Annual Reviews OnlineSearch Annual ReviewsAnnual Review of Genomics and Human Genetics OnlineMost Downloaded Genomics and Human GeneticsReviewsMost Cited Genomics and Human GeneticsReviewsAnnual Review of Genomics and Human GeneticsErrataView Current Editorial CommitteeAll Articles in the Annual Review of Genomics and Human Genetics, Vol. 9Human Telomere Structure and BiologyInfectious Disease in the Genomic EraENU Mutagenesis, a Way Forward to Understand Gene FunctionClinical Utility of Contemporary Molecular CytogeneticsThe Role of Aminoacyl-tRNA Synthetases in Genetic DiseasesA Bird's-Eye View of Sex Chromosome Dosage CompensationLinkage Disequilibrium and Association MappingPositive Selection in the Human Genome: From Genome Scans to Biological SignificanceThe Current Landscape for Direct-to-ConsumerGenetic Testing: Legal, Ethical, and Policy IssuesTranscriptional Control of SkeletogenesisA Mechanistic View of Genomic ImprintingPhylogenetic Inference Using Whole GenomesTransgenerational Epigenetic EffectsEvolution of Dim-Light and Color Vision PigmentsGenetic Basis of Thoracic Aortic Aneurysms and Dissections: Focus on Smooth Muscle Cell Contractile DysfunctionCohesin and Human DiseaseGenetic Predisposition to Breast Cancer: Past, Present, and FutureFrom Linkage Maps to Quantitative Trait Loci: The History and Science of the Utah Genetic Reference ProjectDisordersof Lysosome-Related Organelle Biogenesis: Clinical and Molecular GeneticsNext-Generation DNA Sequencing MethodsAfrican Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease MappingANRV353-GG09-21 ARI 30 July 2008 5:56African Genetic Diversity:Implications for HumanDemographic History,Modern Human Origins,and Complex DiseaseMappingMichael C. Campbell1and Sarah A. Tishkoff1,21Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania 19107; email: [email protected] of Biology, University of Pennsylvania, School of Arts and Sciences,Philadelphia, Pennsylvania 19104; email: [email protected]. Rev. Genomics Hum. Genet. 2008. 9:403–33First published online as a Review in Advance onJuly 1, 2008The Annual Review of Genomics and Human Geneticsis online at genom.annualreviews.orgThis article’s doi:10.1146/annurev.genom.9.081307.164258Copyrightc 2008 by Annual Reviews.All rights reserved1527-8204/08/0922-0403$20.00Key Wordsdisease susceptibility, African populations, genetic variation, humanevolution, linkage disequilibriumAbstractComparative studies of ethnically diverse human populations, partic-ularly in Africa, are important for reconstructing human evolutionaryhistory and for understanding the genetic basis of phenotypic adaptationand complex disease. African populations are characterized by greaterlevels of genetic diversity, extensive population substructure, and lesslinkage disequilibrium (LD) among loci compared to non-African pop-ulations. Africans also possess a number of genetic adaptations that haveevolved in response to diverse climates and diets, as well as exposure toinfectious disease. This review summarizes patterns and the evolution-ary origins of genetic diversity present in African populations, as well astheir implications for the mapping of complex traits, including diseasesusceptibility.403Click here for quick links to Annual Reviews content online, including:• Other articles in this volume• Top cited articles• Top downloaded articles• Our comprehensive searchFurtherANNUALREVIEWSAnnu. Rev. Genom. Human Genet. 2008.9:403-433. Downloaded from arjournals.annualreviews.orgby University of South Carolina - Columbia on 04/05/10. For personal use only.ANRV353-GG09-21 ARI 30 July 2008 5:56INTRODUCTIONOne of the “grand challenges” of the post-genome era is to “develop a detailed under-standing of the heritable variation in the humangenome” (34). By characterizing genetic vari-ation among individuals and populations, wemay gain a better understanding of differentialsusceptibility to disease, differential responseto pharmacological agents, human evolutionaryhistory, and the complex interaction of geneticand environmental factors in producing phe-notypes. Africa is an important region to studyhuman genetic diversity because of its complexpopulation history and the dramatic variation inclimate, diet, and exposure to infectious disease,which result in high levels of genetic and pheno-typic variation in African populations. A betterunderstanding of levels and patterns of variationin African genomes, together with phenotypedata on variable traits, including susceptibilityto disease and drug response, will be criticalfor reconstructing modern human origins, thegenetic basis of adaptation to diverse environ-ments, and the development of more effectivevaccines and other therapeutic treatments fordisease. This information will also be impor-tant for identifying variants that play a role insusceptibility to a number of complex diseasesin people of recent African ancestry (170, 185,204).HUMAN EVOLUTIONARYHISTORY IN AFRICAAfrica is a region of considerable genetic,linguistic, cultural, and phenotypic diversity.There are more than 2000 distinct ethno-linguistic groups in Africa, speaking languagesthat constitute nearly a third of the world’slanguages (http://www.ethnologue.com/)(Figure 1). These populations practice awide range of subsistence patterns includingvarious modes of agriculture, pastoralism,and hunting-gathering. Africans also live inclimates that range from the world’s largestdesert and second largest tropical rainforest tosavanna, swamps, and mountain highlands, andthese climates have, in some cases, undergonedramatic changes in the recent past (103, 170).According to the Out of Africa (OOA) modelof modern human origins, anatomically mod-ern humans originated in Africa and then spreadacross the rest of the globe within the past∼100,000 years (202). The transition to mod-ern humans within Africa was not sudden;rather, the paleobiological record indicates anirregular mosaic of modern, archaic, and re-gional morphological and behavioral traits thatoccurred over a substantial period of time andacross a broad geographic range within Africa(124). The earliest known derived suite of mor-phological traits associated with modern hu-mans appears in fossil remains from Ethiopia,dated to ∼150–190 kya (125, 224). However,this finding does not rule out the existence
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