VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts

Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187 156 extensively annotated matured mRNA transcripts from 36 073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion–insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/

Homeobox Transcription Factors Are Required for Conidiation and Appressorium Development in the Rice Blast Fungus Magnaporthe oryzae

The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including Magnaporthe oryzae. A total of eight genes (MoHOX1 to MoHOX8) encoding putative homeobox transcription factors (TFs) were identified from the M. oryzae genome. Knockout mutants for each MoHOX gene were obtained via homology-dependent gene replacement. Two mutants, ΔMohox3 and ΔMohox5, exhibited no difference to wild-type in growth, conidiation, conidium size, conidial germination, appressorium formation, and pathogenicity. However, the ΔMohox1 showed a dramatic reduction in hyphal growth and increase in melanin pigmentation, compared to those in wild-type. ΔMohox4 and ΔMohox6 showed significantly reduced conidium size and hyphal growth, respectively. ΔMohox8 formed normal appressoria, but failed in pathogenicity, probably due to defects in the development of penetration peg and invasive growth. It is most notable that asexual reproduction was completely abolished in ΔMohox2, in which no conidia formed. ΔMohox2 was still pathogenic through hypha-driven appressoria in a manner similar to that of the wild-type. However, ΔMohox7 was unable to form appressoria either on conidial germ tubes, or at hyphal tips, being non-pathogenic. These factors indicate that M. oryzae is able to cause foliar disease via hyphal appressorium-mediated penetration, and MoHOX7 is mutually required to drive appressorium formation from hyphae and germ tubes. Transcriptional analyses suggest that the functioning of M. oryzae homeobox TFs is mediated through the regulation of gene expression and is affected by cAMP and Ca2+ signaling and/or MAPK pathways. The divergent roles of this gene set may help reveal how the genome and regulatory pathways evolved within the rice blast pathogen and close relatives

GPCRs, G-proteins, effectors and their interactions: human-gpDB, a database employing visualization tools and data integration techniques

G-protein coupled receptors (GPCRs) are a major family of membrane receptors in eukaryotic cells. They play a crucial role in the communication of a cell with the environment. Ligands bind to GPCRs on the outside of the cell, activating them by causing a conformational change, and allowing them to bind to G-proteins. Through their interaction with G-proteins, several effector molecules are activated leading to many kinds of cellular and physiological responses. The great importance of GPCRs and their corresponding signal transduction pathways is indicated by the fact that they take part in many diverse disease processes and that a large part of efforts towards drug development today is focused on them. We present Human-gpDB, a database which currently holds information about 713 human GPCRs, 36 human G-proteins and 99 human effectors. The collection of information about the interactions between these molecules was done manually and the current version of Human-gpDB holds information for about 1663 connections between GPCRs and G-proteins and 1618 connections between G-proteins and effectors. Major advantages of Human-gpDB are the integration of several external data sources and the support of advanced visualization techniques. Human-gpDB is a simple, yet a powerful tool for researchers in the life sciences field as it integrates an up-to-date, carefully curated collection of human GPCRs, G-proteins, effectors and their interactions. The database may be a reference guide for medical and pharmaceutical research, especially in the areas of understanding human diseases and chemical and drug discovery. Database URLs: http://schneider.embl.de/human_gpdb; http://bioinformatics.biol.uoa.gr/human_gpdb