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Plos Genetics : Cross-species Array Comparative Genomic Hybridizat...

By: Gregory S. Barsh

Description : Human cancer genomes are highly complex, making it challenging to identify specific drivers of cancer growth, progression, and tumor maintenance. To bypass this obstacle, we have applied array comparative genomic hybridization (array CGH) to zebrafish embryonal rhabdomyosaroma (ERMS) and utilized cross-species comparison to rapidly identify genomic copy number aberrations and novel candidate oncogenes in human disease. Zebrafish ERMS contain small, focal re...

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Plos Genetics : the Flowering Repressor Svp Underlies a Novel Arab...

By: Julin N. Maloof

Description : The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression ...

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Plos Genetics : Informed Conditioning on Clinical Covariates Incre...

By: Peter M. Visscher

Description : Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-contro...

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Plos Genetics : the Status of Dosage Compensation in the Multiple ...

By: Jeannie T. Lee

Description : Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and ‘‘placentals’’) by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW fem...

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Plos Genetics : the Rts1 Regulatory Subunit of Protein Phosphatase...

By: Orna Cohen-fix

Description : The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclindependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell s...

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Plos Genetics : Colon Stem Cell and Crypt Dynamics Exposed by Cell...

By: Marshall S. Horwitz

Description : Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confir...

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Plos Genetics : Phosphorylation of Chromosome Core Components May ...

By: Mary Ann Handel

Description : Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic ...

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Plos Genetics : the Baker’s Yeast Diploid Genome is Remarkably Sta...

By: Sue Jinks-robertson

Description : Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ,20 veget...

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Plos Genetics : Cdc20 is Critical for Meiosis I and Fertility of F...

By: Orna Cohen-fix

Description : Chromosome missegregation in germ cells is an important cause of unexplained infertility, miscarriages, and congenital birth defects in humans. However, the molecular defects that lead to production of aneuploid gametes are largely unknown. Cdc20, the activating subunit of the anaphase-promoting complex/cyclosome (APC/C), initiates sister-chromatid separation by ordering the destruction of two key anaphase inhibitors, cyclin B1 and securin, at the transitio...

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Plos Genetics : Mechanistic Insight Into the Pathology of Polyalan...

By: Sally Camper

Description : Polyalanine expansions in transcription factors have been associated with eight distinct congenital human diseases. It is thought that in each case the polyalanine expansion causes misfolding of the protein that abrogates protein function. Misfolded proteins form aggregates when expressed in vitro: however, it is less clear whether aggregation is of relevance to these diseases in vivo. To investigate this issue, we used targeted mutagenesis of embryonic ste...

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Plos Genetics : Common Inherited Variation in Mitochondrial Genes ...

By: Peter M. Visscher

Description : Mitochondrial dysfunction has been observed in skeletal muscle of people with diabetes and insulin-resistant individuals. Furthermore, inherited mutations in mitochondrial DNA can cause a rare form of diabetes. However, it is unclear whether mitochondrial dysfunction is a primary cause of the common form of diabetes. To date, common genetic variants robustly associated with type 2 diabetes (T2D) are not known to affect mitochondrial function. One possibilit...

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Plos Genetics : Human Imprinted Chromosomal Regions Are Historical...

By: Trudy MacKay

Description : Human recombination rates vary along the chromosomes as well as between the two sexes. There is growing evidence that epigenetic factors may have an important influence on recombination rates, as well as on crossover position. Using both public database analysis and wet-bench approaches, we revisited the relationship between increased rates of meiotic recombination and genome imprinting. We constructed metric linkage disequilibrium (LD) maps for all human c...

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Plos Genetics : Pseudo–messenger Rna ; Phantoms of the Transcripto...

By: Judith Blake

Description : The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo–messenger RNA to be RNA molecules that resemble protein-coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo–messenger RNAs (approximately half of which are transposonassociate...

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Plos Genetics : Accumulation of Rhodopsin in Late Endosomes Trigge...

By: Norbert Perrimon

Description : Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show tha...

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Plos Genetics : Identification of Neural Crest and Glial Enhancers...

By: Gregory S. Barsh

Description : Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest–derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, ...

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Plos Genetics : Mechanisms Underlying Hypoxia Tolerance in Drosoph...

By: Eric Rulifson

Description : Hypoxia-induced cell injury has been related to multiple pathological conditions. In order to render hypoxia-sensitive cells and tissues resistant to low O2 environment, in this current study, we used Drosophila melanogaster as a model to dissect the mechanisms underlying hypoxia-tolerance. A D. melanogaster strain that lives perpetually in an extremely low-oxygen environment (4% O2, an oxygen level that is equivalent to that over about 4,000 m above Mt. Ev...

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Plos Genetics : Meta-analysis of Genome-wide Scans for Total Body ...

By: Greg Gibson

Description : To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1610211 observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located 6500 kb from rs917727 in 11,052 additional individuals from five in...

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Plos Genetics : Rapid Assessment of Genetic Ancestry in Population...

By: Bruce Walsh

Description : As we move forward from the current generation of genome-wide association (GWA) studies, additional cohorts of different ancestries will be studied to increase power, fine map association signals, and generalize association results to additional populations. Knowledge of genetic ancestry as well as population substructure will become increasingly important for GWA studies in populations of unknown ancestry. Here we propose genotyping pooled DNA samples usin...

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Plos Genetics : the Essential Function of B. Subtilis Rnase III is...

By: Patrick H. Viollier

Description : RNase III–related enzymes play key roles in cleaving double-stranded RNA in many biological systems. Among the bestknown are RNase III itself, involved in ribosomal RNA maturation and mRNA turnover in bacteria, and Drosha and Dicer, which play critical roles in the production of micro (mi)–RNAs and small interfering (si)–RNAs in eukaryotes. Although RNase III has important cellular functions in bacteria, its gene is generally not essential, with the remarka...

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Plos Genetics : Natural Variation at the Frd3 Mate Transporter Loc...

By: Christian S. Hardtke

Description : Zinc (Zn) is essential for the optimal growth of plants but is toxic if present in excess, so Zn homeostasis needs to be finely tuned. Understanding Zn homeostasis mechanisms in plants will help in the development of innovative approaches for the phytoremediation of Zn-contaminated sites. In this study, Zn tolerance quantitative trait loci (QTL) were identified by analyzing differences in the Bay-0 and Shahdara accessions of Arabidopsis thaliana. Fine-scale...

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