High-resolution haplotype structure in the human genome
Abstract
Linkage disequilibrium (LD) analysis is traditionally based on individual genetic markers and often yields an erratic, non-monotonic picture, because the power to detect allelic associations depends on specific properties of each marker, such as frequency and population history. Ideally, LD analysis should be based directly on the underlying haplotype structure of the human genome, but this structure has remained poorly understood. Here we report a high-resolution analysis of the haplotype structure across 500 kilobases on chromosome 5q31 using 103 single-nucleotide polymorphisms (SNPs) in a European-derived population. The results show a picture of discrete haplotype blocks (of tens to hundreds of kilobases), each with limited diversity punctuated by apparent sites of recombination. In addition, we develop an analytical model for LD mapping based on such haplotype blocks. If our observed structure is general (and published data suggest that it may be), it offers a coherent framework for creating a haplotype map of the human genome.
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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 [44]
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- Authors
- Daly, M. J., Rioux, J. D., Schaffner, S. F., Hudson, T. J., & Lander, E. S.
- Affiliations
- Massachusetts Institute of Technology (US)
- McGill Genome Centre (CA)
- Corresponding author
- Daly, Mark J.
- Lander, Eric S.
- Venue
- Nature Genetics
- Published
- 2001-10
- Volume
- 29
- Issue
- 2
- Pages
- 229-232
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1508985588
- Cited by
- 1,717
- References
- 27
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 12 · 2022: 18 · 2021: 29 · 2020: 18 · 2019: 25 · 2018: 21 · 2017: 20 · 2016: 16 · 2015: 24 · 2014: 36 · 2013: 47 · 2012: 61
- FWCI
- 98.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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 Mapping and Diversity in Plants and Animals
- Keywords
- haplotype structure, linkage disequilibrium, haplotype blocks, recombination, single nucleotide polymorphisms, chromosome 5q31, HapMap, European populations, human genome
- MeSH terms
- Base Sequence, Chromosomes, Human, Pair 5, DNA, Haplotypes, Humans, Markov Chains, Molecular Sequence Data, Linkage Disequilibrium, Genome, Human, Polymorphism, Single Nucleotide
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