Haplotype analysis in population genetics and association studies.

Several studies of haplotype structures in the human genome in various populations have been published recently. Such knowledge may provide valuable information on human evolutionary history and lead to the development of more efficient strategies to identify genetic variants that increase susceptibility to human diseases. In this review, we summarize the current understanding of haplotype structure, diversity, and distribution in the human genome, with a focus on statistical issues in using haplotypes for studies of population genetics and evolutionary history, as well as to identify genetic variants underlying complex human traits.

[1]  L. Kruglyak.  Prospects for whole-genome linkage disequilibrium mapping of common disease genes , 1999, Nature Genetics.

[2]  M. Daly,et al.  High-resolution haplotype structure in the human genome , 2001, Nature Genetics.

[3]  S. Tishkoff,et al.  Global Patterns of Linkage Disequilibrium at the CD4 Locus and Modern Human Origins , 1996, Science.

[4]  Andrew G Clark,et al.  Linkage disequilibrium and the mapping of complex human traits. , 2002, Trends in genetics : TIG.

[5]  P. Donnelly,et al.  Association mapping in structured populations. , 2000, American journal of human genetics.

[6]  Daniel J Schaid,et al.  Relative efficiency of ambiguous vs. directly measured haplotype frequencies , 2002, Genetic epidemiology.

[7]  A. Valdés,et al.  Detecting disease-predisposing variants: the haplotype method. , 1997, American journal of human genetics.

[8]  M Farrall,et al.  Measured haplotype analysis of the angiotensin-I converting enzyme gene. , 1998, Human molecular genetics.

[9]  Donald B. Rubin,et al.  Max-imum Likelihood from Incomplete Data , 1972 .

[10]  Michael Knapp,et al.  Efficiency of Haplotype Frequency Estimation when Nuclear Familiy Information Is Included , 2002, Human Heredity.

[11]  Frank Dudbridge,et al.  Haplotype tagging for the identification of common disease genes , 2001, Nature Genetics.

[12]  M. Waterman,et al.  A dynamic programming algorithm for haplotype block partitioning , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R S Judson,et al.  Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K K Kidd,et al.  Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence. , 2000, Human molecular genetics.

[15]  Joni L Rutter,et al.  Efficiency of DNA pooling to estimate joint allele frequencies and measure linkage disequilibrium , 2002, Genetic epidemiology.

[16]  D. Gudbjartsson,et al.  A high-resolution recombination map of the human genome , 2002, Nature Genetics.

[17]  L. Excoffier,et al.  Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. , 1995, Molecular biology and evolution.

[18]  Pardis C Sabeti,et al.  Linkage disequilibrium in the human genome , 2001, Nature.

[19]  N. Kaplan,et al.  On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles , 2002, Genetic epidemiology.

[20]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[21]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[22]  N. Risch.  Searching for genetic determinants in the new millennium , 2000, Nature.

[23]  A. Chakravarti,et al.  Haplotype inference in random population samples. , 2002, American journal of human genetics.

[24]  M. Boehnke,et al.  Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies , 2001, Nature Genetics.

[25]  E. Génin,et al.  Search for multifactorial disease susceptibility genes in founder populations , 2000, Annals of human genetics.

[26]  J. Kere,et al.  Data mining applied to linkage disequilibrium mapping. , 2000, American journal of human genetics.

[27]  N. Risch,et al.  A comparison of linkage disequilibrium measures for fine-scale mapping. , 1995, Genomics.

[28]  N. Schork,et al.  Genetic analysis of case/control data using estimated haplotype frequencies: application to APOE locus variation and Alzheimer's disease. , 2001, Genome research.

[29]  J. Pritchard.  Are rare variants responsible for susceptibility to complex diseases? , 2001, American journal of human genetics.

[30]  Lon R. Cardon,et al.  A first-generation linkage disequilibrium map of human chromosome 22 , 2002, Nature.

[31]  L. Lazzeroni,et al.  A chronology of fine-scale gene mapping by linkage disequilibrium , 2001, Statistical methods in medical research.

[32]  S. Gabriel,et al.  The Structure of Haplotype Blocks in the Human Genome , 2002, Science.

[33]  A. Jeffreys,et al.  Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex , 2001, Nature Genetics.

[34]  J. Stephens,et al.  Haplotype Variation and Linkage Disequilibrium in 313 Human Genes , 2001, Science.

[35]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[36]  K. Kidd,et al.  HAPLO: a program using the EM algorithm to estimate the frequencies of multi-site haplotypes. , 1995, The Journal of heredity.

[37]  A. Clark,et al.  Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus. , 2001, American journal of human genetics.

[38]  S. P. Fodor,et al.  Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21 , 2001, Science.

[39]  C. Sing,et al.  A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping and DNA sequence data. III. Cladogram estimation. , 1992, Genetics.

[40]  K. Roeder,et al.  Genomic Control for Association Studies , 1999, Biometrics.

[41]  J. Gilbert,et al.  SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. , 2000, American journal of human genetics.

[42]  D. Clayton,et al.  Transmission/disequilibrium tests for extended marker haplotypes. , 1999, American journal of human genetics.

[43]  C. Sing,et al.  A cladistic analysis of phenotype associations with haplotypes inferred from restriction endonuclease mapping. II. The analysis of natural populations. , 1988, Genetics.

[44]  Zhaohui S. Qin,et al.  Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms. , 2002, American journal of human genetics.

[45]  Pardis C Sabeti,et al.  Detecting recent positive selection in the human genome from haplotype structure , 2002, Nature.

[46]  Xiaofeng Zhu,et al.  On a semiparametric test to detect associations between quantitative traits and candidate genes using unrelated individuals , 2003, Genetic epidemiology.

[47]  G. Meerman,et al.  Association and haplotype sharing due to identity by descent, with an application to genetic mapping , 1997 .

[48]  Eric S. Lander,et al.  Human genome sequence variation and the influence of gene history, mutation and recombination , 2002, Nature Genetics.

[49]  Richard Judson,et al.  How many SNPs does a genome-wide haplotype map require? , 2002, Pharmacogenomics.

[50]  A. Clark,et al.  Inference of haplotypes from PCR-amplified samples of diploid populations. , 1990, Molecular biology and evolution.

[51]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[52]  Hongyu Zhao,et al.  On the use of DNA pooling to estimate haplotype frequencies , 2003, Genetic epidemiology.

[53]  J. Long,et al.  An E-M algorithm and testing strategy for multiple-locus haplotypes. , 1995, American journal of human genetics.

[54]  S E Hodge,et al.  Logistic regression model for analyzing extended haplotype data , 1998, Genetic epidemiology.

[55]  J. Akey,et al.  Distribution of recombination crossovers and the origin of haplotype blocks: the interplay of population history, recombination, and mutation. , 2002, American journal of human genetics.

[56]  K. Roeder,et al.  Transmission/disequilibrium test meets measured haplotype analysis: family-based association analysis guided by evolution of haplotypes. , 2001, American journal of human genetics.

[57]  Zhaohui S. Qin,et al.  Partition-ligation-expectation-maximization algorithm for haplotype inference with single-nucleotide polymorphisms. , 2002, American journal of human genetics.

[58]  E. Lander,et al.  On the allelic spectrum of human disease. , 2001, Trends in genetics : TIG.