Identification of Susceptibility Genes for Tuberculosis in Southern and West Africans Using Family-Based Linkage Analysis and Linkage Disequilibrium Mapping

2003 ◽  
Vol 104 (s49) ◽  
pp. 56P-56P
Author(s):  
Graham Cooke ◽  
Sarah Campbell ◽  
Richard Bellamy ◽  
Christian Lienhardt ◽  
Oumou Sow ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Linkage Analysis ◽  
Susceptibility Genes ◽  
Linkage Disequilibrium Mapping ◽  
West Africans ◽  
Family Based

Joint Linkage and Linkage Disequilibrium Mapping of Quantitative Trait Loci in Natural Populations

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 779-792 ◽  
Author(s):  
Rongling Wu ◽  
Chang-Xing Ma ◽  
George Casella
Keyword(s):  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Linkage Analysis ◽  
Quantitative Trait ◽  
Genome Mapping ◽  
Linkage Disequilibrium Mapping ◽  
Allelic Association ◽  
Mapping Strategy ◽  
Trait Loci ◽  
New Strategy

AbstractLinkage analysis and allelic association (also referred to as linkage disequilibrium) studies are two major approaches for mapping genes that control simple or complex traits in plants, animals, and humans. But these two approaches have limited utility when used alone, because they use only part of the information that is available for a mapping population. More recently, a new mapping strategy has been designed to integrate the advantages of linkage analysis and linkage disequilibrium analysis for genome mapping in outcrossing populations. The new strategy makes use of a random sample from a panmictic population and the open-pollinated progeny of the sample. In this article, we extend the new strategy to map quantitative trait loci (QTL), using molecular markers within the EM-implemented maximum-likelihood framework. The most significant advantage of this extension is that both linkage and linkage disequilibrium between a marker and QTL can be estimated simultaneously, thus increasing the efficiency and effectiveness of genome mapping for recalcitrant outcrossing species. Simulation studies are performed to test the statistical properties of the MLEs of genetic and genomic parameters including QTL allele frequency, QTL effects, QTL position, and the linkage disequilibrium of the QTL and a marker. The potential utility of our mapping strategy is discussed.

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%.

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.

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