Abstract
The initial belief that haplotype block boundaries and haplotypes were largely shared across populations was a foundation for constructing a haplotype map of the human genome using common SNP markers. The HapMap data document the generality of a block-like pattern of linkage disequilibrium (LD) with regions of low and high haplotype diversity but differences among the populations. Studies of many additional populations demonstrate that LD patterns can be highly variable among populations both across and within geographic regions. Because of this variation, emphasis has shifted to the generalizability of tagSNPs, those SNPs that capture the bulk of variation in a region. We have examined the LD and tagSNP patterns based upon over 2000 individual samples in 38 populations and 134 SNPs in 10 genetically independent loci for a total of 517 kb with an average density of 1 SNP/5 kb. Four different ‘block’ definitions and the pairwise LD tagSNP selection algorithm have been applied. Our results not only confirm large variation in block partition among populations from different regions (agreeing with previous studies including the HapMap) but also show that significant variation can occur among populations within geographic regions. None of the block-defining algorithms produces a consistent pattern within or across all geographic groups. In contrast, tagSNP transferability is much greater than the similarity of LD patterns and, although not perfect, some generalizations of transferability are possible. The analyses show an asymmetric pattern of tagSNP transferability coinciding with the subsetting of variation attributed to the spread of modern humans around the world.
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Acknowledgements
We thank F Black, B Bonne-Tamir, L Cavalli-Sforza, K Dumars, J Friedlaender, D Goldman, E Grigorenko, SLB Kajuna, NJ Karoma, KS Kendler, WC Knowler, S Kungulilo, D Lawrence, R-B Lu, A Odunsi, F Okonofua, F Oronsaye, J Parnas, L Peltonen, LO Schulz, D Upson, D Wallace, KM Weiss, S Williams, OV Zhukova for helping assemble the diverse population collection used in this study. Some cell lines were made available by the Coriell Institute for Medical Research and by the National Laboratory for the Genetics of Israeli Populations. Special thanks are given to the many hundreds of individuals who volunteered to give blood samples for studies. This work was supported in part by NIH GM57672.
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Gu, S., Pakstis, A., Li, H. et al. Significant variation in haplotype block structure but conservation in tagSNP patterns among global populations. Eur J Hum Genet 15, 302–312 (2007). https://doi.org/10.1038/sj.ejhg.5201751
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DOI: https://doi.org/10.1038/sj.ejhg.5201751
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