African populations have the greatest genetic diversity among all human groups, but remain poorly represented in human genomic studies. The hundreds of distinct populations in African can be highly diverged from one another and only the broad outlines of the complex population history of this continent have been inferred from genetic data. We are engaged in several genotyping and genome sequencing projects to discover new genetic variants in Africa and to model the origins of modern humans. The southern African KhoeSan populations are of particular interest given their tremendous diversity and we use a variety of genetic data to resolve patterns of gene flow among sub-Saharan hunter-gatherer groups. Additionally, we are working to understand the role of North African populations during Out-of-Africa expansions and their historical relationships with populations south of the Sahara.
Recent Publications: J Granka, BM Henn, CR Gignoux, JM Kidd, CD Bustamante, MW Feldman. (2012) Limited Evidence for Classic Selective Sweeps in African Populations. Genetics 192:1049-1064
BM Henn*, L Rodríguez-Botigué*, S Gravel, W Wang, A Brisbin, JK Byrnes, K Fadhlaoui-Zid, PA Zalloua, A Moreno, J Bertranpetit, CD Bustamante, D Comas (2012) Genomic Ancestry of North Africans Supports Back-to-Africa Migrations. PLoS Genetics 8(1): e1002397
BM Henn, CR Gignoux, M Jobin, JM Granka, JM Macpherson, JM Kidd, L Rodríguez-Botigué, S Ramachandran, L Hon, A Brisbin, AA Lin, PA Underhill, D Comas, KK Kidd, P Parham, PJ Norman, CD Bustamante, JL Mountain, MW Feldman. (2011) Feature Article: Hunter-gatherer genomic diversity suggests a southern African origin for modern humans. Proc Natl Acad Sci. 108(13): 5154-5162. PMCID: 3069156
The primary demographic signatures in many human populations are ancient bottlenecks associated with the Out-of-Africa expansion 50,000 years ago. From population genetic theory, we expect these events to have had lasting effects on existing patterns of genetic variation, including altered proportions of deleterious alleles in populations that have undergone severe bottlenecks. To test this hypothesis, we have sequenced full genomes from a series of divergent human populations that span the breadth of serial bottlenecks that occurred during the Out-of-Africa expansion. These populations complement the 1000 Genomes Project by establishing a picture of genomic diversity in geographically and ethnically distinct indigenous groups from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia and Mexico. We identify alleles inferred to be deleterious using the predicted impact for protein-coding changes. Using these data, we test the effect of the age and strength of bottlenecks on the distribution of deleterious alleles to define the effect of human history on genetic load of variation observed today.
Recent Publications: BM Henn, LL Cavalli-Sforza, MW Feldman. (2012) The Great Expansion. Proc Natl Acad Sci. 109(44):17758-17764
Genome-wide association studies of common traits or diseases have generally been limited to developed, urban communities in the United States, Europe and Asia. It is not generally feasible to collect large cohorts, on the order of thousands of individuals, in developing countries or in isolated regions of developed countries. Additionally, diverse populations may not carry many of the common or rare variants identified in European/American association studies. There is a need for statistical genomic approaches that can accurately identify genotype/phenotype associations with more cost-effective cohort collection, allowing us to characterize the determinants of variation in any community. Successful application of such approaches in global populations is critical if human genetic research is to deliver on its potential for improving the health for all people. We focus on heritable, easily phenotyped biomedical traits, like skin pigmentation and height, as a model system for understanding genetic architecture in diverse populations with small sample sizes.
Recent Publications: BM Henn*, L Hon*, JM Macpherson, N Eriksson, S Saxonov, I Pe’er, JL Mountain (2012) Cryptic Distant Relatives are Common in both Isolated and Cosmopolitan Genetic Samples. PLoS One 7 (4): e34267
Demographic studies of cohort age, fertility and mortality documented among hunter-gatherer and indigenous populations have a rich history in anthropology. However, this research has almost never been conducted in combination with detailed genetic data for individual subjects. We have been collecting DNA samples and demographic data from KhoeSan populations in the Kalahari Desert and Richtersveld regions of South Africa. Fieldwork is done in collaboration with Prof. Eileen Hoal at Stellenbosch University. During our field seasons, we have observed a relatively high number of elderly individuals (i.e. aged 70 through 100) in the formerly hunter-gatherering ≠Khomani San and pastoralist Nama. Clearly documented measures of senescence and age will facilitate genetic analysis of exome sequence (i.e. protein coding genes) and methylation patterns in these individuals. Paired life history and genomic/epigenetic data are analyzed at candidate loci involved in aging, including extreme longevity and maternal fertility, identified in European/American studies.