Surprised and excited to find such an unlikely match, the scientists contacted the Human Genetic Mutant Cell Depository in Camden, N.J., and requested DNA samples from all the AMD patients on file who had one or both parents who were African American. Dutch researchers and scientists at New York University, who were conducting their own independent studies of the disorder, were also consulted. A dozen more samples were collected. Several more matches were found. In all, genetic material from four African tribes -- the Guéré, Hausa, Ashanti and Ovambo populations -- showed the mutation. By then, Plotz was wondering about possible familial connections among all these Black families. Of the infants' parents who were interviewed, none knew of any relationship with the others, and none had any definitive way of finding out.

Interaction among the four African groups seemed unlikely, given the great distances between their lands. However, Vlach suggested, the Hausa were a highly mobile people who were well known traders across all of West Africa.

"Most of us could bring forth mementos or tales of our forebears in the old country," Plotz acknowledged, holding up a pot made by his great-great grandfather, a coppersmith originally from Lithuania. "Most families have someone drawing a family tree with roots somewhere else in the world -- most, but not all. In particular, not the descendants of African Americans who were forcibly brought here in the Atlantic slave trade, which robbed its victims of their memories and severed them from their roots."

Still searching for a connection between African Americans with AMD to their African counterparts, Plotz consulted with a number of experts on African genealogy, including NIDDK's Dr. Griff Rodgers, who conducts such studies related to sickle cell disease, Dr. Michael Blakey of Howard University's African Burial Ground Project (see NIH Record, Apr. 22, 1997) and -- by virtue of another happenstance -- Dr. John Vlach, professor of American civilization and anthropology and director of the folklife program at George Washington University.

At a social gathering, Plotz mentioned in passing his search for links between certain African groups and African Americans. He was referred to Vlach, who for 18 months collaborated with Plotz on several historical and cultural aspects of the AMD study, including the Grand Rounds presentation.

At issue were three questions: Which of the four African groups currently known to have the AMD mutation might have carried it to the U.S.? What, if any, connections among the groups existed before the slave trade? What are some tangible trans-Atlantic ties connecting African Americans to their African roots?

Using historical geographical data, Vlach suggested that, by process of elimination, the Ashanti people of Ghana were the most likely trans-Atlantic carriers of the mutation.

"While individual Guéré, Hausa or Ovambo might have been brought to the United States sometime between 1619 and 1861," he said, "among the peoples we currently know to be carriers of the trait only the Ashanti appear to have been regularly included in the slave cargoes arriving on our shores. Thousands of them can be identified in every decade of the 18th century. Because they were believed by slave owners to be the most intelligent of all the African peoples, and thus thought to make the best servants, they were deliberately sought out at auctions."

The second question posed more of a problem. Interaction among the groups seemed unlikely, given the great distances between their lands: 500 miles of dense rain forest separated the Guéré from the Ashanti; the Hausa lived more than 600 miles east of the Ashanti; and the Ovambo were located nearly 2,000 miles south of the Hausa. However, Vlach pointed out, the Hausa were a highly mobile people who were well known traders across all of West Africa. More than likely, he suggested, the AMD trait originated at least a thousand years ago in or near their traditional homeland of Nigeria and was spread among the other regions during trade and commerce.

As for tangible items that could link African Americans to these African groups, Vlach said artifacts are rare that could show such specific ties. Language, music, religion and cultural customs are among the wide array of tools historical researchers traditionally use to draw general conclusions about a people. As examples, he showed slides of baskets, musical instruments and burial customs that have survived through generations of Africans and African Americans.

"While comparisons of this sort clearly illustrate artifactual carryovers from Africa to the U.S.," he concluded, "they do not reveal the precise identity of the African contributor. Careful scrutiny of form, materials, and technique can narrow the list of potential contributors, but artifacts rarely provide the specificity we find in the intricacies of a genetic mutation." Consequently, he continued, there will be considerable interest among students of the African diaspora in the AMD research by Plotz and colleagues.

Although the infants whose genetic data helped begin Plotz's quest eventually died from the disorder, and their parents all returned to Africa, their contributions remain a valuable piece of the AMD puzzle. Researcher Raben and others have developed a mouse model of the rare disease -- a crucial step toward finding better treatments and perhaps a cure. They also continue to study the gene in AMD patients, and to collaborate with scientists at Johns Hopkins and other institutions working on solving the medical riddle that debilitates a few thousand people worldwide. But what Plotz really hopes is that people begin to appreciate the big picture, far beyond a 1/2-hour Grand Rounds talk on AMD.

The mouse model of the rare disease AMD was developed by molecular biologist Dr. Nina Raben and colleagues. AMD is indicated by heart failure and abnormal muscle function, as shown at left in the animals' hind legs.

"If the collective human genome is the biological history of our species, recording our relationship to all the other species who have ever lived, then for an individual human being, it is a biography, a document of incredible detail and fidelity with the marks of where it has been and with whom," he concluded. "Historians and anthropologists will one day consult it and, with geneticists, reconstruct an important part of the past."

The findings from the study were published in the April issue of the American Journal of Human Genetics, Vol. 62, p. 991, 1998.
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