Biomedical subjects

Jason E Stajich

Publications and source records attributed to Jason E Stajich.

24 records · Page 2Linked to original sources

PubMed2004

Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray.

The ability to survive and proliferate at 37 degrees C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the human-pathogenic fungus Cryptococcus neoformans during growth at 37 degrees C. Genes with orthologs involved in stress responses were induced during growth at 37 degrees C, suggesting that a conserved transcriptional program is used by C. neoformans to alter gene expression during stressful conditions. A gene encoding the transcription factor homolog Mga2 was induced at 37 degrees C and found to be important for high-temperature growth. Genes encoding fatty acid biosynthetic enzymes were identified as potential targets of Mga2, suggesting that membrane remodeling is an important component of adaptation to high growth temperatures. mga2Delta mutants were extremely sensitive to the ergosterol synthesis inhibitor fluconazole, indicating a coordination of the synthesis of membrane component precursors. Unexpectedly, genes involved in amino acid and pyrimidine biosynthesis were repressed at 37 degrees C, but components of these pathways were found to be required for high-temperature growth. Our findings demonstrate the utility of even partial-genome microarrays for delineating regulatory cascades that contribute to microbial pathogenesis.

Cryptococcus neoformans↗

PubMed2003

The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics.

The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.

Animals↗

PubMed2003

The effects of selection against spurious transcription factor binding sites.

Most genomes contain nucleotide sequences with no known function; such sequences are assumed to be free of constraints, evolving only according to the vagaries of mutation. Here we show that selection acts to remove spurious transcription factor binding site motifs throughout 52 fully sequenced genomes of Eubacteria and Archaea. Examining the sequences necessary for polymerase binding, we find that spurious binding sites are underrepresented in both coding and noncoding regions. The average proportion of spurious binding sites found relative to the expected is 80% in eubacterial genomes and 89% in archaeal genomes. We also estimate the strength of selection against spurious binding sites in the face of the constant creation of new binding sites via mutation. Under conservative assumptions, we estimate that selection is weak, with the average efficacy of selection against spurious binding sites, Nes, of -0.12 for eubacterial genomes and -0.06 for archaeal genomes, similar to that of codon bias. Our results suggest that both coding and noncoding sequences are constrained by selection to avoid specific regions of sequence space.

Archaea↗

PubMed2002

The Bioperl toolkit: Perl modules for the life sciences.

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.

Algorithms↗

PubMed2002

The generic genome browser: a building block for a model organism system database.

The Generic Model Organism System Database Project (GMOD) seeks to develop reusable software components for model organism system databases. In this paper we describe the Generic Genome Browser (GBrowse), a Web-based application for displaying genomic annotations and other features. For the end user, features of the browser include the ability to scroll and zoom through arbitrary regions of a genome, to enter a region of the genome by searching for a landmark or performing a full text search of all features, and the ability to enable and disable tracks and change their relative order and appearance. The user can upload private annotations to view them in the context of the public ones, and publish those annotations to the community. For the data provider, features of the browser software include reliance on readily available open source components, simple installation, flexible configuration, and easy integration with other components of a model organism system Web site. GBrowse is freely available under an open source license. The software, its documentation, and support are available at http://www.gmod.org.

Animals↗

PubMed2001

Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21.

We previously localized and fine-mapped Charcot Marie Tooth 4A (CMT4A), the autosomal recessive, demyelinating peripheral neuropathy, to chromosome 8. Through additional positional cloning, we have identified a good candidate gene, encoding ganglioside-induced differentiation-associated protein-1 (GDAP1). We found three different mutations in four different Tunisian families-two nonsense and one missense mutation. How mutations in GDAP1 lead to CMT4A remains to be understood.

Amino Acid Substitution↗