Finnian Hanrahan

Bio: Finnian Hanrahan is an academic researcher from Trinity College, Dublin. The author has contributed to research in topics: Tight junction & Blood–retinal barrier. The author has an hindex of 5, co-authored 8 publications receiving 1205 citations. Previous affiliations of Finnian Hanrahan include University of Maryland, College Park.

A whole-genome assembly of the domestic cow, Bos taurus

Abstract: Background: The genome of the domestic cow, Bos taurus, was sequenced using a mixture of hierarchical and whole-genome shotgun sequencing methods. Results: We have assembled the 35 million sequence reads and applied a variety of assembly improvement techniques, creating an assembly of 2.86 billion base pairs that has multiple improvements over previous assemblies: it is more complete, covering more of the genome; thousands of gaps have been closed; many erroneous inversions, deletions, and translocations have been corrected; and thousands of single-nucleotide errors have been corrected. Our evaluation using independent metrics demonstrates that the resulting assembly is substantially more accurate and complete than alternative versions. Conclusions: By using independent mapping data and conserved synteny between the cow and human genomes, we were able to construct an assembly with excellent large-scale contiguity in which a large majority (approximately 91%) of the genome has been placed onto the 30 B. taurus chromosomes. We constructed a new cow-human synteny map that expands upon previous maps. We also identified for the first time a portion of the B. taurus Y chromosome.

Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury

Abstract: Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.

Systemic low‐molecular weight drug delivery to pre‐selected neuronal regions

Abstract: We describe a procedure for controlled, periodic, reversible modulation of selected regions of the blood–brain barrier (BBB) or the inner-blood–retina barrier (iBRB) based on incorporation into an AAV-2/9 vector of a doxycycline-inducible gene encoding shRNA targeting claudin-5, one of 30 or so proteins constituting the BBB and iBRB The vector may be introduced stereotaxically into pre-selected regions of the brain or into the retina, rendering these regions permeable to low-molecular weight compounds up to approximately 1 kDa for the period of time during which the inducing agent, doxycycline, is administered in drinking water, but excluding potentially toxic higher molecular weight materials We report on the use of barrier modulation in tandem with systemic drug therapy to prevent retinal degeneration and to suppress laser-induced choroidal neovascularization (CNV), the latter being the hallmark pathology associated with the exudative, or wet, form of age-related macular degeneration (AMD) These observations constitute the basis of a minimally invasive systemic therapeutic modality for retinal diseases, including retinitis pigmentosa and AMD, where, in early stage disease, the iBRB is intact and impervious to systemically administered drugs

Core Gene Set As the Basis of Multilocus Sequence Analysis of the Subclass Actinobacteridae

Abstract: Comparative genomic sequencing is shedding new light on bacterial identification, taxonomy and phylogeny. An in silico assessment of a core gene set necessary for cellular functioning was made to determine a consensus set of genes that would be useful for the identification, taxonomy and phylogeny of the species belonging to the subclass Actinobacteridae which contained two orders Actinomycetales and Bifidobacteriales. The subclass Actinobacteridae comprised about 85% of the actinobacteria families. The following recommended criteria were used to establish a comprehensive gene set; the gene should (i) be long enough to contain phylogenetically useful information, (ii) not be subject to horizontal gene transfer, (iii) be a single copy (iv) have at least two regions sufficiently conserved that allow the design of amplification and sequencing primers and (v) predict whole-genome relationships. We applied these constraints to 50 different Actinobacteridae genomes and made 1,224 pairwise comparisons of the genome conserved regions and gene fragments obtained by using Sequence VARiability Analysis Program (SVARAP), which allow designing the primers. Following a comparative statistical modeling phase, 3 gene fragments were selected, ychF, rpoB, and secY with R2>0.85. Selected sets of broad range primers were tested from the 3 gene fragments and were demonstrated to be useful for amplification and sequencing of 25 species belonging to 9 genera of Actinobacteridae. The intraspecies similarities were 96.3-100% for ychF, 97.8-100% for rpoB and 96.9-100% for secY among 73 strains belonging to 15 species of the subclass Actinobacteridae compare to 99.4-100% for 16S rRNA. The phylogenetic topology obtained from the combined datasets ychF+rpoB+secY was globally similar to that inferred from the 16S rRNA but with higher confidence. It was concluded that multi-locus sequence analysis using core gene set might represent the first consensus and valid approach for investigating the bacterial identification, phylogeny and taxonomy.

Public Health-Driven Research and Innovation for Next-Generation Influenza Vaccines, European Union.

Abstract: Influenza virus infections are a major public health threat. Vaccination is available, but unpredictable antigenic changes in circulating strains require annual modification of seasonal influenza vaccines. Vaccine effectiveness has proven limited, particularly in certain groups, such as the elderly. Moreover, preparedness for upcoming pandemics is challenging because we can predict neither the strain that will cause the next pandemic nor the severity of the pandemic. The European Union fosters research and innovation to develop novel vaccines that evoke broadly protective and long-lasting immune responses against both seasonal and pandemic influenza, underpinned by a political commitment to global public health.

Comparative genomics reveals insights into avian genome evolution and adaptation.

Abstract: Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.

The UCSC Genome Browser database: extensions and updates 2011

Abstract: The University of California Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online public access to a growing database of genomic sequence and annotations for a wide variety of organisms. The Browser is an integrated tool set for visualizing, comparing, analyzing and sharing both publicly available and user-generated genomic data sets. In the past year, the local database has been updated with four new species assemblies, and we anticipate another four will be released by the end of 2011. Further, a large number of annotation tracks have been either added, updated by contributors, or remapped to the latest human reference genome. Among these are new phenotype and disease annotations, UCSC genes, and a major dbSNP update, which required new visualization methods. Growing beyond the local database, this year we have introduced ‘track data hubs’, which allow the Genome Browser to provide access to remotely located sets of annotations. This feature is designed to significantly extend the number and variety of annotation tracks that are publicly available for visualization and analysis from within our site. We have also introduced several usability features including track search and a context-sensitive menu of options available with a right-click anywhere on the Browser's image.

Whole-genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle

Abstract: The 1000 bull genomes project supports the goal of accelerating the rates of genetic gain in domestic cattle while at the same time considering animal health and welfare by providing the annotated sequence variants and genotypes of key ancestor bulls. In the first phase of the 1000 bull genomes project, we sequenced the whole genomes of 234 cattle to an average of 8.3-fold coverage. This sequencing includes data for 129 individuals from the global Holstein-Friesian population, 43 individuals from the Fleckvieh breed and 15 individuals from the Jersey breed. We identified a total of 28.3 million variants, with an average of 1.44 heterozygous sites per kilobase for each individual. We demonstrate the use of this database in identifying a recessive mutation underlying embryonic death and a dominant mutation underlying lethal chrondrodysplasia. We also performed genome-wide association studies for milk production and curly coat, using imputed sequence variants, and identified variants associated with these traits in cattle.