Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans.

Background: Genome variability can have a profound influence on the virulence of pathogenic microbes. The availability of genome sequences for two strains of the AIDS-associated fungal pathogen Cryptococcus neoformans presented an opportunity to use comparative genome hybridization (CGH) to examine genome variability between strains of different mating type, molecular subtype, and ploidy.

Results: Initially, CGH was used to compare the approximately 100 kilobase MATa and MATalpha mating-type regions in serotype A and D strains to establish the relationship between the Log2 ratios of hybridization signals and sequence identity.

An Introduction to BioPerl.

The BioPerl toolkit provides a library of hundreds of routines for processing sequence, annotation, alignment, and sequence analysis reports. It often serves as a bridge between different computational biology applications assisting the user to construct analysis pipelines. This chapter illustrates how BioPerl facilitates tasks such as writing scripts summarizing information from BLAST reports or extracting key annotation details from a GenBank sequence record.

Comparative genomic analysis of fungal genomes reveals intron-rich ancestors.

Background: Eukaryotic protein-coding genes are interrupted by spliceosomal introns, which are removed from transcripts before protein translation. Many facets of spliceosomal intron evolution, including age, mechanisms of origins, the role of natural selection, and the causes of the vast differences in intron number between eukaryotic species, remain debated. Genome sequencing and comparative analysis has made possible whole genome analysis of intron evolution to address these questions.

Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease.

Objective: To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen).

Design: Family-based case-control study.

Setting: Academic medical center clinic.

Evolution of the mating type locus: insights gained from the dimorphic primary fungal pathogens Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii.

Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell identity and fate. Knowledge of MAT locus structure and evolution has been considerably advanced in recent years as a result of genomic analyses that enable the definition of MAT locus sequences in many species as well as provide an understanding of the evolutionary plasticity of this unique region of the genome. Here, we extend this analysis to define the mating type locus of three dimorphic primary human fungal pathogens, Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii, using genomic analysis, direct sequencing, and bioinformatics.

Evolution of budding yeast prion-determinant sequences across diverse fungi.

Prions are transmissible self-replicating alternative states of proteins. Four prions ([PSI+], [URE3], [RNQ+] and [NU+]) can be inherited cytoplasmically in Saccharomyces cerevisiae laboratory strains. In the case of [PSI+], there is increasing evidence that prion formation may engender mechanisms to uncover hidden genetic variation.

Genotype-phenotype study in an FSHD family with a proximal deletion encompassing p13E-11 and D4Z4.

Background: In the majority of facioscapulohumeral muscular dystrophy (FSHD) cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4 repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4 repeat is associated with FSHD. One explanation for this finding is a deletion in the region proximal to the D4Z4 repeat array that encompasses the p13E-11 (D4F104S1) probe-binding site used in the DNA diagnosis.

The evolution of mammalian gene families.

Gene families are groups of homologous genes that are likely to have highly similar functions. Differences in family size due to lineage-specific gene duplication and gene loss may provide clues to the evolutionary forces that have shaped mammalian genomes. Here we analyze the gene families contained within the whole genomes of human, chimpanzee, mouse, rat, and dog.

BASC: an integrated bioinformatics system for Brassica research.

The BASC system provides tools for the integrated mining and browsing of genetic, genomic and phenotypic data. This public resource hosts information on Brassica species supporting the Multinational Brassica Genome Sequencing Project, and is based upon five distinct modules, ESTDB, Microarray, MarkerQTL, CMap and EnsEMBL. ESTDB hosts expressed gene sequences and related annotation derived from comparison with GenBank, UniRef and the genome sequence of Arabidopsis.

A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis.

Background: To date, most fungal phylogenies have been derived from single gene comparisons, or from concatenated alignments of a small number of genes. The increase in fungal genome sequencing presents an opportunity to reconstruct evolutionary events using entire genomes. As a tool for future comparative, phylogenomic and phylogenetic studies, we used both supertrees and concatenated alignments to infer relationships between 42 species of fungi for which complete genome sequences are available.

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis.

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U.

Reconstructing the early evolution of Fungi using a six-gene phylogeny.

The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species.

Comparative genomics in C. elegans, C. briggsae, and other Caenorhabditis species.

The genome of the nematode Caenorhabditis elegans was the first animal genome sequenced. Subsequent sequencing of the Caenorhabditis briggsae genome enabled a comparison of the genomes of two nematode species. In this chapter, we describe the methods that we used to compare the C.

The Cryptococcus neoformans catalase gene family and its role in antioxidant defense.

In the present study, we sought to elucidate the contribution of the Cryptococcus neoformans catalase gene family to antioxidant defense. We employed bioinformatics techniques to identify four members of the C. neoformans catalase gene family and created mutants lacking single or multiple catalase genes.

Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus.

Fungi from the genus Aspergillus are important saprophytes and opportunistic human fungal pathogens that contribute in these and other diverse ways to human well-being. Part of their impact on human well-being stems from the production of small molecular weight secondary metabolites, which may contribute to the ability of these fungi to cause invasive fungal infections and allergic diseases. In this study, we identified one group of enzymes responsible for secondary metabolite production in five Aspergillus species, the non-ribosomal peptide synthetases (NRPS).

Open source tools and toolkits for bioinformatics: significance, and where are we?

This review summarizes important work in open-source bioinformatics software that has occurred over the past couple of years. The survey is intended to illustrate how programs and toolkits whose source code has been developed or released under an Open Source license have changed informatics-heavy areas of life science research. Rather than creating a comprehensive list of all tools developed over the last 2-3 years, we use a few selected projects encompassing toolkit libraries, analysis tools, data analysis environments and interoperability standards to show how freely available and modifiable open-source software can serve as the foundation for building important applications, analysis workflows and resources.

NOS2A and the modulating effect of cigarette smoking in Parkinson's disease.

Objective: Inducible nitric oxide synthase, a protein product of NOS2A, generates nitric oxide as a defense mechanism, but excessive levels threaten cellular survival. NOS2A is a candidate gene for Parkinson's disease (PD) that potentially interacts with cigarette smoking. We examined NOS2A for association with PD risk and age at onset (AAO) and for interaction with smoking.

Evidence of mRNA-mediated intron loss in the human-pathogenic fungus Cryptococcus neoformans.

Introns are a defining feature of eukaryotic genomes, though the mechanism of intron gain or loss is not well understood. Reverse transcription of mRNA followed by homologous recombination with the genome has been posited as a mechanism of intron loss, though little direct evidence of recent loss events has been described to support this model. We find supporting evidence for an mRNA-mediated mechanism of loss through comparative genome analyses that revealed a recent loss of 10 adjacent introns in a 22-exon gene in the human-pathogenic fungus Cryptococcus neoformans.

Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting proteins.

Background: The WW domain is found in a large number of eukaryotic proteins implicated in a variety of cellular processes. WW domains bind proline-rich protein and peptide ligands, but the protein interaction partners of many WW domain-containing proteins in Saccharomyces cerevisiae are largely unknown.

Results: We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S.

Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.

Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive.

Methods: Here, we describe six HMSN VI families with a subacute onset of optic atrophy and subsequent slow recovery of visual acuity in 60% of the patients.

Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak.

Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae, the cause of leprosy. In other pathogens, sexual reproduction yields clones with novel attributes, for example, enabling the efficient, oral transmission of the parasite Toxoplasma gondii.

Likelihoods from summary statistics: recent divergence between species.

We describe an importance-sampling method for approximating likelihoods of population parameters based on multiple summary statistics. In this first application, we address the demographic history of closely related members of the Drosophila pseudoobscura group. We base the maximum-likelihood estimation of the time since speciation and the effective population sizes of the extant and ancestral populations on the pattern of nucleotide variation at DPS2002, a noncoding region tightly linked to a paracentric inversion that strongly contributes to reproductive isolation.

Estimating the tempo and mode of gene family evolution from comparative genomic data.

Comparison of whole genomes has revealed that changes in the size of gene families among organisms is quite common. However, there are as yet no models of gene family evolution that make it possible to estimate ancestral states or to infer upon which lineages gene families have contracted or expanded. In addition, large differences in family size have generally been attributed to the effects of natural selection, without a strong statistical basis for these conclusions.

Investigating hookworm genomes by comparative analysis of two Ancylostoma species.

Background: Hookworms, infecting over one billion people, are the mostly closely related major human parasites to the model nematode Caenorhabditis elegans. Applying genomics techniques to these species, we analyzed 3,840 and 3,149 genes from Ancylostoma caninum and A. ceylanicum.

The genes encoding for D4Z4 binding proteins HMGB2, YY1, NCL, and MYOD1 are excluded as candidate genes for FSHD1B.

Facioscapulohumeral muscular dystrophy is a disease of skeletal muscle, with symptoms including both facial and shoulder girdle weakness and progression to involve the pelvic girdle and extremities in the majority of cases. For most cases of FSHD, the molecular basis of the disease can be identified as a partial deletion of the D4Z4 repeat array on the end of the long arm of chromosome 4. However, in up to 5% of FSHD families there is no linkage to 4q35.