Genome

About: Genome is a research topic. Over the lifetime, 74231 publications have been published within this topic receiving 3819713 citations.

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39

Abstract: The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an ~50 kb ‘plasticity zone’ near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli 0157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C.pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C.pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

GeneHancer: genome-wide integration of enhancers and target genes in GeneCards

Abstract: A major challenge in understanding gene regulation is the unequivocal identification of enhancer elements and uncovering their connections to genes. We present GeneHancer, a novel database of human enhancers and their inferred target genes, in the framework of GeneCards. First, we integrated a total of 434 000 reported enhancers from four different genome-wide databases: the Encyclopedia of DNA Elements (ENCODE), the Ensembl regulatory build, the functional annotation of the mammalian genome (FANTOM) project and the VISTA Enhancer Browser. Employing an integration algorithm that aims to remove redundancy, GeneHancer portrays 285 000 integrated candidate enhancers (covering 12.4% of the genome), 94 000 of which are derived from more than one source, and each assigned an annotation-derived confidence score. GeneHancer subsequently links enhancers to genes, using: tissue co-expression correlation between genes and enhancer RNAs, as well as enhancer-targeted transcription factor genes; expression quantitative trait loci for variants within enhancers; and capture Hi-C, a promoter-specific genome conformation assay. The individual scores based on each of these four methods, along with gene–enhancer genomic distances, form the basis for GeneHancer’s combinatorial likelihood-based scores for enhancer–gene pairing. Finally, we define ‘elite’ enhancer–gene relations reflecting both a high-likelihood enhancer definition and a strong enhancer–gene association. GeneHancer predictions are fully integrated in the widely used GeneCards Suite, whereby candidate enhancers and their annotations are displayed on every relevant GeneCard. This assists in the mapping of non-coding variants to enhancers, and via the linked genes, forms a basis for variant–phenotype interpretation of whole-genome sequences in health and disease. Database URL: http://www.genecards.org/

Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions

Abstract: Candida albicans is an opportunistic fungal pathogen. It exists as a benign commensal organism in healthy individuals but causes infections in susceptible individuals, such as those with diminished immune function (14). Molecular genetic analysis of C. albicans has permitted evaluation of antifungal drug targets and elucidation of requirements for infection and pathogenesis (16). New C. albicans genes have been identified frequently through sequence homology to known genes or gene families. Gene discovery has been facilitated greatly by access to much of the C. albicans genomic sequence (11). Now, the rate-limiting step in analysis of gene function in this diploid organism is the creation of a homozygous disruption mutant. Gene disruption has been accomplished through successive transformations with insertion/deletion alleles that are constructed in vitro (2, 7, 12). These methods have thus far required isolation of substantial DNA segments, and yet new genes of interest are often identified through DNA sequences of 400 to 600 bp (3a). We report here a rapid method for disruption of C. albicans genes with PCR products that contain short regions of homology to the genome.

Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database

Abstract: The Pseudomonas Genome Database (http://www.pseudomonas.com) is well known for the application of community-based annotation approaches for producing a high-quality Pseudomonas aeruginosa PAO1 genome annotation, and facilitating whole-genome comparative analyses with other Pseudomonas strains. To aid analysis of potentially thousands of complete and draft genome assemblies, this database and analysis platform was upgraded to integrate curated genome annotations and isolate metadata with enhanced tools for larger scale comparative analysis and visualization. Manually curated gene annotations are supplemented with improved computational analyses that help identify putative drug targets and vaccine candidates or assist with evolutionary studies by identifying orthologs, pathogen-associated genes and genomic islands. The database schema has been updated to integrate isolate metadata that will facilitate more powerful analysis of genomes across datasets in the future. We continue to place an emphasis on providing high-quality updates to gene annotations through regular review of the scientific literature and using community-based approaches including a major new Pseudomonas community initiative for the assignment of high-quality gene ontology terms to genes. As we further expand from thousands of genomes, we plan to provide enhancements that will aid data visualization and analysis arising from whole-genome comparative studies including more pan-genome and population-based approaches.