Effects of genome-wide copy number variation on expression in mammalian cells
Richard T. Wang,Sangtae Ahn,Sangtae Ahn,Christopher C. Park,Arshad H. Khan,Kenneth Lange,Desmond J. Smith +6 more
TLDR
Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.Abstract:
There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped cis and trans regulatory loci due to copy number change for essentially all genes using a human-hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs). Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an Xist independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained trans ceQTLs with -log10P > 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements. Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome.read more
Citations
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Dosage compensation can buffer copy-number variation in wild yeast
TL;DR: This work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.
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Genetic Architecture of Resistance to Stripe Rust in a Global Winter Wheat Germplasm Collection
TL;DR: An overview of the diversity of Pst resistance in the NSGC winter wheat germplasm core collection is provided, which can be exploited for diversification of stripe rust resistance in breeding programs.
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Unstable genomes elevate transcriptome dynamics
Joshua B. Stevens,Guo Liu,Batoul Y. Abdallah,Steven D. Horne,Karen J. Ye,Steven W. Bremer,Christine J. Ye,Stephen A. Krawetz,Henry H.Q. Heng +8 more
TL;DR: The karyotype, transcriptome, and transcriptome determined pathways are in constant flux during somatic cellular evolution (particularly during the macroevolutionary phase) and this flux is an inextricable feature of CIN and essential for cancer formation.
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Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.
B. Mesquita,Paula Lopes,Ana Rodrigues,Deolinda Pereira,Mariana Afonso,C. Leal,Rui Henrique,Guro Elisabeth Lind,Guro Elisabeth Lind,Carmen Jerónimo,Ragnhild A. Lothe,Ragnhild A. Lothe,Manuel R. Teixeira +12 more
TL;DR: It is shown for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes.
Journal ArticleDOI
Insights into the regulation of human CNV-miRNAs from the view of their target genes
TL;DR: These analyses of CNV-miRNAs provide new insights into the impact of copy number variations on miRNA-mediated post-transcriptional networks and will help to broaden the current understanding of the molecular basis of human phenotypic diversity.
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