Linkage Disequilibrium Mapping of Disease Susceptibility Genes in Human Populations

2000 ◽  
Vol 68 (1) ◽  
pp. 23
Author(s):  
David Clayton
Keyword(s):  
Linkage Disequilibrium ◽  
Disease Susceptibility ◽  
Susceptibility Genes ◽  
Linkage Disequilibrium Mapping ◽  
Human Populations

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

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 Genomics-driven drug discovery based on disease-susceptibility genes

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Kyuto Sonehara ◽  
Yukinori Okada
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Disease Susceptibility ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Drug Repurposing ◽  
Susceptibility Genes ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Associations

AbstractGenome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene–disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.

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.

scholarly journals Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80513 ◽  
Author(s):  
Donald M. Lyall ◽  
Natalie A. Royle ◽  
Sarah E. Harris ◽  
Mark E. Bastin ◽  
Susana Muñoz Maniega ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Disease Susceptibility ◽  
Susceptibility Genes ◽  
Lothian Birth Cohort
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