Perspectives on Human Genetic Variation from the HapMap Project

The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human genetic diversity. In this review we focus on what the HapMap project has taught us about the structure of human genetic variation and the fundamental molecular and evolutionary processes that shape it

Genetic diversity and the emergence of ethnic groups in Central Asia

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Patterns of Haplotype Structure and Recombination in the HapMap ENCODE Region on Chromosome 7q31.33

<p>The estimated recombination rate (in centimorgans per megabase) is shown as a dark blue line, with statistically significant recombination hotspots (see [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010054#pgen-0010054-b15" target="_blank">15</a>] for details) as grey lines. For each analysis panel, each non-redundant haplotype with a frequency of at least 10% is represented by a horizontal line between the starting and ending SNPs (see [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010054#pgen-0010054-b15" target="_blank">15</a>] for details of methodology); the vertical height of these lines is arbitrary. Note that only one of the six hotspots is sufficiently strong to break all common haplotypes.</p

The Relationship between Recombination Rate, Recombination Hotspots, and the Location of Untaggable SNPs

<p>For two HapMap ENCODE regions the estimated recombination rate (dark blue line) and the location of statistically significant hotspots (grey lines) are shown along with the location of SNPs that are untaggable in the YRI (green) CEU (red), or CHB + JPT (purple) panels. Note that most, but not all, untaggable SNPs occur in recombination hotspots.</p

The Relationship between Genealogical History and Allelic Association

<p>The upper part of the figure represents the genealogy for the 13 haplotypes observed in a 40-kb region of Chromosome 1 (between SNPs rs12085605 and rs932087) where there is no evidence for recombination (for no pair of SNPs are all four possible combinations of alleles observed), with the location of polymorphic mutations indicated by circles. The lower part of the figure indicates the relative frequency of each haplotype in the sample from each of the three panels (in greyscale, with white indicating 0% and black indicating 100%). The dotted line in the genealogy indicates a branch of the tree that is not present in the CEU sample and whose removal results in perfect association between SNPs rs12085824 and rs11205476.</p

Where West Meets East: The Complex mtDNA Landscape of the Southwest and Central Asian Corridor

The southwestern and Central Asian corridor has played a pivotal role in the history of humankind, witnessing numerous waves of migration of different peoples at different times. To evaluate the effects of these population movements on the current genetic landscape of the Iranian plateau, the Indus Valley, and Central Asia, we have analyzed 910 mitochondrial DNAs (mtDNAs) from 23 populations of the region. This study has allowed a refinement of the phylogenetic relationships of some lineages and the identification of new haplogroups in the southwestern and Central Asian mtDNA tree. Both lineage geographical distribution and spatial analysis of molecular variance showed that populations located west of the Indus Valley mainly harbor mtDNAs of western Eurasian origin, whereas those inhabiting the Indo-Gangetic region and Central Asia present substantial proportions of lineages that can be allocated to three different genetic components of western Eurasian, eastern Eurasian, and south Asian origin. In addition to the overall composite picture of lineage clusters of different origin, we observed a number of deep-rooting lineages, whose relative clustering and coalescent ages suggest an autochthonous origin in the southwestern Asian corridor during the Pleistocene. The comparison with Y-chromosome data revealed a highly complex genetic and demographic history of the region, which includes sexually asymmetrical mating patterns, founder effects, and female-specific traces of the East African slave trade

Where West Meets East: The Complex mtDNA Landscape of the Southwest and Central Asian Corridor

The southwestern and Central Asian corridor has played a pivotal role in the history of humankind, witnessing numerous waves of migration of different peoples at different times. To evaluate the effects of these population movements on the current genetic landscape of the Iranian plateau, the Indus Valley, and Central Asia, we have analyzed 910 mitochondrial DNAs (mtDNAs) from 23 populations of the region. This study has allowed a refinement of the phylogenetic relationships of some lineages and the identification of new haplogroups in the southwestern and Central Asian mtDNA tree. Both lineage geographical distribution and spatial analysis of molecular variance showed that populations located west of the Indus Valley mainly harbor mtDNAs of western Eurasian origin, whereas those inhabiting the Indo-Gangetic region and Central Asia present substantial proportions of lineages that can be allocated to three different genetic components of western Eurasian, eastern Eurasian, and south Asian origin. In addition to the overall composite picture of lineage clusters of different origin, we observed a number of deep-rooting lineages, whose relative clustering and coalescent ages suggest an autochthonous origin in the southwestern Asian corridor during the Pleistocene. The comparison with Y-chromosome data revealed a highly complex genetic and demographic history of the region, which includes sexually asymmetrical mating patterns, founder effects, and female-specific traces of the East African slave trade