The UCSC Genome Browser Database: update 2006

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.Peer reviewe

Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach

The developmental time of vector insects is important to their population dynamics, evolutionary biology, epidemiology of the diseases they transmit, and to their responses to global climatic change. In various triatomine species vectors of Chagas disease (Triatominae, Reduviidae), a delay in the molt of a small proportion of individuals has been observed, and from an evolutionary ecology approach, we propose the hypothesis that the developmental delay is an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) diapause strategy. We confirmed, by means of a survey among specialists, the existence of the developmental delay in triatomines. Statistical descriptions of the developmental time of 11 species of triatomines showed some degree of bi-modality in nine of them. We predicted by means of an optimization model which genotype, coding for a given frequency of developmental diapause, is expected to evolve. We identified a series of parameters that can be measured in the field and in the laboratory to test the hypothesis of an optimal diapause frequency. We also discuss the importance of these findings for triatomines in terms of global climatic change and epidemiological consequences such as their resistance to insecticides

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibodyâ Associated Vasculitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136726/1/art40034_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136726/2/art40034-sup-0002-suppinfo02.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136726/3/art40034-sup-0001-suppinfo01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136726/4/art40034.pd

Molecular Evolutionary Trends and Feeding Ecology Diversification in the Hemiptera, Anchored by the Milkweed Bug Genome

Background: The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus, a seed feeder of the family Lygaeidae. Results: The 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but also to elucidate patterns of molecular evolution and physiology. We find ongoing, lineage-specific expansion and diversification of repressive C2H2 zinc finger proteins. The discovery of intron gain and turnover specific to the Hemiptera also prompted the evaluation of lineage and genome size as predictors of gene structure evolution. Furthermore, we identify enzymatic gains and losses that correlate with feeding biology, particularly for reductions associated with derived, fluid nutrition feeding. Conclusions: With the milkweed bug, we now have a critical mass of sequenced species for a hemimetabolous insect order and close outgroup to the Holometabola, substantially improving the diversity of insect genomics. We thereby define commonalities among the Hemiptera and delve into how hemipteran genomes reflect distinct feeding ecologies. Given Oncopeltus’s strength as an experimental model, these new sequence resources bolster the foundation for molecular research and highlight technical considerations for the analysis of medium-sized invertebrate genomes

Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system

In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of Runx transcription factor paralogs with apparent functional redundancy. Here we asked what cell type-specific biologies might be supported by the selective expression of Runx paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional non-equivalence between Runx paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA-binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain, and evolutionary reconstruction suggested convergence of RUNT domain residues towards sub-maximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system

Unraveling the forcings controlling the vegetation and climate of the best orbital analogues for the present interglacial in SW Europe

The suitability of MIS 11c and MIS 19c as analogues of our present interglacial and its natural evolution is still debated. Here we examine the regional expression of the Holocene and its orbital analogues over SW Iberia using a model-data comparison approach. Regional tree fraction and climate based on snapshot and transient experiments using the LOVECLIM model are evaluated against the terrestrial-marine profiles from Site U1385 documenting the regional vegetation and climatic changes. The pollen-based reconstructions show a larger forest optimum during the Holocene compared to MIS 11c and MIS 19c, putting into question their analogy in SW Europe. Pollen-based and model results indicate reduced MIS 11c forest cover compared to the Holocene primarily driven by lower winter precipitation, which is critical for Mediterranean forest development. Decreased precipitation was possibly induced by the amplified MIS 11c latitudinal insolation and temperature gradient that shifted the westerlies northwards. In contrast, the reconstructed lower forest optimum at MIS 19c is not reproduced by the simulations probably due to the lack of Eurasian ice sheets and its related feedbacks in the model. Transient experiments with time-varying insolation and CO2 reveal that the SW Iberian forest dynamics over the interglacials are mostly coupled to changes in winter precipitation mainly controlled by precession, CO2 playing a negligible role. Model simulations reproduce the observed persistent vegetation changes at millennial time scales in SW Iberia and the strong forest reductions marking the end of the interglacial "optimum".SFRH/BD/9079/2012, SFRH/BPD/108712/2015, SFRH/BPD/108600/2015info:eu-repo/semantics/publishedVersio