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/ http://genomebiology.com/ The latest articles from Genome Biology (ISSN 1465-6906) published by BioMed Central Background: Because of its polygenic nature, Alzheimer's disease (AD) is believed to be caused not by defects in single genes, but rather by variations in a large number of genes and their complex interactions. A systems biology approach, such as the generation of a network of co-expressed genes and the identification of functional modules and cis-regulatory elements, to extract insights and knowledge from microarray data will lead to a better understanding of complex diseases such as AD. In this study, we perform a series of analyses using co-expression networks, cis-regulatory elements, and functions of co-expressed gene modules, to analyse single-cell gene expression data from normal and AD-affected subjects. Results: We identified six co-expressed gene modules, each of which represented a biological process perturbed in AD. AD-related genes, such as APOE, A2M, PON2 and MAP4, and cardiovascular diseases (CVD)-associated genes, including COMT, CBS and WNK1, all congregated in a single module. Some of the disease-related genes were hub genes while many of them were directly connected to one or more hub genes. Further investigation of this disease-associated module revealed cis-regulatory elements that match to the binding sites of transcription factors involved in AD and CVD. Conclusions: Our results show the extensive links between AD and CVD at the co-expression and co-regulation levels, providing further evidence for the hypothesis that CVD and AD are linked. Our results support the notion that diseases in which the same set of biochemical pathways are affected may tend to co-occur with each other. http://genomebiology.com/2008/9/10/R148 Monika Ray, Jianhua Ruan and Weixiong Zhang Genome Biology 2008, 9:R148 2008-10-08 doi:10.1186/gb-2008-9-10-r148 Genome Biology 1465-6906 9 R148 2008-10-08 Controlled simulations of genome evolution are useful for benchmarking tools. However, many simulators lack extensibility and cannot measure parameters directly from data. These issues are addressed by three new open-source programs: gsimulator (for neutrally-evolving DNA), simgram (for generic structured features) and simgenome (for syntenic genome blocks). Each offers algorithms for parameter measurement and reconstruction of ancestral sequence. All three tools outperform the leading neutral DNA simulator (DAWG) in benchmarks. The programs are available at http://biowiki.org/SimulationTools. http://genomebiology.com/2008/9/10/R147 Avinash Varadarajan, Robert K Bradley and Ian H Holmes Genome Biology 2008, 9:R147 2008-10-08 doi:10.1186/gb-2008-9-10-r147 Genome Biology 1465-6906 9 R147 2008-10-08 Condensin and cohesin are loaded onto yeast chromosomes by a common mechanism at RNA polymerase III transcribed genes. Whereas cohesin translocates from these loading sites to mediate cohesion at secondary locations, condensin remains, bringing distant sites together into clusters. http://genomebiology.com/2008/9/10/236 Marc R Gartenberg and Matthias Merkenschlager Genome Biology 2008, 9:236 2008-10-06 doi:10.1186/gb-2008-9-10-236 Genome Biology 1465-6906 9 236 2008-10-06 Background: Telomeres prevent the ends of eukaryotic chromosomes from being recognised as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harbouring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were subjected to a transcriptomic study. Results: The genome-wide response to uncapped telomeres in yeast cdc13-1 strains, which have telomere capping defects at temperatures above ~27oC, was determined. Telomere uncapping in cdc13-1 strains is associated with the differential expression of over 600 transcripts. Transcripts affecting responses to DNA damage and diverse environmental stresses were statistically over-represented. BNA2, required for the biosynthesis of NAD+, is highly and significantly up-regulated upon telomere uncapping in cdc13-1 strains. We find that deletion of BNA2 and NPT1, which is also involved in NAD+ synthesis, suppresses the temperature sensitivity of cdc13-1 strains, indicating that NAD+ metabolism may be linked to telomere end protection. Conclusion: Our data support the hypothesis that the response to telomere uncapping is related to but distinct from the response to non-telomeric double strand breaks. The induction of environmental stress responses may be a conserved feature of the eukaryotic response to telomere damage. BNA2 which is involved in NAD+ synthesis plays previously unidentified roles in the cellular response to telomere uncapping. http://genomebiology.com/2008/9/10/R146 Amanda Greenall, Guiyuan Lei, Daniel C Swan, Katherine James, Liming Wang, Heiko Peters, Anil Wipat, Darren J Wilkinson and David Lydall Genome Biology 2008, 9:R146 2008-10-01 doi:10.1186/gb-2008-9-10-r146 Genome Biology 1465-6906 9 R146 2008-10-01 Background: The pax2/5/8 genes belonging to the PAX family of transcription factors are key developmental regulators that are involved in the patterning of various embryonic tissues. More particularly, their function in inner ear specification has been widely described. However, little is known about the direct downstream targets and so far, no global approaches have been performed to identify these target genes in this particular tissue. Results: Here we present an original bioinformatics pipeline composed of comparative genomics, database querying and text mining tools, which is designed to rapidly and specifically discover PAX2/5/8 direct downstream targets involved in inner ear development. We provide evidence supported by experimental validation in medaka fish that brain 2 (POU domain, class 3, transcription factor 2), claudin-7, secretory pathway component sec31-like and meteorin-like precursor are novel direct downstream targets of PAX2/5/8. Conclusion: This study illustrates the power of extensive mining of public data repositories using bioinformatics methods to provide answers for a specific biological question. It furthermore demonstrates how the usage of such a combinatorial approach is advantageous for the biologist in terms of experimentation time and costs. http://genomebiology.com/2008/9/10/R145 Mirana Ramialison, Baubak Bajoghli, Narges Aghaallaei, Laurence Ettwiller, Sylvain Gaudan, Beate Wittbrodt, Thomas Czerny and Joachim Wittbrodt Genome Biology 2008, 9:R145 2008-10-01 doi:10.1186/gb-2008-9-10-r145 Genome Biology 1465-6906 9 R145 2008-10-01 Background: Reversible phosphorylation of proteins is involved in a wide range of processes ranging from signaling cascades to the regulation of protein complex assembly. Little is known about the structure and evolution of phosphorylation networks. Recent high-throughput phosphoproteomics studies have resulted in the rapid accumulation of phosphopeptide datasets for many model organisms. We here exploit these novel data for the comparative analysis of phosphorylation events between difference species of eukaryotes. Results: Comparison of phosphoproteomics datasets of six eukaryotes yields an overlap ranging from approximately 700 sites for human and mouse (two large datasets of closely related species) to a single site for fish and yeast (distantly related as well as two of the smallest datasets). Some conserved events seem surprisingly old: those shared by plant and animals suggests conservation over a billion years time-scale. In spite of the hypothesized incomprehensive nature of phosphoproteomics datasets and differences in experimental procedures, we show that the overlap between phosphoproteomes is larger than expected by chance and indicates increased functional relevance. Despite the dynamic nature of the evolution of phosphorylation, the relative overlap between the different datasets is identical to the phylogeny of the species studied. Conclusions: This analysis provides a framework for the generation of biological insights by the comparative analysis of high-throughput phosphoproteomics datasets. We expect the rapidly growing amount of data from high-throughput mass spectrometry analysis to make comparative phosphoproteomics a powerful tool for understanding the evolutionary and functional dynamics of reversible phosphorylation. http://genomebiology.com/2008/9/10/R144 Jos Boekhorst, Bas van Breukelen, Albert JR Heck and Berend Snel Genome Biology 2008, 9:R144 2008-10-01 doi:10.1186/gb-2008-9-10-r144 Genome Biology 1465-6906 9 R144 2008-10-01 A report of the Biochemical Society meeting 'The Molecular Biology of Archaea', St Andrews, UK, 19-21 August 2008. http://genomebiology.com/2008/9/9/321 Andrew T Large and Peter A Lund Genome Biology 2008, 9:321 2008-09-30 doi:10.1186/gb-2008-9-9-321 Genome Biology 1465-6906 9 321 2008-09-30 In the current financial crisis, the house-price 'bubble' has burst with spectacular effects. Big science projects in biology may be on their way to becoming the next scientific bubble. http://genomebiology.com/2008/9/9/110 Gregory A Petsko Genome Biology 2008, 9:110 2008-09-29 doi:10.1186/gb-2008-9-9-110 Genome Biology 1465-6906 9 110 2008-09-29 Background: Defensins, small endogenous peptides with antimicrobial activity, are a pivotal components of innate immune response. A large cluster of defensin genes is located on human chromosome 8p and among them, the beta defensin 1 (DEFB1) promoter has been deeply studied since specific polymorphisms and haplotypes associate with asthma and atopy, susceptibility to severe sepsis, as well as HIV and Candida infection predisposition. Results: Here, we characterize the sequence variation and haplotype structure of the DEFB1 promoter region in 6 human populations. In all of them, we observed high levels of nucleotide variation, an excess of intermediate-frequency alleles, reduced population differentiation and a genealogy with common haplotypes separated by deep branches. Indeed a significant departure from the expectation of evolutionary neutrality was observed in all populations and the possibility that this is due to demographic history alone was ruled out. Also, we verified that the selection signature is restricted to the promoter region and not due to a linked balanced polymorphism. A phylogeny-based estimation indicated that the two major haplotype clades separated around 4.5 million years ago, approximately the time when the human and chimpanzee lineages split. Conclusions: Altogether these features represent strong molecular signatures of long-term balancing selection, a process that is thought to be extremely rare outside MHC genes. Our data indicate that the DEFB1 promoter region carries functional variants and support previous hypotheses whereby alleles predisposing to atopic disorders are widespread in modern societies because they conferred resistance to pathogens in ancient settings. http://genomebiology.com/2008/9/9/R143 Rachele Cagliani, Matteo Fumagalli, Stefania Riva, Uberto Pozzoli, Giacomo P Comi, Giorgia Menozzi, Nereo Bresolin and Manuela Sironi Genome Biology 2008, 9:R143 2008-09-25 doi:10.1186/gb-2008-9-9-r143 Genome Biology 1465-6906 9 R143 2008-09-25 Background: The evolutionary rate of a protein is a basic measure of evolution at the molecular level. Previous studies have shown that genes expressed in the brain have significantly lower evolutionary rates than those expressed in somatic tissues. Results: We study the evolutionary rates of genes expressed in 21 different human brain regions. We find that genes highly expressed in the more recent cortical regions of the brain have lower evolutionary rates than genes highly expressed in sub-cortical regions. This may partially result from the observation that genes which are highly expressed in cortical regions tend to be highly expressed in sub-cortical regions, and thus their evolution faces a richer set of functional constraints. The frequency of mammalian-specific and primate- specific genes is higher in the highly expressed gene sets of sub-cortical brain regions than in those of cortical brain regions. The basic inverse correlation between evolutionary rate and gene expression is significantly stronger in brain vs non-brain tissues, and in cortical vs sub-cortical regions. Extending upon this cortical/sub-cortical trend, this inverse correlation is generally more marked for tissues that are located higher along the cranial vertical axis during development, giving rise to the possibility that these tissues are also more evolutionary recent. Conclusions: We find that (a) cortically-expressed genes are more conserved than sub-cortical ones, and that (b) gene expression levels exert stronger constraints on sequence evolution in cortical vs sub-cortical regions. Taken together, these findings suggest that cortically-expressed genes are under stronger selective pressure than sub-cortically expressed genes. http://genomebiology.com/2008/9/9/R142 Tamir Tuller, Martin Kupiec and Eytan Ruppin Genome Biology 2008, 9:R142 2008-09-23 doi:10.1186/gb-2008-9-9-r142 Genome Biology 1465-6906 9 R142 2008-09-23