bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Structure of the Human Multiple Exostoses 2 Gene and Characterization of Homologs in Mouse andCaenorhabditis elegans
Authors: Clines Gregory A. , Ashley Jennifer A. , Shah Sangeeta , Lovett Michael 
Published: May 2017

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by multiple cartilage-capped outgrowths from the epiphyses of long bones. In some cases, these osteochondromas progress to malignant chondrosarcomas. Alterations in at least three genes (EXT1, EXT2, and EXT3) can cause this disorder. Two of these have been isolated (EXT1 andEXT2) and encode related members of a putative tumor suppressor family. We report here the genomic structure of the humanEXT2 gene consisting of 14 exons (plus 2 alternative exons) covering an estimated 108 kb of chromosome 11p11–13. We have derived the DNA sequences at all exon/intron boundaries throughout this gene—information that is important for the detailed study of mutations in EXT2. We have also characterized the mouse EXT2cDNA and have mapped the mouse locus to chromosome 2 betweenD2Mit15 and Pax6. This mouse homolog should enable transgenic knockout experiments to be initiated to further elucidate gene function. Interestingly, sequence comparisons reveal that the human and mouse EXT genes have at least two homologs in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. This observation opens the way for a functional analysis of these genes in nematodes and other lower organisms.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. U67353–U67368 and U67837.]
The E6–AP Ubiquitin–Protein Ligase (UBE3A) Gene Is Localized within a Narrowed Angelman Syndrome Critical Region
Authors: Sutcliffe James S. , Jiang Yong-hui , Galjaard Robert-Jan , Matsuura Toshinobu , Fang Ping , Kubota Takeo , Christian Susan L. , Bressler Jan , Cattanach Bruce , Ledbetter David H. , Beaudet Arthur L. 
Published: May 2017

Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are distinct clinical phenotypes resulting from maternal and paternal deficiencies, respectively, in human chromosome 15q11–q13. Although several imprinted, paternally expressed transcripts have been identified within the PWS candidate region, no maternally expressed gene has yet been identified within the AS candidate region. We have developed an integrated physical map spanning the PWS and AS candidate regions and localized two breakpoints, including a cryptic t(14;15) translocation associated with AS and a non-AS 15q deletion, which substantially narrow the AS candidate region to ∼250 kb. Mapping data indicate that the entire transcriptional unit of the E6–AP ubiquitin–protein ligase (UBE3A) gene lies within the AS region. TheUBE3Alocus expresses a transcript of ∼5 kb at low to moderate levels in all tissues tested. The mouse homolog ofUBE3Awas cloned and sequenced revealing a high degree of conservation at nucleotide and protein levels. Northern and RT–PCR analysis ofUbe3aexpression in mouse tissues from animals with segmental, paternal uniparental disomy failed to detect substantially reduced or absent expression compared to control animals, failing to provide any evidence for maternal-specific expression from this locus. Recent identification of de novo truncating mutations inUBE3Ataken with these observations indicates that mutations inUBE3Acan lead to AS and suggests that this locus may encode both imprinted and biallelically expressed products.[The sequence data described in this paper have been submitted to the GenBank data library under accession no.U82122.]
Genomic Organization of the Human PEX Gene Mutated in X-Linked Dominant Hypophosphatemic Rickets
Authors: Francis Fiona , Strom Tim M. , Hennig Steffen , Böddrich Annett , Lorenz Bettina , Brandau Oliver , Mohnike Klaus L. , Cagnoli Michele , Steffens Christina , Klages Sven , Borzym Katja , Pohl Thomas , Oudet Claudine , Econs Michael J. , Rowe Peter S.N. , Reinhardt Richard , Meitinger Thomas , Lehrach Hans 
Published: May 2017

X-linked dominant hypophosphatemic rickets (HYP) is the most common form of hereditary rickets. Recently we have cloned thePEX gene and shown it to be mutated and deleted in HYP individuals. We have now completely sequenced a 243-kb genomic region containing PEX and have identified all intron–exon boundary sequences. We show that PEX, homologous to members of a neutral endopeptidase family, has an exon organization that is very similar to neprilysin. We have performed an extensive mutation analysis examining all 22 PEX coding exons in 29 familial and 14 sporadic cases of hypophosphatemia. Sequence changes include missense, frameshift, nonsense, and splice site mutations and intragenic deletions. A mutation was found in 25 (86%) of the 29 familial cases and 8 (57%) of the 14 sporadic cases. Our data provide the first evidence that most of the familial and also a large number of the sporadic cases of hypophosphatemia are caused by loss-of-function mutations in PEX.[The sequence data described in this paper have been submitted to GenBank under accession nos.Y08111–Y08132 and Y10196.]
Ataxia-Telangiectasia Locus: Sequence Analysis of 184 kb of Human Genomic DNA Containing the Entire ATM Gene
Authors: Platzer Matthias , Rotman Galit , Bauer David , Uziel Tamar , Savitsky Kinneret , Bar-Shira Anat , Gilad Shlomit , Shiloh Yosef , Rosenthal André 
Published: May 2017

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity, and cancer predisposition. The genomic organization of the A-T gene, designatedATM, was established recently. To date, more than 100 A-T-associated mutations have been reported in the ATM gene that do not support the existence of one or several mutational hotspots. To allow genotype/phenotype correlations it will be important to find additional ATM mutations. The nature and location of the mutations will also provide insights into the molecular processes that underly the disease. To facilitate the search for ATMmutations and to establish the basis for the identification of transcriptional regulatory elements, we have sequenced and report here 184,490 bp of genomic sequence from the human 11q22–23 chromosomal region containing the entire ATM gene, spanning 146 kb, and 10 kb of the 5′-region of an adjacent gene named E14/NPAT.The latter shares a bidirectional promoter with ATM and is transcribed in the opposite direction. The entire region is transcribed to ∼85% and translated to 5%. Genome-wide repeats were found to constitute 37.2%, with LINE (17.1%) and Alu (14.6%) being the main repetitive elements. The high representation of LINE repeats is attributable to the presence of three full-length LINE-1s, inserted in the same orientation in introns 18 and 63 as well as downstream of the ATM gene. Homology searches suggest that ATM exon 2 could have derived from a mammalian interspersed repeat (MIR). Promoter recognition algorithms identified divergent promoter elements within the CpG island, which lies between the ATM andE14/NPAT genes, and provide evidence for a putative secondATM promoter located within intron 3, immediately upstream of the first coding exon. The low G + C level (38.1%) of theATM locus is reflected in a strongly biased codon and amino acid usage of the gene.[The sequence data described in this paper have been submitted to the GenBank data library under accession no. U82828.]
Sequencing and Functional Analysis of the SNRPN Promoter: In Vitro Methylation Abolishes Promoter Activity
Authors: Huq A.H.M. Mahbubul , Sutcliffe James S. , Nakao Mitsuyoshi , Shen Ying , Gibbs Richard A. , Beaudet Arthur L. 
Published: May 2017

The gene encoding the small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) maps to the Prader–Willi syndrome critical region on chromosome 15 and is expressed preferentially from the paternal allele. A CpG island encompassing the first exon ofSNRPN is methylated on the inactive maternal allele. DNA sequence was determined for a cosmid containing the first three exons of SNRPN and extending 20 kb upstream and 15 kb downstream from the CpG island. This region is extremely rich in Aluelements and other repetitive sequences and contains a single CpG island, which includes numerous short direct repeat sequences. Functional analysis of the first exon revealed strong promoter activity for a 260-bp fragment extending 207 bp upstream from the exon. In vitro methylation of this 260-bp fragment abolished promoter activity completely, suggesting that the silencing of the maternalSNRPN allele may be a direct consequence of methylation of the promoter region.[The sequence data described in this paper have been submitted to the GenBank data library under accession no.U41384.]
A Physical Map of Human Chromosome 7: An Integrated YAC Contig Map with Average STS Spacing of 79 kb
Authors: Bouffard Gerard G. , Idol Jacquelyn R. , Braden Valerie V. , Iyer Leslie M. , Cunningham Aimee F. , Weintraub Lauren A. , Touchman Jeffrey W. , Mohr-Tidwell Rose M. , Peluso Dale C. , Fulton Robert S. , Ueltzen Melinda S. , Weissenbach Jean , Magness Charles L. , Green Eric D. 
Published: May 2017

The construction of highly integrated and annotated physical maps of human chromosomes represents a critical goal of the ongoing Human Genome Project. Our laboratory has focused on developing a physical map of human chromosome 7, a ∼170-Mb segment of DNA that corresponds to an estimated 5% of the human genome. Using a yeast artificial chromosome (YAC)-based sequence-tagged site (STS)-content mapping strategy, 2150 chromosome 7-specific STSs have been established and mapped to a collection of YACs highly enriched for chromosome 7 DNA. The STSs correspond to sequences generated from a variety of DNA sources, with particular emphasis placed on YAC insert ends, genetic markers, and genes. The YACs include a set of relatively nonchimeric clones from a human–hamster hybrid cell line as well as clones isolated from total genomic libraries. For map integration, we have localized 260 STSs corresponding to Genethon genetic markers and 259 STSs corresponding to markers ordered by radiation hybrid (RH) mapping on our YAC contigs. Analysis of the data with the program SEGMAP results in the assembly of 22 contigs that are “anchored” on the Genethon genetic map, the RH map, and/or the cytogenetic map. These 22 contigs are ordered relative to one another, are (in all but 3 cases) oriented relative to the centromere and telomeres, and contain >98% of the mapped STSs. The largest anchored YAC contig, accounting for most of 7p, contains 634 STSs and 1260 YACs. An additional 14 contigs, accounting for ∼1.5% of the mapped STSs, are assembled but remain unanchored on either the genetic or RH map. Therefore, these 14 “orphan” contigs are not ordered relative to other contigs. In our contig maps, adjacent STSs are connected by two or more YACs in >95% of cases. With 2150 mapped STSs, our map provides an average STS spacing of ∼79 kb. The physical map we report here exceeds the goal of 100-kb average STS spacing and should provide an excellent framework for systematic sequencing of the chromosome.[Detailed information about the chromosome 7 physical map can be found at http://www.nhgri.nih.gov/DIR/GTB/CHR7or http://www.cshl.org/gr.]
An ∼1.2-Mb Bacterial Artificial Chromosome Contig Refines the Genetic and Physical Maps of the Lurcher Locus on Mouse Chromosome 6
Authors: De Jager Philip L. , Zuo Jian , Heintz Nathaniel 
Published: May 2017

Lurcher (Lc) is a semidominant mouse mutant that displays a characteristic ataxia in the heterozygous state beginning in the third postnatal week. This symptom results from a neurodegenerative event in the cerebellum: There is a catastrophic loss of Purkinje cells in the heterozygote animal between postnatal days 10 and 15. In an effort to identify the genetic lesion borne by Lc mice, we initiated a cloning project based on the position of the Lcmutation on mouse chromosome 6. We have extended our previous analysis of the genomic segment containing the Lc locus by isolating a set of stable and manipulable genomic clones called bacterial artificial chromosomes (BACs) that cover this region of mouse chromosome 6. These clones provided a good substrate for the isolation of markers that were used to refine the physical map of the locus. Furthermore, 20 of these markers were mapped onto our (B6CBACa-Aw − J/A − Lc × CAST/Ei)F1 × B6CBACa-Aw − J/Abackcross, refining the genetic map and identifying two nonrecombinant markers (D6Rck354 and D6Rck355). These two markers, in conjunction with the closest flanking markers, were used to identify a 110-kb genomic segment that contains all four markers and hence contains the Lc locus. This small genomic segment, covered by multiple BACs, sets the stage for the final effort of this project—the identification of transcripts and of the mutation within theLc locus.[The Lt1 sequence has been submitted to GenBank as two ESTs; the accession numbers are U89356 andU89357.]
A High-Resolution Physical and Transcript Map of the Cri du Chat Region of Human Chromosome 5p
Authors: Church Deanna M. , Yang Julie , Bocian Maureen , Shiang Rita , Wasmuth John J. 
Published: May 2017

A high-resolution physical and transcription map has been generated of a 3.5-Mb region of 5p15.2 that is associated with the Cri du chat (CDC) syndrome. Utilizing a variety of resources including a natural deletion panel, a chromosome specific radiation hybrid panel, and YAC, PAC, and BAC genomic clones we have ordered >60 STSs within this region. Approximately 45% of these STSs were obtained from publicly available whole genome maps, thus allowing for integration of this map with currently available resources. Thirteen of these markers were ESTs. In addition, >70 exon trapped products have been mapped on the natural deletion panel and bacterial clone resource. The combination of these resources has allowed for the identification of 17 transcripts within this region, all of which represent candidate genes for CDC. Further characterization of the genomic contig also revealed that this region of 5p15 contains a large number of repetitive elements.[The sequence data described in this paper have been submitted to GenBank under accession nos. G31374–G31412,B07604–B07657. On-line supplementary material concerning markers used, primers, PCR product sizes, and annealing conditions is available athttp://www.cshl.org/gr.]
Multiplex Sequencing of 1.5 Mb of the Mycobacterium leprae Genome
Authors: Smith Douglas R. , Richterich Peter , Rubenfield Marc , Rice Philip W. , Butler Carol , Lee Hong-Mei , Kirst Susan , Gundersen Kristin , Abendschan Kari , Xu Qinxue , Chung Maria , Deloughery Craig , Aldredge Tyler , Maher James , Lundstrom Ronald , Tulig Craig , Falls Kathleen , Imrich Joan , Torrey Dana , Engelstein Marcy , Breton Gary , Madan Deepika , Nietupski Raymond , Seitz Bruce , Connelly Steven , McDougall Steven , Safer Hershel , Gibson Rene , Doucette-Stamm Lynn , Eiglmeier Karin , Bergh Staffan , Cole Stewart T. , Robison Keith , Richterich Laura , Johnson Jason , Church George M. , Mao Jen-i 
Published: May 2017

The nucleotide sequence of 1.5 Mb of genomic DNA fromMycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to ∼66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 rRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that ofMycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosisproteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.[The sequence data described in this paper have been submitted to GenBank under accession nos. L78811–L78829,U00010–U00023, U15180–U15184, U15186, U15187, L01095, L01536, L04666, and L01263. On-line supplementary information for Table 1 is available at http://www.cshl.org/gr.]
Development of a Comparative Genetic Linkage Map for Armigeres subalbatus Using Aedes aegyptiRFLP Markers
Authors: Ferdig Michael T. , Taft Andrew S. , Severson David W. , Christensen Bruce M. 
Published: May 2017

One of the causative agents of lympahtic filariasis is the nematode parasite Brugia malayi that requires a competent mosquito vector for its development and transmission. Armigeres subalbatus mosquitoes rapidly destroy invading B. malayimicrofilariae via a defense response known as melanotic encapsulation. We have constructed a genetic linkage map for this mosquito species using RFLP markers from Aedes aegypti. This heterologous approach was possible because of the conserved nature of the coding sequences used as markers and provided an experimental framework to evaluate the hypothesis that linkage and gene order are conserved between these mosquito species. Of the 56 Ae. aegypti markers tested, 77% hybridize to genomic DNA digests of Ar. subalbatus under stringent conditions, with 53% of these demonstrating strain-specific polymorphisms. Twenty-six Ae. aegypti markers have been mapped using an F2- segregatingAr. subalbatus population derived from a cross of strains originating in Japan and Malaysia. Linear order of these marker loci is highly conserved between the two species. Only 1 of these markers, LF92, was not linked in the manner predicted by the Ae. aegypti map. In addition, the autosomal sex-determination locus that occurs in linkage group 1 in Ae. aegypti resides in group 3 in Ar. subalbatus. The Ar. subalbatus map provides a basic genetic context that can be utilized in further genetic studies to clarify the genetic basis of parasite resistance in this mosquito and is a necessary precursor to the identification of genome regions that carry genes that determine the encapsulation phenotype.[The composite map and sequence database information for Ae. aegypti markers can be retrieved directly from the Ae. aegypti Genome Database through the World Wide Web: http://klab.agsci.colostate.edu.]
Short-Insert Libraries as a Method of Problem Solving in Genome Sequencing
Authors: McMurray Amanda A. , Sulston John E. , Quail Michael A. 
Published: May 2017

As the Human Genome Project moves into its sequencing phase, a serious problem has arisen. The same problem has been increasingly vexing in the closing phase of the Caenorhabditis elegansproject. The difficulty lies in sequencing efficiently through certain regions in which the templates (DNA substrates for the sequencing process) form complex folded secondary structures that are inaccessible to the enzymes. The solution, however, is simply to break them up. Specifically, the offending fragments are sonicated heavily and recloned, as much smaller fragments, into pUC vector. The sequences obtained from the resulting library can subsequently be assembled, free from the effects of secondary structure, to produce high-quality, complete sequence. Because of the success and simplicity of this procedure, we have begun to use it for the sequencing of all regions in which standard primer walking has been at all difficult.[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. Z93392, Z92540, and Z81558.]
A Software System for Data Analysis in Automated DNA Sequencing
Authors: Giddings Michael C. , Severin Jessica , Westphall Michael , Wu Jiazhen , Smith Lloyd M. 
Published: May 2017

Software for gel image analysis and base-calling in fluorescence-based sequencing consisting of two primary programs, BaseFinder and GelImager, is described. BaseFinder is a framework for trace processing, analysis, and base-calling. BaseFinder is highly extensible, allowing the addition of trace analysis and processing modules without recompilation. Powerful scripting capabilities combined with modularity and multilane handling allow the user to customize BaseFinder to virtually any type of trace processing. We have developed an extensive set of data processing and analysis modules for use with the program in fluorescence-based sequencing. GelImager is a framework for gel image manipulation. It can be used for gel visualization, lane retracking, and as a front end to the Washington University Getlanes program. The programs were designed using a cross-platform development environment, currently allowing them to run in Windows NT, Windows 95, Openstep/Mach, and Rhapsody. Work is ongoing to deploy the software on additional platforms, including Solaris, Linux, and MacOS. This software has been thoroughly tested and debugged in the analysis of >2 million bp of raw sequence data from human chromosome 19 region q13. Overall sequencing accuracy was measured using a significant subset of these data, consisting of ∼600 sequences, by comparing the individual shotgun sequences against the final assembled contigs. Also, results are reported from experiments that analyzed the accuracy of the software and two other well-known base-calling programs for sequencing the M13mp18 vector sequence.[The sequence data described in this paper have been submitted to the GenBank data library under accession no. AF025422]
Exercising library and information literacies through alternate reality gaming
Authors: Jerrett Adam , Bothma Theo J.D. , de Beer Koos 
Published: May 2017

Purpose
Teaching students/library patrons twenty-first century literacies (such as information and library literacies) is important within a library setting. As such, finding an appropriate manner to teach these skills in a practical manner at tertiary level is important. As vehicles for constructivist learning, games provide a unique opportunity to teach these twenty-first century literacies in an engaging, practical, format. The purpose of this paper is to discuss the implementation of an alternate reality game (ARG) to teach these literacies through gameplay.

Design/methodology/approach
An ARG was designed and developed where the core gameplay tasks taught and exercised twenty-first century literacies. The game, once completed, was then analysed as a case study to determine the effectiveness of the game-based approach to literacy learning.

Findings
Throughout the play of the game, players spent increasingly more time in the library, often using it as a common meeting point during play. Players reported that they learnt or exercised the skills that each game task focussed on, additionally noting that the game-based context made the process of learning and exercising these skills more enjoyable.

Originality/value
The findings suggest that the creation of games, whether real world or digital, may be useful in engaging students/patrons with twenty-first century literacies as well as with their local library. The documentation of a successful ARG to teach twenty-first century literacies provides a model for future research to follow when designing engaging library-oriented games.