Sequence assembly and annotation of the bovine major histocompatibility complex (BoLA) class IIb region, and in silico detection of sequence polymorphisms in BoLA IIb

Cattle are vitally important to American agriculture industry, generating over 24.6 billion pounds of beef (by carcass weight), and 79.5 billion dollars in 2005, and over 27 billion dollars in milk sales in 2004. As of July 2006, the U.S. beef and dairy industry is comprised of 104.5 million head of cattle, 32.4 million of which were processed in 2005. The health of the animals has always been an important concern for breeders, as healthy animals grow faster and are more likely to reach market weight. Animals that exhibit natural resistance to disease do not require chemicals to stimulate normal weight gain, and are less prone to disease related wasting. The major histocompatibility complex (MHC) is a collection of genes, many of which function in antigen processing and presentation. The bovine MHC (BoLA) differs from typical mammalian MHCs in that the class II region was disrupted by a chromosomal inversion into two subregions, designated BoLA IIa and BoLA IIb. BoLA IIb was transposed to a position near the centromere on bovine chromosome 23,while BoLA IIa retains its position in BoLA. Comparative sequence analysis of BoLA IIb with the human MHC revealed the location of the region containing the proximal inversion breakpoint. Gene content, order and orientation of BoLA IIb are consistent with the single inversion hypothesis when compared to the corresponding region of the human class II MHC (HLA class II). BoLA IIb spans approximately 450 kb. The genomic sequence of BoLA IIb was used to detect sequence variation through comparison to other bovine sequences, including data from the bovine genome project, and two regions in the BAC scaffold used to develop the BoLA IIb sequence. Analysis of the bovine genome project sequence revealed a total of 10,408 mismatching bases, 30 out of 231 polymorphic microsatellites, and 15 sequences corresponding to the validated SNP panel generated by the bovine genome sequencing project. The two overlapping regions in the BoLA IIb BAC scaffold were found to have 888 polymorphisms, including a total of 6 out of 42 polymorphic microsatellites indicating that each BAC derived from a different chromosome

The Hymenoptera Genome Database

The Hymenoptera Genome Database (HGD) is an informatics resource supporting genomics of hymenopteran insect species. This relational database implements open-source software and components providing access to curated data contributed by an extensive, active research community. HGD includes the genome sequences and annotation data of honey bee _Apis mellifera_ and its pathogens ("http://BeeBase.org":BeeBase.org) the parasitoid wasp _Nasonia vitripennis_ ("http://NasoniaBase.org":NasoniaBase.org) and a portal to the genomes of six species of ants. Together, these species cover approximately 200 MY in the phylogeny of Hymenoptera, allowing to leverage genetic, genome sequence, and gene expression data, as well as the biological knowledge of related model organisms. The availability of resources across an order greatly facilitates comparative genomics and enhances our understanding of the biology of agriculturally important Hymenoptera species through genomics. HGD has supported research contributions from an extensive community from almost 80 institutions in 14 countries. Community annotation efforts are made possible thanks to a remote connection to a Chado database by Apollo Genome Annotation client software. Curated data at HGD includes predicted and annotated gene sets supported with evidence tracks such as ESTs/cDNAs, small RNA sequences and GC composition domains. Data at HGD can be queried using genome browsers and / or BLAST/PSI-BLAST servers, and it may also be downloaded to perform local searches. We encourage the public to access and contribute data to HGD at "http://HymenopteraGenome.org":HymenopteraGenome.org.

This poster contains material included in an article accepted for publication in Nucl. Acids Res.©: 2011. The Database Issue. Published by Oxford University Press

Variation in Intraoperative and Postoperative Utilization for 3 Common General Surgery Procedures.

ObjectiveThe aim of this study was to understand variation in intraoperative and postoperative utilization for common general surgery procedures.Summary background dataReducing surgical costs is paramount to the viability of hospitals.MethodsRetrospective analysis of electronic health record data for 7762 operations from 2 health systems. Adult patients undergoing laparoscopic cholecystectomy, appendectomy, and inguinal/femoral hernia repair between November 1, 2013 and November 30, 2017 were reviewed for 3 utilization measures: intraoperative disposable supply costs, procedure time, and postoperative length of stay (LOS). Crossed hierarchical regression models were fit to understand case-mixed adjusted variation in utilization across surgeons and locations and to rank surgeons.ResultsThe number of surgeons performing each type of operation ranged from 20 to 63. The variation explained by surgeons ranged from 8.9% to 38.2% for supply costs, from 15.1% to 54.6% for procedure time, and from 1.3% to 7.0% for postoperative LOS. The variation explained by location ranged from 12.1% to 26.3% for supply costs, from 0.2% to 2.5% for procedure time, and from 0.0% to 31.8% for postoperative LOS. There was a positive correlation (ρ = 0.49, P = 0.03) between surgeons' higher supply costs and longer procedure times for hernia repair, but there was no correlation between other utilization measures for hernia repair and no correlation between any of the utilization measures for laparoscopic appendectomy or cholecystectomy.ConclusionsSurgeons are significant drivers of variation in surgical supply costs and procedure time, but much less so for postoperative LOS. Intraoperative and postoperative utilization profiles can be generated for individual surgeons and may be an important tool for reducing surgical costs

A high resolution RH map of the bovine major histocompatibility complex

<p>Abstract</p> <p>Background</p> <p>The cattle MHC is termed the bovine leukocyte antigen (BoLA) and, along with the MHCs of other ruminants, is unique in its genomic organization. Consequently, correct and reliable gene maps and sequence information are critical to the study of the BoLA region. The bovine genome sequencing project has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from each other and from conventional gene maps in the BoLA region. To independently compare the accuracies of the different sequence assemblies, we have generated a high resolution map of BoLA using a 12,000_radradiation hybrid panel. Seventy-seven unique sequence tagged site (STS) markers chosen at approximately 50 kb intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions of the bovine MHC were mapped on a 12,000_radbovine radiation hybrid (RH) panel to evaluate the different assemblies of the bovine genome sequence.</p> <p>Results</p> <p>Analysis of the data generated a high resolution RH map of BoLA that was significantly different from the Btau_3.1 assembly of the bovine genome but in good agreement with the Btau_4.0 assembly. Of the few discordancies between the RH map and Btau_4.0, most could be attributed to closely spaced markers that could not be precisely ordered in the RH panel. One probable incorrectly-assembled sequence and three missing sequences were noted in the Btau_4.0 assembly. The RH map of BoLA is also highly concordant with the sequence-based map of HLA (NCBI build 36) when reordered to account for the ancestral inversion in the ruminant MHC.</p> <p>Conclusion</p> <p>These results strongly suggest that studies using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of the Btau_4.0 assembly and indicate that additional research is needed to produce a complete assembly of the BoLA genomic sequences.</p

Trees Grow on Money: Urban Tree Canopy Cover and Environmental Justice

This study examines the distributional equity of urban tree canopy (UTC) cover for Baltimore, MD, Los Angeles, CA, New York, NY, Philadelphia, PA, Raleigh, NC, Sacramento, CA, and Washington, D.C. using high spatial resolution land cover data and census data. Data are analyzed at the Census Block Group levels using Spearman\u27s correlation, ordinary least squares regression (OLS), and a spatial autoregressive model (SAR). Across all cities there is a strong positive correlation between UTC cover and median household income. Negative correlations between race and UTC cover exist in bivariate models for some cities, but they are generally not observed using multivariate regressions that include additional variables on income, education, and housing age. SAR models result in higher r-square values compared to the OLS models across all cities, suggesting that spatial autocorrelation is an important feature of our data. Similarities among cities can be found based on shared characteristics of climate, race/ethnicity, and size. Our findings suggest that a suite of variables, including income, contribute to the distribution of UTC cover. These findings can help target simultaneous strategies for UTC goals and environmental justice concerns

Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor

Factor VIII (fVIII) is a procoagulant protein that binds to activated factor IX (fIXa) on platelet surfaces to form the intrinsic tenase complex. Due to the high immunogenicity of fVIII, generation of antibody inhibitors is a common occurrence in patients during hemophilia A treatment and spontaneously occurs in acquired hemophilia A patients. Non-classical antibody inhibitors, which block fVIII activation by thrombin and formation of the tenase complex, are the most common anti-C2 domain pathogenic inhibitors in hemophilia A murine models and have been identified in patient plasmas. In this study, we report on the X-ray crystal structure of a B domain-deleted bioengineered fVIII bound to the non-classical antibody inhibitor, G99. While binding to G99 does not disrupt the overall domain architecture of fVIII, the C2 domain undergoes an ~8 Å translocation that is concomitant with breaking multiple domain-domain interactions. Analysis of normalized B-factor values revealed several solvent-exposed loops in the C1 and C2 domains which experience a decrease in thermal motion in the presence of inhibitory antibodies. These results enhance our understanding on the structural nature of binding non-classical inhibitors and provide a structural dynamics-based rationale for cooperativity between anti-C1 and anti-C2 domain inhibitors

Structure of Blood Coagulation Factor VIII in Complex with Anti-C2 Domain Inhibitory Antibody

Factor VIII (fVIII) is a procoagulant protein that binds to activated factor IX (fIXa) on platelet surfaces to form the intrinsic tenase complex. Due to the high immunogenicity of fVIII, generation of antibody inhibitors is a common occurrence in patients during hemophilia A treatment and spontaneously occurs in acquired hemophilia A patients. Non-classical antibody inhibitors, which block fVIII activation by thrombin and formation of the tenase complex, are the most common anti-C2 domain pathogenic inhibitors in hemophilia A murine models and have been identified in patient plasmas. In this study, we report on the X-ray crystal structure of a B domain-deleted bioengineered fVIII bound to the non classical antibody inhibitor, G99. While binding to G99 does not disrupt the overall domain architecture of fVIII, the C2 domain undergoes an ~8 Å translocation that is concomitant with breaking multiple domain-domain interactions. Analysis of normalized B-factor values revealed several solvent-exposed loops in the C1 and C2 domains which experience a decrease in thermal motion in the presence of inhibitory antibodies. Our results enhance our understanding on the structural nature of binding non-classical inhibitors and provide a structural dynamics-based rationale for cooperativity between anti-C domain inhibitors

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Bovine Genome Database: integrated tools for genome annotation and discovery

The Bovine Genome Database (BGD; http://BovineGenome.org) strives to improve annotation of the bovine genome and to integrate the genome sequence with other genomics data. BGD includes GBrowse genome browsers, the Apollo Annotation Editor, a quantitative trait loci (QTL) viewer, BLAST databases and gene pages. Genome browsers, available for both scaffold and chromosome coordinate systems, display the bovine Official Gene Set (OGS), RefSeq and Ensembl gene models, non-coding RNA, repeats, pseudogenes, single-nucleotide polymorphism, markers, QTL and alignments to complementary DNAs, ESTs and protein homologs. The Bovine QTL viewer is connected to the BGD Chromosome GBrowse, allowing for the identification of candidate genes underlying QTL. The Apollo Annotation Editor connects directly to the BGD Chado database to provide researchers with remote access to gene evidence in a graphical interface that allows editing and creating new gene models. Researchers may upload their annotations to the BGD server for review and integration into the subsequent release of the OGS. Gene pages display information for individual OGS gene models, including gene structure, transcript variants, functional descriptions, gene symbols, Gene Ontology terms, annotator comments and links to National Center for Biotechnology Information and Ensembl. Each gene page is linked to a wiki page to allow input from the research community