Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Genetic analysis of African populations: human evolution and complex disease

Key Points

  • Africa harbours most of the human genetic diversity in the world.

  • Modern humans are descended from African ancestors who migrated out of Africa in the past 44,000–200,000 years.

  • Complex demographic histories in Africa have shaped the patterns of genetic variation and linkage disequilibrium in modern Africans and their recent descendants, leaving a genetic imprint on their genomes that will allow the determination of their histories.

  • Several complex diseases, such as hypertension, obesity and diabetes, are common in populations of African descent, and dissecting the genetic risk factors of these diseases in sub-Saharan Africa will probably lead to a better understanding of the genetics of these diseases in many human populations.

  • Smaller haplotype blocks in many African populations will allow fine mapping of disease susceptibility alleles.

Abstract

Africa is one of the most ethnically and genetically diverse regions of the world. It is thought to be the ancestral homeland of all modern humans, and is the homeland of millions of people of the recent African diaspora. Because of the central role of African populations in human history, characterizing their patterns of genetic diversity and linkage disequilibrium is crucial for reconstructing human evolution and for understanding the genetic basis of complex diseases.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Distribution of non-biomedical studies of sub-Saharan African genetic diversity.
Figure 2: Model of human demographic history.
Figure 3: Major migration events in Africa.

Similar content being viewed by others

References

  1. Jorde, L. B., Watkins, W. S. & Bamshad, M. J. Population genomics: a bridge from evolutionary history to genetic medicine. Hum. Mol. Genet. 10, 2199–2207 (2001).

    CAS  PubMed  Google Scholar 

  2. Kaufman, J. S., Owoaje, E. E., Rotimi, C. N. & Cooper, R. S. Blood pressure change in Africa: case study from Nigeria. Hum. Biol. 71, 641–657 (1999).

    CAS  PubMed  Google Scholar 

  3. Forrester, T., Cooper, R. S. & Weatherall, D. Emergence of Western diseases in the tropical world: the experience with chronic cardiovascular diseases. Br. Med. Bull. 54, 463–473 (1998).

    CAS  PubMed  Google Scholar 

  4. Cooke, G. S. & Hill, A. V. Genetics of susceptibility to human infectious disease. Nature Rev. Genet. 2, 967–977 (2001).

    CAS  PubMed  Google Scholar 

  5. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. Chakravarti, A. To a future of genetic medicine. Nature 409, 822–823 (2001).

    CAS  PubMed  Google Scholar 

  7. Reich, D. E. & Lander, E. S. On the allelic spectrum of human disease. Trends Genet. 17, 502–510 (2001).

    CAS  PubMed  Google Scholar 

  8. Gabriel, S. B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225–2229 (2002).Recent and extensive data on haplotype structure and LD in African, European and Asian populations, showing shorter haplotype blocks in African populations.

    CAS  PubMed  Google Scholar 

  9. Weiss, K. M. & Clark, A. G. Linkage disequilibrium and the mapping of complex human traits. Trends Genet. 18, 19–24 (2002).

    CAS  PubMed  Google Scholar 

  10. Pritchard, J. K. Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet. 69, 124–137 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Chakravarti, A. Population genetics — making sense out of sequence. Nature Genet. 21, 56–60 (1999).

    CAS  PubMed  Google Scholar 

  12. Wright, A. F., Carothers, A. D. & Pirastu, M. Population choice in mapping genes for complex diseases. Nature Genet. 23, 397–404 (1999).

    CAS  PubMed  Google Scholar 

  13. Nordborg, M. On the probability of Neanderthal ancestry. Am. J. Hum. Genet. 63, 1237–1240 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wall, J. D. Detecting ancient admixture in humans using sequence polymorphism data. Genetics 154, 1271–1279 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Templeton, A. Out of Africa again and again. Nature 416, 45–51 (2002).

    CAS  PubMed  Google Scholar 

  16. Cavalli-Sforza, L. L., Menozzi, P. & Piazza, A. (eds) in The History and Geography of Human Genes 413 (Princeton Univ. Press, New Jersey, 1994).

    Google Scholar 

  17. Chen, Y. S., Torroni, A., Excoffier, L., Santachiara-Benerecetti, A. S. & Wallace, D. C. Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups. Am. J. Hum. Genet. 57, 133–149 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen, Y. S. et al. mtDNA variation in the South African Kung and Khwe and their genetic relationships to other African populations. Am. J. Hum. Genet. 66, 1362–1383 (2000).An extensive analysis of RFLP variation in mtDNA from ethnically diverse African populations. The data from this study support an east African source for migration out of Africa.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Jorde, L. B. et al. The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. Am. J. Hum. Genet. 66, 979–988 (2000).An extensive analysis of nucleotide diversity in the D-loop of mtDNA from ethnically diverse African populations, showing more diversity in Africa.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Watson, E. et al. mtDNA sequence diversity in Africa. Am. J. Hum. Genet. 59, 437–444 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Watson, E., Forster, P., Richards, M. & Bandelt, H. J. Mitochondrial footprints of human expansions in Africa. Am. J. Hum. Genet. 61, 691–704 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ingman, M., Kaessmann, H., Paabo, S. & Gyllensten, U. Mitochondrial genome variation and the origin of modern humans. Nature 408, 708–713 (2000).

    CAS  PubMed  Google Scholar 

  23. Jorde, L. B. et al. Origins and affinities of modern humans: a comparison of mitochondrial and nuclear genetic data. Am. J. Hum. Genet. 57, 523–538 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Underhill, P. A. et al. Y chromosome sequence variation and the history of human populations. Nature Genet. 26, 358–361 (2000).

    CAS  PubMed  Google Scholar 

  25. Hammer, M. F. et al. Hierarchical patterns of global human Y-chromosome diversity. Mol. Biol. Evol. 18, 1189–1203 (2001).

    CAS  PubMed  Google Scholar 

  26. Hammer, M. F. et al. Out of Africa and back again: nested cladistic analysis of human Y chromosome variation. Mol. Biol. Evol. 15, 427–441 (1998).

    CAS  PubMed  Google Scholar 

  27. Tishkoff, S. A. et al. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science 271, 1380–1387 (1996).

    CAS  PubMed  Google Scholar 

  28. Alonso, S. & Armour, J. A. A highly variable segment of human subterminal 16p reveals a history of population growth for modern humans outside Africa. Proc. Natl Acad. Sci. USA 98, 864–869 (2001).

    CAS  PubMed  Google Scholar 

  29. Tishkoff, S. A. et al. A global haplotype analysis of the myotonic dystrophy locus: implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations. Am. J. Hum. Genet. 62, 1389–1402 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Tishkoff, S. A. et al. Short tandem-repeat polymorphism/Alu haplotype variation at the PLAT locus: implications for modern human origins. Am. J. Hum. Genet. 67, 901–925 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kidd, K. K. et al. A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. Hum. Genet. 103, 211–227 (1998).

    CAS  PubMed  Google Scholar 

  32. Calafell, F., Shuster, A., Speed, W. C., Kidd, J. R. & Kidd, K. K. Short tandem repeat polymorphism evolution in humans. Eur. J. Hum. Genet. 6, 38–49 (1998).

    CAS  PubMed  Google Scholar 

  33. Stoneking, M. et al. Alu insertion polymorphisms and human evolution: evidence for a larger population size in Africa. Genome Res. 7, 1061–1071 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Armour, J. A. et al. Minisatellite diversity supports a recent African origin for modern humans. Nature Genet. 13, 154–160 (1996).

    CAS  PubMed  Google Scholar 

  35. Kidd, J. R. et al. Haplotypes and linkage disequilibrium at the phenylalanine hydroxylase locus, PAH, in a global representation of populations. Am. J. Hum. Genet. 66, 1882–1899 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zietkiewicz, E. et al. Nuclear DNA diversity in worldwide distributed human populations. Gene 205, 161–171 (1997).

    CAS  PubMed  Google Scholar 

  37. Zietkiewicz, E. et al. Genetic structure of the ancestral population of modern humans. J. Mol. Evol. 47, 146–155 (1998).

    CAS  PubMed  Google Scholar 

  38. Labuda, D., Zietkiewicz, E. & Yotova, V. Archaic lineages in the history of modern humans. Genetics 156, 799–808 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Harris, E. E. & Hey, J. X chromosome evidence for ancient human histories. Proc. Natl Acad. Sci. USA 96, 3320–3324 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Quintana-Murci, L. et al. Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa. Nature Genet. 23, 437–441 (1999).

    CAS  PubMed  Google Scholar 

  41. Tishkoff, S. A., Kidd, K. K. & Clark, A. G. in Trinational Workshop on Molecular Evolution (eds von Haeseler, A. & Uyenoyama, M.) 181–198 (Duke Univ. Publ. Group, Durham, North Carolina, 1998).

    Google Scholar 

  42. Tishkoff, S. A. et al. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293, 455–462 (2001).

    CAS  PubMed  Google Scholar 

  43. Jin, L. et al. Distribution of haplotypes from a chromosome 21 region distinguishes multiple prehistoric human migrations. Proc. Natl Acad. Sci. USA 96, 3796–3800 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kaessmann, H., Heissig, F., von Haeseler, A. & Paabo, S. DNA sequence variation in a non-coding region of low recombination on the human X chromosome. Nature Genet. 22, 78–81 (1999).

    CAS  PubMed  Google Scholar 

  45. Goldstein, D. B., Ruiz Linares, A., Cavalli-Sforza, L. L. & Feldman, M. W. Genetic absolute dating based on microsatellites and the origin of modern humans. Proc. Natl Acad. Sci. USA 92, 6723–6727 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Semino, O., Santachiara-Benerecetti, A. S., Falaschi, F., Cavalli-Sforza, L. L. & Underhill, P. A. Ethiopians and Khoisan share the deepest clades of the human Y-chromosome phylogeny. Am. J. Hum. Genet. 70, 265–268 (2002).

    CAS  PubMed  Google Scholar 

  47. Jorde, L. B., Bamshad, M. & Rogers, A. R. Using mitochondrial and nuclear DNA markers to reconstruct human evolution. Bioessays 20, 126–136 (1998).

    CAS  PubMed  Google Scholar 

  48. Wall, J. D. & Przeworski, M. When did the human population size start increasing? Genetics 155, 1865–1874 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Sherry, S. T., Harpending, H. C., Batzer, M. A. & Stoneking, M. Alu evolution in human populations: using the coalescent to estimate effective population size. Genetics 147, 1977–1982 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sherry, S. T. et al. Mismatch distributions of mtDNA reveal recent human population expansions. Hum. Biol. 66, 761–775 (1994).

    CAS  PubMed  Google Scholar 

  51. Kimmel, M. et al. Signatures of population expansion in microsatellite repeat data. Genetics 148, 1921–1930 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Reich, D. E. & Goldstein, D. B. Genetic evidence for a Paleolithic human population expansion in Africa. Proc. Natl Acad. Sci. USA 95, 8119–8123 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Relethford, J. H. & Jorde, L. B. Genetic evidence for larger African population size during recent human evolution. Am. J. Phys. Anthropol. 108, 251–260 (1999).

    CAS  PubMed  Google Scholar 

  54. Przeworski, M., Hudson, R. R. & Di Rienzo, A. Adjusting the focus on human variation. Trends Genet. 16, 296–302 (2000).

    CAS  PubMed  Google Scholar 

  55. Harpending, H. & Rogers, A. Genetic perspectives on human origins and differentiation. Annu. Rev. Genomics Hum. Genet. 1, 361–385 (2000).

    CAS  PubMed  Google Scholar 

  56. Poloni, E. S. et al. Human genetic affinities for Y-chromosome P49a,f/TaqI haplotypes show strong correspondence with linguistics. Am. J. Hum. Genet. 61, 1015–1035 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Seielstad, M. T., Minch, E. & Cavalli-Sforza, L. L. Genetic evidence for a higher female migration rate in humans. Nature Genet. 20, 278–280 (1998).

    CAS  PubMed  Google Scholar 

  58. Mountain, J. L. Molecular evolution and modern human origins. Evol. Anthropol. 7, 21–37 (1998).An informative review of molecular studies of modern human origins.

    Google Scholar 

  59. Briscoe, D., Stephens, J. C. & O'Brien, S. J. Linkage disequilibrium in admixed populations: applications in gene mapping. J. Hered. 85, 59–63 (1994).

    CAS  PubMed  Google Scholar 

  60. Lahr, M. M. & Foley, R. A. Towards a theory of modern human origins: geography, demography and diversity on recent human evolution. Yb. Phys. Anthropol. 41, 137–176 (1998).An important discussion of how historical climatic changes in Africa have influenced the emergence of modern humans and variation in modern African populations.

    Google Scholar 

  61. Scozzari, R. et al. Combined use of biallelic and microsatellite Y-chromosome polymorphisms to infer affinities among African populations. Am. J. Hum. Genet. 65, 829–846 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Passarino, G. et al. Different genetic components in the Ethiopian population, identified by mtDNA and Y-chromosome polymorphisms. Am. J. Hum. Genet. 62, 420–434 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Soodyall, H., Vigilant, L., Hill, A. V., Stoneking, M. & Jenkins, T. mtDNA control-region sequence variation suggests multiple independent origins of an 'Asian-specific' 9-bp deletion in sub-Saharan Africans. Am. J. Hum. Genet. 58, 595–608 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Thomas, M. G. et al. Y chromosomes traveling south: the Cohen modal haplotype and the origins of the Lemba — the 'Black Jews of Southern Africa'. Am. J. Hum. Genet. 66, 674–686 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Reich, D. E. et al. Linkage disequilibrium in the human genome. Nature 411, 199–204 (2001).

    CAS  PubMed  Google Scholar 

  66. Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genet. 22, 139–144 (1999).

    CAS  PubMed  Google Scholar 

  67. Pritchard, J. K. & Przeworski, M. Linkage disequilibrium in humans: models and data. Am. J. Hum. Genet. 69, 1–14 (2001).A comprehensive review of models of LD and the impact of demographic history and selection on levels and patterns of LD.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Peterson, R. J., Goldman, D. & Long, J. C. Effects of worldwide population subdivision on ALDH2 linkage disequilibrium. Genome Res. 9, 844–852 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Mateu, E. et al. Worldwide genetic analysis of the CFTR region. Am. J. Hum. Genet. 68, 103–117 (2001).

    CAS  PubMed  Google Scholar 

  70. Daly, M. J., Rioux, J. D., Schaffner, S. F., Hudson, T. J. & Lander, E. S. High-resolution haplotype structure in the human genome. Nature Genet. 29, 229–232 (2001).

    CAS  PubMed  Google Scholar 

  71. Zhu, X. et al. Localization of a small genomic region associated with elevated ACE. Am. J. Hum. Genet. 67, 1144–1153 (2000).A demonstration that populations of African descent can be used to fine-map QTLs, where the use of non-African populations had failed to do so as precisely.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Weatherall, D. J. & Clegg, J. B. Inherited haemoglobin disorders: an increasing global health problem. Bull. World Health Organ. 79, 704–712 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Cooper, R. et al. The prevalence of hypertension in seven populations of west African origin. Am. J. Public Health 87, 160–168 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Kaufman, J. S., Durazo-Arvizu, R. A., Rotimi, C. N., McGee, D. L. & Cooper, R. S. Obesity and hypertension prevalence in populations of African origin. The Investigators of the International Collaborative Study on Hypertension in Blacks. Epidemiology 7, 398–405 (1996).

    CAS  PubMed  Google Scholar 

  75. Cooper, R. S. et al. Prevalence of NIDDM among populations of the African diaspora. Diabetes Care 20, 343–348 (1997).

    CAS  PubMed  Google Scholar 

  76. Rotimi, C. N. et al. In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study. Ann. Epidemiol. 11, 51–58 (2001).

    CAS  PubMed  Google Scholar 

  77. Rotimi, C. N. et al. Prevalence of diabetes and impaired glucose tolerance in Nigerians, Jamaicans and US blacks. Ethnic Dis. 9, 190–200 (1999).

    CAS  Google Scholar 

  78. Colilla, S., Rotimi, C., Cooper, R., Goldberg, J. & Cox, N. Genetic inheritance of body mass index in African-American and African families. Genet. Epidemiol. 18, 360–376 (2000).

    CAS  PubMed  Google Scholar 

  79. Rotimi, C. N. et al. Distribution of anthropometric variables and the prevalence of obesity in populations of west African origin: the International Collaborative Study on Hypertension in Blacks (ICSHIB). Obesity Res. 3 (Suppl. 2), 95–105 (1995).

    Google Scholar 

  80. Moore, J. H. & Williams, S. M. New strategies for identifying gene–gene interactions in hypertension. Ann. Med. 34, 88–95 (2002).

    CAS  PubMed  Google Scholar 

  81. Templeton, A. R. in Epistasis and the Evolutionary Process (eds Wade, M. J., Brodie, E. D. & Wolf, J. B.) 41–57 (Oxford Univ. Press, New York, 2000).

    Google Scholar 

  82. Williams, S. M. et al. Combinations of variations in multiple genes are associated with hypertension. Hypertension 36, 2–6 (2000).This study shows the importance of examining several genes simultaneously for association with complex diseases, such as hypertension, even when independent analysis of genes does not indicate an association.

    CAS  PubMed  Google Scholar 

  83. Eberhardt, M. S. et al. Health United States, 2001 with Urban and Rural Health Chartbook (National Center for Health Statistics, Hyattsville, Maryland, 2001).

    Google Scholar 

  84. Williams, D. R. Black–White differences in blood pressure: the role of social factors. Ethnic Dis. 2, 126–141 (1992).

    CAS  Google Scholar 

  85. James, S. A. in Hypertension in Blacks: Epidemiology, Pathophysiology and Treatment (eds Hall, W. D., Saunders, E. & Shulman, N. B.) (Yearbook Medical Publ., Chicago, Illinois, 1985).

    Google Scholar 

  86. Rotimi, C. N. et al. Maximum-likelihood generalized heritability estimate for blood pressure in Nigerian families. Hypertension 33, 874–878 (1999).

    CAS  PubMed  Google Scholar 

  87. Gu, C. et al. Familial resemblance for resting blood pressure with particular reference to racial differences: preliminary analyses from the HERITAGE Family Study. Hum. Biol. 70, 77–90 (1998).

    CAS  PubMed  Google Scholar 

  88. Unwin, N. et al. Noncommunicable diseases in sub-Saharan Africa: where do they feature in the health research agenda? Bull. World Health Organ. 79, 947–953 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Edwards, R. et al. Hypertension prevalence and care in an urban and rural area of Tanzania. J. Hypertens. 18, 145–152 (2000).

    CAS  PubMed  Google Scholar 

  90. Cooper, R. S. et al. Heritability of angiotensin-converting enzyme and angiotensinogen: a comparison of US blacks and Nigerians. Hypertension 35, 1141–1147 (2000).An important observation that documents the role of environmental variability across populations and among individuals, and its effect on the ability to detect genetic factors.

    CAS  PubMed  Google Scholar 

  91. Caulfield, M. et al. Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J. Clin. Invest. 96, 687–692 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Rotimi, C. et al. Angiotensinogen gene in human hypertension. Lack of an association of the 235T allele among African Americans. Hypertension 24, 591–594 (1994).

    CAS  PubMed  Google Scholar 

  93. Rotimi, C. et al. Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians. Circulation 95, 2348–2350 (1997).

    CAS  PubMed  Google Scholar 

  94. Kardia, S. L. Context-dependent genetic effects in hypertension. Curr. Hypertens. Rep. 2, 32–38 (2000).

    CAS  PubMed  Google Scholar 

  95. Walker, A. R., Adam, F. & Walker, B. F. World pandemic of obesity: the situation in Southern African populations. Public Health 115, 368–372 (2001).

    CAS  PubMed  Google Scholar 

  96. Aspray, T. J. et al. Rural and urban differences in diabetes prevalence in Tanzania: the role of obesity, physical inactivity and urban living. Trans. R. Soc. Trop. Med. Hyg. 94, 637–644 (2000).

    CAS  PubMed  Google Scholar 

  97. Bray, G. A. Complications of obesity. Ann. Intern. Med. 103, 1052–1062 (1985).

    CAS  PubMed  Google Scholar 

  98. Folsom, A. R. et al. Implications of obesity for cardiovascular disease in blacks: the CARDIA and ARIC studies. Am. J. Clin. Nutr. 53 (Suppl.), 1604–1611 (1991).

    Google Scholar 

  99. Burke, G. L. et al. Obesity and overweight in young adults: the CARDIA study. Prev. Med. 19, 476–488 (1990).

    CAS  PubMed  Google Scholar 

  100. Luke, A. et al. Heritability of obesity-related traits among Nigerians, Jamaicans and US black people. Int. J. Obes. Relat. Metab. Disord. 25, 1034–1041 (2001).

    CAS  PubMed  Google Scholar 

  101. Parra, E. J. et al. Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina. Am. J. Phys. Anthropol. 114, 18–29 (2001).

    CAS  PubMed  Google Scholar 

  102. Argyropoulos, G. et al. Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J. Clin. Invest. 102, 1345–1351 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Kimm, S. Y. et al. Racial differences in the relation between uncoupling protein genes and resting energy expenditure. Am. J. Clin. Nutr. 75, 714–719 (2002).

    CAS  PubMed  Google Scholar 

  104. Yanovski, J. A. et al. Associations between uncoupling protein 2, body composition, and resting energy expenditure in lean and obese African American, white, and Asian children. Am. J. Clin. Nutr. 71, 1405–1420 (2000).

    CAS  PubMed  Google Scholar 

  105. Siffert, W. et al. Worldwide ethnic distribution of the G protein β3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J. Am. Soc. Nephrol. 10, 1921–1930 (1999).

    CAS  PubMed  Google Scholar 

  106. Mbanya, J. C., Sobngwi, E. & Mbanya, D. N. HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls. Eur. J. Immunogenet. 28, 459–462 (2001).

    CAS  PubMed  Google Scholar 

  107. Cisse, A. et al. Distribution of HLA-DQA1 and -DQB1 alleles and DQA1–DQB1 genotypes among Senegalese patients with insulin-dependent diabetes mellitus. Tissue Antigens 47, 333–337 (1996).

    CAS  PubMed  Google Scholar 

  108. Chauffert, M. et al. Susceptibility to type 1 diabetes in the Senegalese population is linked to HLA-DQ and not TAP and LMP genes. Diabetes Care 20, 1299–1303 (1997).

    CAS  PubMed  Google Scholar 

  109. Garcia-Pacheco, J. M. et al. Distribution of HLA-DQA1, -DQB1 and DRB1 alleles in black IDDM patients and controls from Zimbabwe. Tissue Antigens 40, 145–149 (1992).

    CAS  PubMed  Google Scholar 

  110. Pirie, F. J., Hammond, M. G., Motala, A. A. & Omar, M. A. HLA class II antigens in South African Blacks with type I diabetes. Tissue Antigens 57, 348–352 (2001).

    CAS  PubMed  Google Scholar 

  111. King, H., Aubert, R. E. & Herman, W. H. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 21, 1414–1431 (1998).

    CAS  PubMed  Google Scholar 

  112. Relethford, J. H. Genetics and the Search for Modern Human Origins (John Wiley & Sons, New York, 2001).

    Google Scholar 

  113. Slatkin, M. Linkage disequilibrium in growing and stable populations. Genetics 137, 331–336 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Benatar, S. R. & Singer, P. A. A new look at international research ethics. BMJ 321, 824–826 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Emanuel, E. J., Wendler, D. & Grady, C. What makes clinical research ethical? JAMA 283, 2701–2711 (2000).

    CAS  PubMed  Google Scholar 

  116. Rando, J. C. et al. Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, near-eastern, and sub-Saharan populations. Annls Hum. Genet. 62, 531–550 (1998).

    CAS  Google Scholar 

  117. Scozzari, R. et al. Differential structuring of human populations for homologous X and Y microsatellite loci. Am. J. Hum. Genet. 61, 719–733 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Spedini, G. et al. The peopling of sub-Saharan Africa: the case study of Cameroon. Am. J. Phys. Anthropol. 110, 143–162 (1999).

    CAS  PubMed  Google Scholar 

  119. Destro-Bisol, G. et al. Microsatellite variation in Central Africa: an analysis of intrapopulational and interpopulational genetic diversity. Am. J. Phys. Anthropol. 112, 319–337 (2000).

    CAS  PubMed  Google Scholar 

  120. Spurdle, A. & Jenkins, T. The Y-specific p21A1/TaqI polymorphism occurs in four major population groups. Hum. Hered. 43, 31–34 (1993).

    CAS  PubMed  Google Scholar 

  121. Forster, P. et al. A short tandem repeat-based phylogeny for the human Y chromosome. Am. J. Hum. Genet. 67, 182–196 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Krings, M. et al. mtDNA analysis of Nile River Valley populations: a genetic corridor or a barrier to migration? Am. J. Hum. Genet. 64, 1166–1176 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the reviewers C. Freund and E. Clayton for useful comments and/or discussion on earlier versions of this paper, and K. Powell and H. Mortensen for assistance with figure 1. S.A.T. was supported by a Burroughs Welcome Fund Career Award, a David and Lucile Packard Career Award and a US National Science Foundation grant. S.M.W. was supported by the US National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Sarah A. Tishkoff or Scott M. Williams.

Related links

Related links

DATABASES

Cancer.gov

prostate cancer

Locuslink

ACE

AGT

ATRAP

CD4

DM1

FY

GNB3

HBB

MC1R

PDHA1

PLAT

renin

UCP2

UCP3

OMIM

type 1 diabetes

type 2 diabetes

FURTHER INFORMATION

Ethnologue

dbSNP summary

Encyclopedia of Life Sciences

Insulin action: molecular basis of diabetes

Population genetics of modern human evolution

Online Mendelian Inheritance in Man database

Sarah Tishkoff's lab

Single Nucleotide Polymorphism (SNP) Consortium

WHO report: Services for the prevention and management of genetic disorders and birth defects in developing countries

Glossary

MODERN HUMANS

Homo sapiens sapiens. Anatomically modern humans who appear in the fossil record 150,000–200,000 years ago and who are descended from Homo erectus.

HAPLOTYPE

A set of genetic markers that is present on one chromosome.

LINKAGE DISEQUILIBRIUM

(LD). The condition in which the frequency of a particular haplotype for two loci is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

HOMO ERECTUS

Species of the genus Homo from which modern humans descend, which originated 1.8 million years ago.

EFFECTIVE POPULATION SIZE

(Ne). The theoretical number of breeding individuals, the genetic variation of which can be explained solely by mutation and genetic drift. Ne is related to, but never exceeds, actual population size (N), is most strongly influenced by bottleneck events and reflects the size of a population at its minimum.

GENETIC DRIFT

The random fluctuation that occurs in allele frequencies as genes are transmitted from one generation to the next. This is because allele frequencies in any sample of gametes that perpetuate the population might not represent those of the adults in the previous generation.

GENE CONVERSION

A specific type of recombination, which results in non-reciprocal genetic exchange, in which the sequence of one DNA strand is used to alter the sequence of the other.

BALANCING SELECTION

The maintenance of genetic polymorphism owing to selection.

POPULATION SUBDIVISION

A population sample that is not genetically homogeneous but, rather, is composed of more than one subpopulation with low levels of gene flow.

F ST

A measure of population subdivision that indicates the proportion of genetic diversity found between populations relative to the amount within populations.

COALESCENCE

The convergence of alleles, in a modern population, back in time to a common ancestor.

HERITABILITY

The fraction of the phenotypic variance due to genetic variance.

QUANTITATIVE TRAIT LOCUS

(QTL). A genetic locus that is identified through the statistical analysis of complex traits (such as body weight). These traits are typically affected by more than one gene and by the environment.

ANGIOTENSINOGEN

The precursor molecule that is cleaved by angiotensin-I-converting enzyme into angiotensin II.

NA+/H+ EXCHANGER

The system through which extracellular sodium ions are traded for intracellular hydrogen ions to adjust or maintain cellular pH, as well as cell volume. This exchanger has been implicated in the development of essential hypertension.

HUMAN LEUKOCYTE ANTIGEN

(HLA). Also known as major histocompatibility complex (MHC). A glycoprotein found on the surface of antigen-presenting cells that presents antigen for recognition by helper T cells.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tishkoff, S., Williams, S. Genetic analysis of African populations: human evolution and complex disease. Nat Rev Genet 3, 611–621 (2002). https://doi.org/10.1038/nrg865

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg865

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing