Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21
Abstract
Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.
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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 [45]
Cites
The Future of Genetic Studies of Complex Human Diseases
Risch, N., & Merikangas, K. (1996) · Science · doi:10.1126/science.273.5281.1516 · Cited by 5,355 · see citing works
Principles of Population Genetics.
Cormack, R. M., Hartl, D. L., & Clark, A. G. (1990) · Biometrics · doi:10.2307/2531471 · Cited by 5,283 · see citing works
Statistical tests of neutrality of mutations.
Fu, Y., & Li, W. (1993) · Genetics · doi:10.1093/genetics/133.3.693 · Cited by 4,051 · see citing works
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms
The International SNP Map Working Group, Laboratories:, C. S. H., Sachidanandam, R., Weissman, D., Schmidt, S. C., Kakol, J. M., Stein, L. D., National Center for Biotechnology Information:, Marth, G., Sherry, S., et al. (2001) · Nature · doi:10.1038/35057149 · Cited by 2,977 · see citing works
Wang, D. G., Fan, J., Siao, C.-J., Berno, A. J., Young, P. R., Sapolsky, R., Ghandour, G., Perkins, N., Winchester, E., Spencer, J. B., et al. (1998) · Science · doi:10.1126/science.280.5366.1077 · Cited by 2,162 · see citing works
Self-citationMaximum-likelihood estimation of molecular haplotype frequencies in a diploid population.
(1995) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040269 · Cited by 1,950 · see citing works
Linkage disequilibrium in the human genome
Reich, D., Cargill, M., Gabriel, S., Ireland, J. S., Sabeti, P. C., Richter, D. J., Lavery, T., Kouyoumjian, R., Farhadian, S., Ward, R. H., et al. (2001) · Nature · doi:10.1038/35075590 · Cited by 1,763 · see citing works
Characterization of single-nucleotide polymorphisms in coding regions of human genes
Cargill, M., Altshuler, D., Ireland, J., Sklar, P., Ardlie, K., Patil, N., Lane, C. R., Lim, E. P., Kalyanaraman, N., Nemesh, J., et al. (1999) · Nature Genetics · doi:10.1038/10290 · Cited by 1,547 · see citing works
Self-citationAccessing Genetic Information with High-Density DNA Arrays
Chee, M. S., Robert Che-An, Y. A. N. G., Hubbell, E. A., Berno, A. J., Huang, X. C., Stern, D. T., Winkler, J., Lockhart, D. J., Morris, M. S., & Fodor, S. P. A. (1996) · Science · doi:10.1126/science.274.5287.610 · Cited by 1,493 · see citing works
Self-citationProspects for whole-genome linkage disequilibrium mapping of common disease genes
Kruglyak, L. (1999) · Nature Genetics · doi:10.1038/9642 · Cited by 1,416 · see citing works
The New Genomics: Global Views of Biology
Lander, E. S. (1996) · Science · doi:10.1126/science.274.5287.536 · Cited by 1,174 · see citing works
Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis
Halushka, M. K., Fan, J., Bentley, K., Hsie, L., Shen, N., Weder, A. B., Cooper, R., Lipshutz, R. J., & Chakravarti, A. (1999) · Nature Genetics · doi:10.1038/10297 · Cited by 1,011 · see citing works
Self-citationA DNA polymorphism discovery resource for research on human genetic variation.Preprint
Collins, F., Brooks, L., & Chakravarti, A. (1998) · Genome Research · doi:10.1101/gr.8.12.1229 · Cited by 919 · see citing works
Variation is the spice of life
Kruglyak, L., & Nickerson, D. A. (2001) · Nature Genetics · doi:10.1038/85776 · Cited by 912 · see citing works
Haplotype Variation and Linkage Disequilibrium in 313 Human Genes
Stephens, J. C., Schneider, J. A., Tanguay, D. A., Choi, J. Y., Acharya, T., Stanley, S. E., Jiang, R., Messer, C. J., Chew, A., Han, J.-H., et al. (2001) · Science · doi:10.1126/science.1059431 · Cited by 873 · see citing works
An SNP map of the human genome generated by reduced representation shotgun sequencing
Altshuler, D., Pollara, V. J., Cowles, C. R., Etten, W. J. V., Baldwin, J., Linton, L., & Lander, E. S. (2000) · Nature · doi:10.1038/35035083 · Cited by 725 · see citing works
Failure of adipocyte differentiation causes type II diabetes mellitus?
Danforth, E. (2000) · Nature Genetics · doi:10.1038/79111 · Cited by 487 · see citing works
Clark, A. G., Weiss, K. M., Nickerson, D. A., Taylor, S. L., Buchanan, A., Stengård, J., Salomaa, V., Vartiainen, E., Perola, M., Boerwinkle, E., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/301977 · Cited by 435 · see citing works
Fullerton, S. M., Clark, A. G., Weiss, K. M., Nickerson, D. A., Taylor, S. L., Stengård, J., Salomaa, V. V., Vartiainen, E. A., Perola, M., Boerwinkle, E., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/303070 · Cited by 429 · see citing works
Single-nucleotide polymorphisms in the public domain: how useful are they?
Marth, G., Yeh, R. T., Minton, M. R., Donaldson, R., Li, Q., Duan, S., Davenport, R., Miller, R. D., & Kwok, P. (2001) · Nature Genetics · doi:10.1038/86864 · Cited by 164 · see citing works
Douglas, J. A., Boehnke, M., Gillanders, E. M., Trent, J. M., & Gruber, S. B. (2001) · Nature Genetics · doi:10.1038/ng582 · Cited by 158 · see citing works
Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCR
Michalatos-Beloin, S. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.23.4841 · Cited by 139 · see citing works
Loss of information due to ambiguous haplotyping of SNPs
Hodge, S. E., Boehnke, M., & Spence, M. A. (1999) · Nature Genetics · doi:10.1038/7687 · Cited by 82 · see citing works
Yang, Z.-Y., Wong, G. K., Eberle, M. A., et al. (2000) · Nature Genetics · doi:10.1038/79113 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858 · see citing works
Population Structure and Eigenanalysis
Patterson, N., Price, A. L., & Reich, D. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020190 · Cited by 5,280 · see citing works
Botstein, D., & Risch, N. (2003) · Nature Genetics · doi:10.1038/ng1090 · Cited by 1,503 · see citing works
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Candidate-gene approaches for studying complex genetic traits: practical considerations
Tabor, H. K., Risch, N. J., & Myers, R. M. (2002) · Nature Reviews Genetics · doi:10.1038/nrg796 · Cited by 1,076 · see citing works
Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene
Alarcón, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., Sebat, J., Wigler, M., Martin, C. L., Ledbetter, D. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.005 · Cited by 818 · see citing works
Genealogical trees, coalescent theory and the analysis of genetic polymorphisms
Rosenberg, N. A., & Nordborg, M. (2002) · Nature Reviews Genetics · doi:10.1038/nrg795 · Cited by 750 · see citing works
Chromosome 21 and Down syndrome: from genomics to pathophysiology
Antonarakis, S. E., Lyle, R., Dermitzakis, E. T., Reymond, A., & Deutsch, S. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1448 · Cited by 703 · see citing works
An initial map of insertion and deletion (INDEL) variation in the human genome
Mills, R. E., Luttig, C. T., Larkins, C. E., Beauchamp, A., Tsui, C., Pittard, W. S., & Devine, S. E. (2006) · Genome Research · doi:10.1101/gr.4565806 · Cited by 673 · see citing works
Haplotype blocks and linkage disequilibrium in the human genome
Wall, J. D., & Pritchard, J. K. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1123 · Cited by 642 · see citing works
Circadian Rhythms: Mechanisms and Therapeutic Implications
Levi, F., & Schibler, U. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105208 · Cited by 645 · see citing works
Common deletions and SNPs are in linkage disequilibrium in the human genome
Hinds, D. A., Kloek, A. P., Jen, M., Chen, X., & Frazer, K. A. (2006) · Nature Genetics · doi:10.1038/ng1695 · Cited by 372 · see citing works
Self-citationFreimer, N., & Sabatti, C. (2003) · Nature Genetics · doi:10.1038/ng0503-15 · Cited by 372 · see citing works
Definition And Clinical Importance Of Haplotypes.
Crawford, D. C., & Nickerson, D. A. (2005) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104540 · Cited by 344 · see citing works
A Genomewide Association Study of Skin Pigmentation in a South Asian Population
Stokowski, R. P., Pant, P. V. K., Dadd, T., Fereday, A., Hinds, D. A., Jarman, C., Filsell, W., Ginger, R. S., Green, M. R., van der Ouderaa, F. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/522235 · Cited by 315 · see citing works
Self-citationNext is now: new technologies for sequencing of genomes, transcriptomes, and beyond
Lister, R., Gregory, B. D., & Ecker, J. R. (2009) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2008.11.004 · Cited by 274 · see citing works
Genetic approaches to stature, pubertal timing, and other complex traits
Palmert, M. R., & Hirschhorn, J. N. (2003) · Molecular Genetics and Metabolism · doi:10.1016/s1096-7192(03)00107-0 · Cited by 135 · see citing works
Finding Haplotype Block Boundaries by Using the Minimum-Description-Length Principle
Anderson, E. C., & Novembre, J. (2003) · The American Journal of Human Genetics · doi:10.1086/377106 · Cited by 90 · see citing works
Understanding the accuracy of statistical haplotype inference with sequence data of known phase
Andrés, A. M., Clark, A. G., Shimmin, L., Boerwinkle, E., Sing, C. F., & Hixson, J. E. (2007) · Genetic Epidemiology · doi:10.1002/gepi.20185 · Cited by 68 · see citing works
Optimal selection of SNP markers for disease association studies.
Halldórsson, B. V., Istrail, S., & De La Vega, F. M. (2004) · Human Heredity · doi:10.1159/000083546 · Cited by 65 · see citing works
Genetic Analysis of Multiple Sclerosis in Europeans
Barcellos, L. F., & Thomson, G. (2003) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.08.004 · Cited by 25 · see citing works
- Authors
- Patil, N., Berno, A. J., Hinds, D. A., Barrett, W. A., Doshi, J. M., Hacker, C. R., Kautzer, C. R., Lee, D. H., Marjoribanks, C., McDonough, D. P., Nguyen, B. T. N., Norris, M. C., Sheehan, J. B., Shen, N., Stern, D., Stokowski, R. P., Thomas, D. J., Trulson, M. O., Vyas, K. R., Frazer, K. A., Fodor, S. P. A., & Cox, D. R.
- Affiliations
- Perlegen (United States) (US)
- Corresponding author
- Cox, David R.
- Venue
- Science
- Published
- 2001-11-23
- Volume
- 294
- Issue
- 5547
- Pages
- 1719-1723
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2135732313
- Cited by
- 1,145
- References
- 24
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 12 · 2019: 13 · 2018: 15 · 2017: 9 · 2016: 10 · 2015: 14 · 2014: 14 · 2013: 14 · 2012: 25
- FWCI
- 72.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (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 diversity and population structure
- Keywords
- haplotype diversity, chromosome 21, single nucleotide polymorphisms, haplotype blocks, oligonucleotide microarrays, somatic cell genetics, disease association
- MeSH terms
- Algorithms, Alleles, Animals, Chromosomes, Human, Pair 21, Ethnicity, Gene Frequency, Haplotypes, Humans, Hybrid Cells, Mutation, Random Allocation, Sensitivity and Specificity, Genetic Variation, Genome, Human, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Racial Groups
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