The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Santiago Rodriguez - One of the best experts on this subject based on the ideXlab platform.
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sampling variance and distribution of the d measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
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Sampling variance and distribution of the D′ measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
C Zapata - One of the best experts on this subject based on the ideXlab platform.
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sampling variance and distribution of the d measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
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Sampling variance and distribution of the D′ measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
Carla Carollo - One of the best experts on this subject based on the ideXlab platform.
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sampling variance and distribution of the d measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
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Sampling variance and distribution of the D′ measure of overall gametic Disequilibrium between multiallelic loci
Annals of Human Genetics, 2001Co-Authors: C Zapata, Carla Carollo, Santiago RodriguezAbstract:The development of the theory of estimation of gametic Disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The D' coefficient is one of the most commonly used measures of the extent of overall Disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall Disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D^' between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D^' was investigated under different scenarios of Disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D^', conditioned on the sample size, number of alleles and their frequencies, and Disequilibrium components. It was found that the sampling distribution of D^' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall Disequilibrium, which is relevant to evaluate Disequilibrium between multiallelic loci in populations.
Philippe Leray - One of the best experts on this subject based on the ideXlab platform.
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Visualization of pairwise and multilocus linkage Disequilibrium structure using latent forests.
PLoS ONE, 2011Co-Authors: Raphaël Mourad, Christine Sinoquet, Christian Dina, Philippe LerayAbstract:Linkage Disequilibrium study represents a major issue in statistical genetics as it plays a fundamental role in gene mapping and helps us to learn more about human history. The linkage Disequilibrium complex structure makes its exploratory data analysis essential yet challenging. Visualization methods, such as the triangular heat map implemented in Haploview, provide simple and useful tools to help understand complex genetic patterns, but remain insufficient to fully describe them. Probabilistic graphical models have been widely recognized as a powerful formalism allowing a concise and accurate modeling of dependences between variables. In this paper, we propose a method for short-range, long-range and chromosome-wide linkage Disequilibrium visualization using forests of hierarchical latent class models. Thanks to its hierarchical nature, our method is shown to provide a compact view of both pairwise and multilocus linkage Disequilibrium spatial structures for the geneticist. Besides, a multilocus linkage Disequilibrium measure has been designed to evaluate linkage Disequilibrium in hierarchy clusters. To learn the proposed model, a new scalable algorithm is presented. It constrains the dependence scope, relying on physical positions, and is able to deal with more than one hundred thousand single nucleotide polymorphisms. The proposed algorithm is fast and does not require phase genotypic data.
Andrew Collins - One of the best experts on this subject based on the ideXlab platform.
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Exome-based linkage Disequilibrium maps of individual genes: functional clustering and relationship to disease
Human Genetics, 2013Co-Authors: Jane Gibson, William Tapper, Sarah Ennis, Andrew CollinsAbstract:Exome sequencing identifies thousands of DNA variants and a proportion of these are involved in disease. Genotypes derived from exome sequences provide particularly high-resolution coverage enabling study of the linkage Disequilibrium structure of individual genes. The extent and strength of linkage Disequilibrium reflects the combined influences of mutation, recombination, selection and population history. By constructing linkage Disequilibrium maps of individual genes, we show that genes containing OMIM-listed disease variants are significantly under - represented amongst genes with complete or very strong linkage Disequilibrium ( P = 0.0004). In contrast, genes with disease variants are significantly over - represented amongst genes with levels of linkage Disequilibrium close to the average for genes not known to contain disease variants ( P = 0.0038). Functional clustering reveals, amongst genes with particularly strong linkage Disequilibrium, significant enrichment of essential biological functions (e.g. phosphorylation, cell division, cellular transport and metabolic processes). Strong linkage Disequilibrium, corresponding to reduced haplotype diversity, may reflect selection in utero against deleterious mutations which have profound impact on the function of essential genes. Genes with very weak linkage Disequilibrium show enrichment of functions requiring greater allelic diversity (e.g. sensory perception and immune response). This category is not enriched for genes containing disease variation. In contrast, there is significant enrichment of genes containing disease variants amongst genes with more average levels of linkage Disequilibrium. Mutations in these genes may less likely lead to in utero lethality and be subject to less intense selection.
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Linkage Disequilibrium and Association Mapping - Linkage Disequilibrium and Association Mapping
Methods in molecular biology (Clifton N.J.), 2007Co-Authors: Andrew CollinsAbstract:The basis for recent developments on the characterization of the linkage-Disequilibrium structure of the genome and the application of association mapping to genes for common human diseases is described. Patterns of linkage Disequilibrium are now understood, for a number of human populations, in unprecedented detail. This information not only provides a vital resource for the design and execution of powerful association-mapping studies, but opens new avenues of research into the genetic history of human populations and the effects of natural selection, mutation, and recombination on the genomic landscape.
