http://globalgenomics.com The latest research articles published by Genome Biology 2010-06-25T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ A report on the 23rd annual meeting on 'The Biology of Genomes', 11-15 May 2010, Cold Spring Harbor, USA.Meeting reportRecent advances in high-throughput sequencing technologies have greatly increased the scale and scope of genomics research, and this was evident throughout the recent Biology of Genomes meeting at the Cold Spring Harbor Laboratory. Here we describe some highlights of the meeting. http://globalgenomics.com/2010/11/6/306 Genome Biology 2010, 11:306 2010-06-25T00:00:00Z doi:10.1186/gb-2010-11-6-306 Genome Biology 1465-6906 11 306 2010-06-25T00:00:00Z XML A subset of X-linked genes escapes silencing by X inactivation and is expressed from both X chromosomes in mammalian females. Species-specific differences in the identity of these genes have recently been discovered, suggesting a role in the evolution of sex differences. Chromatin analyses have aimed to discover how genes remain expressed within a repressive environment. http://globalgenomics.com/2010/11/6/213 Genome Biology 2010, 11:213 2010-06-24T00:00:00Z doi:10.1186/gb-2010-11-6-213 Genome Biology 1465-6906 11 213 2010-06-24T00:00:00Z XML Background: Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non-mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologues of chicken, zebra finch, a lizard and three mammalian species. Results: We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton. Conclusions: Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between omega and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes. http://globalgenomics.com/2010/11/6/R68 Kiwoong Nam Carina Mugal Benoit Nabholz Holger Schielzeth Jochen Wolf Niclas Backstrom Axel Kunstner Christopher Balakrishnan Andreas Heger Chris Ponting David Clayton Hans Ellegren Genome Biology 2010, 11:R68 2010-06-23T00:00:00Z doi:10.1186/gb-2010-11-6-r68 Genome Biology 1465-6906 11 R68 2010-06-23T00:00:00Z PDF Background: The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3. Results: To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3. Conclusions: Integration of heterogeneous genome-wide datasets is key to build accurate transcriptional networks. By such integration, here we provide a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data. http://globalgenomics.com/2010/11/6/R67 Francisco Ferrezuelo Neus Colomina Bruce Futcher Marti Aldea Genome Biology 2010, 11:R67 2010-06-23T00:00:00Z doi:10.1186/gb-2010-11-6-r67 Genome Biology 1465-6906 11 R67 2010-06-23T00:00:00Z PDF Background: Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies are infertile in vivo and in vitro. We have previously shown that sperm from these males, although having grossly malformed heads, were able to fertilize oocytes via intracytoplasmic sperm injection (ICSI) and yield live offspring. However, in continuing ICSI trials we noted a reduced efficiency when cryopreserved sperm were used and with epididymal sperm as compared to testicular sperm. In the present study we tested if NPYq deficiency is associated with sperm DNA damage - a known cause of poor ICSI success. Results: We observed that epididymal sperm from mice with severe NPYq deficiency (i.e. deletion of nine-tenths or the entire NPYq gene complement) are impaired in oocyte activation ability following ICSI and there is an increased incidence of oocyte arrest and paternal chromosome breaks. Comet assays revealed increased DNA damage in both epididymal and testicular sperm from these mice, with epididymal sperm more severely affected. In all mice the level of DNA damage was increased by freezing. Epididymal sperm from mice with severe NPYq deficiencies also suffered from impaired membrane integrity and abnormal chromatin condensation and suboptimal chromatin protamination. It is therefore likely that the increased DNA damage associated with NPYq deficiency is a consequence of disturbed chromatin remodeling. Conclusions: This study provides the first evidence of DNA damage in sperm from mice with NPYq deficiencies and indicates that NPYq-encoded genes may play a role in processes regulating chromatin remodeling and thus in maintaining DNA integrity in sperm. http://globalgenomics.com/2010/11/6/R66 Yasuhiro Yamauchi Jonathan Riel Zoia Stoytcheva Paul Burgoyne Monika Ward Genome Biology 2010, 11:R66 2010-06-23T00:00:00Z doi:10.1186/gb-2010-11-6-r66 Genome Biology 1465-6906 11 R66 2010-06-23T00:00:00Z PDF Background: Hemiascomycetous yeasts have intron-poor genomes with very few cases of alternative splicing. Most of the reported examples result from intron retention in Saccharomyces cerevisiae and some have been shown to be functionally significant. Here we used transcriptome-wide approaches to evaluate the mechanisms underlying the generation of alternative transcripts in Yarrowia lipolytica, a yeast highly divergent from S. cerevisiae. Results: Experimental investigation of Y. lipolytica gene models identified several cases of alternative splicing, mostly generated by intron retention, principally affecting the first intron of the gene. The retention of introns almost invariably creates a premature termination codon, as a direct consequence of the structure of intron boundaries. An analysis of Y. lipolytica introns revealed that introns of multiples of three nucleotides in length, particularly those without stop codons, were underrepresented. In other organisms, premature termination codon-containing transcripts are targeted for degradation by the nonsense-mediated mRNA decay (NMD) machinery. In Y. lipolytica, homologs of Saccharomyces cerevisiae UPF1 and UPF2 genes were identified, but not UPF3. The inactivation of Y. lipolytica UPF1 and UPF2 resulted in the accumulation of unspliced transcripts of a test set of genes. Conclusions: Y. lipolytica is the hemiascomycete with the most intron-rich genome sequenced to date, and it has several unusual genes with large introns or alternative transcription start sites, or introns in the 5'UTR. Our results suggest Y. lipolytica intron structure is subject to significant constraints, leading to the under-representation of stop-free introns. Consequently, intron-containing transcripts are degraded by a functional NMD pathway. http://globalgenomics.com/2010/11/6/R65 Meryem Mekouar Isabelle Blanc-Lenfle Christophe Ozanne Corinne Da Silva Corinne Cruaud Patrick Wincker Claude Gaillardin Cecile Neuveglise Genome Biology 2010, 11:R65 2010-06-23T00:00:00Z doi:10.1186/gb-2010-11-6-r65 Genome Biology 1465-6906 11 R65 2010-06-23T00:00:00Z PDF Background: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21. Results: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, thirty-two human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass-spectroscopy analysis. Conclusions: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders. http://globalgenomics.com/2010/11/6/R64 Rossella De Cegli Antonio Romito Simona Iacobacci Lei Mao Mario Lauria Anthony Fedele Joachim Klose Christelle Borel Patrick Descombes Stylianos Antonarakis Diego di Bernardo Sandro Banfi Andrea Ballabio Gilda Cobellis Genome Biology 2010, 11:R64 2010-06-22T00:00:00Z doi:10.1186/gb-2010-11-6-r64 Genome Biology 1465-6906 11 R64 2010-06-22T00:00:00Z PDF The canonical processing of precursor microRNAs requires the endonuclease Dicer. A recent study shows that microRNAs can be processed independently of Dicer but instead require Argonaute 2. http://globalgenomics.com/2010/11/6/123 Genome Biology 2010, 11:123 2010-06-21T00:00:00Z doi:10.1186/gb-2010-11-6-123 Genome Biology 1465-6906 11 123 2010-06-21T00:00:00Z XML Background: In mammals, the dynamics of DNA methylation, in particular the regulated, active removal of cytosine methylation has remained a mystery, partly due to the lack of appropriate model systems to study DNA demethylation. Previous work has largely focused on proliferating cell types that are mitotically arrested using pharmacological inhibitors to distinguish between active and passive mechanisms of DNA demethylation. Results: We explored this epigenetic phenomenon in a natural setting of post-mitotic cells: the differentiation of human peripheral blood monocytes into macrophages or dendritic cells, which proceeds without cell division. Using a global, comparative CpG methylation profiling approach we identified many novel examples of active DNA demethylation and characterised accompanying transcriptional and epigenetic events at these sites during monocytic differentiation. We show that active DNA demethylation is not restricted to proximal promoters and that the time-course of demethylation varies for individual CpGs. Irrespective of their location, the removal of methylated cytosines always coincided with the appearance of activating histone marks. Conclusions: Demethylation events are highly reproducible in monocyte-derived dendritic cells from different individuals. Our data suggest that active DNA demethylation is a precisely targeted event that parallels or follows the modification of histones, but is not necessarily coupled to alterations in transcriptional activity. http://globalgenomics.com/2010/11/6/R63 Maja Klug Sven Heinz Claudia Gebhard Lucia Schwarzfischer Stefan Krause Reinhard Andreesen Michael Rehli Genome Biology 2010, 11:R63 2010-06-18T00:00:00Z doi:10.1186/gb-2010-11-6-r63 Genome Biology 1465-6906 11 R63 2010-06-18T00:00:00Z PDF We have developed a solution-based method for targeted DNA capture-sequencing that is directed to the complete human exome. Using this approach allows the discovery of greater than 95% of all expected heterozygous singe base variants, requires as little as 3Gbp of raw sequence data and constitutes an effective tool for identifying rare coding alleles in large scale genomic studies. http://globalgenomics.com/2010/11/6/R62 Matthew Bainbridge Min Wang Daniel Burgess Christie Kovar Matthew Rodesch Mark D'Ascenzo Jacob Kitzman Yuan-Qing Wu Irene Newsham Todd Richmond Jeffrey Jedeloh Donna Muzny Thomas Albert Richard Gibbs Genome Biology 2010, 11:R62 2010-06-17T00:00:00Z doi:10.1186/gb-2010-11-6-r62 Genome Biology 1465-6906 11 R62 2010-06-17T00:00:00Z PDF