African-American responses to the Human Genome Project

Public Understanding of Science

Volumn 8, Issue 3, 1999, Pages 181-191

  Jackson, Fatimah ^a,b  

^a UNIVERSITY OF MARYLAND   (United States)

^b NATIONAL ACADEMY OF SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0041097171     PISSN: 09636625     EISSN: None     Source Type: Journal    
DOI: 10.1088/0963-6625/8/3/303     Document Type: Article

References (48)

1. L. Goodman, "The Human Genome Project Aims for 2003," Genome Research 8 (1998): 997-999; R. Waterston and J. E. Sulston, "The Human Genome Project: Reaching the Finish Line," Science 282 (1998): 53-54; A. Berger, 1998 "Human Genome Project to Complete Ahead of Schedule," British Medical Journal 317 (1998): 834; M. Wadman, "Human Genome Project Aims to Finish 'Working Draft' Next Year," Nature 398 (1999): 177.
2. L. Goodman, "The Human Genome Project Aims for 2003," Genome Research 8 (1998): 997-999; R. Waterston and J. E. Sulston, "The Human Genome Project: Reaching the Finish Line," Science 282 (1998): 53-54; A. Berger, 1998 "Human Genome Project to Complete Ahead of Schedule," British Medical Journal 317 (1998): 834; M. Wadman, "Human Genome Project Aims to Finish 'Working Draft' Next Year," Nature 398 (1999): 177.
3. L. Goodman, "The Human Genome Project Aims for 2003," Genome Research 8 (1998): 997-999; R. Waterston and J. E. Sulston, "The Human Genome Project: Reaching the Finish Line," Science 282 (1998): 53-54; A. Berger, 1998 "Human Genome Project to Complete Ahead of Schedule," British Medical Journal 317 (1998): 834; M. Wadman, "Human Genome Project Aims to Finish 'Working Draft' Next Year," Nature 398 (1999): 177.
4. L. Goodman, "The Human Genome Project Aims for 2003," Genome Research 8 (1998): 997-999; R. Waterston and J. E. Sulston, "The Human Genome Project: Reaching the Finish Line," Science 282 (1998): 53-54; A. Berger, 1998 "Human Genome Project to Complete Ahead of Schedule," British Medical Journal 317 (1998): 834; M. Wadman, "Human Genome Project Aims to Finish 'Working Draft' Next Year," Nature 398 (1999): 177.
5. This massive technological molecular biology effort aims to reflect the "normal" sequence for 100,000 genes and accurately depict the ancestral and functional affinities among these genes (E. S. Lander, "The New Genomics: Global Views on Biology," Science 274 (1996): 536-539). Extremely well funded by the American Congress, the HGP is constructing genetic and physical maps of the human genome, determining the sequence of human DNA, and identifying the complete set of human genes (as outlined in M. S. Guyer and F. S. Collins, "How is the Human Genome Project Doing, and What Have We Learned So Far?," Proceedings of the National Academy of Sciences of the United States of America 92 (1995): 10841-10848.) The HGP has been greatly facilitated by important and on-going technological advances that make the identification and assessment of genes more rapid. In so doing, the HGP is genetically defining the human being, at least North Atlantic European humans, and setting a model molecular template for our species that promises to have wide implications for all humans.
6. This massive technological molecular biology effort aims to reflect the "normal" sequence for 100,000 genes and accurately depict the ancestral and functional affinities among these genes (E. S. Lander, "The New Genomics: Global Views on Biology," Science 274 (1996): 536-539). Extremely well funded by the American Congress, the HGP is constructing genetic and physical maps of the human genome, determining the sequence of human DNA, and identifying the complete set of human genes (as outlined in M. S. Guyer and F. S. Collins, "How is the Human Genome Project Doing, and What Have We Learned So Far?," Proceedings of the National Academy of Sciences of the United States of America 92 (1995): 10841-10848.) The HGP has been greatly facilitated by important and on-going technological advances that make the identification and assessment of genes more rapid. In so doing, the HGP is genetically defining the human being, at least North Atlantic European humans, and setting a model molecular template for our species that promises to have wide implications for all humans.
7. F. S. Collins, M. S. Guyer, and A. Chakravarti, "Variations on a Theme: Cataloging Human DNA Sequence Variation," Science 278 (1997): 1580-1581; F. S. Collins, A. Patrinos, E. Jordan, A. Chakravarti, R. Gesteland, and L. Walters, "New Goals for the U.S. Human Genome Project: 1998-2003," Science 282 (1998): 682-689.
8. F. S. Collins, M. S. Guyer, and A. Chakravarti, "Variations on a Theme: Cataloging Human DNA Sequence Variation," Science 278 (1997): 1580-1581; F. S. Collins, A. Patrinos, E. Jordan, A. Chakravarti, R. Gesteland, and L. Walters, "New Goals for the U.S. Human Genome Project: 1998-2003," Science 282 (1998): 682-689.
9. C. Wills, Exons, Introns, and Talking Genes: The Science Behind the Human Genome Project (New York: Harper Collins, 1991) 277-279.
10. R. W. Wallace, "The Human Genome Diversity Project: Medical Benefits Versus Ethical Concerns," Molecular Medicine Today 4 (1998): 59-62.
11. J. Marks, Human Biodiversity: Genes, Race, and History (New York: Aldine de Gruyter, 1995).
12. The HGP has long been more than just a study of the structure of the human genome: the function of the genes has increasingly been an integral part of HGP's rationale and design. The HGP is touted as providing the structural periodic table from which functional genomics will emerge (E. S. Lander, "The New Genomics: Global Views on Biology," Science 274 (1996): 536-539). Indeed, the rapid progress made in characterizing genes and mRNAs (short-sequence tags) have accelerated the call to interface DNA mapping and sequencing data with protein information (H. Leffers, K. Dejgaard, B. Honore, P. Madsen, M. S. Nielsen, and J. E. Celis, "cDNA Expression and Human Two-dimensional Gel Protein atabases: Towards Integrating DNA and Protein Information," Electrophoresis 17 (II) (1996): 1713-1719). The shift to studies of functional genomics is seen as the natural sequel to the earlier focus of the HGP on structural genomics. While structural genomics provides information of disease gene sequence and expression, functional genomics represents a new paradigm to elucidate gene function and gene pathway. Proteins orchestrate most cellular functions, therefore establishing the "norm" and identifying abnormal proteins is a critical step toward the control of disease-associated genes.
13. The HGP has long been more than just a study of the structure of the human genome: the function of the genes has increasingly been an integral part of HGP's rationale and design. The HGP is touted as providing the structural periodic table from which functional genomics will emerge (E. S. Lander, "The New Genomics: Global Views on Biology," Science 274 (1996): 536-539). Indeed, the rapid progress made in characterizing genes and mRNAs (short-sequence tags) have accelerated the call to interface DNA mapping and sequencing data with protein information (H. Leffers, K. Dejgaard, B. Honore, P. Madsen, M. S. Nielsen, and J. E. Celis, "cDNA Expression and Human Two-dimensional Gel Protein atabases: Towards Integrating DNA and Protein Information," Electrophoresis 17 (II) (1996): 1713-1719). The shift to studies of functional genomics is seen as the natural sequel to the earlier focus of the HGP on structural genomics. While structural genomics provides information of disease gene sequence and expression, functional genomics represents a new paradigm to elucidate gene function and gene pathway. Proteins orchestrate most cellular functions, therefore establishing the "norm" and identifying abnormal proteins is a critical step toward the control of disease-associated genes.
14. This structural-functional link has been the most salient rationale and major applied science justification for the HGP. Each day the gap between structural genomics and functional genomics shrinks. The link between these two aspects of the HGP was the rationale given to criticisms of the nascent HGP by many biologists. These criticisms centered on the complaint that the HGP would just be a listing of gene locations. HGP backers quickly emphasized the functional genomics tie to structural studies. Indeed, the HGP was sold to the U.S. Congress and the American people on the promise to identify and manipulate disease genes of public health significance (especially cancers with a genetic basis) in order to effect disease control. Indeed, rapid progress in the HGP has already stimulated many promising investigations into gene therapy and DNA diagnosis of human diseases through mutation or polymorphism analysis of disease-causing genes. This has resulted in an array of new DNA based drugs (Y. Baba, "Analysis of Disease-causing Genes and DNA-based Drugs by Capillary Electrophoresis: Towards DNA Diagnosis and Gene Therapy for Human Diseases," Journal of Chromatography 687 (1996): 271-302; R. G. Werner, "Identification and Development of New Biopharmaceuticals," Arzneimittelforschung 48 (1998): 523-530), new targeted therapeutics, and new gene-based diagnostics (C. W. Dykes, "Genes, Disease and Medicine," British Journal of Clinical Pharmacology 42 (1996): 683-695; F. S. Collins, "Genetics: an Explosion of Knowledge is Transforming Clinical Practice," Geriatrics 54 (1999): 41-47).
15. This structural-functional link has been the most salient rationale and major applied science justification for the HGP. Each day the gap between structural genomics and functional genomics shrinks. The link between these two aspects of the HGP was the rationale given to criticisms of the nascent HGP by many biologists. These criticisms centered on the complaint that the HGP would just be a listing of gene locations. HGP backers quickly emphasized the functional genomics tie to structural studies. Indeed, the HGP was sold to the U.S. Congress and the American people on the promise to identify and manipulate disease genes of public health significance (especially cancers with a genetic basis) in order to effect disease control. Indeed, rapid progress in the HGP has already stimulated many promising investigations into gene therapy and DNA diagnosis of human diseases through mutation or polymorphism analysis of disease-causing genes. This has resulted in an array of new DNA based drugs (Y. Baba, "Analysis of Disease-causing Genes and DNA-based Drugs by Capillary Electrophoresis: Towards DNA Diagnosis and Gene Therapy for Human Diseases," Journal of Chromatography 687 (1996): 271-302; R. G. Werner, "Identification and Development of New Biopharmaceuticals," Arzneimittelforschung 48 (1998): 523-530), new targeted therapeutics, and new gene-based diagnostics (C. W. Dykes, "Genes, Disease and Medicine," British Journal of Clinical Pharmacology 42 (1996): 683-695; F. S. Collins, "Genetics: an Explosion of Knowledge is Transforming Clinical Practice," Geriatrics 54 (1999): 41-47).
16. This structural-functional link has been the most salient rationale and major applied science justification for the HGP. Each day the gap between structural genomics and functional genomics shrinks. The link between these two aspects of the HGP was the rationale given to criticisms of the nascent HGP by many biologists. These criticisms centered on the complaint that the HGP would just be a listing of gene locations. HGP backers quickly emphasized the functional genomics tie to structural studies. Indeed, the HGP was sold to the U.S. Congress and the American people on the promise to identify and manipulate disease genes of public health significance (especially cancers with a genetic basis) in order to effect disease control. Indeed, rapid progress in the HGP has already stimulated many promising investigations into gene therapy and DNA diagnosis of human diseases through mutation or polymorphism analysis of disease-causing genes. This has resulted in an array of new DNA based drugs (Y. Baba, "Analysis of Disease-causing Genes and DNA-based Drugs by Capillary Electrophoresis: Towards DNA Diagnosis and Gene Therapy for Human Diseases," Journal of Chromatography 687 (1996): 271-302; R. G. Werner, "Identification and Development of New Biopharmaceuticals," Arzneimittelforschung 48 (1998): 523-530), new targeted therapeutics, and new gene-based diagnostics (C. W. Dykes, "Genes, Disease and Medicine," British Journal of Clinical Pharmacology 42 (1996): 683-695; F. S. Collins, "Genetics: an Explosion of Knowledge is Transforming Clinical Practice," Geriatrics 54 (1999): 41-47).
17. This structural-functional link has been the most salient rationale and major applied science justification for the HGP. Each day the gap between structural genomics and functional genomics shrinks. The link between these two aspects of the HGP was the rationale given to criticisms of the nascent HGP by many biologists. These criticisms centered on the complaint that the HGP would just be a listing of gene locations. HGP backers quickly emphasized the functional genomics tie to structural studies. Indeed, the HGP was sold to the U.S. Congress and the American people on the promise to identify and manipulate disease genes of public health significance (especially cancers with a genetic basis) in order to effect disease control. Indeed, rapid progress in the HGP has already stimulated many promising investigations into gene therapy and DNA diagnosis of human diseases through mutation or polymorphism analysis of disease-causing genes. This has resulted in an array of new DNA based drugs (Y. Baba, "Analysis of Disease-causing Genes and DNA-based Drugs by Capillary Electrophoresis: Towards DNA Diagnosis and Gene Therapy for Human Diseases," Journal of Chromatography 687 (1996): 271-302; R. G. Werner, "Identification and Development of New Biopharmaceuticals," Arzneimittelforschung 48 (1998): 523-530), new targeted therapeutics, and new gene-based diagnostics (C. W. Dykes, "Genes, Disease and Medicine," British Journal of Clinical Pharmacology 42 (1996): 683-695; F. S. Collins, "Genetics: an Explosion of Knowledge is Transforming Clinical Practice," Geriatrics 54 (1999): 41-47).
18. D. D. Phoenix, S. M. Lybrook, R. W. Trottier, F. C. Hodgin, and L. A. Crandall, "Sickle Cell Screening Policies as Portent: How Will the Human Genome Project Affect Public Sector Genetic Services?," Journal of the National Medical Association 87 (1995): 807-812; R. Murray, 1996 "Clinical Perspectives on Human Genome Testing: Contrasting Sickle Cell versus Tay-Sachs Screening Programs in the US," PAPER presented at the Health Law Conference, Seton Hall Law School, Newark, NJ, November 4, 1996.
19. D. D. Phoenix, S. M. Lybrook, R. W. Trottier, F. C. Hodgin, and L. A. Crandall, "Sickle Cell Screening Policies as Portent: How Will the Human Genome Project Affect Public Sector Genetic Services?," Journal of the National Medical Association 87 (1995): 807-812; R. Murray, 1996 "Clinical Perspectives on Human Genome Testing: Contrasting Sickle Cell versus Tay-Sachs Screening Programs in the US," PAPER presented at the Health Law Conference, Seton Hall Law School, Newark, NJ, November 4, 1996.
20. L. L. Cavalli-Sforza, P. Menozzi, and A. Piazza, The History and Geography of Human Genes (Princeton, NJ: Princeton University Press, 1994)
21. The roots of Western bioethics were in the concerns of the 1970s which emphasized individual self-determination, dignity, and the development of medical technologies.
22. L. S. Parker, "Bioethics for Human Geneticists: Models for Reasoning and Methods for Teaching," American Journal of Human Genetics 54 (1994): 137-147.
23. Parker, "Bioethics for Human Geneticists."
24. Population Reference Bureau, World Population Figures. Mid-Year 1998 (Arlington, VA: PRB, 1998).
25. P. A. Trangenstein and C. Hetteberg, "Genetics on the World Wide Web," AACN Clinical Issues 9 (1998): 574-581.
26. K. M. Weiss, "Is There a Paradigm Shift in Genetics? Lessons From the Study of Human Diseases," Molecular Phylogenetics and Evolution 5 (1996): 259-265.
27. L.-C. Tsui, "The Spectrum of Cystic Fibrosis Mutations," Trends in Genetics 8 (1992): 391-398; CFGAC (Cystic Fibrosis Genetic Analysis Consortium), "Population Variation of Common Cystic Fibrosis Mutations," Human Mutation 4 (1994): 167-177.
28. L.-C. Tsui, "The Spectrum of Cystic Fibrosis Mutations," Trends in Genetics 8 (1992): 391-398; CFGAC (Cystic Fibrosis Genetic Analysis Consortium), "Population Variation of Common Cystic Fibrosis Mutations," Human Mutation 4 (1994): 167-177.
29. F. L. C. Jackson, "Taxonomic Implications of the Human Genome Project (HGP)," American Journal of Human Biology 9 (1997): 130.
30. See D. L. Gabard, "Homosexuality and the Human Genome Project: Private and Public Choices," Journal of Homosexuality 37 (1999): 25-51.
31. The molecular genetics of asthma is a good example of genotypic diversity in a disease of public health significance in America. This inflammatory airways disorder is phenotypically heterogeneous and appears to have an important genetic component to disease expression. When linkage studies were done on an ethnically diverse, cross-section of affected families with the disease, linkage to six novel regions was detected (CSGA (Collaborative Study on the Genetics of Asthma), "A Genome-wide Search for Asthma Susceptibility Loci in Ethnically Diverse Populations, Nature Genetics 15 (1997): 389-392). However, the significant regions differed among African-Americans, European-Americans, and Hispanic-Americans. Had this diversity not been a part of the study's original research design, ethnic differences in the specific genome regions linked to asthma-associated phenotypes would not have been detected. Non-represented groups could never expect to so clearly benefit from such important scientific effort and insight.
32. R. E. Pratt and V. J. Dzau, "Genomics and Hypertension: Concepts, Potentials, and Opportunities, Hypertension 33 (1999): 238-247.
33. C. R. McCarthy, "Historical Background of Clinical Trials Involving Women and Minorities," Academic Mediane 69 (1996): 695-698.
34. M. B. Mahowald, M. S. Verp, and R. R. Anderson, "Genetic Counseling: Clinical and Ethical Challenges," Annual Review of Genetics 32 (1998): 547-559.
35. M. Dodson and R. Williamson, "Indigenous Peoples and the Morality of the Human Genome Diversity Project," Journal of Medical Ethics 25 (1999): 204-208.
36. F. L. C. Jackson, "Concerns and Priorities in Genetic Studies: Insights From Recent African American Biohistory, Seton Hall Law Review 27 (1997): 951-970.
37. I. S. Mittman, "Commentary: We Must All Be Equal Partners in the New Age of Genetics," The Scientist, II (20) (October 13, 1997): 8.
38. K. Berge, U. Pettersson, P. Riis, and K. E. Tranoy, "Genetics in Democratic Societies: The Nordic Perspective," Clinical Genetics 48 (1995): 199-208.
39. G. R. Gillett, "Medical Ethics in a Multicultural Context," Journal of Internal Medicine 238 (1995): 531-537.
40. K. Chang, "UM Professor Questions Diversity of the HGP," Baltimore Sun, Maryland Section (February 22, 1997): 1B, 3B.
41. Jackson, "Concerns and Priorities in genetic studies."
42. Several research efforts, including those of the Genomic Models Research Group (GMRG) at the University of Maryland attempted to reconstruct the historical origins of various geographical subgroups of African-Americans. The GMRG carefully studied customs manifests, naval records, the narratives of enslaved African-Americans, the diaries of slave owners, and various census documents to identify variation in the African origins of Africans imported into three different American ports (F. L. C. Jackson, D. L. Foster, M. G. Franke, K. A. Miller, T. L. Goodrich, S. F. Harvey, and J. O. Keene, "An Ethnogenetic Model-based Sampling Strategy for Determining Regional Patterns of Variation in African Marker Genes and Gene Products," Proceedings of IUAES Inter-Congress Meetings on Demography and Human Evolution, Florence, Italy (Florence: IUAES, 1995); F. L. C Jackson, K. R. Reed, T. L. Tetrault, and M. G. Franke, "Ethnogenetic Layering of the Crescent States: Using a Model-based Strategy for Population Genetic Sampling," American Journal of Human Biology 8 (1996): 118). Significant regional variation was observed in the ancestral African origins of African-Americans residing near three major ports of entry. For example, into Chesapeake Bay, 38 per cent of the Africans came from ethnic groups located at or near the Bight of Biafra, 16 per cent from Central African groups, 16 per cent from groups indigenous to the Gold Coast, 15 per cent from ethnic groups of Senegambia, and 11 per cent from the ethnic groups of Upper Guinea. In the Mississippi Delta, 32 per cent of the Africans came from ethnic groups located in or around the Senegambia region, 25 per cent from Central African groups, 25 per cent from ethnic groups of the Bight of Benin, and much smaller proportions from groups of the Bight of Biafra (8 per cent) and Upper Guinea (6 per cent). On the Carolina Coast regions, 40 per cent of the Africans came from ethnic groups of Central Africa, 25 per cent from ethnic groups of Senegambia, 18 per cent from Upper Guinea groups, and much smaller proportions from ethnic groups of the Gold Coast (9 per cent), Bight of Biafra (7 per cent), and Bight of Benin (3 per cent). Important regional variation was also observed in the identities of resident Native American ethnic groups and the ethnic identities of the colonizing European groups at each site. Knowing more about the ancestral origins of various groups of African-Americans enhanced the scientific rationale for studying the molecular status of possible disease genes in this group. These ancestral origins data also strengthened the case for including African-Americans in linkage disequilibrium studies.
43. Several research efforts, including those of the Genomic Models Research Group (GMRG) at the University of Maryland attempted to reconstruct the historical origins of various geographical subgroups of African-Americans. The GMRG carefully studied customs manifests, naval records, the narratives of enslaved African-Americans, the diaries of slave owners, and various census documents to identify variation in the African origins of Africans imported into three different American ports (F. L. C. Jackson, D. L. Foster, M. G. Franke, K. A. Miller, T. L. Goodrich, S. F. Harvey, and J. O. Keene, "An Ethnogenetic Model-based Sampling Strategy for Determining Regional Patterns of Variation in African Marker Genes and Gene Products," Proceedings of IUAES Inter-Congress Meetings on Demography and Human Evolution, Florence, Italy (Florence: IUAES, 1995); F. L. C Jackson, K. R. Reed, T. L. Tetrault, and M. G. Franke, "Ethnogenetic Layering of the Crescent States: Using a Model-based Strategy for Population Genetic Sampling," American Journal of Human Biology 8 (1996): 118). Significant regional variation was observed in the ancestral African origins of African-Americans residing near three major ports of entry. For example, into Chesapeake Bay, 38 per cent of the Africans came from ethnic groups located at or near the Bight of Biafra, 16 per cent from Central African groups, 16 per cent from groups indigenous to the Gold Coast, 15 per cent from ethnic groups of Senegambia, and 11 per cent from the ethnic groups of Upper Guinea. In the Mississippi Delta, 32 per cent of the Africans came from ethnic groups located in or around the Senegambia region, 25 per cent from Central African groups, 25 per cent from ethnic groups of the Bight of Benin, and much smaller proportions from groups of the Bight of Biafra (8 per cent) and Upper Guinea (6 per cent). On the Carolina Coast regions, 40 per cent of the Africans came from ethnic groups of Central Africa, 25 per cent from ethnic groups of Senegambia, 18 per cent from Upper Guinea groups, and much smaller proportions from ethnic groups of the Gold Coast (9 per cent), Bight of Biafra (7 per cent), and Bight of Benin (3 per cent). Important regional variation was also observed in the identities of resident Native American ethnic groups and the ethnic identities of the colonizing European groups at each site. Knowing more about the ancestral origins of various groups of African-Americans enhanced the scientific rationale for studying the molecular status of possible disease genes in this group. These ancestral origins data also strengthened the case for including African-Americans in linkage disequilibrium studies.
44. Kittles, in press.
45. In inbred groups, non-allelic genes are usually associated randomly in a population at equilibrium. When random mating occurs, particularly between groups that had previously been geographically isolated, it takes a long time for linked genes to re-establish equilibrium (which occurs when all gamete frequencies are equal). In general, the length of time it takes two linked loci to reach a linkage equilibrium is inversely proportional to the distance between the loci - that is, the closer the two loci are on a chromosome (hence the smaller the chance of recombination). When a post-1492 CE population such as African-Americans is formed from the amalgamation of various west and central African ethnic groups, gene flow with north and west European ethnic groups, and gene flow with eastern and southern Native American ethnic groups, quantifying the degree of linkage disequilibrium can accelerate the search for candidate disease genes.
46. See L. Putman, "US Firm Claims it Can 'Sequence Human Genome in 3 Years'," Lancet 351 (1998): 1566; J. Stephenson, "Private Venture Galvanizes Public Effort on Human Genome Project," Journal of the American Medical Association 279 (1998): 1933, 1935.
47. See L. Putman, "US Firm Claims it Can 'Sequence Human Genome in 3 Years'," Lancet 351 (1998): 1566; J. Stephenson, "Private Venture Galvanizes Public Effort on Human Genome Project," Journal of the American Medical Association 279 (1998): 1933, 1935.
48. Jackson, FLC 1998 Scientific limitations and ethical ramifications of a non-representative Human Genome Project: African American responses. Science and Engineering Ethics 4: 155-170.