The Structure of Haplotype Blocks in the Human Genome
Abstract
Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease.
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Nearby variants form a block-like structure consisting of regions with little evidence for historical recombination and limited haplotype diversity; within such regions, genotypes of common SNPs can be inferred from a few empirically determined tag SNPs.
“Nearby variants were observed to form a block-like structure consisting of regions characterized by little evidence for historical recombination and limited haplo-type diversity (44, 45). Within such regions, which soon proved general (46), genotypes of common SNPs could be inferred from knowledge of only a few empirically determined tag SNPs (45–47).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [46]
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- Authors
- Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., Liu-Cordero, S. N., Rotimi, C., Adeyemo, A., Cooper, R., Ward, R., Lander, E. S., Daly, M. J., & Altshuler, D.
- Affiliations
- Massachusetts Institute of Technology (US)
- Howard University (US)
- University of Ibadan (NG)
- Loyola University Medical Center (US)
- University of Oxford (GB)
- Harvard University (US)
- Corresponding author
- Altshuler, David
- ORCID
- Venue
- Science
- Published
- 2002-06-21
- Volume
- 296
- Issue
- 5576
- Pages
- 2225-2229
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2152664025
- Cited by
- 5,863
- References
- 25
- Citations by year
- 2026: 80 · 2025: 96 · 2024: 112 · 2023: 139 · 2022: 161 · 2021: 187 · 2020: 167 · 2019: 178 · 2018: 159 · 2017: 175 · 2016: 171 · 2015: 200 · 2014: 203 · 2013: 246 · 2012: 318
- FWCI
- 167.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- haplotype blocks, HapMap, human genome, recombination, common genetic variants, disease gene mapping, genetic association studies, allele frequency, population variation
- MeSH terms
- Africa, Alleles, Black or African American, China, Chromosome Mapping, Computer Simulation, Europe, Genotype, Haplotypes, Humans, Japan, Models, Genetic, Recombination, Genetic, Genetic Variation, Linkage Disequilibrium, Genome, Human, Computational Biology, Polymorphism, Single Nucleotide, Black People, White People, Asian People
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