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1762 records returned

ProPhylER: A curated online resource for protein function and structure based on evolutionary constraint analyses [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure are relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The "ProPhylER Interface" displays predictive analyses in sequence space; the "CrystalPainter" maps evolutionary constrai...
Source: Genome Research - November 19, 2009 Category: Genetics & Stem Cells Authors: Binkley, J., Karra, K., Kirby, A., Hosobuchi, M., Stone, E. A., Sidow, A. Tags: RESOURCES Source Type: journals

Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethy...
Source: Genome Research - November 19, 2009 Category: Genetics & Stem Cells Authors: Fei, T., Xia, K., Li, Z., Zhou, B., Zhu, S., Chen, H., Zhang, J., Chen, Z., Xiao, H., Han, J.-D. J., Chen, Y.-G. Tags: LETTERS Source Type: journals

An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methioni...
Source: Genome Research - November 19, 2009 Category: Genetics & Stem Cells Authors: Liu, H.-H., Lu, P., Guo, Y., Farrell, E., Zhang, X., Zheng, M., Bosano, B., Zhang, Z., Allard, J., Liao, G., Fu, S., Chen, J., Dolim, K., Kuroda, A., Usuka, J., Cheng, J., Tao, W., Welch, K., Liu, Y., Pease, J., de Keczer, S. A., Masjedizadeh, M., Hu, J.- Tags: LETTERS Source Type: journals

Genome-wide mapping of alternative splicing in Arabidopsis thaliana [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alternative splicing can enhance transcriptome plasticity and proteome diversity. In plants, alternative splicing can be manifested at different developmental stages, and is frequently associated with specific tissue types or environmental conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at single-base resolution using the Illumina platform for ultrahigh-throughput RNA sequencing (RNA-seq). Deep transcriptome sequencing confirmed a majority of annotated introns and identified thousands of novel alternatively spliced mRNA isoforms. Our analysis suggests that at least ~42% of intron-containing genes...
Source: Genome Research - November 18, 2009 Category: Genetics & Stem Cells Authors: Filichkin, S. A., Priest, H. D., Givan, S. A., Shen, R., Bryant, D. W., Fox, S. E., Wong, W.-K., Mockler, T. C. Tags: LETTERS Source Type: journals

Inferring tumor progression from genomic heterogeneity [METHODS AND RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). B...
Source: Genome Research - November 10, 2009 Category: Genetics & Stem Cells Authors: Navin, N., Krasnitz, A., Rodgers, L., Cook, K., Meth, J., Kendall, J., Riggs, M., Eberling, Y., Troge, J., Grubor, V., Levy, D., Lundin, P., Maner, S., Zetterberg, A., Hicks, J., Wigler, M. Tags: METHODS AND RESOURCES Source Type: journals

Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Whereas most nontyphoidal Salmonella (NTS) are associated with gastroenteritis, there has been a dramatic increase in reports of NTS-associated invasive disease in sub-Saharan Africa. Salmonella enterica serovar Typhimurium isolates are responsible for a significant proportion of the reported invasive NTS in this region. Multilocus sequence analysis of invasive S. Typhimurium from Malawi and Kenya identified a dominant type, designated ST313, which currently is rarely reported outside of Africa. Whole-genome sequencing of a multiple drug resistant (MDR) ST313 NTS isolate, D23580, identified a distinct prophage repertoire a...
Source: Genome Research - November 9, 2009 Category: Genetics & Stem Cells Authors: Kingsley, R. A., Msefula, C. L., Thomson, N. R., Kariuki, S., Holt, K. E., Gordon, M. A., Harris, D., Clarke, L., Whitehead, S., Sangal, V., Marsh, K., Achtman, M., Molyneux, M. E., Cormican, M., Parkhill, J., MacLennan, C. A., Heyderman, R. S., Dougan, G Tags: LETTERS Source Type: journals

Industrial fuel ethanol yeasts contain adaptive copy number changes in genes involved in vitamin B1 and B6 biosynthesis [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fuel ethanol is now a global energy commodity that is competitive with gasoline. Using microarray-based comparative genome hybridization (aCGH), we have determined gene copy number variations (CNVs) common to five industrially important fuel ethanol Saccharomyces cerevisiae strains responsible for the production of billions of gallons of fuel ethanol per year from sugarcane. These strains have significant amplifications of the telomeric SNO and SNZ genes, which are involved in the biosynthesis of vitamins B6 (pyridoxine) and B1 (thiamin). We show that increased copy number of these genes confers the ability to grow more ef...
Source: Genome Research - November 6, 2009 Category: Genetics & Stem Cells Authors: Stambuk, B. U., Dunn, B., Alves, S. L., Duval, E. H., Sherlock, G. Tags: LETTERS Source Type: journals

Predictable dynamic program of timing of DNA replication in human cells [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The organization of mammalian DNA replication is poorly understood. We have produced high-resolution dynamic maps of the timing of replication in human erythroid, mesenchymal, and embryonic stem (ES) cells using TimEX, a method that relies on gaussian convolution of massive, highly redundant determinations of DNA copy-number variations during S phase to produce replication timing profiles. We first obtained timing maps of 3% of the genome using high-density oligonucleotide tiling arrays and then extended the TimEX method genome-wide using massively parallel sequencing. We show that in untransformed human cells, timing of r...
Source: Genome Research - November 5, 2009 Category: Genetics & Stem Cells Authors: Desprat, R., Thierry-Mieg, D., Lailler, N., Lajugie, J., Schildkraut, C., Thierry-Mieg, J., Bouhassira, E. E. Tags: METHODS Source Type: journals

A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains [RESEARCH]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study identifies an ERV-K-type family in rats that shows obvious signs of recent activity. Ongoing retrotranspositional activity may significantly add to genomic variability among inbred rat strains. (Source: Genome Research)
Source: Genome Research - November 3, 2009 Category: Genetics & Stem Cells Authors: Wang, Y., Liska, F., Gosele, C., Sedova, L., Kren, V., Krenova, D., Ivics, Z., Hubner, N., Izsvak, Z. Tags: RESEARCH Source Type: journals

DNA methylation programming and reprogramming in primate embryonic stem cells [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA methylation is an important epigenetic mechanism, affecting normal development and playing a key role in reprogramming epigenomes during stem cell derivation. Here we report on DNA methylation patterns in native monkey embryonic stem cells (ESCs), fibroblasts, and ESCs generated through somatic cell nuclear transfer (SCNT), identifying and comparing epigenome programming and reprogramming. We characterize hundreds of regions that are hyper- or hypomethylated in fibroblasts compared to native ESCs and show that these are conserved in human cells and tissues. Remarkably, the vast majority of these regions are reprogramme...
Source: Genome Research - November 3, 2009 Category: Genetics & Stem Cells Authors: Cohen, N. M., Dighe, V., Landan, G., Reynisdottir, S., Palsson, A., Mitalipov, S., Tanay, A. Tags: LETTERS Source Type: journals

Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation [ARTICLES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The glucocorticoid steroid hormone cortisol is released by the adrenal glands in response to stress and serves as a messenger in circadian rhythms. Transcriptional responses to this hormonal signal are mediated by the glucocorticoid receptor (GR). We determined GR binding throughout the human genome by using chromatin immunoprecipitation followed by next-generation DNA sequencing, and measured related changes in gene expression with mRNA sequencing in response to the glucocorticoid dexamethasone (DEX). We identified 4392 genomic positions occupied by the GR and 234 genes with significant changes in expression in response t...
Source: Genome Research - November 3, 2009 Category: Genetics & Stem Cells Authors: Reddy, T. E., Pauli, F., Sprouse, R. O., Neff, N. F., Newberry, K. M., Garabedian, M. J., Myers, R. M. Tags: ARTICLES Source Type: journals

Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression [ARTICLES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transcription factor GATA1 regulates an extensive program of gene activation and repression during erythroid development. However, the associated mechanisms, including the contributions of distal versus proximal cis-regulatory modules, co-occupancy with other transcription factors, and the effects of histone modifications, are poorly understood. We studied these problems genome-wide in a Gata1 knockout erythroblast cell line that undergoes GATA1-dependent terminal maturation, identifying 2616 GATA1-responsive genes and 15,360 GATA1-occupied DNA segments after restoration of GATA1. Virtually all occupied DNA segments ha...
Source: Genome Research - November 3, 2009 Category: Genetics & Stem Cells Authors: Cheng, Y., Wu, W., Ashok Kumar, S., Yu, D., Deng, W., Tripic, T., King, D. C., Chen, K.-B., Zhang, Y., Drautz, D., Giardine, B., Schuster, S. C., Miller, W., Chiaromonte, F., Zhang, Y., Blobel, G. A., Weiss, M. J., Hardison, R. C. Tags: ARTICLES Source Type: journals

A positive but complex association between meiotic double-strand break hotspots and open chromatin in Saccharomyces cerevisiae [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
During meiosis, chromatin undergoes extensive changes to facilitate recombination, homolog pairing, and chromosome segregation. To investigate the relationship between chromatin organization and meiotic processes, we used formaldehyde-assisted isolation of regulatory elements (FAIRE) to map open chromatin during the transition from mitosis to meiosis in the budding yeast Saccharomyces cerevisiae. We found that meiosis-induced opening of chromatin is associated with meiotic DSB hotpots. The positive association between open chromatin and DSB hotspots is most prominent 3 h into meiosis, when the early meiotic genes DMC1 and ...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Berchowitz, L. E., Hanlon, S. E., Lieb, J. D., Copenhaver, G. P. Tags: LETTERS Source Type: journals

The NIH Human Microbiome Project [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approa...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: The NIH HMP Working Group, Peterson, J., Garges, S., Giovanni, M., McInnes, P., Wang, L., Schloss, J. A., Bonazzi, V., McEwen, J. E., Wetterstrand, K. A., Deal, C., Baker, C. C., Di Francesco, V., Howcroft, T. K., Karp, R. W., Lunsford, R. D., Wellington, Tags: RESOURCES Source Type: journals

Large-scale RACE approach for proactive experimental definition of C. elegans ORFeome [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although a highly accurate sequence of the Caenorhabditis elegans genome has been available for 10 years, the exact transcript structures of many of its protein-coding genes remain unsettled. Approximately two-thirds of the ORFeome has been verified reactively by amplifying and cloning computationally predicted transcript models; still a full third of the ORFeome remains experimentally unverified. To fully identify the protein-coding potential of the worm genome including transcripts that may not satisfy existing heuristics for gene prediction, we developed a computational and experimental platform adapting rapid amplifica...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Salehi-Ashtiani, K., Lin, C., Hao, T., Shen, Y., Szeto, D., Yang, X., Ghamsari, L., Lee, H., Fan, C., Murray, R. R., Milstein, S., Svrzikapa, N., Cusick, M. E., Roth, F. P., Hill, D. E., Vidal, M. Tags: RESOURCES Source Type: journals

A single-base resolution map of an archaeal transcriptome [METHODS AND RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study highlights transcriptome sequencing as a key tool for understanding the mechanisms and extent of RNA-based regulation for bacteria and archaea. (Source: Genome Research)
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Wurtzel, O., Sapra, R., Chen, F., Zhu, Y., Simmons, B. A, Sorek, R. Tags: METHODS AND RESOURCES Source Type: journals

Singapore Genome Variation Project: A haplotype map of three Southeast Asian populations [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human ...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Teo, Y.-Y., Sim, X., Ong, R. T.H., Tan, A. K.S., Chen, J., Tantoso, E., Small, K. S., Ku, C.-S., Lee, E. J.D., Seielstad, M., Chia, K.-S. Tags: RESOURCES Source Type: journals

Windshield splatter analysis with the Galaxy metagenomic pipeline [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we use organic matter collected by a moving vehicle to design and test a comprehensive pipeline for phylogenetic profiling of metagenomic samples that includes all steps from processing and quality control of data generated by next-generation sequencing technologies to statistical analyses and data visualization. To the best of our knowledge, this is also the first publication that features a live online supplement providing access to exact analyses and workflows used in the article. (Source: Genome Research)
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Kosakovsky Pond, S., Wadhawan, S., Chiaromonte, F., Ananda, G., Chung, W.-Y., Taylor, J., Nekrutenko, A., The Galaxy Team Tags: RESOURCES Source Type: journals

mGene: Accurate SVM-based gene finding with an application to nematode genomes [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a highly accurate gene-prediction system for eukaryotic genomes, called mGene. It combines in an unprecedented manner the flexibility of generalized hidden Markov models (gHMMs) with the predictive power of modern machine learning methods, such as Support Vector Machines (SVMs). Its excellent performance was proved in an objective competition based on the genome of the nematode Caenorhabditis elegans. Considering the average of sensitivity and specificity, the developmental version of mGene exhibited the best prediction performance on nucleotide, exon, and transcript level for ab initio and multiple-genome gene-...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Schweikert, G., Zien, A., Zeller, G., Behr, J., Dieterich, C., Ong, C. S., Philips, P., De Bona, F., Hartmann, L., Bohlen, A., Kruger, N., Sonnenburg, S., Ratsch, G. Tags: RESOURCES Source Type: journals

LookSeq: A browser-based viewer for deep sequencing data [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sequencing a genome to great depth can be highly informative about heterogeneity within an individual or a population. Here we address the problem of how to visualize the multiple layers of information contained in deep sequencing data. We propose an interactive AJAX-based web viewer for browsing large data sets of aligned sequence reads. By enabling seamless browsing and fast zooming, the LookSeq program assists the user to assimilate information at different levels of resolution, from an overview of a genomic region to fine details such as heterogeneity within the sample. A specific problem, particularly if the sample is...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Manske, H. M., Kwiatkowski, D. P. Tags: RESOURCES Source Type: journals

Automatic analysis of dividing cells in live cell movies to detect mitotic delays and correlate phenotypes in time [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Live-cell imaging allows detailed dynamic cellular phenotyping for cell biology and, in combination with small molecule or drug libraries, for high-content screening. Fully automated analysis of live cell movies has been hampered by the lack of computational approaches that allow tracking and recognition of individual cell fates over time in a precise manner. Here, we present a fully automated approach to analyze time-lapse movies of dividing cells. Our method dynamically categorizes cells into seven phases of the cell cycle and five aberrant morphological phenotypes over time. It reliably tracks cells and their progeny an...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Harder, N., Mora-Bermudez, F., Godinez, W. J., Wunsche, A., Eils, R., Ellenberg, J., Rohr, K. Tags: METHODS Source Type: journals

An ensemble model of competitive multi-factor binding of the genome [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hundreds of different factors adorn the eukaryotic genome, binding to it in large number. These DNA binding factors (DBFs) include nucleosomes, transcription factors (TFs), and other proteins and protein complexes, such as the origin recognition complex (ORC). DBFs compete with one another for binding along the genome, yet many current models of genome binding do not consider different types of DBFs together simultaneously. Additionally, binding is a stochastic process that results in a continuum of binding probabilities at any position along the genome, but many current models tend to consider positions as being either bi...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Wasson, T., Hartemink, A. J. Tags: METHODS Source Type: journals

Distinguishing direct versus indirect transcription factor-DNA interactions [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transcriptional regulation is largely enacted by transcription factors (TFs) binding DNA. Large numbers of TF binding motifs have been revealed by ChIP-chip experiments followed by computational DNA motif discovery. However, the success of motif discovery algorithms has been limited when applied to sequences bound in vivo (such as those identified by ChIP-chip) because the observed TF–DNA interactions are not necessarily direct: Some TFs predominantly associate with DNA indirectly through protein partners, while others exhibit both direct and indirect binding. Here, we present the first method for distinguishing betw...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Gordan, R., Hartemink, A. J., Bulyk, M. L. Tags: METHODS Source Type: journals

Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS) [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Manipulating the mouse genome is a widespread technology with important applications in many biological fields ranging from cancer research to developmental biology. Likewise, correlations between copy number variations (CNVs) and human diseases are emerging. We have developed the reference-query pyrosequencing (RQPS) method, which is based on quantitative pyrosequencing and uniquely designed probes containing single nucleotide variations (SNVs), to offer a simple and affordable genotyping solution capable of identifying homologous recombinants independent of the homology arm size, determining the micro-amplification statu...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Liu, Z., Obenauf, A. C., Speicher, M. R., Kopan, R. Tags: METHODS Source Type: journals

Rapid inexpensive genome-wide association using pooled whole blood [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome-wide association studies (GWAS) have now successfully identified important genetic variants associated with many human traits and diseases. The high cost of genotyping arrays in large data sets remains the major barrier to wider utilization of GWAS. We have developed a novel method in which whole blood from cases and controls, respectively, is pooled prior to DNA extraction for genotyping. We demonstrate proof of principle by clearly identifying the associated variants for eye color, age-related macular degeneration, and pseudoexfoliation syndrome in cohorts not previously studied. Blood pooling has the potential to...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Craig, J. E., Hewitt, A. W., McMellon, A. E., Henders, A. K., Ma, L., Wallace, L., Sharma, S., Burdon, K. P., Visscher, P. M., Montgomery, G. W., MacGregor, S. Tags: METHODS Source Type: journals

Repertoire and evolution of miRNA genes in four divergent nematode species [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
miRNAs are ~22-nt RNA molecules that play important roles in post-transcriptional regulation. We have performed small RNA sequencing in the nematodes Caenorhabditis elegans, C. briggsae, C. remanei, and Pristionchus pacificus, which have diverged up to 400 million years ago, to establish the repertoire and evolutionary dynamics of miRNAs in these species. In addition to previously known miRNA genes from C. elegans and C. briggsae we demonstrate expression of many of their homologs in C. remanei and P. pacificus, and identified in total more than 100 novel expressed miRNA genes, the majority of which belong to P. pacificus....
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: de Wit, E., Linsen, S. E.V., Cuppen, E., Berezikov, E. Tags: LETTERS Source Type: journals

Profiling the repertoire of phenotypes influenced by environmental cues that occur during asexual reproduction [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe that clones sharing the same morphological features, which arose from the same founder mother, constitute a repertoire of variants with distinct behavioral and physiological traits. Our results suggest that the prevailing environmental conditions influence the recruitment of adaptive phenotypes from a cohort of clonal individuals exhibiting considerable molecular diversity. However, we observed that the variability might be reduced or enhanced by external factors, but is never abolished in accordance with a model of stochastically produced phenotypes. This overall mechanism allows the renewal of colonies from a...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Dombrovsky, A., Arthaud, L., Ledger, T. N., Tares, S., Robichon, A. Tags: LETTERS Source Type: journals

Deeply conserved chordate noncoding sequences preserve genome synteny but do not drive gene duplicate retention [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Animal genomes possess highly conserved cis-regulatory sequences that are often found near genes that regulate transcription and development. Researchers have proposed that the strong conservation of these sequences may affect the evolution of the surrounding genome, both by repressing rearrangement, and possibly by promoting duplicate gene retention. Conflicting data, however, have made the validity of these propositions unclear. Here, we use a new computational method to identify phylogenetically conserved noncoding elements (PCNEs) in a manner that is not biased by rearrangement and duplication. This method is powerful ...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Hufton, A. L., Mathia, S., Braun, H., Georgi, U., Lehrach, H., Vingron, M., Poustka, A. J., Panopoulou, G. Tags: LETTERS Source Type: journals

Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
DNA methylation is a vital epigenetic mark that participates in establishing and maintaining chromatin structures and regulates gene transcription during mammalian development and cellular differentiation. Differences in epigenetic patterns between individuals may contribute to phenotypic variation and disease susceptibility; however, little is known about the extent of such variation or how different epigenetic patterns are established. Here we have compared DNA methylation profiles of macrophages from two inbred mouse strains (C57BL/6 and BALB/c) at 181 large genomic intervals that were selected based on differential gen...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Schilling, E., El Chartouni, C., Rehli, M. Tags: LETTERS Source Type: journals

Complex selection on 5' splice sites in intron-rich organisms [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In contrast to the typically streamlined genomes of prokaryotes, many eukaryotic genomes are riddled with long intergenic regions, spliceosomal introns, and repetitive elements. What explains the persistence of these and other seemingly suboptimal structures? There are three general hypotheses: (1) the structures in question are not actually suboptimal but optimal, being favored by selection, for unknown reasons; (2) the structures are not suboptimal, but of (essentially) equal fitness to "optimal" ones; or (3) the structures are truly suboptimal, but selection is too weak to systematically eliminate them. The 5' splice si...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Irimia, M., Roy, S. W., Neafsey, D. E., Abril, J. F., Garcia-Fernandez, J., Koonin, E. V. Tags: LETTERS Source Type: journals

Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
How miRNAs recognize their target sites is a puzzle that many experimental and computational studies aimed to solve. Several features, such as perfect pairing of the miRNA seed, additional pairing in the 3' region of the miRNA, relative position in the 3' UTR, and the A/U content of the environment of the putative site, have been found to be relevant. Here we have used a large number of previously published data sets to assess the power that various sequence and structure features have in distinguishing between putative sites that do and those that do not appear to be functional. We found that although different data sets ...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Hausser, J., Landthaler, M., Jaskiewicz, L., Gaidatzis, D., Zavolan, M. Tags: LETTERS Source Type: journals

5'-Transducing SVA retrotransposon groups spread efficiently throughout the human genome [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
SVA elements represent the youngest family of hominid non-LTR retrotransposons, which alter the human genome continuously. They stand out due to their organization as composite repetitive elements. To draw conclusions on the assembly process that led to the current organization of SVA elements and on their transcriptional regulation, we initiated our study by assessing differences in structures of the 116 SVA elements located on human chromosome 19. We classified SVA elements into seven structural variants, including novel variants like 3'-truncated elements and elements with 5'-flanking sequence transductions. We establis...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Damert, A., Raiz, J., Horn, A. V., Lower, J., Wang, H., Xing, J., Batzer, M. A., Lower, R., Schumann, G. G. Tags: LETTERS Source Type: journals

Exon-trapping mediated by the human retrotransposon SVA [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genome...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Hancks, D. C., Ewing, A. D., Chen, J. E., Tokunaga, K., Kazazian, H. H. Tags: LETTERS Source Type: journals

The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for involvement of low transcription and trimethylation of histone H3 lysine 27 (H3K27me3). Here, we used methylated DNA immunoprecipitation (MeDIP) combined with a CGI oligonucleotide microarray analysis, and identified 5510 and 521 genes with promoter CGIs resistant and susceptible, respectively, to DNA methylation in prostate cancer cell lines. Expression analysis revealed that the susc...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Takeshima, H., Yamashita, S., Shimazu, T., Niwa, T., Ushijima, T. Tags: LETTERS Source Type: journals

Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transcription factors play an important role in orchestrating the activation of specific networks of genes through targeting their proximal promoter and distal enhancer regions. However, it is unclear how the specificity of downstream responses is maintained by individual members of transcription-factor families and, in most cases, what their target repertoire is. We have used ChIP-chip analysis to identify the target genes of the ETS-domain transcription factor ELK1. Two distinct modes of ELK1 target gene selection are identified; the first involves redundant promoter binding with other ETS-domain family members; the seco...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Boros, J., Donaldson, I. J., O'Donnell, A., Odrowaz, Z. A., Zeef, L., Lupien, M., Meyer, C. A., Liu, X. S., Brown, M., Sharrocks, A. D. Tags: LETTERS Source Type: journals

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions o...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Nayak, R. R., Kearns, M., Spielman, R. S., Cheung, V. G. Tags: LETTERS Source Type: journals

Population genomics in a disease targeted primary cell model [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The common genetic variants associated with complex traits typically lie in noncoding DNA and may alter gene regulation in a cell type-specific manner. Consequently, the choice of tissue or cell model in the dissection of disease associations is important. We carried out an expression quantitative trait loci (eQTL) study of primary human osteoblasts (HOb) derived from 95 unrelated donors of Swedish origin, each represented by two independently derived primary lines to provide biological replication. We combined our data with publicly available information from a genome-wide association study (GWAS) of bone mineral density ...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Grundberg, E., Kwan, T., Ge, B., Lam, K. C.L., Koka, V., Kindmark, A., Mallmin, H., Dias, J., Verlaan, D. J., Ouimet, M., Sinnett, D., Rivadeneira, F., Estrada, K., Hofman, A., van Meurs, J. M., Uitterlinden, A., Beaulieu, P., Graziani, A., Harmsen, E., L Tags: LETTERS Source Type: journals

Phylogenomics of primates and their ancestral populations [PERSPECTIVE]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome assemblies are now available for nine primate species, and large-scale sequencing projects are underway or approved for six others. An explicitly evolutionary and phylogenetic approach to comparative genomics, called phylogenomics, will be essential in unlocking the valuable information about evolutionary history and genomic function that is contained within these genomes. However, most phylogenomic analyses so far have ignored the effects of variation in ancestral populations on patterns of sequence divergence. These effects can be pronounced in the primates, owing to large ancestral effective population sizes rela...
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Siepel, A. Tags: PERSPECTIVE Source Type: journals

Every genome sequence needs a good map [COMMENTARY]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Genome Research)
Source: Genome Research - November 2, 2009 Category: Genetics & Stem Cells Authors: Lewin, H. A., Larkin, D. M., Pontius, J., O'Brien, S. J. Tags: COMMENTARY Source Type: journals

Do genetic recombination and gene density shape the pattern of DNA elimination in rice long terminal repeat retrotransposons? [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In flowering plants, the accumulation of small deletions through unequal homologous recombination (UR) and illegitimate recombination (IR) is proposed to be the major process counteracting genome expansion, which is caused primarily by the periodic amplification of long terminal repeat retrotransposons (LTR-RTs). However, the full suite of evolutionary forces that govern the gain or loss of transposable elements (TEs) and their distribution within a genome remains unclear. Here, we investigated the distribution and structural variation of LTR-RTs in relation to the rates of local genetic recombination (GR) and gene densiti...
Source: Genome Research - October 28, 2009 Category: Genetics & Stem Cells Authors: Tian, Z., Rizzon, C., Du, J., Zhu, L., Bennetzen, J. L., Jackson, S. A., Gaut, B. S., Ma, J. Tags: LETTERS Source Type: journals

The completion of the Mammalian Gene Collection (MGC) [RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transc...
Source: Genome Research - October 28, 2009 Category: Genetics & Stem Cells Authors: The MGC Project Team, Temple, G., Gerhard, D. S., Rasooly, R., Feingold, E. A., Good, P. J., Robinson, C., Mandich, A., Derge, J. G., Lewis, J., Shoaf, D., Collins, F. S., Jang, W., Wagner, L., Shenmen, C. M., Misquitta, L., Schaefer, C. F., Buetow, K. H. Tags: RESOURCES Source Type: journals

Human capacitance to dosage imbalance: Coping with inefficient selection [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proteins rely on associations to improve packing quality and thus maintain structural integrity. This makes packing deficiency a likely determinant of dosage sensitivity, that is, of the fitness impact of concentration imbalances relative to the stoichiometry of the protein complexes. This hypothesis was validated by examining evolution-related dosage imbalances: Duplicates of genes encoding for deficiently packed proteins are less likely to be retained than genes coding for well-packed proteins. This selection pressure is apparent in unicellular organisms, but is mitigated in higher eukaryotes. In human, this effect revea...
Source: Genome Research - October 28, 2009 Category: Genetics & Stem Cells Authors: Fernandez, A., Chen, J. Tags: LETTERS Source Type: journals

Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 spec...
Source: Genome Research - October 27, 2009 Category: Genetics & Stem Cells Authors: Jackson, A. P., Gamble, J. A., Yeomans, T., Moran, G. P., Saunders, D., Harris, D., Aslett, M., Barrell, J. F., Butler, G., Citiulo, F., Coleman, D. C., de Groot, P. W.J., Goodwin, T. J., Quail, M. A., McQuillan, J., Munro, C. A., Pain, A., Poulter, R. T. Tags: LETTERS Source Type: journals

A novel strategy of transcription regulation by intra-genic nucleosome ordering [RESEARCH]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Numerous studies of chromatin structure showed that nucleosome free regions (NFRs) located at 5' gene ends contribute to transcription initiation regulation. Here, we determine the role of intragenic chromatin structure on gene expression regulation. We show that, along S. cerevisiae genes, nucleosomes are highly organized following two types of architecture that depend only on the distance between the NFRs located at the 5' and 3' gene ends. In the first type, this distance constraints in vivo the positioning of n nucleosomes regularly organized in a "crystal-like" array. In the second type, this distance is such that the...
Source: Genome Research - October 26, 2009 Category: Genetics & Stem Cells Authors: Vaillant, C., Palmeira, L., Chevereau, G., Audit, B., d'Aubenton-Carafa, Y., Thermes, C., Arneodo, A. Tags: RESEARCH Source Type: journals

Detection of non-neutral substitution rates on mammalian phylogenies [METHODS AND RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Methods for detecting nucleotide substitution rates that are faster or slower than expected under neutral drift are widely used to identify candidate functional elements in genomic sequences. However, most existing methods consider either reductions (conservation) or increases (acceleration) in rate but not both, or assume selection acts uniformly across the branches of a phylogeny. Here we examine the more general problem of detecting departures from the neutral rate of substitution in either direction, possibly in a clade-specific manner. We consider four statistical, phylogenetic tests for addressing this problem: a lik...
Source: Genome Research - October 26, 2009 Category: Genetics & Stem Cells Authors: Pollard, K., Hubisz, M., Siepel, A. Tags: METHODS AND RESOURCES Source Type: journals

Genome-wide mapping of alternative splicing in Arabidopsis thaliana [RESEARCH]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alternative splicing (AS) can enhance transcriptome plasticity and proteome diversity. In plants, alternative splicing can be manifested at different developmental stages, and is frequently associated with specific tissue types or environmental conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at single-base resolution using the Illumina platform for ultra-high-throughput RNA sequencing (RNA-seq). Deep transcriptome sequencing confirmed a majority of annotated introns and identified thousands of novel alternatively spliced mRNA isoforms. Our analysis suggests that at least ~42% of intron-containing...
Source: Genome Research - October 26, 2009 Category: Genetics & Stem Cells Authors: Filichkin, S. A., Priest, H. D., Givan, S. A., Shen, R., Bryant, D. W., Fox, S. E., Wong, W.-K., Mockler, T. C Tags: RESEARCH Source Type: journals

Two-parameter characterization of chromosome-scale recombination rate [METHODS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The genome-wide recombination rate (RR) of a species is often described by one parameter, the ratio between total genetic map length (G) and physical map length (P), measured in centimorgans per megabase (cM/Mb). The value of this parameter varies greatly between species, but the cause for these differences is not entirely clear. A constraining factor of overall RR in a species, which may cause increased RR for smaller chromosomes, is the requirement of at least one chiasma per chromosome (or chromosome arm) per meiosis. In the present study, we quantify the relative excess of recombination events on smaller chromosomes by...
Source: Genome Research - October 26, 2009 Category: Genetics & Stem Cells Authors: Li, W., Freudenberg, J. Tags: METHODS Source Type: journals

ProPhylER: A Curated Online Resource for Protein Function and Structure Based on Evolutionary Constraint Analyses [METHODS AND RESOURCES]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure is relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9,000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The ProPhylER Interface displays predictive analyses in sequence space; the CrystalPainter maps evolutionary constraints ...
Source: Genome Research - October 21, 2009 Category: Genetics & Stem Cells Authors: Binkley, J., Karra, K., Kirby, A., Hosobuchi, M., Stone, E. A, Sidow, A. Tags: METHODS AND RESOURCES Source Type: journals

High-resolution nucleosome mapping reveals transcription-dependent promoter packaging [methods and resources]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome-wide mapping of nucleosomes has revealed a great deal about the relationships between chromatin structure and control of gene expression, and has lead to mechanistic hypotheses regarding the rules by which chromatin structure is established. High-throughput sequencing has recently become the technology of choice for chromatin mapping studies, yet analysis of these experiments is still in its infancy. Here, we introduce a model for calling nucleosome positions from deep sequencing maps of chromatin structure and apply it to maps from S. cerevisiae. We analyze digestion series where nucleosomes are isolated from under...
Source: Genome Research - October 21, 2009 Category: Genetics & Stem Cells Authors: Weiner, A., Hughes, A., Yassour, M., Rando, O., Friedman, N. Tags: METHODS AND RESOURCES Source Type: journals

Comparison of diverse developmental transcriptomes reveals that coexpression of gene neighbors is not evolutionarily conserved [LETTERS]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genomic analyses have shown that adjacent genes are often coexpressed. However, it remains unclear whether the observed coexpression is a result of functional organization or a consequence of adjacent active chromatin or transcriptional read-through, which may be free of selective biases. Here, we compare temporal expression profiles of one-to-one orthologs in conserved or divergent genomic positions in two genetically distant nematode species—Caenorhabditis elegans and C. briggsae—that share a near-identical developmental program. We find, for all major patterns of temporal expression, a substantive amount of ...
Source: Genome Research - October 21, 2009 Category: Genetics & Stem Cells Authors: Yanai, I., Hunter, C. P. Tags: LETTERS Source Type: journals