http://precedings.nature.com/subjects/genetics/ Recently posted documents in Genetics & Genomics Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3931/version/1 Synthetic "microDNAs (MIDs)"is a new class of ~ 20-25 nucleotide-long DNAs capable of repressing the activity of the target gene at the level of transcription by mechanisms that have not been clarified yet. However they are designed to target non-coding regions of the cancer causing genes, thus interfering with transcription. The inhibition might be possible through the direct binding of MIDs to cis-regulatory sites and/or to some Transcription Factors (TF) that normally activate transcription. Synthetic MIDs in some ways are similar to the newly discovered microRNAs a mechanism by which cell regulates its genetic activities at post-transcriptional level. Synthetic MIDs can provide a powerful tool to prevent massive production of mRNA by undesired gene activities. Therefore drugs are not required to interact with overwhelming number of mRNA and microRNA copies that may present unwanted side effects. In vitro studies suggest that the inhibition of the target gene starts after the first round of DNA replication, usually 24 hours after treatment depending on cell doubling time. Cell growth suppression maximizes at day 6 or 7 and the inhibition effect is sustained for weeks. We have shown that blocking of both bcl-2 and k-ras transcription by their specific microDNA Inhibitors induced apoptosis in HL60 leukemia cells and B-cell lymphomas. http://precedings.nature.com/documents/3931/version/1 Wed, 04 Nov 2009 10:28:46 UTC MicroDNAs and Transcriptional Regulation hdl:10101/npre.2009.3931.1 2009-11-04 Nature Precedings 2009-11-04T10:28:46Z Manuscript Cancer Genetics & Genomics Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3925/version/1 Sheko is African taurine cattle, valued for its milk yield, adaptation to humid tsetse infested environment and trypanotolerance. We used 30 microsatellite markers in analyzing 30 DNA samples. We found high genetic diversity and no genetic bottlenecks in endangered Sheko cattle. Sheko cattle have not undergone recent genetic bottlenecks, in spite of drastic reduction in its overall demographic population size. The results were supported by three statistical methods: (i) detection of heterozygosity excess (ii) a mode-shift indicator of allele distribution pattern (iii) the ratio of the number of alleles to the range of allele size, M-ratio test. This breed reflects historical and cultural identity of local communities and represents a unique component of the global domestic animal biodiversity that deserve priority for conservation. http://precedings.nature.com/documents/3925/version/1 Tue, 03 Nov 2009 15:15:15 UTC No evidence for a recent genetic bottleneck in the endangered Sheko cattle breed (African Bos taurus) revealed by microsatellite analysis hdl:10101/npre.2009.3925.1 2009-11-03 Markos Tibbo Nature Precedings 2009-11-03T15:15:15Z Manuscript Genetics & Genomics http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3913.1 A new approach to design a dynamic model of genes with multiple autonomous regulatory modules by evolution in silico is proposed. The approach is based on Genetic Algorithms, with new crossover operators especially designed for these purposes. The approach exploits the subbasin-portal architecture of the fitness functions suitable for this kind of evolutionary modeling. The effectiveness of the approach is demonstrated on a series of benchmark tests. http://dx.doi.org/10.1038/npre.2009.3913.1 Thu, 29 Oct 2009 10:09:24 UTC Design of a dynamic model of genes with multiple autonomous regulatory modules by evolution in silico doi:10.1038/npre.2009.3913.1 2009-10-29 Nature Precedings 2009-10-29T10:09:24Z Manuscript Biotechnology Developmental Biology Genetics & Genomics Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3905/version/1 Context: Notwithstanding the great number of studies on the etiology and pathophysiology of schizophrenia, both issues remain far from being fully understood. Schizophrenia seems to be related to several biochemical abnormalities, which point to a multi-factor etiology and pathophysiology, as well as to the perspective that several etiologically diverse disorders might coexist within this nosographic entity. On the other hand, identical twins reveal a high concordance for schizophrenia. From that standpoint, the perspective that structurally-related proteins may play an important and yet non-deterministic role seems attractive. Among these proteins, it is suggestive that Neuregulin 1 exerts a pivotal role. Objective: This paper aims to uncover the most prominent relations that Neuregulin 1 establishes with schizophrenia. Method: Several bioinformatical methods are used in order to present: 1. A visual representation of Neuregulin 1’s main molecular pathways, associated with a discussion about their importance to schizophrenia research; 2. A new heatmap of Neuregulin 1 and its receptor’s expression in brain tissues most relevant to the understanding of schizophrenia, created after the development of new R programming scripts (described elsewhere), which facilitate the analysis of gene expression profiles in public datasets; 3. A conceptual map of the literature retrieved using the keywords ‘Neuregulin 1 and human’ in PubMed, followed by a discussion of the most relevant sub-topics. Results: Neuregulin 1 polymorphisms affect several brain tissues and contribute to the etiology and pathophysiology of schizophrenia. Suggestively, Neuregulin 1 partially bridges the ‘molecular gap’ that schizophrenia establishes in relation to bipolar disorder and Alzheimer disease, which involves genes that affect several brain networks, at the same time that they are highly dependent on noxious environmental variables to be triggered. http://precedings.nature.com/documents/3905/version/1 Wed, 28 Oct 2009 11:15:17 UTC The Role of Neuregulin 1 in Schizophrenia: A Bioinformatics Approach hdl:10101/npre.2009.3905.1 2009-10-28 Alvaro M. Dias Nature Precedings 2009-10-28T11:15:17Z Manuscript Genetics & Genomics Neuroscience Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3896/version/1 Although there is evidence for the involvement of genes of serotonergic and dopaminergic systems in the manifestation of the Behavioural and Psychological Symptoms in Dementia (BPSD), genetic association studies are contradictory. We used 1008 probable AD patients from the UK and applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of 11 polymorphisms in the serotonergic and dopaminergic systems, on four behavioural sub-phenotypes, namely "psychosis"," moods", "agitation" and "behavioural dyscontrol", as well as on 12 NPI items. Significant findings included the association of DRD1 A48G with "psychosis" (p=0.037), the association of DAT1 VNTR with "agitation" (p=0.006) and the association of DRD4 with "moods" sub-phenotype (p=0.008). In addition, associations were identified between DRD1 A48G and DAT1 VNTR with aberrant motor behaviour (AMB) symptoms (p=0.001 and p=0.015 respectively), between DRD4 and sleep disturbances (p=0.018) and between 5HTTLPR and apathy (p=0.033). Finally, significant interactions were observed between COMT Val158Met and 5HTTLPR with "psychosis" (p=0.026), between HTTLPR and STin2 with "psychosis" (p=0.005), between DAT1 3'UTR VNTR and COMT Val158Met with "agitation" (p=0.0001) and between DAT1 3'UTR VNTR and 5HTTLPR with the "moods" factor (p=0.0027). The complexity of the interrelations between genetic variation, behavioural symptoms and clinical variables was efficiently captured by this MIMIC model. http://precedings.nature.com/documents/3896/version/1 Mon, 26 Oct 2009 17:32:00 UTC Genes of the serotonergic and dopaminergic pathways and their interaction affect the expression of Behavioural and Psychological Symptoms in Dementia (BPSD). hdl:10101/npre.2009.3896.1 2009-10-26 Petroula Proitsi Nature Precedings 2009-10-26T17:32:00Z Manuscript Genetics & Genomics Neuroscience http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3900.1 Analyzing of sequences similarities is the first and most important method used to find out the function of unknown nucleotides. Searching of homologs should be done carefully not to loose any important ones. Having thousands of results from various long-read sequencing projects (ie. differentially expressed tags, genomic polymorphons or BAC ends), the by-hand ability to retrieve interesting (to our goal) similarities in hundreds of Blast results decreases rapidly. Decreasing the number of retrieved sequences by giving more stringency in e-value threshold or displaying less results could lead to false deductions. Functional genomics, proteomics and metabolomics could give us answers to the role of nucleotide sequences. It makes the need to annotate as much of the homologies as we can, to proper molecular function, biological process and cellular component (as its proposed by widely accepted Gene Ontology Consortium annotations or MapMan mappings by Max-Planc-Institute). To facilitate fast retrieval of interesting Blast homologies and making right deductions about the biological role of sequences, in big sequencing projects, the new Perl script BRAGOMAP was written. The program make use of some of BioPerl modules as well as the power of regex text-mining in the Perl itself. The script gives us the possibility to find interesting sequence similarities by using keywords and giving points for each one found. It collects all important information from the GenBank data and puts it in different columns of tab-delimited file for further use. If we were interested (for example) in flower differentiation genes we could use the keywords (flower, ovule, anther, etc.) and/or filter all the homologies isolated from flower tissues in a special development stage. We can also filter results by choosing similarities to interesting genes or protein products. This script retrieve also all standard information from the Blast and GenBank files as Description, ACC no., E-value, Similarity positions, Query Length, Percent of Similarity etc. Automatic GO and MapMan annotations are done by looking for genes, protein products and /or DB references in the proper mappings files. Here we present the usefulness of the script in analyzing sequence similarities and annotations mapping of 3855 BAC ends obtained from the HindIII BAC genomic library of cucumber (Cucumis sativus L., line B10). http://dx.doi.org/10.1038/npre.2009.3900.1 Mon, 26 Oct 2009 11:35:28 UTC BRAGOMAP – a new Perl script for high throughoutput blast results analysis including GO and MapMan automatic annotations doi:10.1038/npre.2009.3900.1 2009-10-26 Rafal Woycicki Nature Precedings 2009-10-26T11:35:28Z Poster Genetics & Genomics Bioinformatics Plant Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3894/version/1 We extend a cognitive paradigm for gene expression to the epigenetic epidemiology of mental disorders, recognizing the fundamental role that culture plays in human biology as another heritage mechanism parallel to, and interacting with, the more familiar genetic and epigenetic systems. In the mathematical model, culture acts as another tunable epigenetic catalyst that both directs developmental trajectories and becomes convoluted with individual ontology via a mutually interacting crosstalk mediated by a social interaction that is itself culturally driven. We call for the incorporation of embedding culture as an essential component of the epigenetic regulation of human mental development and its dysfunctions, bringing what is perhaps the central reality of human biology into the center of biological psychiatry. The cultural and epigenetic systems of heritage may well provide the ‘missing’ heritability of complex diseases now under so much intense discussion. http://precedings.nature.com/documents/3894/version/1 Fri, 23 Oct 2009 11:39:41 UTC The cultural epigenetics of psychopathology: The missing heritability of complex diseases found? hdl:10101/npre.2009.3894.1 2009-10-23 Rodrick Wallace Nature Precedings 2009-10-23T11:39:41Z Manuscript Developmental Biology Genetics & Genomics Neuroscience http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3886/version/1 Viruses are the most abundant life forms and the repertoire of viral genes is greater than that of cellular genes. It is also evident that viruses have played a major role in driving cellular evolution, and yet, viruses are not part of mainstream biology, nor are they included in the Tree of Life. A reason for this major paradox in biology is the misleading dogma of viruses as viral particles and their enigmatic evolutionary origin. This article presents an alternative view about the nature of viruses based on their properties during the intracellular stage of their life cycle, when viruses express features comparable to those of many parasitic cellular species. Supporting this view about the nature of viruses is a novel hypothetical evolutionary model for their origin from parasitic cellular species that fused with their host cells. By losing their membrane and cellular structure within the host cell, these new types of parasitic species gained full access to precursors for the synthesis of their specific molecules and to the host’s information processing machineries, such as translation, which created unique parasitic and evolutionary opportunities. To identify viruses during their intracellular stage of their life cycle, in which their specific molecules are free or dispersed within the host cell, this paper introduces the concept of “molecular structure” and labels viruses as “molecular organisms.” Among the extant viruses, the life cycle of poxviruses and other complex viruses that fuse with their host cells provides compelling evidence for the fusion model. One of the most remarkable implications of fusion model is that new viral lineages originated from parasitic cellular species throughout the history of life, and that this process might still be active. Surprisingly, it appears that several parasitic cellular species are currently evolving into molecular organisms. More remarkably though, according to this model, several parasites that are currently classified as cellular organisms are in fact genuine molecular organisms. The current evidence for the fusion hypothesis is strong and it is fully testable using both experimental and phylogenetic approaches. The academic and research implications of this model, which supports the inclusion of viruses in the Tree of Life, are highly significant. Some of these implications are discussed in more detail in two other articles of this series, which presents a unifying model for the origin and evolution of cellular and viral domains, including the origin of life. http://precedings.nature.com/documents/3886/version/1 Fri, 23 Oct 2009 11:33:49 UTC The Origin and Evolution of Viruses as Molecular Organisms hdl:10101/npre.2009.3886.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:33:49Z Manuscript Genetics & Genomics Microbiology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3888/version/1 The cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains – Bacteria, Archaea and Eukarya – from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery – the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth – the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology. http://precedings.nature.com/documents/3888/version/1 Fri, 23 Oct 2009 11:11:22 UTC A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains hdl:10101/npre.2009.3888.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:11:22Z Manuscript Genetics & Genomics Immunology Microbiology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3874/version/1 This study leads to a new algebra. An algebra is defined on the common mechanisms of chromosomal mutation. The algebra (SΨ(C), *, ’, Δ, D) is constructed for a given C and Ψ. This algebra represents the most common chromosomal mutational mechanisms. This can lead to a new way to manipulate chromosomal mutation with higher structures of abstract mathematics. The first proposal of the algebra was reported in Mazumdar et al., 2007. http://precedings.nature.com/documents/3874/version/1 Tue, 20 Oct 2009 16:41:18 UTC Chromosomal mutational algebra: a new algebra to manipulate chromosomal mutation hdl:10101/npre.2009.3874.1 2009-10-20 Dipankar Mazumdar Nature Precedings 2009-10-20T16:41:18Z Manuscript Genetics & Genomics Bioinformatics http://creativecommons.org/licenses/by/3.0/