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• W2026559287 abstract "Vulnerability to abused drugs is influenced by multiple genes unique to each drug and to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly, this implies the action of a common group of genes. Simultaneous analysis of multiple responses to multiple drugs has been attempted infrequently. We performed multivariate analyses of published strain responses to four drugs. Genetic similarity in responses did not simply track pharmacological class. Withdrawal severity and preference for ethanol and diazepam were affected by many genes in common, although inversely. We focused on behavioral responses, but there is a growing archival database of physiological, pharmacological and biochemical strain traits. The genomics community is increasingly focusing on single-nucleotide polymorphism and haplotype-based gene mapping approaches, for which inbred strain data are also useful. Thus, similar analyses should be applicable to other laboratories, traits and genotypes. Vulnerability to abused drugs is influenced by multiple genes unique to each drug and to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly, this implies the action of a common group of genes. Simultaneous analysis of multiple responses to multiple drugs has been attempted infrequently. We performed multivariate analyses of published strain responses to four drugs. Genetic similarity in responses did not simply track pharmacological class. Withdrawal severity and preference for ethanol and diazepam were affected by many genes in common, although inversely. We focused on behavioral responses, but there is a growing archival database of physiological, pharmacological and biochemical strain traits. The genomics community is increasingly focusing on single-nucleotide polymorphism and haplotype-based gene mapping approaches, for which inbred strain data are also useful. Thus, similar analyses should be applicable to other laboratories, traits and genotypes. alternative forms of a gene at a specific locus on a chromosome. a type of multivariate analysis that groups variables based on their similarity to one another in terms of individual (strain) differences on each variable. The groupings are achieved through a hierarchical, iterative process and the results are displayed as a branching tree (dendrogram). Cluster analysis is often used to determine the phylogenetic similarity of receptor subtypes, for example. second filial generation, generated by crossing two inbred strains to obtain an F1 generation that is heterozygous for any gene where the inbreds have a different allele. F1 mice are then crossed to obtain the F2 generation. Individual F2 mice might, therefore, be homozygous or heterozygous, depending on the gene. a bivariate correlation coefficient based on genetic covariance rather than phenotypic covariance. This statistic can be estimated by the Pearson correlation between two traits based on inbred strain means (genetic correlation) rather than individual mice (phenotypic correlation). the genetic constitutions of organisms. For each gene, an individual might be a homozygote (i.e. it possess two identical alleles) or a heterozygote (i.e. it possess two different alleles). Inbred strains (see later) are obligate homozygotes at each gene locus. a set of closely linked alleles that tend to be inherited as a unit. Variation in haplotypes rather than in individual alleles are often used as the object of genetic studies seeking association (or linkage) of particular forms of a gene with a disease. at each gene, all members of an inbred strain possess the same two identical alleles. All same-sex members of an inbred strain are, therefore, genetically identical. Inbred strains are typically produced by >20 generations of brother–sister matings. a type of multivariate analysis similar to cluster analysis or principal components analysis. Relationships among multiple variables are displayed in a graphic plot resembling a map. Map distance reflects the collective degree of overall similarity among multiple variables based on individual differences (strains in the current case) on each variable. in contrast to statistical analyses that consider a single variable for analysis, or two variables (bivariate), multivariate approaches simultaneously consider variation for more than two variables. The primary goal is to assess higher-order relationships among variables that extend beyond the bivariate case of looking at all possible pairs of variables. any measured traits. Phenotypes in the current paper include drug withdrawal severity and change in body temperature after a given dose of a given drug. a bivariate correlation coefficient based on phenotypic covariance. The general degree of relationship between individuals’ scores on two phenotypes. The underlying covariance used to estimate phenotypic correlations can be partitioned into genetic covariance and environmental covariance (i.e. all that is not genetic). The genetic covariance determines the genetic correlation (see above). a genetic difference of a single nucleotide within a DNA sequence resulting in different alleles within a given population. SNPs are very common (approximately every 1000 bases) and can be used singly, or as part of a haplotype (see above), to track inheritance." @default.
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• W2026559287 date "2008-11-01" @default.
• W2026559287 modified "2023-09-23" @default.
• W2026559287 title "Multivariate analyses reveal common and drug-specific genetic influences on responses to four drugs of abuse" @default.
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• W2026559287 doi "https://doi.org/10.1016/j.tips.2008.07.010" @default.
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