bluuebunny/crossref_metadata_2025_split huggingface dataset:
BugBase predicts organism-level microbiome phenotypes
Authors: Ward Tonya , Larson Jake , Meulemans Jeremy , Hillmann Ben , Lynch Joshua , Sidiropoulos Dimitri , Spear John R. , Caporaso Greg , Blekhman Ran , Knight Rob , Fink Ryan , Knights Dan 
Published: May 2017

AbstractShotgun metagenomics and marker gene amplicon sequencing can be used to directly measure or predict the functional repertoire of the microbiotaen masse, but current methods do not readily estimate the functional capability of individual microorganisms. Here we present BugBase, an algorithm that predicts organism-level coverage of functional pathways as well as biologically interpretable phenotypes such as oxygen tolerance, Gram staining and pathogenic potential, within complex microbiomes using either whole-genome shotgun or marker gene sequencing data. We find BugBase’s organism-level pathway coverage predictions to be statistically higher powered than current ‘bag-of-genes’ approaches for discerning functional changes in both host-associated and environmental microbiomes.
Exon-based phylogenomics strengthens the phylogeny of Neotropical cichlids and identifies remaining conflicting clades (Cichliformes: Cichlidae: Cichlinae)
Authors: Ilves Katriina L. , Torti Dax , Lépez-Fernández Hernán 
Published: May 2017

AbstractThe phenotypic, geographic, and species diversity of cichlid fishes have made them a group of great interest for studying evolutionary processes. Here we present a targeted-exon next-generation sequencing approach for investigating the evolutionary relationships of cichlid fishes (Cichlidae), with focus on the Neotropical subfamily Cichlinae using a set of 923 primarily single-copy exons designed through mining of the Nile tilapia (Oreochromis niloticus) genome. Sequence capture and assembly were robust, leading to a complete dataset of 415 exons for 139 species (147 terminals) that consisted of 128 Neotropical species, six African taxa, and five Indo-Malagasy cichlids. Gene and species trees were calculated using alternative partitioning schemes and reconstruction methods. In general, all methods yielded similar topologies to previously hypothesized relationships within the Cichlinae and clarified several relationships that were previously poorly supported or in conflict. Additional work will be needed to fully resolve all aspects of Cichlinae phylogeny. Overall, this approach yielded a well-resolved phylogeny of Neotropical cichlids that will be of utility for future assessments of the evolutionary and ecological processes within this diverse group of fishes. Furthermore, the general methodology employed here of exon targeting and capture should be applicable to any group of organisms with the availability of a reference genome.
Identification of Three Additional Genes Contiguous to the Glucocerebrosidase Locus on Chromosome 1q21: Implications for Gaucher Disease
Authors: Winfield Suzanne L. , Tayebi Nahid , Martin Brian M. , Ginns Edward I. , Sidransky Ellen 
Published: May 2017

Gaucher disease results from the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3.2.1.45). Although the functional gene for glucocerebrosidase (GBA) and its pseudogene (psGBA), located in close proximity on chromosome 1q21, have been studied extensively, the flanking sequence has not been well characterized. The recent identification of human metaxin (MTX) immediately downstream of psGBA prompted a closer analysis of the sequence of the entire region surrounding theGBA gene. We now report the genomic DNA sequence and organization of a 75-kb region around GBA, including the duplicated region containing GBA and MTX. The origin and endpoints of the duplication leading to the pseudogenes forGBA and MTX are now clearly established. We also have identified three new genes within the 32 kb of sequence upstream toGBA, all of which are transcribed in the same direction asGBA. Of these three genes, the gene most distal toGBA is a protein kinase (clk2). The second gene,propin1, has a 1.5-kb cDNA and shares homology to a rat secretory carrier membrane protein 37 (SCAMP37). Finally,cote1, a gene of unknown function lies most proximal toGBA. The possible contributions of these closely arrayed genes to the more atypical presentations of Gaucher disease is now under investigation.[The sequence data described in this paper have been submitted to the GenBank data library under accession no.AF023268.]
Steady-State Transcript Levels of the Porphobilinogen Deaminase Gene in Patients with Acute Intermittent Porphyria
Authors: Mustajoki Sami , Kauppinen Raili , Mustajoki Pertti , Suomalainen Anu , Peltonen Leena 
Published: May 2017

PCR-based solid-phase minisequencing method was used to analyze the steady-state mRNA levels of the porphobilinogen deaminase gene in eight patients with acute intermittent porphyria. The patients had the earlier characterized mutations 517C → T (R173W), 518G → A (R173Q), 673C → G (R225G), 673C → T (R225X), 713T → G (L278P), and 1073delA (frame shift). All mutations, except the missense mutation 517C → T in exon 10, affected the steady-state transcript levels of the mutant allele. The mutant mRNA levels in lymphocytes varied from 5% to 95% of the corresponding wild-type allele levels. In contrast to the CRIM-negative mutation 517C → T, the CRIM-positive mutation in the same codon 518G → A resulted in reduction of the steady-state transcript level of the mutant allele to 65% of that of the normal allele. The two mutations, 673C → G or T, affecting the same nucleotide in exon 12 also differed considerably in their effect on mRNA levels: The transcript level of the allele with a missense mutation was decreased to 80% of that of the normal allele, whereas a nonsense mutation at the same position resulted in a dramatic decrease (fivefold) in the levels of the mutant transcript. Our data showed large variations between the levels of mutant transcript in AIP patients and these variations did not correlate either to CRIM class, to the location of the disease causing mutation in the PBGD gene, or to the clinical phenotype of AIP.[The sequence data described in this paper have been submitted to EMBL under accession nos. AJ002126–AJ002137.]
The Comparative Genomic Structure and Sequence of the Surfeit Gene Homologs in the Puffer Fish Fugu rubripes and their Association with CpG-Rich Islands
Authors: Armes Niall , Gilley Jonathan , Fried Mike 
Published: May 2017

The puffer fish Fugu rubripes (Fugu) has a compact genome approximately one-seventh the size of man, mainly owing to small intron size and the presence of few dispersed repetitive DNA elements, which greatly facilitates the study of its genes at the genomic level. It has been shown previously that, whereas the Surfeit genes are tightly clustered at a single locus in mammals and birds, the genes are found at three separate loci in the Fugu genome. Here, Fugu gene homologs of all six Surfeit genes (Surf-1 to Surf-6) have been cloned and sequenced, and their gene structure has been compared with that of their mammalian and avian homologs. The predicted protein products of each gene are well conserved between vertebrate species, and in most cases their gene structures are identical to their mammalian and avian homologs except for the Fugu Surf-6 gene, which was found to lack an intron present in the mouse gene. In addition, we have identified conserved regulatory elements at the 5′ and 3′ ends of theSurf-3/rpL7a gene by comparison with the mammalian and chickenSurf-3/rpL7a gene homologs, including the presence of a polypyrimidine tract at the extreme 5′ end of this ribosomal protein gene. The Fugu Surfeit gene homologs appear to be associated with CpG-rich islands, like the Surfeit genes in higher vertebrates, but these Fugu CpG islands are similar to the nonclassical islands characteristic of other fish species. Our observations support the use of the Fugu genome to study vertebrate gene structure, to predict the structure of mammalian genes, and to identify vertebrate regulatory elements.[The sequence data described in this paper have been submitted to the data library under accession nos. Y15170 (Surf-2, Surf-4), Y15171(Surf-3, Surf-1, Surf-6), and Y15172(Surf-5.)]
A First-Generation Whole Genome–Radiation Hybrid Map Spanning the Mouse Genome
Authors: McCarthy Linda C. , Terrett Jonathan , Davis Maria E. , Knights Catherine J. , Smith Angela L. , Critcher Ricky , Schmitt Karin , Hudson Jim , Spurr Nigel K. , Goodfellow Peter N. 
Published: May 2017

We have assembled a first-generation anchor map of the mouse genome using a panel of 94 whole-genome–radiation hybrids (WG–RHs) and 271 sequence-tagged sites (STSs). This is the first genome-wide RH anchor map of a model organism. All of the STSs have been previously localized on the genetic map and are located 8.8 Mb apart on average. This mouse WG–RH panel, known as T31, has an average retention frequency of 27.6% and an estimated potential resolution of 145 kb, making it a powerful resource for efficient large-scale expressed sequence tag mapping.[All of the mapping data for the maps presented here have been deposited at the Research Genetics, Inc., web site and can be freely accessed and downloaded athttp://www.resgen.com/.]
Large-Scale Comparative Sequence Analysis of the Human and Murine Bruton’s Tyrosine Kinase Loci Reveals Conserved Regulatory Domains
Authors: Oeltjen John C. , Malley Tracy M. , Muzny Donna M. , Miller Webb , Gibbs Richard A. , Belmont John W. 
Published: May 2017

Large-scale genomic DNA sequencing of orthologous and paralogous loci in different species should contribute to a basic understanding of the evolution of both the protein-coding regions and noncoding regulatory elements. We compared 93 kb of human sequence to 89 kb of mouse sequence in the Bruton’s tyrosine kinase (BTK) region. In addition to showing the conservation of both position and orientation of the five functionally unrelated genes in the region (BTK, α-d-galactosidase A, L44L, FTP-3, and FCI-12), the comparison revealed conservation of clusters of noncoding sequence flanking the first exon of each gene. Furthermore, in the sequence comparison at the BTK locus, the conservation of clusters of noncoding sequence extends throughout the locus; the noncoding sequence is more highly conserved in the BTK locus in comparison to the flanking loci. This suggests a correlation with the complex developmental regulation of expression of btk. To determine whether a highly conserved 3.5-kb segment flanking the first exon of BTK contains transcriptional regulatory signals, we tested various portions of the segment for promoter and expression activity in several appropriate cell lines. The results demonstrate the contribution of the conserved region flanking the first exon to the cell lineage-specific expression pattern of btk. These data show the usefulness of large scale sequence comparisons to focus investigation on regions of noncoding sequence that play essential roles in complex gene regulation.[The sequence data described in this paper have been submitted to GenBank under accession nos.U78027andU58105.]
Analysis of the 1.1-Mb Human α/δ T-Cell Receptor Locus with Bacterial Artificial Chromosome Clones
Authors: Boysen Cecilie , Simon Melvin I. , Hood Leroy 
Published: May 2017

Bacterial artificial chromosome (BAC) clones are effective mapping and sequencing reagents. The 1.1-Mb α/δ T-cell receptor locus of humans was mapped and partially sequenced with BAC clones. Seventeen BAC clones covered the 1.1-Mb α/δ locus, with the exception of one small gap that was expected from the coverage that a 3.7-fold BAC library is likely to provide. The end sequences of the BAC inserts could be obtained directly from the BAC DNA by sequencing with the chain terminator chemistry. Five complete BAC inserts were sequenced directly by the shotgun approach. The ends of the 17 BAC inserts were distributed evenly across the locus. By several independent criteria, the BAC clones faithfully represented the genomic DNA, with the exception of a single clone with a 68-kb deletion. These BAC features led to the proposal of a new approach to sequence the human genome.[The sequenced BAC clones, BAC956, BAC810, BAC480, BAC378, and BAC129, have been submitted to GenBank under accession nos.U85199, U85198, U85197, U85196, and U85195, respectively.]
Cloning, Characterization, and Copy Number of the Murine Survival Motor Neuron Gene: Homolog of the Spinal Muscular Atrophy-Determining Gene
Authors: DiDonato Christine J. , Chen Xiao-Ning , Noya David , Korenberg Julie R. , Nadeau Joseph H. , Simard Louise R. 
Published: May 2017

Because of a 500-kb inverted duplication, there are two copies of the survival motor neuron (SMN) gene in humans, cenSMN and telSMN. Both genes produce identical ubiquitously expressed transcripts; however, only mutations in telSMN are responsible for spinal muscular atrophy (SMA), the second most common autosomal recessive childhood disease. We have cloned the murine homolog Smn and mapped the gene to Chromosome 13 within the conserved syntenic region of human chromosome 5q13. We show that the Smn transcript (1.4 kb) is expressed as early as embryonic day 7. In contrast to humans, we found no evidence of alternative splicing. The predicted amino acid sequence between mouse and human SMN is 82% identical, and a putative nuclear localization signal is conserved. FISH data indicate that the duplication of the SMA region observed in humans is not present in the mouse. We also found no evidence of multiple Smn genes using Southern blot hybridization and single-strand conformation analysis. Using these methods, we detected at least four copies of Naipexon 5 clustering distal to Smn. Finally, three biallelic markers were identified within the Smn coding region; two are silent polymorphisms, whereas the third changes a cysteine residue to a tyrosine residue in exon 7. Overall, our results indicate thatSmn is single copy within the mouse genome, which should facilitate gene disruption experiments to create an animal model of SMA.[The murine Smn cDNA sequence has been submitted to GenBank under accession no. U77714. The Mouse Genome Database accession no. for FISH mapping of Smn andNaip is MGD-INEX-31 and for the genetic mapping of theSmn exon 2b microsatellite marker is MGD-CREX-705.]
Clone–Contig and STS Maps of the Hereditary Hemochromatosis Region on Human Chromosome 6p21.3–p22
Authors: Lauer Peter , Meyer Nicole C. , Prass Cynthia E. , Starnes Steven M. , Wolff Roger K. , Gnirke Andreas 
Published: May 2017

YAC-based and bacterial-clone based STS-content maps were constructed that served as the framework physical maps for the positional cloning of a candidate gene for hereditary hemochromatosis. The YAC-based map comprises 43 YACs and 86 STS and spans ∼8 Mb of DNA between the class I region of the major histocompatibility complex on human chromosome 6p21.3 and D6S276 in 6p22. Comparison with published maps revealed a hole in the MIT/Whitehead and CEPH YAC maps that includes the immediate region around the hemochromatosis gene itself. Approximately 3 Mb of DNA was covered by a bacterial clone contig that consists of 38 BACs, 45 PACs, 26 P1 clones and one λ phage. The bacterial clone-based STS map comprises 153 STSs. A contiguous block of 8 STSs could be amplified from both human chromosome 6 and 5. Further characterization of selected STSs and bacterial clones by radiation hybrid mapping and fluorescence in situ hybridization, respectively, revealed the presence of a multicopy DNA segment, more than one bacterial clone length in size, which is duplicated near the chromosome-6 centromere and part of which is present in multiple copies on chromosome 5. Possible implications of the incomplete public YAC–contig map and of the multicopy segment for physical mapping and linkage disequilibrium studies of the hemochromatosis candidate region are discussed.[The sequence data described in this paper have been submitted to GenBank under accession nos. G31205–G31325.]
Computational and Biological Analysis of 680 kb of DNA Sequence from the Human 5q31 Cytokine Gene Cluster Region
Authors: Frazer Kelly A. , Ueda Yukihiko , Zhu Yiwen , Gifford Vincent R. , Garofalo Maria R. , Mohandas Narla , Martin Christopher H. , Palazzolo Michael J. , Cheng Jan-Fang , Rubin Edward M. 
Published: May 2017

With the human genome project advancing into what will be a 7- to 10-year DNA sequencing phase, we are presented with the challenge of developing strategies to convert genomic sequence data, as they become available, into biologically meaningful information. We have analyzed 680 kb of noncontiguous DNA sequence from a 1-Mb region of human chromosome 5q31, coupling computational analysis with gene expression studies of tissues isolated from humans as well as from mice containing human YAC transgenes. This genomic interval has been noted previously for containing the cytokine gene cluster and a quantitative trait locus associated with inflammatory diseases. Our analysis identified and verified expression of 16 new genes, as well as 7 previously known genes. Of the total of 23 genes in this region, 78% had similarity matches to sequences in protein databases and 83% had exact expressed sequence tag (EST) database matches. Comparative mapping studies of eight of the new human genes discovered in the 5q31 region revealed that all are located in the syntenic region of mouse chromosome 11q. Our analysis demonstrates an approach for examining human sequence as it is made available from large sequencing programs and has resulted in the discovery of several biomedically important genes, including a cyclin, a transcription factor that is homologous to an oncogene, a protein involved in DNA repair, and several new members of a family of transporter proteins.[The sequence data described in this paper are available via the internet athttp://www-hgc.lbl.gov/sequencearchive.html.]
Cloning of Two Human Homologs of the Drosophila single-minded Gene SIM1 on Chromosome 6q and SIM2 on 21q Within the Down Syndrome Chromosomal Region
Authors: Chrast Roman , Scott Hamish S. , Chen Haiming , Kudoh Jun , Rossier Colette , Minoshima Shinsei , Wang Yimin , Shimizu Nobuyoshi , Antonarakis Stylianos E. 
Published: May 2017

As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3–q21 and 21q22.2, respectively;SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, andDrosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3′ ends. Northern blot analysis revealed one mRNA SIM1 species of ∼9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis.[The sequence data described in this paper have been submitted to GenBank under accession nos. U70212, U80456, U80457, and AB003185.]
PowerBLAST: A New Network BLAST Application for Interactive or Automated Sequence Analysis and Annotation
Authors: Zhang Jinghui , Madden Thomas L. 
Published: May 2017

As the rate of DNA sequencing increases, analysis by sequence similarity search will need to become much more efficient in terms of sensitivity, specificity, automation potential, and consistency in annotation. PowerBLAST was developed, in part, to address these problems. PowerBLAST includes a number of options for masking repetitive elements and low complexity subsequences. It also has the capacity to restrict the search to any level of NCBI’s taxonomy index, thus supporting “comparative genomics” applications. Postprocessing of the BLAST output using the SIM series of algorithms produces optimal, gapped alignments, and multiple alignments when a region of the query sequence matches multiple database sequences. PowerBLAST is capable of processing sequences of any length because it divides long query sequences into overlapping fragments and then merges the results after searching. The results may be viewed graphically, as a textual representation, or as an HTML page with links to GenBank and Entrez. For matching database sequences, annotated features are superimposed on the aligned query sequence in the output, thus greatly increasing the ease of interpretation. Such features may be used for automated annotation of new sequence because PowerBLAST output in ASN.1 form may be “dragged and dropped” into NCBI’s Sequin program for sequence annotation and submission. PowerBLAST is capable of analyzing and annotating a 100-kb query in 60 min on NCBI’s BLAST server.[THC BLAST is available athttp://www.ncbi.nlm.nih.gov/cgi-bin/THCBlast/nph-thcblast]
High-Resolution Physical and Transcriptional Mapping of the Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Locus on Chromosome 21q22.3 by FISH
Authors: Aaltonen Johanna , Horelli-Kuitunen Nina , Fan Jian-Bing , Björses Petra , Perheentupa Jaakko , Myers Richard , Palotie Aarno , Peltonen Leena 
Published: May 2017

Autoimmune–polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED, PGD type I) is an autosomal recessive disease enriched in the Finnish population. Previously, we have assigned APECED to a 2.6-cM interval on chromosome 21q22.3 by linkage analysis in 14 Finnish families. This subtelomeric region of 21q22.3 seems to have sequence features resulting in its under-representation in large insert genomic libraries, and only a few large insert clones have been available for positional cloning to date. Here, we report the refined localization of the APECED gene and a visual physical map of 800 kb covering the critical chromosomal region for the gene. In the construction of the physical map, the recently developed fiber FISH techniques were essential for the orientation of the cosmid P1, PAC, and BAC clones in relation to each other. We also localized two cDNAs within this genomic region by fiber FISH combined with the highly sensitive tyramide-based detection method. These data will facilitate the final cloning of theAPECED gene and any other novel gene in this complex genomic region.[On-line supplement for primer sequences, PCR product size, and annealing temperatures is available athttp://www.cshl.org/gr.]