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Parallel selection mapping using artificially selected mice reveals body weight control loci (gene expression)

ABSTRACT: Understanding how polygenic traits evolve and respond to selection is a major unsolved problem, because challenges exist for identifying genes underlying a complex trait and understanding how multi-locus selection operates in the genome. Here we used artificial selection experiments to study polygenic response to selection. Inbred strains from seven independent long-term selection experiments in mice for extreme bodyweight (“High” lines weigh 77-42g vs. 40-16g in “Controls” lines), were genotyped at 527,572 SNPs to identify genetic variants controlling bodyweight. We identified 67 high-resolution parallel selected regions (PSRs) where multiple High lines share variants rarely found among the Controls. By comparing allele frequencies in one selection experiment against its unselected control, we found classical selective sweep signatures centered on the PSRs. Multiple lines of evidence support two G protein-coupled receptors GPR133 and Prlhr, as positional candidate genes controlling bodyweight. Artificial selection may mimic natural selection in the wild: compared to control loci, we detected reduced heterozygosity in PSRs in wild populations of unusually large mice on islands. Many PSRs overlap loci associated with human height variation, possibly through evolutionary conservation of functional pathways. Our data suggest that parallel selection on complex traits may evoke parallel responses at many genes involved in diverse but relevant pathways. These samples were used to test the enrichment of certain gene functional categories.

ORGANISM(S): Mus musculus

PROVIDER: GSE36443 | GEO | 2012/06/30

SECONDARY ACCESSION(S): PRJNA155829

REPOSITORIES: GEO

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Project description:Understanding how polygenic traits evolve and respond to selection is a major unsolved problem, because challenges exist for identifying genes underlying a complex trait and understanding how multi-locus selection operates in the genome. Here we used artificial selection experiments to study polygenic response to selection. Inbred strains from seven independent long-term selection experiments in mice for extreme bodyweight (M-bM-^@M-^\HighM-bM-^@M-^] lines weigh 77-42g vs. 40-16g in M-bM-^@M-^\ControlsM-bM-^@M-^] lines), were genotyped at 527,572 SNPs to identify genetic variants controlling bodyweight. We identified 67 high-resolution parallel selected regions (PSRs) where multiple High lines share variants rarely found among the Controls. By comparing allele frequencies in one selection experiment against its unselected control, we found classical selective sweep signatures centered on the PSRs. Multiple lines of evidence support two G protein-coupled receptors GPR133 and Prlhr, as positional candidate genes controlling bodyweight. Artificial selection may mimic natural selection in the wild: compared to control loci, we detected reduced heterozygosity in PSRs in wild populations of unusually large mice on islands. Many PSRs overlap loci associated with human height variation, possibly through evolutionary conservation of functional pathways. Our data suggest that parallel selection on complex traits may evoke parallel responses at many genes involved in diverse but relevant pathways. These samples were used to test the enrichment of certain gene functional categories. Mouse tissue samples (muscle and liver) were collected from 44 and 45 days old males from each of the nine out of thirteen lines (5 High lines: BEHi, DUHi, EDHi, MUHi, ROHi and 4 Control lines: BELi, EDLi, MULi and ROLi; n=23 total) at the University of Edinburgh. Frozen tissue samples were stored at -80M-BM-:C until use. Tissues were dissociated using TissueLyser II with steel beads (both Qiagen) following manufacturersM-bM-^@M-^Y instructions. mRNA was extracted and purified using TRIzol Reagent and the PureLink RNA Mini Kit (Life Technologies GmbH, Darmstadt, Germany). cDNA was synthesized using Maxima First Strand cDNA synthesis kit (Thermo Fisher Scientific, St. Leon-Rot, Germany). Muscle and liver cDNA samples were hybridized on a Mouse GE 4x44k Microarray (Agilent Technologies, Inc., Waldbronn, Germany) according to manufacturerM-bM-^@M-^Ys recommendations. Three technical replicate each was done on pooled cDNA samples from each mouse line.

Project description:A study evaluating the effect of stress resistance selection of Drosophila melanogaster. Abstract Here, we report a detailed analysis of changes in gene expression in Drosophila melanogaster selected for multiple eological relevant environmental stress resistance traits. We analyzed females from three biological replicates from seven selection regimes and one control regime using whole genome gene expression arrays. Replicated selection lines were selected for resistance to acute heat survival, high temperature knock down, constant 30°C during development, cold shock survival, desiccation and starvation, respectively. Additionally, a set of replicated lines was selected for increased longevity. When compared to gene expression profiles of control lines, we were able to detect consistent selection responses at the transcript level in each specific selection regime and also found a group of differentially expressed genes that were generally changed among all selected lines. Replicated selection lines clustered together, i.e. showed similar changes in gene expression (compared to controls) and thus showed that 10 generations of artificial selection gives a clear signal among gene expression profiles. The changes in gene expression in lines selected for increased longevity, desiccation and starvation resistance, respectively, showed high similarities. Cold resistance selected lines showed little differentiation from controls. Different methods of heat selection (heat survival, heat knock down and constant 30°C) showed little similarity verifying that different mechanism are involved in high temperature adaptation. The direction of change in gene expression in the selected lines showed a consistent pattern for each selection regime. For most selection regimes and in the comparison of all selected lines and controls exclusively up- or down regulation of gene expression among significant differentially expressed genes was found. The different responses to selection expressed in individual selection regimes and among all selected lines indicate that we have identified genes involved in stress specific and general stress response mechanisms. Keywords: control versus selected

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Parallel selection mapping using artificially selected mice reveals body weight control loci (gene expression)

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