African American Genome Mappers Pledge To Carry On Despite Grant Rejection

Researchers working on a large-scale plan to develop a linkage map of the genome of African Americans a project similar to the Human Genome Project (HGP)_vow to continue their efforts, despite being rejected for funding by the National Institutes of Health. As they pursue other sources of funding, they say they will carry on with the project in a loosely associated alliance of smaller research efforts at Howard University and other institutions. "It is just too important a project to be dismantled," declares Fatimah Jackson, an associate professor of anthropology at the University of Maryland, College Park. "We're hoping to get funding from different sources and continue with our efforts to carry out different components of the research." The project_to identify marker genes and thereby survey genomic diversity within the African American population_was the brainchild of Georgia Dunston, an associate professor of microbiology at Howard University. The basic premise for her proposal_called the Genomic Research in African American Pedigrees (G-RAP) project_is that the HGP is limited in its applicability to the human population as a whole, since the DNA being sequenced is exclusively from Caucasian sources. "We need to expand the reference genome to make it relevant to all populations," she states. "We know enough about [human] evolution and genome diversity to conclude that the Africans are the most genetically diverse people." Because of this greater diversity, the researchers contend, many of the variations in the genes African populations have accumulated over generations would go undetected if genome research were conducted on Caucasian DNA only. Furthermore, Dunston points out, there are a number of diseases_sickle-cell anemia and certain forms of hypertension, diabetes, and kidney failure, for example_to which African American populations seem especially susceptible. Thus, determining their genetic heterogeneity would be an important way to find disease/gene correlations in African Americans, she contends. Since their funding request was rejected by NIH late last year, the group has been pursuing support from numerous government agencies and private foundations. In the meantime, the various researchers are working on relevant projects, looking for genetic linkages to specific diseases with a view toward tying the information together when the plan is financed. Dunston was the principal investigator for a group of eight re-searchers at Howard University who in 1991 received a two- year, $240,000 planning grant from NIH to conduct pilot studies and formulate a design for establishing a resource of reference families from the African American population. HGP officials recognize the parallels with their massive effort. "The point of the Human Genome Project is to provide a reference set of maps and sequences of the human genome, and develop a basic set of technologies for wider applications in genomic research," notes Mark Guyer, assistant director for program coordination at the National Center for Human Genome Research (NCHGR), NIH's component of the HGP, in Bethesda, Md. Agreeing that genetic data from African American populations would serve to enhance the broad goals of the human genome initiative, Guyer adds, "We supported [Howard University's] early effort in finding African American families, as we recognized the limitations in reporting DNA polymorphisms from only one DNA source. It would tell us whether there are real differences at the genetic level from one group of people to another and, hence, if the map we are producing is appropriate or not as representative of the human genome." "The idea of the project, as we understood it, was to come up with a reference of African American families to complement the existing CEPH family panel since DNA from a base of more families would give a higher-resolution genomic map," says Bettie Graham, chief of the mapping technology branch at NCHGR. She is referring to the set of Caucasian families used for the HGP studies, set up by the Center d'Etude du Polymorphisme Humain (CEPH) in Paris. Graham was program director for the 1991 planning grant. However, when the Howard University group submitted their project grant application to NCHGR in 1994_a year after the planning grant expired_they did not succeed in getting funded. As Dunston describes it, the Howard project described a much more comprehensive undertaking than HGP officials envisioned: "The outcome of our planning project was too broad for a single agency to fund. The response we got from the [NCHGR] was that the amount of money we asked for was too much." "The plan was not what we had envisioned_it was for a much larger project than we had anticipated," confirms Graham. "One of the problems of the NCHGR is that we are limited in what we are able to support. A lot of people have difficulties sometimes in fitting their projects within our goals." In the face of the rejection, Dunston says, "We are going ahead individually, trying to gain support for the individual parts of the project." Dunston herself has received a smaller NIH grant from the National Center for Research Resources, under the Research Centers in Minority Institutions Interdisciplinary program, to fund certain aspects of the original proposal. In addition, she recently received a fellowship from a visiting investigator program at NCHGR, which she says will "provide an opportunity for collaborative studies that will enhance the laboratory component of [G-RAP]." Another G-RAP researcher, biostatistician George Bonney, who is now the chairman of the biostatistics department at the Fox Chase Cancer Center in Philadelphia, seems less optimistic about the future of the project. "Unless there is money, it's going to be difficult to move forward with it," he says. Of his own studies on the genetic epidemiology of breast cancer among African American women, he comments, "It's relevant to the aims of the project_trying to find appropriate linkage markers but it's nowhere as grand as the original project." Jackson applied for funding from the National Science Foundation for the anthropological component of the study, and was unsuccessful because NSF felt its focus was too narrow. However, she says she is determined not to abandon the project_she will merely continue with it on a somewhat smaller scale. For instance, she used her sampling model to conduct a pilot study for the project in three counties in Maryland, where she was able to identify "long-standing families with very deep genealogies going back over five or six generations." She points out the irony in the various federal agencies' stances on funding the plan: "First they said it was too big; now it's too small." According to the group's proposal, the Howard study involves the following components: screening and recruiting appropriate families to serve as the source of DNA; establishing a core facility at Howard to be "the site of storage of all the core samples and a central processing unit for the initial characterization of the genetic material obtained from the reference families"; setting up an advisory panel at Howard to assess the utilization of the reference material; and developing a data-management, or "informatics," facility to store and analyze the genetic data as it accumulates. Of all the pieces, "the first area how we were going to identify the reference families_was the most challenging," recounts Dunston. "We clearly recognized that the existing methods of sampling were inadequate." So she recruited Jackson, who developed sampling strategies based on ethnohistorical data. "The science of the project begins with the identification of appropriate families," Jackson explains. "By using a model- based sampling system, we can generate a more powerful, anthropologically sophisticated and less expensive set of families" from whom to obtain DNA. "Based on the assumption that the bulk of the African American people came from the slave trade, we have developed a model that focuses on the so-called Crescent States_extending from Massachusetts down the coast to eastern Texas_for identifying the source families." A major component of the study would thus involve an intensive search for records to trace genealogies of African American populations in these areas. Jackson notes that the history of the slave trade_obtained through maritime and plantation records_yields interesting clues to the source of diversity among the African Americans today. "We know, for instance, that people in the Mid-Atlantic states, such as Virginia, preferred to have their slaves from the Gold Coast, and that in Louisiana_where they grew rice_they brought people from Senegal and Gambia." G-RAP is one of a number of parallel projects to build on the developing technologies of the human genome project and add to knowledge about the human genome in general. In particular, Dunston agrees, it is similar to the Human Genome Diversity Project (HGDP)_an effort to survey genetic diversity among isolated, indigenous populations from around the world, conceived by Stanford University population geneticist Luca Cavalli-Sforza. Various participants in and observers of both projects have expressed divergent opinions about the value of such endeavors. Proponents like Dunston argue for the importance of such initiatives in determining predispositions of various peoples to diseases, for instance. But others have been critical, particularly of the HGDP, for its perceived potential to promote racism and exploitation (P. Kahn, Science, 266:720-2, 1994). They say that, much as blood types and physical differences have been used in the past to discriminate, HGDP would provide a gene-based rationale for dividing the races. However, most scientists contend that the research is far from exploitive_and, in fact, not including the entire population in the project would be racist. "The advantages are legitimate in such projects because we are attempting to learn more about a group we know less," observes William Schneider, a professor of history at Indiana University who has studied and written extensively about the use and abuse of population variations in blood types. "But the danger [of projects like G-RAP] is that it could strengthen the notion that African Americans and Caucasians are different. "I just find it ironical that in wanting to study itself, a group has come full circle and doing what was done to them [sampling blood to differentiate them] by others." (The Scientist, Vol:9, #5, pg.1, March 6, 1995)

African American Genome Mappers Pledge To Carry On Despite Grant Rejection

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