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Open AccessJournal ArticleDOI

Genetic compensation: A phenomenon in search of mechanisms.

TLDR
This review revisits studies reporting genetic compensation in higher eukaryotes and outlines possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.
Abstract
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.

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Reciprocal abrogation of PKM isoforms: contradictory outcomes and differing impact of splicing signal on CRISPR/Cas9 mediates gene editing in keratinocytes

TL;DR: Here, CRISPR/Cas9 genome editing of the PKM gene in HaCaT reveals an unexpected mutational bias at the 3'SS of exon 9 whereas no preference for any particular kind of mutation at exon 10 3'splice, thus unveiling an essential role for PKM1 in growth and metabolic balance of Ha CaT keratinocytes.
Posted ContentDOI

Phosphatidylinositol Cycle Disruption is Central to Atypical Hemolytic-Uremic Syndrome Caused by Diacylglycerol Kinase Epsilon Deficiency

TL;DR: This paper applies mass spectrometry lipidomics to two novel models of DGKE deficiency to investigate how this defect impacts the levels of diacylglycerol, PA and related phosphoinositides in endothelia, and shows that the critical abnormality caused by DGke deficiency is not high diacyLglycersol, but rather low PtdIns(4,5)P2.
Posted ContentDOI

Membrane composition influences the conformation and function of the dopamine transporter in vivo

TL;DR: It is found that the lipid environment of the dopamine transporter (DAT) is necessary for mice to respond to amphetamine but not cocaine, because the localization of DAT to cholesterol-rich membranes is required for a DAT conformation that is essential for reverse transport of dopamine.
Posted ContentDOI

ATR16 Syndrome: Mechanisms Linking Monosomy to Phenotype

TL;DR: The degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but also depends on their genetic background, and there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome.
References
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Journal ArticleDOI

Network biology: understanding the cell's functional organization

TL;DR: This work states that rapid advances in network biology indicate that cellular networks are governed by universal laws and offer a new conceptual framework that could potentially revolutionize the view of biology and disease pathologies in the twenty-first century.
Journal ArticleDOI

Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
Journal ArticleDOI

Functional profiling of the Saccharomyces cerevisiae genome.

Guri Giaever, +72 more
- 25 Jul 2002 - 
TL;DR: It is shown that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment, and less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal Growth in four of the tested conditions.
Journal ArticleDOI

Gene Action in the X -chromosome of the Mouse ( Mus musculus L.)

TL;DR: Ohno and Hauschka1 showed that in female mice one chromosome of mammary carcinoma cells and of normal diploid cells of the ovary, mammary gland and liver was heteropyKnotic and suggested that the so-called sex chromatin was composed of one heteropyknotic X-chromosome.
Journal ArticleDOI

The Transcriptional Landscape of the Mammalian Genome

Piero Carninci, +197 more
- 02 Sep 2005 - 
TL;DR: Detailed polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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