Genetic mapping of complex traits.

Statistical genetic mapping methods are powerful tools for finding genes that contribute to complex human traits. Mapping methods combine knowledge of the biological mechanisms of inheritance and the randomness inherent in those mechanisms to locate, with increasing precision, trait genes on the human genome. We provide an overview of the two major classes of mapping methods, genetic linkage analysis and linkage disequilibrium analysis, and related concepts of genetic inheritance.

[1]  R. Elston,et al.  A comparison of sib‐pair linkage tests for disease susceptibility loci , 1985, Genetic epidemiology.

[2]  R C Elston,et al.  Man bites dog? The validity of maximizing lod scores to determine mode of inheritance. , 1989, American journal of medical genetics.

[3]  F. Wright,et al.  Linkage disequilibrium mapping in isolated populations: the example of Finland revisited. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Eric S. Lander,et al.  Asymptotic distribution of the likelihood ratio test that a mixture of two binomials is a single binomial , 1995 .

[5]  W. Ewens,et al.  Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). , 1993, American journal of human genetics.

[6]  M Farrall,et al.  Two-locus maximum lod score analysis of a multifactorial trait: joint consideration of IDDM2 and IDDM4 with IDDM1 in type 1 diabetes. , 1995, American journal of human genetics.

[7]  B. Weir,et al.  Are moment bounds on the recombination fraction between a marker and a disease locus too good to be true? Allelic association mapping revisited for simple genetic diseases in the Finnish population. , 1995, American journal of human genetics.

[8]  B S Weir,et al.  Maximum-likelihood estimation of gene location by linkage disequilibrium. , 1994, American journal of human genetics.

[9]  N E Morton,et al.  Significance levels in complex inheritance. , 1998, American journal of human genetics.

[10]  S W Guo,et al.  Linkage disequilibrium measures for fine-scale mapping: a comparison. , 1997, Human heredity.

[11]  R. Elston,et al.  The probabilistic determination of identity-by-descent sharing for pairs of relatives from pedigrees. , 1990, American journal of human genetics.

[12]  N. Morton Sequential tests for the detection of linkage. , 1955, American journal of human genetics.

[13]  W. G. Hill,et al.  Estimation of linkage disequilibrium in randomly mating populations , 1974, Heredity.

[14]  Laurent Excoffier,et al.  Testing for linkage disequilibrium in genotypic data using the Expectation-Maximization algorithm , 1996, Heredity.

[15]  Davison Db,et al.  Editorial: Whither Computational Biology , 1994, J. Comput. Biol..

[16]  N. Risch Linkage strategies for genetically complex traits. I. Multilocus models. , 1990, American journal of human genetics.

[17]  Eric S. Lander,et al.  Faster Multipoint Linkage Analysis Using Fourier Transforms , 1998, J. Comput. Biol..

[18]  D. Schaid,et al.  Sib‐pair linkage tests for disease susceptibility loci: Common tests vs. the asymptotically most powerful test , 1990, Genetic epidemiology.

[19]  R. Elston,et al.  The investigation of linkage between a quantitative trait and a marker locus , 1972, Behavior genetics.

[20]  K Lange,et al.  Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. , 1996, American journal of human genetics.

[21]  P. Holmans,et al.  Asymptotic properties of affected-sib-pair linkage analysis. , 1993, American journal of human genetics.

[22]  S A Seuchter,et al.  Linkage analysis in nuclear families. 1: Optimality criteria for affected sib-pair tests. , 1994, Human heredity.

[23]  R. Elston,et al.  A general model for the genetic analysis of pedigree data. , 1971, Human heredity.

[24]  N. Morton,et al.  The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. , 1956, American journal of human genetics.

[25]  E. Lander,et al.  Construction of multilocus genetic linkage maps in humans. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Brown,et al.  Sample sizes required to detect linkage disequilibrium between two or three loci. , 1975, Theoretical population biology.

[27]  Robert C. Elston,et al.  Some Recent Developments in the Theoretical Aspects of Segregation Analysis , 1993 .

[28]  B Rannala,et al.  Likelihood analysis of disequilibrium mapping, and related problems. , 1998, American journal of human genetics.

[29]  R C Elston,et al.  A faster and more general hidden Markov model algorithm for multipoint likelihood calculations. , 1997, Human heredity.

[30]  H. Jennings The Numerical Results of Diverse Systems of Breeding, with Respect to Two Pairs of Characters, Linked or Independent, with Special Relation to the Effects of Linkage. , 1917, Genetics.

[31]  E. Thompson Genetic epidemiology: a review of the statistical basis. , 1986, Statistics in medicine.

[32]  Hilda Geiringer,et al.  Further Remarks on Linkage Theory in Mendelian Heredity , 1945 .

[33]  D W Fulker,et al.  The power of interval mapping of quantitative trait loci, using selected sib pairs. , 1994, American journal of human genetics.

[34]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[35]  D J Schaid,et al.  Relative‐risk regression models using cases and their parents , 1995, Genetic epidemiology.

[36]  R C Elston,et al.  1996 William Allan Award Address. Algorithms and inferences: the challenge of multifactorial diseases. , 1997, American journal of human genetics.

[37]  C. Amos,et al.  On the asymptotic behavior of the estimate of the recombination fraction under the null hypothesis of no linkage when the model is misspecified , 1990, Genetic epidemiology.

[38]  W S Watkins,et al.  Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. , 1994, American journal of human genetics.

[39]  Eric Lander,et al.  Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland , 1992, Nature Genetics.

[40]  L Kruglyak,et al.  Parametric and nonparametric linkage analysis: a unified multipoint approach. , 1996, American journal of human genetics.

[41]  C. Amos Robust variance-components approach for assessing genetic linkage in pedigrees. , 1994, American journal of human genetics.

[42]  B S Weir,et al.  Likelihood methods for locating disease genes in nonequilibrium populations. , 1995, American journal of human genetics.

[43]  L. Lazzeroni,et al.  Linkage disequilibrium and gene mapping: an empirical least-squares approach. , 1998, American journal of human genetics.

[44]  M. Xiong,et al.  Fine-scale genetic mapping based on linkage disequilibrium: theory and applications. , 1997, American journal of human genetics.

[45]  L. Almasy,et al.  Multipoint quantitative-trait linkage analysis in general pedigrees. , 1998, American journal of human genetics.

[46]  J J Faraway,et al.  Distribution of the admixture test for the detection of linkage under heterogeneity , 1993, Genetic epidemiology.

[47]  M. Delbrück,et al.  Mutations of Bacteria from Virus Sensitivity to Virus Resistance. , 1943, Genetics.

[48]  W. Bodmer,et al.  Human genetics: the molecular challenge. , 1987, BioEssays : news and reviews in molecular, cellular and developmental biology.

[49]  M. Daly,et al.  Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. , 1995, American journal of human genetics.

[50]  E. Wijsman,et al.  Linkage between quantitative trait and marker loci: Methods using all relative pairs , 1993, Genetic epidemiology.

[51]  J. Olson Likelihood-based models for genetic linkage analysis using affected sib pairs. , 1997, Human heredity.

[52]  G. Casella,et al.  Statistical Inference , 2003, Encyclopedia of Social Network Analysis and Mining.

[53]  R. B. Robbins Some Applications of Mathematics to Breeding Problems. , 1917, Genetics.

[54]  L. Jorde Linkage disequilibrium as a gene-mapping tool. , 1995, American journal of human genetics.

[55]  Bruce S. Weir Genetic Data Analysis , 1990 .

[56]  W J Ewens,et al.  The TDT and other family-based tests for linkage disequilibrium and association. , 1996, American journal of human genetics.

[57]  R C Elston,et al.  Lods, wrods, and mods: The interpretation of lod scores calculated under different models , 1994, Genetic epidemiology.

[58]  G. Carey,et al.  Linkage analysis of quantitative traits: increased power by using selected samples. , 1991, American journal of human genetics.

[59]  E. Lander,et al.  Complete multipoint sib-pair analysis of qualitative and quantitative traits. , 1995, American journal of human genetics.

[60]  K B Jacobs,et al.  Exact transmission‐disequilibrium tests with multiallelic markers , 1997, Genetic epidemiology.

[61]  N. Risch,et al.  Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs. , 1990, American journal of human genetics.

[62]  C I Amos,et al.  Guess LOD approach: Sufficient conditions for robustness , 1995, Genetic epidemiology.

[63]  J. Terwilliger A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci. , 1995, American journal of human genetics.

[64]  C. A. Smith,et al.  Testing for heterogeneity of recombination fraction values in Human Genetics , 1963, Annals of human genetics.

[65]  J. Witte,et al.  Genetic dissection of complex traits , 1996, Nature Genetics.

[66]  K. Roeder,et al.  Disequilibrium mapping: composite likelihood for pairwise disequilibrium. , 1996, Genomics.

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

[68]  N. Risch,et al.  Mapping quantitative trait loci with extreme discordant sib pairs: sampling considerations. , 1996, American journal of human genetics.

[69]  W. G. Hill,et al.  Linkage disequilibrium in finite populations , 1968, Theoretical and Applied Genetics.

[70]  N Risch,et al.  Extreme discordant sib pairs for mapping quantitative trait loci in humans. , 1995, Science.

[71]  J. Green,et al.  Sibling Method for Detecting HLA-linked genes in disease. , 2008, Tissue antigens.

[72]  R. Elston,et al.  Robust methods for the detection of genetic linkage for quantitative data from pedigrees , 1989, Genetic epidemiology.

[73]  B S Weir,et al.  Testing Hypotheses about Linkage Disequilibrium with Multiple Alleles. , 1978, Genetics.

[74]  A. Whittemore,et al.  A class of tests for linkage using affected pedigree members. , 1994, Biometrics.