scholarly journals Cost-Effective Designs for Linkage Disequilibrium Mapping of Complex Traits

2003 ◽  
Vol 72 (5) ◽  
pp. 1213-1220 ◽  
Author(s):  
Susan K. Service ◽  
Lodewijk A. Sandkuijl ◽  
Nelson B. Freimer
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Traits ◽  
Cost Effective ◽  
Linkage Disequilibrium Mapping

scholarly journals Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 899-909
Author(s):  
Rongling Wu ◽  
Zhao-Bang Zeng
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Traits ◽  
Positional Cloning ◽  
Genome Structure ◽  
Natural Populations ◽  
Linkage Disequilibrium Mapping ◽  
Linkage Disequilibria ◽  
Time Simulation ◽  
New Strategy ◽  
Fisher Scoring Algorithm

Abstract A new strategy for studying the genome structure and organization of natural populations is proposed on the basis of a combined analysis of linkage and linkage disequilibrium using known polymorphic markers. This strategy exploits a random sample drawn from a panmictic natural population and the open-pollinated progeny of the sample. It is established on the principle of gene transmission from the parental to progeny generation during which the linkage between different markers is broken down due to meiotic recombination. The strategy has power to simultaneously capture the information about the linkage of the markers (as measured by recombination fraction) and the degree of their linkage disequilibrium created at a historic time. Simulation studies indicate that the statistical method implemented by the Fisher-scoring algorithm can provide accurate and precise estimates for the allele frequencies, recombination fractions, and linkage disequilibria between different markers. The strategy has great implications for constructing a dense linkage disequilibrium map that can facilitate the identification and positional cloning of the genes underlying both simple and complex traits.

A Haplotype-Based Algorithm for Multilocus Linkage Disequilibrium Mapping of Quantitative Trait Loci With Epistasis

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1533-1548 ◽  
Author(s):  
Xiang-Yang Lou ◽  
George Casella ◽  
Ramon C Littell ◽  
Mark C K Yang ◽  
Julie A Johnson ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Association Studies ◽  
Natural Populations ◽  
Evolutionary Relationship ◽  
Linkage Disequilibrium Mapping ◽  
Trait Loci

AbstractFor tightly linked loci, cosegregation may lead to nonrandom associations between alleles in a population. Because of its evolutionary relationship with linkage, this phenomenon is called linkage disequilibrium. Today, linkage disequilibrium-based mapping has become a major focus of recent genome research into mapping complex traits. In this article, we present a new statistical method for mapping quantitative trait loci (QTL) of additive, dominant, and epistatic effects in equilibrium natural populations. Our method is based on haplotype analysis of multilocus linkage disequilibrium and exhibits two significant advantages over current disequilibrium mapping methods. First, we have derived closed-form solutions for estimating the marker-QTL haplotype frequencies within the maximum-likelihood framework implemented by the EM algorithm. The allele frequencies of putative QTL and their linkage disequilibria with the markers are estimated by solving a system of regular equations. This procedure has significantly improved the computational efficiency and the precision of parameter estimation. Second, our method can detect marker-QTL disequilibria of different orders and QTL epistatic interactions of various kinds on the basis of a multilocus analysis. This can not only enhance the precision of parameter estimation, but also make it possible to perform whole-genome association studies. We carried out extensive simulation studies to examine the robustness and statistical performance of our method. The application of the new method was validated using a case study from humans, in which we successfully detected significant QTL affecting human body heights. Finally, we discuss the implications of our method for genome projects and its extension to a broader circumstance. The computer program for the method proposed in this article is available at the webpage http://www.ifasstat.ufl.edu/genome/~LD.

scholarly journals Fine Mapping of a Quantitative Trait Locus for Twinning Rate Using Combined Linkage and Linkage Disequilibrium Mapping

Genetics ◽  
2002 ◽  
Vol 161 (1) ◽  
pp. 373-379 ◽  
Author(s):  
Theo H E Meuwissen ◽  
Astrid Karlsen ◽  
Sigbjørn Lien ◽  
Ingrid Olsaker ◽  
Mike E Goddard
Keyword(s):  
Quantitative Trait Locus ◽  
Linkage Disequilibrium ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Middle Part ◽  
Linkage Disequilibrium Mapping ◽  
Chromosome 5 ◽  
Linkage Information ◽  
Linkage Disequilibrium Information ◽  
Trait Locus

Abstract A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.

Protein Variation in ADH and ADH-RELATED in Drosophila pseudoobscura: Linkage Disequilibrium Between Single Nucleotide Polymorphisms and Protein Alleles

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 673-687
Author(s):  
Stephen W Schaeffer ◽  
C Scott Walthour ◽  
Donna M Toleno ◽  
Anna T Olek ◽  
Ellen L Miller
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Drosophila Pseudoobscura ◽  
Linkage Disequilibrium Mapping ◽  
Nucleotide Polymorphisms ◽  
Neutral Model ◽  
Significant Linkage Disequilibrium ◽  
Single Nucleotide ◽  
Synonymous Sites ◽  
Significant Linkage

Abstract A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

Sign in / Sign up

Export Citation Format

Share Document