A haplotype map of the human genome
NaturePublished 1 October 2005Open access
Citations5,868
SJR quartileQ1
SJR score18.29
SNIP10.16
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Abstract
Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.
Keywords
Biochemistry, Genetics and Molecular Biology
Nature GeneticsGene Ontology: tool for the unification of biology
44,650 Citations2000Michael Ashburner, Catherine A. Ball +18 more
The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.
NatureInitial sequencing and comparative analysis of the mouse genome
7,249 Citations2002Asif T. Chinwalla, R Waterston +221 more
The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
NatureThe International HapMap Project
6,170 Citations2003Richard A. Gibbs, John W. Belmont +181 more
The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
ScienceThe Structure of Haplotype Blocks in the Human Genome
5,921 Citations2002Stacey Gabriel, S. F. Schaffner +16 more
It is shown 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.
NatureAssociation of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
5,559 Citations2001Jean‐Pierre Hugot, Mathias Chamaillard +18 more
It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
NatureA frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
5,015 Citations2001Yasunori Ogura, Denise K. Bonen +15 more
It is shown that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease, and a link between an innate immune response to bacterial components and development of disease is suggested.
ScienceComplement Factor H Polymorphism in Age-Related Macular Degeneration
4,514 Citations2005Robert J. Klein, Caroline J. Zeiss +13 more
Scienceα-Synuclein Locus Triplication Causes Parkinson's Disease
4,407 Citations2003A. B. Singleton, Andrew Singleton +22 more
ScienceIdentification of the Cystic Fibrosis Gene: Genetic Analysis
4,129 Citations1989Bat-Sheva Kerem, Johanna M. Rommens +6 more
Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations.
Medical Principles and PracticeUpdate on Key Emerging Challenges in Cystic Fibrosis
3,665 Citations2014Mark T. Jennings, Kristin A. Riekert +1 more
The ultimate challenge of treating the underlying cause of CF by correcting the dysfunction of the CF transmembrane conductance regulator chloride channel is reviewed, as agents to correct channel function will likely significantly alter CF clinical outcomes and treatment approaches in the next decade.
The American Journal of Human GeneticsA Comparison of Bayesian Methods for Haplotype Reconstruction from Population Genotype Data
3,533 Citations2003Matthew Stephens, Peter Donnelly
A new algorithm is introduced that combines the modeling strategy of one method with the computational strategies of another and outperforms all three existing methods for inferring haplotypes from genotype data in a population sample.
ScienceGenetic Structure of Human Populations
3,059 Citations2002Noah A. Rosenberg, Jonathan K. Pritchard +5 more
General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.
Nature GeneticsDetection of large-scale variation in the human genome
2,910 Citations2004A. John Iafrate, Lars Feuk +6 more
ScienceLarge-Scale Copy Number Polymorphism in the Human Genome
2,588 Citations2004Jonathan Sebat, B. Lakshmi +19 more
It is shown that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans.
Cellular Physiology and BiochemistryTherapy of CF-Patients with Amitriptyline and Placebo - a Randomised, Double-Blind, Placebo-Controlled Phase IIb Multicenter, Cohort-Study
2,534 Citations2013Lutz Nährlich, Jochen G. Mainz +15 more
Amitriptyline is safe in CF-patients, increases FEV1 and reduces ceramide in lung cells of CF patients, according to a phase IIb randomised, double-blind, placebo-controlled study.
NatureInitial sequence of the chimpanzee genome and comparison with the human genome
2,500 Citations2005Tarjei S. Mikkelsen
It is found that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles.
ScienceThe ENCODE (ENCyclopedia Of DNA Elements) Project
2,493 Citations2004
The ENCyclopedia Of DNA Elements (ENCODE) Project is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function.
ScienceComplement Factor H Polymorphism and Age-Related Macular Degeneration
2,447 Citations2005Albert O. Edwards, Robert Ritter +4 more
Significant association was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H.
ScienceComplement Factor H Variant Increases the Risk of Age-Related Macular Degeneration
2,415 Citations2005Jonathan L. Haines, Michael A. Hauser +12 more
DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57, which likely explains ∼43% of AMD in older adults.
NatureAssociation of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
2,178 Citations2003Hironori Ueda, Joanna M. M. Howson +51 more
NatureDetecting recent positive selection in the human genome from haplotype structure
2,150 Citations2002Pardis C. Sabeti, David Reich +15 more
A framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations is introduced, and the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection.
Cytogenetic and Genome Research22q11.21 Deletion Syndromes: A Review of Proximal, Central, and Distal Deletions and Their Associated Features
1,962 Citations2015Rachel D. Burnside
This review concisely delineates each interval of LCR22A-H, the most common recurrent microdeletion in humans, and classifies the reported literature accordingly.
Nature GeneticsA high-resolution recombination map of the human genome
1,782 Citations2002Augustine Kong, Daníel F. Guðbjartsson +14 more
Recombination rates are significantly correlated with both cytogenetic structures and sequence and paternal chromosomes show many differences in locations of recombination maxima, suggesting that there is some underlying component determined by both genetic and environmental factors that affects maternal recombination rates.
NatureLinkage disequilibrium in the human genome
1,782 Citations2001David Reich, Michele Cargill +9 more
The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000–53,000 years ago, implying that LD mapping is likely to be practical in this population.
Nature GeneticsThe common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes
1,759 Citations2000David Altshuler, Joel N. Hirschhorn +14 more
The data implicate inherited variation in PPARgamma in the pathogenesis of type 2 diabetes, and its modest effect translates into a large population attributable risk-influencing as much as 25% of type 1 diabetes in the general population.
Nature GeneticsHigh-resolution haplotype structure in the human genome
1,717 Citations2001Mark J. Daly, John D. Rioux +3 more
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 offers a coherent framework for creating a haplotype map of the human genome.
Nature GeneticsEfficiency and power in genetic association studies
1,697 Citations2005Paul I. W. de Bakker, Roman Yelensky +4 more
A haplotype-based tagging method is demonstrated that uniformly outperforms single-marker tests and methods for prioritization that markedly increase tagging efficiency, and is robust to the completeness of the reference panel from which tags are selected.
NatureA second-generation linkage map of the human genome
1,697 Citations1992Jean Weissenbach, Gàbor Gyapay +6 more
A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families.
The American Journal of Human GeneticsSelecting a Maximally Informative Set of Single-Nucleotide Polymorphisms for Association Analyses Using Linkage Disequilibrium
1,605 Citations2004Christopher S. Carlson, Michael A. Eberle +4 more
It is demonstrated that, although common variation tends to be shared between populations, tagSNPs should be selected separately for populations with different ancestries.
GeneticsSTATISTICAL PROPERTIES OF THE NUMBER OF RECOMBINATION EVENTS IN THE HISTORY OF A SAMPLE OF DNA SEQUENCES
1,594 Citations1985Richard R. Hudson, Norman Kaplan
It is found that RM is often much less than R, therefore, the number of recombination events may be greatly under-estimated in a parsimonious reconstruction of the history of a sample.
The American Journal of Human GeneticsA Missense Single-Nucleotide Polymorphism in a Gene Encoding a Protein Tyrosine Phosphatase (PTPN22) Is Associated with Rheumatoid Arthritis
1,504 Citations2004Ann B. Begovich, Victoria Carlton +26 more
It is shown that the risk allele of a missense SNP in PTPN22 disrupts the P1 proline-rich motif that is important for interaction with Csk, potentially altering these proteins' normal function as negative regulators of T-cell activation.
Annual Review of BiochemistryMISMATCH REPAIR IN REPLICATION FIDELITY, GENETIC RECOMBINATION, AND CANCER BIOLOGY
1,498 Citations1996Paul Modrich, Robert S. Lahue
Homologs of bacterial MutS and MutL, which play key roles in mismatch recognition and initiation of repair, have been identified in yeast and mammalian cells and results in a large increase in spontaneous mutability.
The American Journal of Human GeneticsA Note on Exact Tests of Hardy-Weinberg Equilibrium
1,473 Citations2005Janis Wigginton, David J. Cutler +1 more
These methods adequately control type I error in large and small samples and are computationally efficient and will be useful for quality assessment of genotype data and for the detection of genetic association or population stratification in very large data sets.
Nature GeneticsProspects for whole-genome linkage disequilibrium mapping of common disease genes
1,428 Citations1999Leonid Kruglyak
Nature GeneticsA functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes
1,408 Citations2004Nunzio Bottini, Lucia Musumeci +11 more
A single-nucleotide polymorphism in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D).
ScienceRecent Segmental Duplications in the Human Genome
1,396 Citations2002Jeffrey A. Bailey, Zhiping Gu +8 more
A method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity.
The American Journal of Human GeneticsLinkage Disequilibrium in Humans: Models and Data
1,330 Citations2001Jonathan K. Pritchard, Molly Przeworski
This review describes recent empirical and theoretical work on the extent of linkage disequilibrium in the human genome, comparing the predictions of simple population-genetic models to available data and some implications that the emerging patterns of LD have for association-mapping strategies.
Nature GeneticsA Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity
1,330 Citations1998Samir S. Deeb, Lluís Fajas +7 more
It is reported that a relatively common Pro12Ala substitution in PPARγ2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns and among Japanese Americans.
The American Journal of Human GeneticsGenetic Signatures of Strong Recent Positive Selection at the Lactase Gene
1,193 Citations2004Todd Bersaglieri, Pardis C. Sabeti +7 more
It is estimated that strong selection occurred within the past 5,000-10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection the authors observe are among the strongest yet seen for any gene in the genome.
ScienceWhole-Genome Patterns of Common DNA Variation in Three Human Populations
1,179 Citations2005David A. Hinds, Laura L. Stuvé +6 more
This work has characterized whole-genome patterns of common human DNA variation by genotyping 1,586,383 single-nucleotide polymorphisms (SNPs) in 71 Americans of European, African, and Asian ancestry and indicates that these SNPs capture most common genetic variation as a result of linkage disequilibrium.
Nature GeneticsHaplotype tagging for the identification of common disease genes
1,178 Citations2001Gillian C.L. Johnson, Laura Esposito +19 more
This work shows how knowledge of the common haplotypes and the SNPs that tag them can be used to explain the often complex patterns of LD between adjacent markers and provide key fine-mapping data within regions of strong LD.
ScienceA Fine-Scale Map of Recombination Rates and Hotspots Across the Human Genome
1,175 Citations2005Simon Myers, Leonardo Bottolo +3 more
A high-resolution genetic map of the human genome is presented, based on statistical analyses of genetic variation data, and more than 25,000 recombination hotspots are identified, together with motifs and sequence contexts that play a role in hotspot activity.
ScienceBlocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21
1,150 Citations2001Nila Patil, Anthony Berno +20 more
High-density oligonucleotide arrays are used 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.
ScienceThe Influence of <i>CCL3L1</i> Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility
1,140 Citations2005Enrique A. González, Hemant Kulkarni +20 more
It is shown that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5.
GeneticsModeling Linkage Disequilibrium and Identifying Recombination Hotspots Using Single-Nucleotide Polymorphism Data
1,124 Citations2003Na Li, Matthew Stephens
The model overcomes limitations of existing approaches to understanding, summarizing, and interpreting LD by relating patterns of LD directly to the underlying recombination process and is competitive with the very best of current available methods for recombination rate estimates.
The American Journal of Human GeneticsComprehensive Human Genetic Maps: Individual and Sex-Specific Variation in Recombination
1,097 Citations1998Karl W. Broman, Jeffrey C. Murray +3 more
Nature GeneticsIdentification of a variant associated with adult-type hypolactasia
1,030 Citations2002Nabil Enattah, Timo Sahi +4 more
A DNA variant, C/T−13910, completely associates with biochemically verified lactase non-persistence in Finnish families and a sample set of 236 individuals from four different populations, indicating that it is very old.
ScienceThe Fine-Scale Structure of Recombination Rate Variation in the Human Genome
1,028 Citations2004Gil McVean, Simon Myers +4 more
It is demonstrated that recombination hotspots are a ubiquitous feature of the human genome, occurring on average every 200 kilobases or less, but recombination occurs preferentially outside genes.
NatureLevels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster
1,018 Citations1992David J Begun, Charles F. Aquadro
For 20 gene regions from across the genome, the amount of nucleotide diversity in natural populations of D. melanogaster is positively correlated with the regional rate of recombination, and it is suggested that the correlation may result from genetic hitch-hiking associated with the fixation of advantageous mutants.
Nature Reviews GeneticsThe human Y chromosome: an evolutionary marker comes of age
967 Citations2003Mark A. Jobling, Chris Tyler‐Smith
The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution.
Trends in GeneticsGenome architecture, rearrangements and genomic disorders
921 Citations2002Paweł Stankiewicz, James R. Lupski
An increasing number of human diseases are recognized to result from recurrent DNA rearrangements involving unstable genomic regions, in which the clinical phenotype is a consequence of abnormal dosage of gene(s) located within the rearranged genomes.
CellA missense mutation of the endothelin-B receptor gene in multigenic hirschsprung's disease
895 Citations1994Erik G. Puffenberger, Kiminori Hosoda +5 more
This work has identified in HSCR patients a G-->T missense mutation in EDNRB exon 4 that substitutes the highly conserved Trp-276 residue in the fifth transmembrane helix of the G protein-coupled receptor with a Cys residue (W276C).
Nature GeneticsA common inversion under selection in Europeans
872 Citations2005Hreinn Stefánsson, Agnar Helgason +25 more
It is shown that the H2 lineage is undergoing positive selection in the Icelandic population, such that carrier females have more children and have higher recombination rates than noncarriers.
Nature GeneticsIntensely punctate meiotic recombination in the class II region of the major histocompatibility complex
854 Citations2001Alec J. Jeffreys, Liisa Kauppi +1 more
Analysis of a 216-kb segment of the class II region of the major histocompatibility complex of the MHC shows that crossovers are far from randomly distributed at the molecular level and that recombination hot spots can profoundly affect LD patterns.
Genome ResearchA Nomenclature System for the Tree of Human Y-Chromosomal Binary Haplogroups
807 Citations2002The Y Chromosome Consortium
A simple set of rules was developed to unambiguously label the different clades nested within a single most parsimonious phylogeny, which supersedes and unifies past nomenclatures and allows the inclusion of additional mutations and haplogroups yet to be discovered.
Annals of Human GeneticsThe phylogeography of Y chromosome binary haplotypes and the origins of modern human populations
801 Citations2001P. A. Underhill, Giuseppe Passarino +6 more
A set of unique event polymorphisms associated with the non‐recombining portion of the Y‐chromosome (NRY) addresses this issue by providing evidence concerning successful migrations originating from Africa, which can be interpreted as subsequent colonizations, differentiations and migrations overlaid upon previous population ranges.
DiabetesA Polymorphic Locus Near the Human Insulin Gene Is Associated with Insulin-dependent Diabetes Melliitus
744 Citations1984Graeme I. Bell, Shiro Horita +1 more
The genotype at this locus of 393 unrelated diabetic and nondiabetic individuals is determined and differences were observed in the genotypie and allelic frequencies between groups of different races.
Proceedings of the National Academy of SciencesIdentification of a gene causing human cytochrome <i>c</i> oxidase deficiency by integrative genomics
573 Citations2003Vamsi K. Mootha, Patricia Lepage +15 more
Data sets of RNA and protein expression are used to identify the gene causing Leigh syndrome, French-Canadian type (LSFC), a human cytochrome c oxidase deficiency that maps to chromosome 2p16-21, providing definitive genetic proof that LRPPRC indeed causes LSFC.
Nature GeneticsLinkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland
569 Citations1992Johanna Hästbacka, Albert de la Chapelle +4 more
Using classical methods for analysing bacterial cultures, striking linkage disequilibrium for diastrophic dysplasia in Finland is reported, indicating that the DTD gene should lie within 0.06 centimorgans of the CSF1R gene.
Cancer ResearchAn Integrated View of Copy Number and Allelic Alterations in the Cancer Genome Using Single Nucleotide Polymorphism Arrays
548 Citations2004Xiaojun Zhao, Cheng Li +11 more
The simultaneous measurement of DNA copy number changes and loss of heterozygosity events by SNP arrays should strengthen the ability to discover cancer-causing genes and to refine cancer diagnosis.
The American Journal of Human GeneticsReduced-Median-Network Analysis of Complete Mitochondrial DNA Coding-Region Sequences for the Major African, Asian, and European Haplogroups
534 Citations2002Corinna Herrnstadt, Joanna L. Elson +9 more
This work used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups.
Nature MethodsGenotyping over 100,000 SNPs on a pair of oligonucleotide arrays
493 Citations2004Hajime Matsuzaki, Shoulian Dong +16 more
This work presents a genotyping method for simultaneously scoring 116,204 SNPs using oligonucleotide arrays with reproducibility and accuracy at call rates >99, and accuracy as measured by inheritance in trios and concordance with the HapMap Project.
Nature GeneticsDNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene
477 Citations1998Deborah A. Nickerson, Scott L. Taylor +8 more
The complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation is reported, showing the pattern of sequence variation that exists in introns as well as exons.
Annual Review of NeuroscienceApolipoprotein E and Alzheimer's Disease
472 Citations1996Warren J. Strittmatter, Allen D. Roses
Several hypotheses of disease pathogenesis are now based on the relevance of apolipoprotein E, which has been demonstrated with the defining pathological lesions of Alzheimer's disease, the neurofibrillary tangle and neuritic plaque.
The American Journal of Human GeneticsA High-Density Admixture Map for Disease Gene Discovery in African Americans
467 Citations2004Michael W. Smith, Nick Patterson +30 more
This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts, and is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
NatureA common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk
466 Citations2005E Emison, Andrew S. McCallion +8 more
It is shown that a common non-coding RET variant within a conserved enhancer-like sequence in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribution to risk than rare alleles do.
Proceedings of the National Academy of SciencesAdmixture as a tool for finding linked genes and detecting that difference from allelic association between loci.
460 Citations1988Ranajit Chakraborty, Kenneth M. Weiss
It is shown that substantial disequilibrium remains today under widely applicable situations, which can be detected without requiring inordinately close linkage between trait and marker loci.
Nature GeneticsARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF
436 Citations2000James C. Engert, Pierre Bérubé +12 more
The cloning of this gene, SACS, which encodes the protein sacsin, which is the largest to be identified in any vertebrate organism is reported, and the presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding.
Human HeredityDetecting Disease Associations due to Linkage Disequilibrium Using Haplotype Tags: A Class of Tests and the Determinants of Statistical Power
422 Citations2003Juliet Chapman, Jason D. Cooper +2 more
The role of the R2 measure of association between a causal locus and various methods of scoring of marker haplotypes is highlighted and the simplest method of scoring (locus coding), which does not require phase resolution, is shown generally to be more powerful than scoring methods that include haplotype information.
Genome ResearchLinkage Disequilibrium and the Search for Complex Disease Genes
409 Citations2000Lynn B. Jorde
These techniques are summarized and the evolutionary factors that can confound or enhance disequilibrium analysis will be discussed, and some thoughts will be offered on the optimal choice of markers and populations for LD analysis.
Human HeredityChoosing Haplotype-Tagging SNPS Based on Unphased Genotype Data Using a Preliminary Sample of Unrelated Subjects with an Example from the Multiethnic Cohort Study
407 Citations2003Daniel O. Stram, Christopher A. Haiman +5 more
An approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes.
NatureA first-generation linkage disequilibrium map of human chromosome 22
403 Citations2002Elisabeth Dawson, Gonçalo R. Abecasis +27 more
This study demonstrates the feasibility of developing genome-wide maps of LD and shows a strong correlation between high LD and low recombination frequency in the extant genetic map, suggesting that historical and contemporary recombination rates are similar.
Annual Review of GeneticsMEIOTIC RECOMBINATION HOTSPOTS
369 Citations1995Michael Lichten, Alastair S. H. Goldman
This article reviews what is known about meiotic recombination hotspots loci, or regions that display a greater than average frequency of meiotic exchange, in Saccharomyces cerevisiae.
ScienceComparison of Fine-Scale Recombination Rates in Humans and Chimpanzees
367 Citations2005Wendy Winckler, Simon Myers +9 more
Local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence, in humans and chimpanzees, by analyzing polymorphism data in both species.
Nature MedicineAdvantage of rare HLA supertype in HIV disease progression
352 Citations2003Elizabeth Trachtenberg, Bette Korber +13 more
The correlation of the frequency of the HLA supertypes with viral load suggests that HIV adapts to the most frequent alleles in the population, providing a selective advantage for those individuals who express rare alleles.
The American Journal of Human GeneticsA Comparison of Phasing Algorithms for Trios and Unrelated Individuals
339 Citations2006Jonathan Marchini, David J. Cutler +9 more
A comprehensive assessment of the methods applied to both trios and to unrelated individuals, with a focus on genomic-scale problems, concludes that all the methods considered will provide highly accurate estimates of haplotypes when applied to trio data sets.
Genome ResearchIdentification and Characterization of Multi-Species Conserved Sequences
336 Citations2003Elliott H. Margulies
Annual Review of Genomics and Human GeneticsThe Inherited Basis of Diabetes Mellitus: Implications for the Genetic Analysis of Complex Traits
331 Citations2003José C. Florez, Joel N. Hirschhorn +1 more
The lessons learned from an extensive body of evidence on the division of diabetes into different subtypes based on clinical phenotype are used to illustrate general implications for the genetic analysis of complex traits.
Nature Reviews GeneticsIntegrating ethics and science in the International HapMap Project
326 Citations2004Morris W. Foster
Questions about how to conduct genetic variation research that uses identified populations in an ethical way are raised, including how to involve members of a population in evaluating the risks and benefits posed for everyone who shares that identity.
NatureGenetic interactions between polymorphisms that affect gene expression in yeast
312 Citations2005Rachel B. Brem, John D. Storey +2 more
The results indicate that genetic interactions are widespread in the genetics of transcript levels, and that many QTLs will be missed by single-locus tests but can be detected by two-stage tests that allow for interactions.
Human GenomicsWhole genome DNA copy number changes identified by high density oligonucleotide arrays
282 Citations2004Jing Huang, Wen Wei +8 more
A novel algorithm that uses a recently developed high-density oligonucleotide array-based SNP genotyping method, whole genome sampling analysis (WGSA), to identify genome-wide chromosomal gains and losses at high resolution and can tolerate samples which contain a mixture of both tumour and normal DNA.
Nature GeneticsAdmixture mapping for hypertension loci with genome-scan markers
277 Citations2005Xiaofeng Zhu, Amy Luke +9 more
Admirixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program suggests that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans.
Nature GeneticsChromosome-wide distribution of haplotype blocks and the role of recombination hot spots
277 Citations2003Michael Phillips, Robert Lawrence +33 more
A first-generation haplotype map of chromosome 19 is constructed using publicly available genetic markers and evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered.
NatureComparison of human genetic and sequence-based physical maps
276 Citations2001Adong Yu, Chengfeng Zhao +9 more
Estimates of female, male and sex-average recombination rates for about 60% of the genome are described and several chromosomal regions up to 6 Mb in length are identified with particularly low (deserts) or high (jungles) recombination rates.
Nature GeneticsEvidence for substantial fine-scale variation in recombination rates across the human genome
274 Citations2004Dana C. Crawford, Tushar Bhangale +5 more
A new statistical method is applied, which overcomes limitations, to infer patterns of fine-scale recombination rate variation in 74 genes, and finds extensive rate variation both within and among genes.
NatureNumerous potentially functional but non-genic conserved sequences on human chromosome 21
246 Citations2002Emmanouil T. Dermitzakis, Alexandre Reymond +9 more
The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably the understanding of the role of sequence conservation in mammalian genomes.
Proceedings of the National Academy of SciencesLinkage disequilibrium mapping in isolated populations: The example of Finland revisited
243 Citations1998Albert de la Chapelle, Fred A. Wright
The statistical issues of fine mapping by linkage disequilibrium are reviewed and it is suggested that improved methodologies may be necessary to map diseases of complex etiology that may have arisen from multiple founding mutations.
Nature Reviews GeneticsMapping by admixture linkage disequilibrium: advances, limitations and guidelines
224 Citations2005Michael W. Smith, Stephen J. O’Brien
PubMedMaximum-likelihood estimation of gene location by linkage disequilibrium.
206 Citations1994William G. Hill, B. S. Weir
The likelihood of precise information on map position will not be obtained from estimates of linkage disequilibrium, because it is found that the likelihood is not very dependent on the degree of selection at the loci and is very flat.
The American Journal of Human GeneticsSelection and Evaluation of Tagging SNPs in the Neuronal-Sodium-Channel Gene SCN1A: Implications for Linkage-Disequilibrium Gene Mapping
190 Citations2003Mike E. Weale, Chantal Depondt +6 more
The results indicate that tSNPs will not easily identify discrepant SNPs, which lie on importantly discriminating but apparently short genealogical branches, which could significantly complicate tagging approaches for phenotypes influenced by variants that have experienced positive selection.
Proceedings of the National Academy of SciencesWhole-genome shotgun assembly and comparison of human genome assemblies
184 Citations2004Sorin Istrail, Granger G. Sutton +34 more
The analysis of WGSA shows 97% order and orientation agreement with NCBI Build 34, where most of the 3% of sequence out of order is due to scaffold placement problems as opposed to assembly errors within the scaffolds themselves.
GeneticsBounds on the Minimum Number of Recombination Events in a Sample History
184 Citations2003Simon Myers, Robert Griffiths
Statistics that give a lower bound on the number of recombination events in the history of a sample, on the basis of the patterns of variation in the sample DNA, are introduced.
Nucleic Acids ResearchEvolutionary conservation of histone macroH2A subtypes and domains
151 Citations1998John R. Pehrson, Reina N. Fuji
The origin of the non-histone domain was examined by comparing its sequence to proteins found in bacteria and RNA viruses, and these comparisons indicate that this domain is derived from a gene that originated prior to the appearance of eukaryotes, and suggest that the non thehistone region has retained the basic function of its ancestral gene.
Nature GeneticsExhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies
150 Citations2004Shin Lin, Aravinda Chakravarti +1 more
An algorithm and statistical method is described that efficiently and exhaustively exploits haplotype information by subjecting alleles from sliding windows of all sizes to transmission disequilibrium tests and can detect both common and rare disease variants of small effect.
Nature GeneticsPriorities and standards in pharmacogenetic research
127 Citations2005Anna C. Need, Arno G. Motulsky +1 more
As the attention of researchers begins to shift toward more systematic pharmacogenetic investigations, it is suggested some priorities and standards for pharmacogenetics research.
The American Journal of Human GeneticsLocalization of a Small Genomic Region Associated with Elevated ACE
121 Citations2000Xiaofeng Zhu, Colin A. McKenzie +8 more
Analyses of the same polymorphisms in 98 unrelated Europeans in the Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study resulted in fewer haplotypes than were observed among the Afro-Caribbean subjects, suggesting that populations with greater genetic diversity may be especially informative for fine-scale mapping.
Genome ResearchSequence features in regions of weak and strong linkage disequilibrium
96 Citations2005Albert V. Smith, Daryl J. Thomas +2 more
Genotype data generated by the International HapMap Project is used to dissect the relationship between sequence features and the degree of linkage disequilibrium in the genome and suggest an evolutionary justification for the heterogeneity in linkage disequ equilibrium.
The American Journal of Human GeneticsLocation Score and Haplotype Analyses of the Locus for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay, in Chromosome Region 13q11
91 Citations1999Andréa Richter, John D. Rioux +11 more
Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation.
PubMedResistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis.
79 Citations1997Björn Dahlbäck
…