Telomerase activation by genomic rearrangements in high-risk neuroblastoma

Science.gov (United States)

Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

2016-01-01

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

A general heuristic for genome rearrangement problems.

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Dias, Ulisses; Galvão, Gustavo Rodrigues; Lintzmayer, Carla Négri; Dias, Zanoni

2014-06-01

In this paper, we present a general heuristic for several problems in the genome rearrangement field. Our heuristic does not solve any problem directly, it is rather used to improve the solutions provided by any non-optimal algorithm that solve them. Therefore, we have implemented several algorithms described in the literature and several algorithms developed by ourselves. As a whole, we implemented 23 algorithms for 9 well known problems in the genome rearrangement field. A total of 13 algorithms were implemented for problems that use the notions of prefix and suffix operations. In addition, we worked on 5 algorithms for the classic problem of sorting by transposition and we conclude the experiments by presenting results for 3 approximation algorithms for the sorting by reversals and transpositions problem and 2 approximation algorithms for the sorting by reversals problem. Another algorithm with better approximation ratio can be found for the last genome rearrangement problem, but it is purely theoretical with no practical implementation. The algorithms we implemented in addition to our heuristic lead to the best practical results in each case. In particular, we were able to improve results on the sorting by transpositions problem, which is a very special case because many efforts have been made to generate algorithms with good results in practice and some of these algorithms provide results that equal the optimum solutions in many cases. Our source codes and benchmarks are freely available upon request from the authors so that it will be easier to compare new approaches against our results.

Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project.

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Higgins, Anne W; Alkuraya, Fowzan S; Bosco, Amy F; Brown, Kerry K; Bruns, Gail A P; Donovan, Diana J; Eisenman, Robert; Fan, Yanli; Farra, Chantal G; Ferguson, Heather L; Gusella, James F; Harris, David J; Herrick, Steven R; Kelly, Chantal; Kim, Hyung-Goo; Kishikawa, Shotaro; Korf, Bruce R; Kulkarni, Shashikant; Lally, Eric; Leach, Natalia T; Lemyre, Emma; Lewis, Janine; Ligon, Azra H; Lu, Weining; Maas, Richard L; MacDonald, Marcy E; Moore, Steven D P; Peters, Roxanna E; Quade, Bradley J; Quintero-Rivera, Fabiola; Saadi, Irfan; Shen, Yiping; Shendure, Jay; Williamson, Robin E; Morton, Cynthia C

2008-03-01

Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes. Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation.

TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements.

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Kamila Maliszewska-Olejniczak

2015-07-01

Full Text Available Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs. Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium

Refining borders of genome-rearrangements including repetitions

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JA Arjona-Medina

2016-10-01

Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.

Genome-wide signatures of 'rearrangement hotspots' within segmental duplications in humans.

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Mohammed Uddin

Full Text Available The primary objective of this study was to create a genome-wide high resolution map (i.e., >100 bp of 'rearrangement hotspots' which can facilitate the identification of regions capable of mediating de novo deletions or duplications in humans. A hierarchical method was employed to fragment segmental duplications (SDs into multiple smaller SD units. Combining an end space free pairwise alignment algorithm with a 'seed and extend' approach, we have exhaustively searched 409 million alignments to detect complex structural rearrangements within the reference-guided assembly of the NA18507 human genome (18× coverage, including the previously identified novel 4.8 Mb sequence from de novo assembly within this genome. We have identified 1,963 rearrangement hotspots within SDs which encompass 166 genes and display an enrichment of duplicated gene nucleotide variants (DNVs. These regions are correlated with increased non-allelic homologous recombination (NAHR event frequency which presumably represents the origin of copy number variations (CNVs and pathogenic duplications/deletions. Analysis revealed that 20% of the detected hotspots are clustered within the proximal and distal SD breakpoints flanked by the pathogenic deletions/duplications that have been mapped for 24 NAHR-mediated genomic disorders. FISH Validation of selected complex regions revealed 94% concordance with in silico localization of the highly homologous derivatives. Other results from this study indicate that intra-chromosomal recombination is enhanced in genic compared with agenic duplicated regions, and that gene desert regions comprising SDs may represent reservoirs for creation of novel genes. The generation of genome-wide signatures of 'rearrangement hotspots', which likely serve as templates for NAHR, may provide a powerful approach towards understanding the underlying mutational mechanism(s for development of constitutional and acquired diseases.

Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

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Meller Jaroslaw

2007-03-01

Full Text Available Abstract Background Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. Results We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance. In particular, Cinteny provides: i integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii flexibility to adjust the parameters and re-compute the results on-the-fly; iii ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org. Conclusion Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances

Phylogenetic signal from rearrangements in 18 Anopheles species by joint scaffolding extant and ancestral genomes.

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Anselmetti, Yoann; Duchemin, Wandrille; Tannier, Eric; Chauve, Cedric; Bérard, Sèverine

2018-05-09

Genomes rearrangements carry valuable information for phylogenetic inference or the elucidation of molecular mechanisms of adaptation. However, the detection of genome rearrangements is often hampered by current deficiencies in data and methods: Genomes obtained from short sequence reads have generally very fragmented assemblies, and comparing multiple gene orders generally leads to computationally intractable algorithmic questions. We present a computational method, ADSEQ, which, by combining ancestral gene order reconstruction, comparative scaffolding and de novo scaffolding methods, overcomes these two caveats. ADSEQ provides simultaneously improved assemblies and ancestral genomes, with statistical supports on all local features. Compared to previous comparative methods, it runs in polynomial time, it samples solutions in a probabilistic space, and it can handle a significantly larger gene complement from the considered extant genomes, with complex histories including gene duplications and losses. We use ADSEQ to provide improved assemblies and a genome history made of duplications, losses, gene translocations, rearrangements, of 18 complete Anopheles genomes, including several important malaria vectors. We also provide additional support for a differentiated mode of evolution of the sex chromosome and of the autosomes in these mosquito genomes. We demonstrate the method's ability to improve extant assemblies accurately through a procedure simulating realistic assembly fragmentation. We study a debated issue regarding the phylogeny of the Gambiae complex group of Anopheles genomes in the light of the evolution of chromosomal rearrangements, suggesting that the phylogenetic signal they carry can differ from the phylogenetic signal carried by gene sequences, more prone to introgression.

DNA rearrangements from γ-irradiated normal human fibroblasts preferentially occur in transcribed regions of the genome

International Nuclear Information System (INIS)

Forrester, H.B.; Radford, I.R.

2003-01-01

Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA rearrangements were detected in several different regions of the genome of human fibroblast cells that were exposed to 30 Gy of γ-irradiation and then incubated for 24 hours at 37 deg C. There was a 3- to 5-fold increase in the number of products amplified from irradiated as compared with control cells in the target regions 5' to the C-MYC, CDKN1A, RB1, and FGFR2 genes. Sequences were examined from 121 DNA rearrangements. Approximately half of the PCR products were derived from possible inter-chromosomal rearrangements and the remainder were from intra-chromosomal events. A high proportion of the sequences that rearranged with target regions were located in genes, suggesting that rearrangements may occur preferentially in transcribed regions. Eighty-four percent of the sequences examined by reverse transcriptase PCR were from transcribed sequences in IMR-90 cells. The distribution of DNA rearrangements within the target regions is non-random and homology occurs between the sequences involved in rearrangements in some cases but is not

Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

DEFF Research Database (Denmark)

Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders

2009-01-01

BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovaria...

Radiation-induced genomic instability driven by de novo chromosomal rearrangement hot spots

International Nuclear Information System (INIS)

Grosovsky, A.J.; Allen, R.N.; Moore, S.R.

2003-01-01

Genomic instability has become generally recognized as a critical contributor to tumor progression by generating the necessary number of genetic alterations required for expression of a clinically significant malignancy. Our study of chromosomal instability investigates the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in instability acting predominantly in cis. Here we present an analysis of the karyotypic distribution of instability associated chromosomal rearrangements in TK6 and derivative human lymphoblasts. Karyotypic analysis performed on a total of 455 independent clones included 183 rearrangements distributed among 100 separate unstable clones. The results demonstrate that the breakpoints of chromosomal rearrangements in unstable clones are non-randomly distributed throughout the genome. This pattern is statistically significant, and incompatible with expectations for random breakage associated with loss or alteration of a trans-acting factor. Furthermore, specific chromosomal breakage hot spots associated with instability have been identified; these occur in several independent unstable clones and are often repeatedly broken and rejoined during the outgrowth of an individual clone. In complimentary studies, genomic instability was generated without any exposure to a DNA-damaging agent, but rather by transfection with alpha heterochromatin DNA. In a prospective analysis, human-hamster hybrid AL cells containing a single human chromosome 11 were transfected with heterochromatic alpha DNA repeats and clones were analyzed by chromosome 11 painting. Transfection with alpha DNA was associated with karyotypic heterogeneity in 40% of clones examined; control transfections with plasmid alone did not lead to karyotypic heterogeneity

Screening for genomic rearrangements at BRCA1 locus in Iranian ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Home; Journals; Journal of Genetics; Volume 92; Issue 1. Screening for genomic rearrangements at BRCA1 locus in Iranian women with breast cancer using multiplex ligation-dependent probe amplification. Vahid R. Yassaee Babak Emamalizadeh Mir Davood Omrani. Research Note Volume 92 Issue 1 ...

Deep ancestry of programmed genome rearrangement in lampreys.

Science.gov (United States)

Timoshevskiy, Vladimir A; Lampman, Ralph T; Hess, Jon E; Porter, Laurie L; Smith, Jeramiah J

2017-09-01

In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma. Copyright © 2017 Elsevier Inc. All rights reserved.

Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer.

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Bernard, Guillaume; Chan, Cheong Xin; Ragan, Mark A

2016-07-01

Alignment-free (AF) approaches have recently been highlighted as alternatives to methods based on multiple sequence alignment in phylogenetic inference. However, the sensitivity of AF methods to genome-scale evolutionary scenarios is little known. Here, using simulated microbial genome data we systematically assess the sensitivity of nine AF methods to three important evolutionary scenarios: sequence divergence, lateral genetic transfer (LGT) and genome rearrangement. Among these, AF methods are most sensitive to the extent of sequence divergence, less sensitive to low and moderate frequencies of LGT, and most robust against genome rearrangement. We describe the application of AF methods to three well-studied empirical genome datasets, and introduce a new application of the jackknife to assess node support. Our results demonstrate that AF phylogenomics is computationally scalable to multi-genome data and can generate biologically meaningful phylogenies and insights into microbial evolution.

Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

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Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

2015-01-01

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understanding how certain distinctive features of the cancer genome, including clustered mutagenesis, tandem segmental duplications, complex breakpoints, chromothripsis, chromoplexy and chromoanasynthesis may arise. PMID:26726318

Extensive gene rearrangements in the mitochondrial genomes of two egg parasitoids, Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae).

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Chen, Long; Chen, Peng-Yan; Xue, Xiao-Feng; Hua, Hai-Qing; Li, Yuan-Xi; Zhang, Fan; Wei, Shu-Jun

2018-05-04

Animal mitochondrial genomes usually exhibit conserved gene arrangement across major lineages, while those in the Hymenoptera are known to possess frequent rearrangements, as are those of several other orders of insects. Here, we sequenced two complete mitochondrial genomes of Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae). In total, 37 mitochondrial genes were identified in both species. The same gene arrangement pattern was found in the two species, with extensive gene rearrangement compared with the ancestral insect mitochondrial genome. Most tRNA genes and all protein-coding genes were encoded on the minority strand. In total, 15 tRNA genes and seven protein-coding genes were rearranged. The rearrangements of cox1 and nad2 as well as most tRNA genes were novel. Phylogenetic analysis based on nucleotide sequences of protein-coding genes and on gene arrangement patterns produced identical topologies that support the relationship of (Agaonidae + Pteromalidae) + Trichogrammatidae in Chalcidoidea. CREx analysis revealed eight rearrangement operations occurred from presumed ancestral gene order of Chalcidoidea to form the derived gene order of Trichogramma. Our study shows that gene rearrangement information in Chalcidoidea can potentially contribute to the phylogeny of Chalcidoidea when more mitochondrial genome sequences are available.

Flexibility and symmetry of prokaryotic genome rearrangement reveal lineage-associated core-gene-defined genome organizational frameworks.

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Kang, Yu; Gu, Chaohao; Yuan, Lina; Wang, Yue; Zhu, Yanmin; Li, Xinna; Luo, Qibin; Xiao, Jingfa; Jiang, Daquan; Qian, Minping; Ahmed Khan, Aftab; Chen, Fei; Zhang, Zhang; Yu, Jun

2014-11-25

The prokaryotic pangenome partitions genes into core and dispensable genes. The order of core genes, albeit assumed to be stable under selection in general, is frequently interrupted by horizontal gene transfer and rearrangement, but how a core-gene-defined genome maintains its stability or flexibility remains to be investigated. Based on data from 30 species, including 425 genomes from six phyla, we grouped core genes into syntenic blocks in the context of a pangenome according to their stability across multiple isolates. A subset of the core genes, often species specific and lineage associated, formed a core-gene-defined genome organizational framework (cGOF). Such cGOFs are either single segmental (one-third of the species analyzed) or multisegmental (the rest). Multisegment cGOFs were further classified into symmetric or asymmetric according to segment orientations toward the origin-terminus axis. The cGOFs in Gram-positive species are exclusively symmetric and often reversible in orientation, as opposed to those of the Gram-negative bacteria, which are all asymmetric and irreversible. Meanwhile, all species showing strong strand-biased gene distribution contain symmetric cGOFs and often specific DnaE (α subunit of DNA polymerase III) isoforms. Furthermore, functional evaluations revealed that cGOF genes are hub associated with regard to cellular activities, and the stability of cGOF provides efficient indexes for scaffold orientation as demonstrated by assembling virtual and empirical genome drafts. cGOFs show species specificity, and the symmetry of multisegmental cGOFs is conserved among taxa and constrained by DNA polymerase-centric strand-biased gene distribution. The definition of species-specific cGOFs provides powerful guidance for genome assembly and other structure-based analysis. Prokaryotic genomes are frequently interrupted by horizontal gene transfer (HGT) and rearrangement. To know whether there is a set of genes not only conserved in position

Highly rearranged mitochondrial genome in Nycteria parasites (Haemosporidia) from bats.

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Karadjian, Gregory; Hassanin, Alexandre; Saintpierre, Benjamin; Gembu Tungaluna, Guy-Crispin; Ariey, Frederic; Ayala, Francisco J; Landau, Irene; Duval, Linda

2016-08-30

Haemosporidia parasites have mostly and abundantly been described using mitochondrial genes, and in particular cytochrome b (cytb). Failure to amplify the mitochondrial cytb gene of Nycteria parasites isolated from Nycteridae bats has been recently reported. Bats are hosts to a diverse and profuse array of Haemosporidia parasites that remain largely unstudied. There is a need to obtain more molecular data from chiropteran parasites. Such data would help to better understand the evolutionary history of Haemosporidia, which notably include the Plasmodium parasites, malaria's agents. We use next-generation sequencing to obtain the complete mitochondrial genome of Nycteria parasites from African Nycteris grandis (Nycteridae) and Rhinolophus alcyone (Rhinolophidae) and Asian Megaderma spasma (Megadermatidae). We report four complete mitochondrial genomes, including two rearranged mitochondrial genomes within Haemosporidia. Our results open outlooks into potentially undiscovered Haemosporidian diversity.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

NARCIS (Netherlands)

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

DEFF Research Database (Denmark)

Staaf, Johan; Törngren, Therese; Rambech, Eva

2008-01-01

Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridizat......Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic...... deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...... from several 100 kb, including large flanking regions, to rearrangements, allowing convenient design...

Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Directory of Open Access Journals (Sweden)

Ariel M Pani

2010-08-01

Full Text Available Intellectual disability (ID affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450 region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications, one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information

Extensive genome rearrangements and multiple horizontal gene transfers in a population of pyrococcus isolates from Vulcano Island, Italy.

Science.gov (United States)

White, James R; Escobar-Paramo, Patricia; Mongodin, Emmanuel F; Nelson, Karen E; DiRuggiero, Jocelyne

2008-10-01

The extent of chromosome rearrangements in Pyrococcus isolates from marine hydrothermal vents in Vulcano Island, Italy, was evaluated by high-throughput genomic methods. The results illustrate the dynamic nature of the genomes of the genus Pyrococcus and raise the possibility of a connection between rapidly changing environmental conditions and adaptive genomic properties.

Genomic regulatory landscapes and chromosomal rearrangements

DEFF Research Database (Denmark)

Ladegaard, Elisabete L Engenheiro

2008-01-01

The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes is that they ......The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

Comparative mitochondrial genome analysis reveals the evolutionary rearrangement mechanism in Brassica.

Science.gov (United States)

Yang, J; Liu, G; Zhao, N; Chen, S; Liu, D; Ma, W; Hu, Z; Zhang, M

2016-05-01

The genus Brassica has many species that are important for oil, vegetable and other food products. Three mitochondrial genome types (mitotype) originated from its common ancestor. In this paper, a B. nigra mitochondrial main circle genome with 232,407 bp was generated through de novo assembly. Synteny analysis showed that the mitochondrial genomes of B. rapa and B. oleracea had a better syntenic relationship than B. nigra. Principal components analysis and development of a phylogenetic tree indicated maternal ancestors of three allotetraploid species in Us triangle of Brassica. Diversified mitotypes were found in allotetraploid B. napus, in which napus-type B. napus was derived from B. oleracea, while polima-type B. napus was inherited from B. rapa. In addition, the mitochondrial genome of napus-type B. napus was closer to botrytis-type than capitata-type B. oleracea. The sub-stoichiometric shifting of several mitochondrial genes suggested that mitochondrial genome rearrangement underwent evolutionary selection during domestication and/or plant breeding. Our findings clarify the role of diploid species in the maternal origin of allotetraploid species in Brassica and suggest the possibility of breeding selection of the mitochondrial genome. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Extensive Genome Rearrangements and Multiple Horizontal Gene Transfers in a Population of Pyrococcus Isolates from Vulcano Island, Italy▿ †

Science.gov (United States)

White, James R.; Escobar-Paramo, Patricia; Mongodin, Emmanuel F.; Nelson, Karen E.; DiRuggiero, Jocelyne

2008-01-01

The extent of chromosome rearrangements in Pyrococcus isolates from marine hydrothermal vents in Vulcano Island, Italy, was evaluated by high-throughput genomic methods. The results illustrate the dynamic nature of the genomes of the genus Pyrococcus and raise the possibility of a connection between rapidly changing environmental conditions and adaptive genomic properties. PMID:18723649

Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy

DEFF Research Database (Denmark)

Mefford, Heather C; Clauin, Severine; Sharp, Andrew J

2007-01-01

predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One...

Recurrent Reciprocal Genomic Rearrangements of 17q12 Are Associated with Renal Disease, Diabetes, and Epilepsy

OpenAIRE

Mefford, Heather C. ; Clauin, Séverine ; Sharp, Andrew J. ; Moller, Rikke S. ; Ullmann, Reinhard ; Kapur, Raj ; Pinkel, Dan ; Cooper, Gregory M. ; Ventura, Mario ; Ropers, H. Hilger ; Tommerup, Niels ; Eichler, Evan E. ; Bellanne-Chantelot, Christine 

2007-01-01

Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three inde...

Sorting permutations by prefix and suffix rearrangements.

Science.gov (United States)

Lintzmayer, Carla Negri; Fertin, Guillaume; Dias, Zanoni

2017-02-01

Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations. We give 2-approximation and ([Formula: see text])-approximation algorithms for these problems, where [Formula: see text] is a constant divided by the number of breakpoints (pairs of consecutive elements that should not be consecutive in the identity permutation) in the input permutation. We also give bounds for the diameters concerning these problems and provide ways of improving the practical results of our algorithms.

Raalin, a transcript enriched in the honey bee brain, is a remnant of genomic rearrangement in Hymenoptera.

Science.gov (United States)

Tirosh, Y; Morpurgo, N; Cohen, M; Linial, M; Bloch, G

2012-06-01

We identified a predicted compact cysteine-rich sequence in the honey bee genome that we called 'Raalin'. Raalin transcripts are enriched in the brain of adult honey bee workers and drones, with only minimum expression in other tissues or in pre-adult stages. Open-reading frame (ORF) homologues of Raalin were identified in the transcriptomes of fruit flies, mosquitoes and moths. The Raalin-like gene from Drosophila melanogaster encodes for a short secreted protein that is maximally expressed in the adult brain with negligible expression in other tissues or pre-imaginal stages. Raalin-like sequences have also been found in the recently sequenced genomes of six ant species, but not in the jewel wasp Nasonia vitripennis. As in the honey bee, the Raalin-like sequences of ants do not have an ORF. A comparison of the genome region containing Raalin in the genomes of bees, ants and the wasp provides evolutionary support for an extensive genome rearrangement in this sequence. Our analyses identify a new family of ancient cysteine-rich short sequences in insects in which insertions and genome rearrangements may have disrupted this locus in the branch leading to the Hymenoptera. The regulated expression of this transcript suggests that it has a brain-specific function. © 2012 The Authors. Insect Molecular Biology © 2012 The Royal Entomological Society.

A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination.

Science.gov (United States)

León-Ortiz, Ana María; Panier, Stephanie; Sarek, Grzegorz; Vannier, Jean-Baptiste; Patel, Harshil; Campbell, Peter J; Boulton, Simon J

2018-01-18

Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Whole Genome Analyses of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements

Science.gov (United States)

Egan, Jan B.; Barrett, Michael T.; Champion, Mia D.; Middha, Sumit; Lenkiewicz, Elizabeth; Evers, Lisa; Francis, Princy; Schmidt, Jessica; Shi, Chang-Xin; Van Wier, Scott; Badar, Sandra; Ahmann, Gregory; Kortuem, K. Martin; Boczek, Nicole J.; Fonseca, Rafael; Craig, David W.; Carpten, John D.; Borad, Mitesh J.; Stewart, A. Keith

2014-01-01

Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2. PMID:24505276

Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

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Jan B Egan

Full Text Available Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

The rearranged mitochondrial genome of Leptopilina boulardi (Hymenoptera: Figitidae, a parasitoid wasp of Drosophila

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Daniel S. Oliveira

Full Text Available Abstract The partial mitochondrial genome sequence of Leptopilina boulardi (Hymenoptera: Figitidae was characterized. Illumina sequencing was used yielding 35,999,679 reads, from which 102,482 were utilized in the assembly. The length of the sequenced region of this partial mitochondrial genome is 15,417 bp, consisting of 13 protein-coding, two rRNA, and 21tRNA genes (the trnaM failed to be sequenced and a partial A+T-rich region. All protein-coding genes start with ATN codons. Eleven protein-coding genes presented TAA stop codons, whereas ND6 and COII that presented TA, and T nucleotides, respectively. The gene pattern revealed extensive rearrangements compared to the typical pattern generally observed in insects. These rearrangements involve two protein-coding and two ribosomal genes, along with the 16 tRNA genes. This gene order is different from the pattern described for Ibalia leucospoides (Ibaliidae, Cynipoidea, suggesting that this particular gene order can be variable among Cynipoidea superfamily members. A maximum likelihood phylogenetic analysis of the main groups of Apocrita was performed using amino acid sequence of 13 protein-coding genes, showing monophyly for the Cynipoidea superfamily within the Hymenoptera phylogeny.

DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

OpenAIRE

Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

2012-01-01

DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up...

Additions, losses, and rearrangements on the evolutionary route from a reconstructed ancestor to the modern Saccharomyces cerevisiae genome.

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Jonathan L Gordon

2009-05-01

Full Text Available Comparative genomics can be used to infer the history of genomic rearrangements that occurred during the evolution of a species. We used the principle of parsimony, applied to aligned synteny blocks from 11 yeast species, to infer the gene content and gene order that existed in the genome of an extinct ancestral yeast about 100 Mya, immediately before it underwent whole-genome duplication (WGD. The reconstructed ancestral genome contains 4,703 ordered loci on eight chromosomes. The reconstruction is complete except for the subtelomeric regions. We then inferred the series of rearrangement steps that led from this ancestor to the current Saccharomyces cerevisiae genome; relative to the ancestral genome we observe 73 inversions, 66 reciprocal translocations, and five translocations involving telomeres. Some fragile chromosomal sites were reused as evolutionary breakpoints multiple times. We identified 124 genes that have been gained by S. cerevisiae in the time since the WGD, including one that is derived from a hAT family transposon, and 88 ancestral loci at which S. cerevisiae did not retain either of the gene copies that were formed by WGD. Sites of gene gain and evolutionary breakpoints both tend to be associated with tRNA genes and, to a lesser extent, with origins of replication. Many of the gained genes in S. cerevisiae have functions associated with ethanol production, growth in hypoxic environments, or the uptake of alternative nutrient sources.

Construction of carrier state viruses with partial genomes of the segmented dsRNA bacteriophages

International Nuclear Information System (INIS)

Sun Yang; Qiao Xueying; Mindich, Leonard

2004-01-01

The cystoviridae are bacteriophages with genomes of three segments of dsRNA enclosed within a polyhedral capsid. Two members of this family, PHI6 and PHI8, have been shown to form carrier states in which the virus replicates as a stable episome in the host bacterium while expressing reporter genes such as kanamycin resistance or lacα. The carrier state does not require the activity of all the genes necessary for phage production. It is possible to generate carrier states by infecting cells with virus or by electroporating nonreplicating plasmids containing cDNA copies of the viral genomes into the host cells. We have found that carrier states in both PHI6 and PHI8 can be formed at high frequency with all three genomic segments or with only the large and small segments. The large genomic segment codes for the proteins that constitute the inner core of the virus, which is the structure responsible for the packaging and replication of the genome. In PHI6, a carrier state can be formed with the large and middle segment if mutations occur in the gene for the major structural protein of the inner core. In PHI8, carrier state formation requires the activity of genes 8 and 12 of segment S

Balanced into array : genome-wide array analysis in 54 patients with an apparently balanced de novo chromosome rearrangement and a meta-analysis

NARCIS (Netherlands)

Feenstra, Ilse; Hanemaaijer, Nicolien; Sikkema-Raddatz, Birgit; Yntema, Helger; Dijkhuizen, Trijnie; Lugtenberg, Dorien; Verheij, Joke; Green, Andrew; Hordijk, Roel; Reardon, William; de Vries, Bert; Brunner, Han; Bongers, Ernie; de Leeuw, Nicole; van Ravenswaaij-Arts, Conny

2011-01-01

High-resolution genome-wide array analysis enables detailed screening for cryptic and submicroscopic imbalances of microscopically balanced de novo rearrangements in patients with developmental delay and/or congenital abnormalities. In this report, we added the results of genome-wide array analysis

Divergence of RNA polymerase α subunits in angiosperm plastid genomes is mediated by genomic rearrangement.

Science.gov (United States)

Blazier, J Chris; Ruhlman, Tracey A; Weng, Mao-Lun; Rehman, Sumaiyah K; Sabir, Jamal S M; Jansen, Robert K

2016-04-18

Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP α subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled and analyzed from each of the three angiosperm families. Multiple lines of evidence indicated that the rpoA sequences are likely functional despite retaining as low as 30% nucleotide sequence identity with rpoA genes from outgroups in the same angiosperm order. The ratio of non-synonymous to synonymous substitutions indicated that these genes are under purifying selection, and bioinformatic prediction of conserved domains indicated that functional domains are preserved. One of the lineages (Pelargonium, Geraniaceae) contains species with multiple rpoA-like ORFs that show evidence of ongoing inter-paralog gene conversion. The plastid genomes containing these divergent rpoA genes have experienced extensive structural rearrangement, including large expansions of the inverted repeat. We propose that illegitimate recombination, not positive selection, has driven the divergence of rpoA.

Programmed Rearrangement in Ciliates: Paramecium.

Science.gov (United States)

Betermier, Mireille; Duharcourt, Sandra

2014-12-01

Programmed genome rearrangements in the ciliate Paramecium provide a nice illustration of the impact of transposons on genome evolution and plasticity. During the sexual cycle, development of the somatic macronucleus involves elimination of ∼30% of the germline genome, including repeated DNA (e.g., transposons) and ∼45,000 single-copy internal eliminated sequences (IES). IES excision is a precise cut-and-close process, in which double-stranded DNA cleavage at IES ends depends on PiggyMac, a domesticated piggyBac transposase. Genome-wide analysis has revealed that at least a fraction of IESs originate from Tc/mariner transposons unrelated to piggyBac. Moreover, genomic sequences with no transposon origin, such as gene promoters, can be excised reproducibly as IESs, indicating that genome rearrangements contribute to the control of gene expression. How the system has evolved to allow elimination of DNA sequences with no recognizable conserved motif has been the subject of extensive research during the past two decades. Increasing evidence has accumulated for the participation of noncoding RNAs in epigenetic control of elimination for a subset of IESs, and in trans-generational inheritance of alternative rearrangement patterns. This chapter summarizes our current knowledge of the structure of the germline and somatic genomes for the model species Paramecium tetraurelia, and describes the DNA cleavage and repair factors that constitute the IES excision machinery. We present an overview of the role of specialized RNA interference machineries and their associated noncoding RNAs in the control of DNA elimination. Finally, we discuss how RNA-dependent modification and/or remodeling of chromatin may guide PiggyMac to its cognate cleavage sites.

Genome organization influences partner selection for chromosomal rearrangements

NARCIS (Netherlands)

Wijchers, P.J.; de Laat, W.

2010-01-01

Chromosomal rearrangements occur as a consequence of the erroneous repair of DNA double-stranded breaks, and often underlie disease. The recurrent detection of specific tumorigenic rearrangements suggests that there is a mechanism behind chromosomal partner selection involving the shape of the

Chromoanasynthetic Genomic Rearrangement Identified in a N-Ethyl-N-Nitrosourea (ENU Mutagenesis Screen in Caenorhabditis elegans

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Omar A. Itani

2016-02-01

Full Text Available Chromoanasynthesis is a recently discovered phenomenon in humans with congenital diseases that is characterized by complex genomic rearrangements (CGRs resulting from aberrant repair of catastrophic chromosomal damage. How these CGRs are induced is not known. Here, we describe the structure and function of dpDp667, a causative CGR that emerged from a Caenorhabditis elegans dauer suppressor screen in which animals were treated with the point mutagen N-ethyl-N-nitrosourea (ENU. dpDp667 comprises nearly 3 Mb of sequence on the right arm of the X chromosome, contains three duplications and one triplication, and is devoid of deletions. Sequences from three out of the four breakpoint junctions in dpDp667 reveal microhomologies that are hallmarks of chromoanasynthetic CGRs. Our findings suggest that environmental insults and physiological processes that cause point mutations may give rise to chromoanasynthetic rearrangements associated with congenital disease. The relatively subtle phenotype of animals harboring dpDp667 suggests that the prevalence of CGRs in the genomes of mutant and/or phenotypically unremarkable animals may be grossly underestimated.

Application of the inter-line PCR for the analyse of genomic rearrangements in radiation-transformed mammalian cell lines

International Nuclear Information System (INIS)

Leibhard, S.; Smida, J.

1996-01-01

Repetitive DNA sequences of the LINE-family (long interspersed elements) that are widely distributed among the mammalian genome can be activated or altered by the exposure to ionizing radiation [1]. By the integration at new sites in the genome alterations in the expression of genes that are involved in cell transformation and/or carcinogenesis may occur [2, 3]. A new technique -the inter-LINE PCR - has been developed in order to detect and analyse such genomic rearrangements in radiation-transformed cell lines. From the sites of transformation- or tumour-specific changes in the genome it might be possible to develop new tumour markers for diagnostic purpose. (orig.) [de

A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas.

Science.gov (United States)

Hippolyte, Isabelle; Bakry, Frederic; Seguin, Marc; Gardes, Laetitia; Rivallan, Ronan; Risterucci, Ange-Marie; Jenny, Christophe; Perrier, Xavier; Carreel, Françoise; Argout, Xavier; Piffanelli, Pietro; Khan, Imtiaz A; Miller, Robert N G; Pappas, Georgios J; Mbéguié-A-Mbéguié, Didier; Matsumoto, Takashi; De Bernardinis, Veronique; Huttner, Eric; Kilian, Andrzej; Baurens, Franc-Christophe; D'Hont, Angélique; Cote, François; Courtois, Brigitte; Glaszmann, Jean-Christophe

2010-04-13

The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana) in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin). Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7%) deviated (p DArTs) covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker segregation.

Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea.

Science.gov (United States)

Höglund, P; Sormaala, M; Haila, S; Socha, J; Rajaram, U; Scheurlen, W; Sinaasappel, M; de Jonge, H; Holmberg, C; Yoshikawa, H; Kere, J

2001-09-01

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events. Copyright 2001 Wiley-Liss, Inc.

Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

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Francesca Duraturo

2013-01-01

Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

Rare genomic rearrangement in a boy with Williams-Beuren syndrome associated to XYY syndrome and intriguing behavior.

Science.gov (United States)

Dutra, Roberta L; Piazzon, Flavia B; Zanardo, Évelin A; Costa, Thais Virginia Moura Machado; Montenegro, Marília M; Novo-Filho, Gil M; Dias, Alexandre T; Nascimento, Amom M; Kim, Chong Ae; Kulikowski, Leslie D

2015-12-01

Williams-Beuren syndrome (WBS) is caused by a hemizygous contiguous gene microdeletion of 1.55-1.84 Mb at 7q11.23 region. Approximately, 28 genes have been shown to contribute to classical phenotype of SWB with presence of dysmorphic facial features, supravalvular aortic stenosis (SVAS), intellectual disability, and overfriendliness. With the use of Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques, is possible define with more accuracy partial or atypical deletion and refine the genotype-phenotype correlation. Here, we report on a rare genomic structural rearrangement in a boy with atypical deletion in 7q11.23 and XYY syndrome with characteristic clinical signs, but not sufficient for the diagnosis of WBS. Cytogenetic analysis of G-banding showed a karyotype 47,XYY. Analysis of DNA with the technique of MLPA (Multiplex Ligation-dependent Probe Amplification) using kits a combination of kits (P064, P036, P070, and P029) identified an atypical deletion on 7q11.23. In addition, high resolution SNP Oligonucleotide Microarray Analysis (SNP-array) confirmed the alterations found by MLPA and revealed others pathogenic CNVs, in the chromosomes 7 and X. The present report demonstrates an association not yet described in literature, between Williams-Beuren syndrome and 47,XYY. The identification of atypical deletion in 7q11.23 concomitant to additional pathogenic CNVs in others genomic regions allows a better comprehension of clinical consequences of atypical genomic rearrangements. © 2015 Wiley Periodicals, Inc.

Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: implications for interpretation of structural variation in genomes and the future of clinical cytogenetics.

Science.gov (United States)

Dong, Zirui; Wang, Huilin; Chen, Haixiao; Jiang, Hui; Yuan, Jianying; Yang, Zhenjun; Wang, Wen-Jing; Xu, Fengping; Guo, Xiaosen; Cao, Ye; Zhu, Zhenzhen; Geng, Chunyu; Cheung, Wan Chee; Kwok, Yvonne K; Yang, Huanming; Leung, Tak Yeung; Morton, Cynthia C; Cheung, Sau Wai; Choy, Kwong Wai

2017-11-02

PurposeRecent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected.MethodsThe 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold).ResultsWith this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene.ConclusionOur study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.170.

webMGR: an online tool for the multiple genome rearrangement problem.

Science.gov (United States)

Lin, Chi Ho; Zhao, Hao; Lowcay, Sean Harry; Shahab, Atif; Bourque, Guillaume

2010-02-01

The algorithm MGR enables the reconstruction of rearrangement phylogenies based on gene or synteny block order in multiple genomes. Although MGR has been successfully applied to study the evolution of different sets of species, its utilization has been hampered by the prohibitive running time for some applications. In the current work, we have designed new heuristics that significantly speed up the tool without compromising its accuracy. Moreover, we have developed a web server (webMGR) that includes elaborate web output to facilitate navigation through the results. webMGR can be accessed via http://www.gis.a-star.edu.sg/~bourque. The source code of the improved standalone version of MGR is also freely available from the web site. Supplementary data are available at Bioinformatics online.

A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas

Directory of Open Access Journals (Sweden)

Matsumoto Takashi

2010-04-01

Full Text Available Abstract Background The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. Results An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin. Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7% deviated (p Conclusions We propose a synthetic map with 11 linkage groups containing 489 markers (167 SSRs and 322 DArTs covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms

NARCIS (Netherlands)

Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

2012-01-01

Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed

The complete mitochondrial genomes of two rice planthoppers, Nilaparvata lugens and Laodelphax striatellus: conserved genome rearrangement in Delphacidae and discovery of new characteristics of atp8 and tRNA genes.

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Zhang, Kai-Jun; Zhu, Wen-Chao; Rong, Xia; Zhang, Yan-Kai; Ding, Xiu-Lei; Liu, Jing; Chen, Da-Song; Du, Yu; Hong, Xiao-Yue

2013-06-22

Nilaparvata lugens (the brown planthopper, BPH) and Laodelphax striatellus (the small brown planthopper, SBPH) are two of the most important pests of rice. Up to now, there was only one mitochondrial genome of rice planthopper has been sequenced and very few dependable information of mitochondria could be used for research on population genetics, phylogeographics and phylogenetic evolution of these pests. To get more valuable information from the mitochondria, we sequenced the complete mitochondrial genomes of BPH and SBPH. These two planthoppers were infected with two different functional Wolbachia (intracellular endosymbiont) strains (wLug and wStri). Since both mitochondria and Wolbachia are transmitted by cytoplasmic inheritance and it was difficult to separate them when purified the Wolbachia particles, concomitantly sequencing the genome of Wolbachia using next generation sequencing method, we also got nearly complete mitochondrial genome sequences of these two rice planthoppers. After gap closing, we present high quality and reliable complete mitochondrial genomes of these two planthoppers. The mitogenomes of N. lugens (BPH) and L. striatellus (SBPH) are 17, 619 bp and 16, 431 bp long with A + T contents of 76.95% and 77.17%, respectively. Both species have typical circular mitochondrial genomes that encode the complete set of 37 genes which are usually found in metazoans. However, the BPH mitogenome also possesses two additional copies of the trnC gene. In both mitochondrial genomes, the lengths of the atp8 gene were conspicuously shorter than that of all other known insect mitochondrial genomes (99 bp for BPH, 102 bp for SBPH). That two rearrangement regions (trnC-trnW and nad6-trnP-trnT) of mitochondrial genomes differing from other known insect were found in these two distantly related planthoppers revealed that the gene order of mitochondria might be conservative in Delphacidae. The large non-coding fragment (the A+T-rich region) putatively

Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

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Han, Kyudong; Sen, Shurjo K; Wang, Jianxin; Callinan, Pauline A; Lee, Jungnam; Cordaux, Richard; Liang, Ping; Batzer, Mark A

2005-01-01

Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

Mapping of Micro-Tom BAC-End Sequences to the Reference Tomato Genome Reveals Possible Genome Rearrangements and Polymorphisms

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Asamizu, Erika; Shirasawa, Kenta; Hirakawa, Hideki; Sato, Shusei; Tabata, Satoshi; Yano, Kentaro; Ariizumi, Tohru; Shibata, Daisuke; Ezura, Hiroshi

2012-01-01

A total of 93,682 BAC-end sequences (BESs) were generated from a dwarf model tomato, cv. Micro-Tom. After removing repetitive sequences, the BESs were similarity searched against the reference tomato genome of a standard cultivar, “Heinz 1706.” By referring to the “Heinz 1706” physical map and by eliminating redundant or nonsignificant hits, 28,804 “unique pair ends” and 8,263 “unique ends” were selected to construct hypothetical BAC contigs. The total physical length of the BAC contigs was 495, 833, 423 bp, covering 65.3% of the entire genome. The average coverage of euchromatin and heterochromatin was 58.9% and 67.3%, respectively. From this analysis, two possible genome rearrangements were identified: one in chromosome 2 (inversion) and the other in chromosome 3 (inversion and translocation). Polymorphisms (SNPs and Indels) between the two cultivars were identified from the BLAST alignments. As a result, 171,792 polymorphisms were mapped on 12 chromosomes. Among these, 30,930 polymorphisms were found in euchromatin (1 per 3,565 bp) and 140,862 were found in heterochromatin (1 per 2,737 bp). The average polymorphism density in the genome was 1 polymorphism per 2,886 bp. To facilitate the use of these data in Micro-Tom research, the BAC contig and polymorphism information are available in the TOMATOMICS database. PMID:23227037

Extensive Genomic Diversity among Bovine-Adapted Staphylococcus aureus: Evidence for a Genomic Rearrangement within CC97.

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Kathleen E Budd

Full Text Available Staphylococcus aureus is an important pathogen associated with both human and veterinary disease and is a common cause of bovine mastitis. Genomic heterogeneity exists between S. aureus strains and has been implicated in the adaptation of specific strains to colonise particular mammalian hosts. Knowledge of the factors required for host specificity and virulence is important for understanding the pathogenesis and management of S. aureus mastitis. In this study, a panel of mastitis-associated S. aureus isolates (n = 126 was tested for resistance to antibiotics commonly used to treat mastitis. Over half of the isolates (52% demonstrated resistance to penicillin and ampicillin but all were susceptible to the other antibiotics tested. S. aureus isolates were further examined for their clonal diversity by Multi-Locus Sequence Typing (MLST. In total, 18 different sequence types (STs were identified and eBURST analysis demonstrated that the majority of isolates grouped into clonal complexes CC97, CC151 or sequence type (ST 136. Analysis of the role of recombination events in determining S. aureus population structure determined that ST diversification through nucleotide substitutions were more likely to be due to recombination compared to point mutation, with regions of the genome possibly acting as recombination hotspots. DNA microarray analysis revealed a large number of differences amongst S. aureus STs in their variable genome content, including genes associated with capsule and biofilm formation and adhesion factors. Finally, evidence for a genomic arrangement was observed within isolates from CC97 with the ST71-like subgroup showing evidence of an IS431 insertion element having replaced approximately 30 kb of DNA including the ica operon and histidine biosynthesis genes, resulting in histidine auxotrophy. This genomic rearrangement may be responsible for the diversification of ST71 into an emerging bovine adapted subgroup.

Complex genomic rearrangement in CCS-LacZ transgenic mice.

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Stroud, Dina Myers; Darrow, Bruce J; Kim, Sang Do; Zhang, Jie; Jongbloed, Monique R M; Rentschler, Stacey; Moskowitz, Ivan P G; Seidman, Jonathan; Fishman, Glenn I

2007-02-01

The cardiac conduction system (CCS)-lacZ insertional mouse mutant strain genetically labels the developing and mature CCS. This pattern of expression is presumed to reflect the site of transgene integration rather than regulatory elements within the transgene proper. We sought to characterize the genomic structure of the integration locus and identify nearby gene(s) that might potentially confer the observed CCS-specific transcription. We found rearrangement of chromosome 7 between regions D1 and E1 with altered transcription of multiple genes in the D1 region. Several lines of evidence suggested that regulatory elements from at least one gene, Slco3A1, influenced CCS-restricted reporter gene expression. In embryonic hearts, Slco3A1 was expressed in a spatial pattern similar to the CCS-lacZ transgene and was similarly neuregulin-responsive. At later stages, however, expression patterns of the transgene and Slco3A1 diverged, suggesting that the Slco3A1 locus may be necessary, but not sufficient to confer CCS-specific transgene expression in the CCS-lacZ line. (c) 2007 Wiley-Liss, Inc.

Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) affected by environmental factors.

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Wang, Qiuxia; Liu, Huitao; Gao, Ainong; Yang, Xinming; Liu, Weihua; Li, Xiuquan; Li, Lihui

2012-01-01

Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae affected by environmental factors.

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Qiuxia Wang

Full Text Available Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng J.L.Yang et al. (2n = 6x = 42, StStPPYY, collected from different environments, were studied using genome in situ hybridization (GISH. We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15% and Y (22.22%, in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05. The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01. Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

The Organelle Genomes of Hassawi Rice (Oryza sativa L.) and Its Hybrid in Saudi Arabia: Genome Variation, Rearrangement, and Origins

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Zhang, Tongwu; Hu, Songnian; Zhang, Guangyu; Pan, Linlin; Zhang, Xiaowei; Al-Mssallem, Ibrahim S.; Yu, Jun

2012-01-01

Hassawi rice (Oryza sativa L.) is a landrace adapted to the climate of Saudi Arabia, characterized by its strong resistance to soil salinity and drought. Using high quality sequencing reads extracted from raw data of a whole genome sequencing project, we assembled both chloroplast (cp) and mitochondrial (mt) genomes of the wild-type Hassawi rice (Hassawi-1) and its dwarf hybrid (Hassawi-2). We discovered 16 InDels (insertions and deletions) but no SNP (single nucleotide polymorphism) is present between the two Hassawi cp genomes. We identified 48 InDels and 26 SNPs in the two Hassawi mt genomes and a new type of sequence variation, termed reverse complementary variation (RCV) in the rice cp genomes. There are two and four RCVs identified in Hassawi-1 when compared to 93–11 (indica) and Nipponbare (japonica), respectively. Microsatellite sequence analysis showed there are more SSRs in the genic regions of both cp and mt genomes in the Hassawi rice than in the other rice varieties. There are also large repeats in the Hassawi mt genomes, with the longest length of 96,168 bp and 96,165 bp in Hassawi-1 and Hassawi-2, respectively. We believe that frequent DNA rearrangement in the Hassawi mt and cp genomes indicate ongoing dynamic processes to reach genetic stability under strong environmental pressures. Based on sequence variation analysis and the breeding history, we suggest that both Hassawi-1 and Hassawi-2 originated from the Indonesian variety Peta since genetic diversity between the two Hassawi cultivars is very low albeit an unknown historic origin of the wild-type Hassawi rice. PMID:22870184

Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

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Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

2009-09-18

Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human genome; however, appear to have a higher propensity than others to rearrange in any host system. Thus, techniques to detect and accurately characterize such rearrangements need to be developed. We developed a technique termed 'Quantitative DNA Fiber Mapping (QDFM)' that allows accurate tagging of sequence elements of interest with near kilobase accuracy and optimized it for delineation of rearrangements in recombinant DNA clones. This paper demonstrates the power of this microscopic approach by investigating YAC rearrangements. In our examples, high-resolution physical maps for regions within the immunoglobulin lambda variant gene cluster were constructed for three different YAC clones carrying deletions of 95 kb and more. Rearrangements within YACs could be demonstrated unambiguously by pairwise mapping of cosmids along YAC DNA molecules. When coverage by YAC clones was not available, distances between cosmid clones were estimated by hybridization of cosmids onto DNA fibers prepared from human genomic DNA. In addition, the QDFM technology provides essential information about clone stability facilitating closure of the maps of the human genome as well as those of model organisms.

Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts.

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Martínez-Alberola, Fernando; Del Campo, Eva M; Lázaro-Gimeno, David; Mezquita-Claramonte, Sergio; Molins, Arantxa; Mateu-Andrés, Isabel; Pedrola-Monfort, Joan; Casano, Leonardo M; Barreno, Eva

2013-01-01

Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt) in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae.

Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts.

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Fernando Martínez-Alberola

Full Text Available Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae.

Bootstrapping phylogenies inferred from rearrangement data

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Lin Yu

2012-08-01

Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

Bootstrapping phylogenies inferred from rearrangement data.

Science.gov (United States)

Lin, Yu; Rajan, Vaibhav; Moret, Bernard Me

2012-08-29

Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its support values follow a similar scale and its receiver

MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement

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Zhang Liqing

2010-01-01

Full Text Available Abstract Background Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (i.e., the random duplication model. However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (i.e., the tandem duplication model. Results In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (i.e., the so-called inparalogs, using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs, and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments

Comparison between fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis in translocation carriers.

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Lee, Vivian C Y; Chow, Judy F C; Lau, Estella Y L; Yeung, William S B; Ho, P C; Ng, Ernest H Y

2015-02-01

To compare the pregnancy outcome of the fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis of translocation carriers. Historical cohort. A teaching hospital in Hong Kong. All preimplantation genetic diagnosis treatment cycles performed for translocation carriers from 2001 to 2013. Overall, 101 treatment cycles for preimplantation genetic diagnosis in translocation were included: 77 cycles for reciprocal translocation and 24 cycles for Robertsonian translocation. Fluorescent in-situ hybridisation and array comparative genomic hybridisation were used in 78 and 11 cycles, respectively. The ongoing pregnancy rate per initiated cycle after array comparative genomic hybridisation was significantly higher than that after fluorescent in-situ hybridisation in all translocation carriers (36.4% vs 9.0%; P=0.010). The miscarriage rate was comparable with both techniques. The testing method (array comparative genomic hybridisation or fluorescent in-situ hybridisation) was the only significant factor affecting the ongoing pregnancy rate after controlling for the women's age, type of translocation, and clinical information of the preimplantation genetic diagnosis cycles by logistic regression (odds ratio=1.875; P=0.023; 95% confidence interval, 1.090-3.226). This local retrospective study confirmed that comparative genomic hybridisation is associated with significantly higher pregnancy rates versus fluorescent in-situ hybridisation in translocation carriers. Array comparative genomic hybridisation should be the technique of choice in preimplantation genetic diagnosis cycles in translocation carriers.

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

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Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

2012-06-28

Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Mitochondrial genome of the Komodo dragon: efficient sequencing method with reptile-oriented primers and novel gene rearrangements.

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Kumazawa, Yoshinori; Endo, Hideki

2004-04-30

The mitochondrial genome of the Komodo dragon (Varanus komodoensis) was nearly completely sequenced, except for two highly repetitive noncoding regions. An efficient sequencing method for squamate mitochondrial genomes was established by combining the long polymerase chain reaction (PCR) technology and a set of reptile-oriented primers designed for nested PCR amplifications. It was found that the mitochondrial genome had novel gene arrangements in which genes from NADH dehydrogenase subunit 6 to proline tRNA were extensively shuffled with duplicate control regions. These control regions had 99% sequence similarity over 700 bp. Although snake mitochondrial genomes are also known to possess duplicate control regions with nearly identical sequences, the location of the second control region suggested independent occurrence of the duplication on lineages leading to snakes and the Komodo dragon. Another feature of the mitochondrial genome of the Komodo dragon was the considerable number of tandem repeats, including sequences with a strong secondary structure, as a possible site for the slipped-strand mispairing in replication. These observations are consistent with hypotheses that tandem duplications via the slipped-strand mispairing may induce mitochondrial gene rearrangements and may serve to maintain similar copies of the control region.

"Is It Worth Knowing?" Focus Group Participants' Perceived Utility of Genomic Preconception Carrier Screening.

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Schneider, Jennifer L; Goddard, Katrina A B; Davis, James; Wilfond, Benjamin; Kauffman, Tia L; Reiss, Jacob A; Gilmore, Marian; Himes, Patricia; Lynch, Frances L; Leo, Michael C; McMullen, Carmit

2016-02-01

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing for preconception carrier screening, compared to usual care. Using a discussion guide, a trained qualitative moderator facilitated the audio-recorded focus groups. Sixteen individuals participated. Thematic analysis of transcripts started with a grounded approach and subsequently focused on participants' perceptions of the value of genetic information. Analysis uncovered two orientations toward genomic preconception carrier screening: "certain" individuals desiring all possible screening information; and "hesitant" individuals who were more cautious about its value. Participants revealed valuable information about barriers to screening: fear/anxiety about results; concerns about the method of returning results; concerns about screening necessity; and concerns about partner participation. All participants recommended offering choice to patients to enhance the value of screening and reduce barriers. Overall, two groups of likely users of genome sequencing for preconception carrier screening demonstrated different perceptions of the advantages or disadvantages of screening, suggesting tailored approaches to education, consent, and counseling may be warranted with each group.

Precise detection of rearrangement breakpoints in mammalian chromosomes

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Gautier Christian

2008-06-01

Full Text Available Abstract Background Genomes undergo large structural changes that alter their organisation. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. We developed a method to precisely delimit rearrangement breakpoints on a genome by comparison with the genome of a related species. Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them. Results Given some reliable and non overlapping synteny blocks, the core of the method consists in refining the regions that are not contained in them. By aligning each breakpoint sequence against its specific orthologous sequences in the other species, we can look for weak similarities inside the breakpoint, thus extending the synteny blocks and narrowing the breakpoints. The identification of the narrowed breakpoints relies on a segmentation algorithm and is statistically assessed. Since this method requires as input synteny blocks with some properties which, though they appear natural, are not verified by current methods for detecting such blocks, we further give a formal definition and provide an algorithm to compute them. The whole method is applied to delimit breakpoints on the human genome when compared to the mouse and dog genomes. Among the 355 human-mouse and 240 human-dog breakpoints, 168 and 146 respectively span less than 50 Kb. We compared the resulting breakpoints with some publicly available ones and show that we achieve a better resolution. Furthermore, we suggest that breakpoints are rarely reduced to a point, and instead consist in often large regions that can be distinguished from the sequences around in terms of segmental duplications, similarity with related species, and transposable elements. Conclusion Our method leads to smaller

Analysis of gene order data supports vertical inheritance of the leukotoxin operon and genome rearrangements in the 5' flanking region in genus Mannheimia

DEFF Research Database (Denmark)

Larsen, Jesper; Kuhnert, Peter; Frey, Joachim

2007-01-01

subclades, thus reaffirming the hypothesis of vertical inheritance of the leukotoxin operon. The presence of individual 5' flanking regions in M. haemolytica + M. glucosida and M. granulomatis reflects later genome rearrangements within each subclade. The evolution of the novel 5' flanking region in M...

Gene activation by induced DNA rearrangements

International Nuclear Information System (INIS)

Schnipper, L.E.; Chan, V.; Sedivy, J.; Jat, P.; Sharp, P.A.

1989-01-01

A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.

Science.gov (United States)

Sharp, Andrew J; Hansen, Sierra; Selzer, Rebecca R; Cheng, Ze; Regan, Regina; Hurst, Jane A; Stewart, Helen; Price, Sue M; Blair, Edward; Hennekam, Raoul C; Fitzpatrick, Carrie A; Segraves, Rick; Richmond, Todd A; Guiver, Cheryl; Albertson, Donna G; Pinkel, Daniel; Eis, Peggy S; Schwartz, Stuart; Knight, Samantha J L; Eichler, Evan E

2006-09-01

Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.

Large Clinically Consequential Imbalances Detected at the Breakpoints of Apparently Balanced and Inherited Chromosome Rearrangements

OpenAIRE

South, Sarah T.; Rector, Lyndsey; Aston, Emily; Rowe, Leslie; Yang, Samuel P.

2010-01-01

When a chromosome abnormality is identified in a child with a developmental delay and/or multiple congenital anomalies and the chromosome rearrangement appears balanced, follow-up studies often examine both parents for this rearrangement. If either clinically unaffected parent has a chromosome abnormality with a banding pattern identical to the affected child's study, then it is assumed that the chromosome rearrangement is balanced and directly inherited from the normal carrier parent. It is ...

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

Science.gov (United States)

Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B

2017-02-01

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

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Rafael B. Blasco

2014-11-01

Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

The Mimivirus Genome Encodes a Mitochondrial Carrier That Transports dATP and dTTP▿

Science.gov (United States)

Monné, Magnus; Robinson, Alan J.; Boes, Christoph; Harbour, Michael E.; Fearnley, Ian M.; Kunji, Edmund R. S.

2007-01-01

Members of the mitochondrial carrier family have been reported in eukaryotes only, where they transport metabolites and cofactors across the mitochondrial inner membrane to link the metabolic pathways of the cytosol and the matrix. The genome of the giant virus Mimiviridae mimivirus encodes a member of the mitochondrial carrier family of transport proteins. This viral protein has been expressed in Lactococcus lactis and is shown to transport dATP and dTTP. As the 1.2-Mb double-stranded DNA mimivirus genome is rich in A and T residues, we speculate that the virus is using this protein to target the host mitochondria as a source of deoxynucleotides for its replication. PMID:17229695

Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy.

Science.gov (United States)

Mefford, Heather C; Clauin, Severine; Sharp, Andrew J; Moller, Rikke S; Ullmann, Reinhard; Kapur, Raj; Pinkel, Dan; Cooper, Gregory M; Ventura, Mario; Ropers, H Hilger; Tommerup, Niels; Eichler, Evan E; Bellanne-Chantelot, Christine

2007-11-01

Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One of the microdeletions, identified in a fetus with multicystic dysplastic kidneys, encompasses the TCF2 gene on 17q12, previously shown to be mutated in maturity-onset diabetes, as well as in a subset of pediatric renal abnormalities. Fine-scale mapping of the breakpoints in different patient cohorts revealed a recurrent 1.5-Mb de novo deletion in individuals with phenotypes that ranged from congenital renal abnormalities to maturity-onset diabetes of the young type 5. We also identified the reciprocal duplication, which appears to be enriched in samples from patients with epilepsy. We describe the first example of a recurrent genomic disorder associated with diabetes.

Digging deeper: new gene order rearrangements and distinct patterns of codons usage in mitochondrial genomes among shrimps from the Axiidea, Gebiidea and Caridea (Crustacea: Decapoda

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Mun Hua Tan

2017-03-01

Full Text Available Background Whole mitochondrial DNA is being increasingly utilized for comparative genomic and phylogenetic studies at deep and shallow evolutionary levels for a range of taxonomic groups. Although mitogenome sequences are deposited at an increasing rate into public databases, their taxonomic representation is unequal across major taxonomic groups. In the case of decapod crustaceans, several infraorders, including Axiidea (ghost shrimps, sponge shrimps, and mud lobsters and Caridea (true shrimps are still under-represented, limiting comprehensive phylogenetic studies that utilize mitogenomic information. Methods Sequence reads from partial genome scans were generated using the Illumina MiSeq platform and mitogenome sequences were assembled from these low coverage reads. In addition to examining phylogenetic relationships within the three infraorders, Axiidea, Gebiidea, and Caridea, we also investigated the diversity and frequency of codon usage bias and mitogenome gene order rearrangements. Results We present new mitogenome sequences for five shrimp species from Australia that includes two ghost shrimps, Callianassa ceramica and Trypaea australiensis, along with three caridean shrimps, Macrobrachium bullatum, Alpheus lobidens, and Caridina cf. nilotica. Strong differences in codon usage were discovered among the three infraorders and significant gene order rearrangements were observed. While the gene order rearrangements are congruent with the inferred phylogenetic relationships and consistent with taxonomic classification, they are unevenly distributed within and among the three infraorders. Discussion Our findings suggest potential for mitogenome rearrangements to be useful phylogenetic markers for decapod crustaceans and at the same time raise important questions concerning the drivers of mitogenome evolution in different decapod crustacean lineages.

Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

Science.gov (United States)

Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

2017-10-05

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

OpenAIRE

Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

2015-01-01

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understandin...

Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

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Ludwig Hieber

2011-01-01

Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

Lessons Learned From A Study Of Genomics-Based Carrier Screening For Reproductive Decision Making.

Science.gov (United States)

Wilfond, Benjamin S; Kauffman, Tia L; Jarvik, Gail P; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Gilmore, Marian; Himes, Patricia; Kraft, Stephanie A; Porter, Kathryn M; Schneider, Jennifer L; Punj, Sumit; Leo, Michael C; Dickerson, John F; Lynch, Frances L; Clarke, Elizabeth; Rope, Alan F; Lutz, Kevin; Goddard, Katrina A B

2018-05-01

Genomics-based carrier screening is one of many opportunities to use genomic information to inform medical decision making, but clinicians, health care delivery systems, and payers need to determine whether to offer screening and how to do so in an efficient, ethical way. To shed light on this issue, we conducted a study in the period 2014-17 to inform the design of clinical screening programs and guide further health services research. Many of our results have been published elsewhere; this article summarizes the lessons we learned from that study and offers policy insights. Our experience can inform understanding of the potential impact of expanded carrier screening services on health system workflows and workforces-impacts that depend on the details of the screening approach. We found limited patient or health system harms from expanded screening. We also found that some patients valued the information they learned from the process. Future policy discussions should consider the value of offering such expanded carrier screening in health delivery systems with limited resources.

Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

Science.gov (United States)

Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

2018-04-17

The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological

The diverse effects of complex chromosome rearrangements and chromothripsis in cancer development

NARCIS (Netherlands)

De Pagter, Mirjam S.; Kloosterman, Wigard P.

2015-01-01

In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in

The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

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Eichler Evan E

2008-08-01

Full Text Available Abstract Background It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs. This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements. Results Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA. Conclusion We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12.

Science.gov (United States)

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2010-03-01

Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.

Structural variation and rates of genome evolution in the grass family seen through comparison of sequences of genomes greatly differing in size.

Science.gov (United States)

Dvorak, Jan; Wang, Le; Zhu, Tingting; Jorgensen, Chad M; Deal, Karin R; Dai, Xiongtao; Dawson, Matthew W; Müller, Hans-Georg; Luo, Ming-Cheng; Ramasamy, Ramesh K; Dehghani, Hamid; Gu, Yong Q; Gill, Bikram S; Distelfeld, Assaf; Devos, Katrien M; Qi, Peng; You, Frank M; Gulick, Patrick J; McGuire, Patrick E

2018-05-16

Homology was searched with genes annotated in the Aegilops tauschii pseudomolecules against genes annotated in the pseudomolecules of tetraploid wild emmer wheat, Brachypodium distachyon, sorghum, and rice. Similar searches were initiated with genes annotated in the rice pseudomolecules. Matrices of colinear genes and rearrangements in their order were constructed. Optical Bionano genome maps were constructed and used to validate rearrangements unique to the wild emmer and Ae. tauschii genomes. Most common rearrangements were short paracentric inversions and short intrachromosomal translocations. Intrachromosomal translocations outnumbered segmental intrachromosomal duplications. The densities of paracentric inversion lengths were approximated by exponential distributions in all six genomes. Densities of colinear genes along the Ae. tauschii chromosomes were highly correlated with meiotic recombination rates but those of rearrangements were not, suggesting different causes of the erosion of gene colinearity and evolution of major chromosome rearrangements. Frequent rearrangements sharing breakpoints suggested that chromosomes have been rearranged recurrently at some sites. The distal 4 Mb of the short arms of rice chromosomes Os11 and Os12 and corresponding regions in the sorghum, B. distachyon, and Triticeae genomes contain clusters of interstitial translocations including from 1 to 7 colinear genes. The rates of acquisition of major rearrangements were greater in the wild emmer wheat and Ae. tauschii genomes than in the lineage preceding their divergence or in the B. distachyon, rice, and sorghum lineages. It is suggested that synergy between large quantities of dynamic transposable elements and annual growth habit caused the fast evolution of the Triticeae genomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The complete mitochondrial genome sequence of the spider habronattus oregonensis reveals rearranged and extremely truncated tRNAs

International Nuclear Information System (INIS)

Masta, Susan E.; Boore, Jeffrey L.

2004-01-01

We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TYC arm stem pairings, and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3' aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3' aminoacyl acceptor stems in order to allow the tRNAs to function. At least seven tRN As are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunit 2 and 3 genes apparently use UUG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381 bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that post transcriptional RNA editing can likely maintain function of the tRNAs while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome

Application of the inter-line PCR for the analyse of genomic rearrangements in radiation-transformed mammalian cell lines; Anwendung der Inter-Line PCR zur Analyse von genomischen Veraenderungen in strahlentransformierten Saeugerzellinien

Energy Technology Data Exchange (ETDEWEB)

Leibhard, S.; Smida, J. [Muenchen Univ. (Germany). Strahlenbiologisches Inst.; Eckardt-Schupp, F.; Hieber, L. [GSF-Inst. fuer Strahlenbiologie, Oberschleissheim (Germany)

1996-12-31

Repetitive DNA sequences of the LINE-family (long interspersed elements) that are widely distributed among the mammalian genome can be activated or altered by the exposure to ionizing radiation [1]. By the integration at new sites in the genome alterations in the expression of genes that are involved in cell transformation and/or carcinogenesis may occur [2, 3]. A new technique - the inter-LINE PCR - has been developed in order to detect and analyse such genomic rearrangements in radiation-transformed cell lines. From the sites of transformation- or tumour-specific changes in the genome it might be possible to develop new tumour markers for diagnostic purpose. (orig.) [Deutsch] Repetitive DNA-Sequenzen der LINE-Familie, die weit verbreitet im Genom von Saeugerzellen vorkommen, koennen durch Exposition mit ionisierender Strahlung aktiviert und veraendert werden [1]. Durch eine Neu- bzw. Reintegration an anderen Positionen im Genom kann es zu bedeutenden Veraenderungen im Genom der Zelle kommen. Die Expression von Genen, die bei den Prozessen der Zelltransformation bzw. der Karzinogenese beteiligt sind, kann dadurch veraendert werden [2, 3]. Mithilfe der von uns entwickelten Inter-LINE PCR und der anschliessenden Analyse der veraenderten Produktmuster nach gelelektrophoretischer Auftrennung koennen solche `genomic rearrangements` unter Beteiligung von LINE-Elementen untersucht und naeher charakterisiert werden. Durch Klonierung und Sequenzierung transformations- bzw. tumorspezifischer PCR-Produkte sollte es moeglich sein Tumormarker fuer diagnostische Zwecke zu entwickeln. Die Methode wurde fuer die Analyse von Zellen des Syrischen Hamster aufgebaut, sie ist jedoch universell fuer alle Saeuger anwendbar. (orig.)

A complex genomic rearrangement involving the endothelin 3 locus causes dermal hyperpigmentation in the chicken.

Directory of Open Access Journals (Sweden)

Ben Dorshorst

2011-12-01

Full Text Available Dermal hyperpigmentation or Fibromelanosis (FM is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3, a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals.

A unifying model of genome evolution under parsimony.

Science.gov (United States)

Paten, Benedict; Zerbino, Daniel R; Hickey, Glenn; Haussler, David

2014-06-19

Parsimony and maximum likelihood methods of phylogenetic tree estimation and parsimony methods for genome rearrangements are central to the study of genome evolution yet to date they have largely been pursued in isolation. We present a data structure called a history graph that offers a practical basis for the analysis of genome evolution. It conceptually simplifies the study of parsimonious evolutionary histories by representing both substitutions and double cut and join (DCJ) rearrangements in the presence of duplications. The problem of constructing parsimonious history graphs thus subsumes related maximum parsimony problems in the fields of phylogenetic reconstruction and genome rearrangement. We show that tractable functions can be used to define upper and lower bounds on the minimum number of substitutions and DCJ rearrangements needed to explain any history graph. These bounds become tight for a special type of unambiguous history graph called an ancestral variation graph (AVG), which constrains in its combinatorial structure the number of operations required. We finally demonstrate that for a given history graph G, a finite set of AVGs describe all parsimonious interpretations of G, and this set can be explored with a few sampling moves. This theoretical study describes a model in which the inference of genome rearrangements and phylogeny can be unified under parsimony.

A sequence-based survey of the complex structural organization of tumor genomes

Energy Technology Data Exchange (ETDEWEB)

Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

2008-04-03

The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

Recurrence of Chromosome Rearrangements and Reuse of DNA Breakpoints in the Evolution of the Triticeae Genomes

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Wanlong Li

2016-12-01

Full Text Available Chromosomal rearrangements (CRs play important roles in karyotype diversity and speciation. While many CR breakpoints have been characterized at the sequence level in yeast, insects, and primates, little is known about the structure of evolutionary CR breakpoints in plant genomes, which are much more dynamic in genome size and sequence organization. Here, we report identification of breakpoints of a translocation between chromosome arms 4L and 5L of Triticeae, which is fixed in several species, including diploid wheat and rye, by comparative mapping and analysis of the draft genome and chromosome survey sequences of the Triticeae species. The wheat translocation joined the ends of breakpoints downstream of a WD40 gene on 4AL and a gene of the PMEI family on 5AL. A basic helix-loop-helix transcription factor gene in 5AL junction was significantly restructured. Rye and wheat share the same position for the 4L breakpoint, but the 5L breakpoint positions are not identical, although very close in these two species, indicating the recurrence of 4L/5L translocations in the Triticeae. Although barley does not carry the translocation, collinearity across the breakpoints was violated by putative inversions and/or transpositions. Alignment with model grass genomes indicated that the translocation breakpoints coincided with ancient inversion junctions in the Triticeae ancestor. Our results show that the 4L/5L translocation breakpoints represent two CR hotspots reused during Triticeae evolution, and support breakpoint reuse as a widespread mechanism in all eukaryotes. The mechanisms of the recurrent translocation and its role in Triticeae evolution are also discussed.

Oligonucleotide arrays vs. metaphase-comparative genomic hybridisation and BAC arrays for single-cell analysis: first applications to preimplantation genetic diagnosis for Robertsonian translocation carriers.

Science.gov (United States)

Ramos, Laia; del Rey, Javier; Daina, Gemma; García-Aragonés, Manel; Armengol, Lluís; Fernandez-Encinas, Alba; Parriego, Mònica; Boada, Montserrat; Martinez-Passarell, Olga; Martorell, Maria Rosa; Casagran, Oriol; Benet, Jordi; Navarro, Joaquima

2014-01-01

Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈ 20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers.

Oligonucleotide arrays vs. metaphase-comparative genomic hybridisation and BAC arrays for single-cell analysis: first applications to preimplantation genetic diagnosis for Robertsonian translocation carriers.

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Laia Ramos

Full Text Available Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈ 20 kb. Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14(q10;q10. Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers.

Oligonucleotide Arrays vs. Metaphase-Comparative Genomic Hybridisation and BAC Arrays for Single-Cell Analysis: First Applications to Preimplantation Genetic Diagnosis for Robertsonian Translocation Carriers

Science.gov (United States)

Ramos, Laia; del Rey, Javier; Daina, Gemma; García-Aragonés, Manel; Armengol, Lluís; Fernandez-Encinas, Alba; Parriego, Mònica; Boada, Montserrat; Martinez-Passarell, Olga; Martorell, Maria Rosa; Casagran, Oriol; Benet, Jordi; Navarro, Joaquima

2014-01-01

Comprehensive chromosome analysis techniques such as metaphase-Comparative Genomic Hybridisation (CGH) and array-CGH are available for single-cell analysis. However, while metaphase-CGH and BAC array-CGH have been widely used for Preimplantation Genetic Diagnosis, oligonucleotide array-CGH has not been used in an extensive way. A comparison between oligonucleotide array-CGH and metaphase-CGH has been performed analysing 15 single fibroblasts from aneuploid cell-lines and 18 single blastomeres from human cleavage-stage embryos. Afterwards, oligonucleotide array-CGH and BAC array-CGH were also compared analysing 16 single blastomeres from human cleavage-stage embryos. All three comprehensive analysis techniques provided broadly similar cytogenetic profiles; however, non-identical profiles appeared when extensive aneuploidies were present in a cell. Both array techniques provided an optimised analysis procedure and a higher resolution than metaphase-CGH. Moreover, oligonucleotide array-CGH was able to define extra segmental imbalances in 14.7% of the blastomeres and it better determined the specific unbalanced chromosome regions due to a higher resolution of the technique (≈20 kb). Applicability of oligonucleotide array-CGH for Preimplantation Genetic Diagnosis has been demonstrated in two cases of Robertsonian translocation carriers 45,XY,der(13;14)(q10;q10). Transfer of euploid embryos was performed in both cases and pregnancy was achieved by one of the couples. This is the first time that an oligonucleotide array-CGH approach has been successfully applied to Preimplantation Genetic Diagnosis for balanced chromosome rearrangement carriers. PMID:25415307

A Genomics Approach to Tumor Gemome Analysis

National Research Council Canada - National Science Library

Collins, Colin

2002-01-01

Genomes of solid tumors are often highly rearranged and these rearrangements promote cancer progression through disruption of genes mediating immortality, survival, metastasis, and resistance to therapy...

Genome-wide detection of chromosomal rearrangements, indels, and mutations in circular chromosomes by short read sequencing

DEFF Research Database (Denmark)

Skovgaard, Ole; Bak, Mads; Løbner-Olesen, Anders

2011-01-01

a combination of WGS and genome copy number analysis, for the identification of mutations that suppress the growth deficiency imposed by excessive initiations from the Escherichia coli origin of replication, oriC. The E. coli chromosome, like the majority of bacterial chromosomes, is circular, and DNA...... replication is initiated by assembling two replication complexes at the origin, oriC. These complexes then replicate the chromosome bidirectionally toward the terminus, ter. In a population of growing cells, this results in a copy number gradient, so that origin-proximal sequences are more frequent than...... origin-distal sequences. Major rearrangements in the chromosome are, therefore, readily identified by changes in copy number, i.e., certain sequences become over- or under-represented. Of the eight mutations analyzed in detail here, six were found to affect a single gene only, one was a large chromosomal...

A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

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Ashley S. Chaffin

2016-07-01

Full Text Available Hexaploid oat ( L., 2 = 6 = 42 is a member of the Poaceae family and has a large genome (∼12.5 Gb containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP array and genotyping-by-sequencing (GBS were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice ( L. reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes.

Brain function in carriers of a genome-wide supported bipolar disorder variant.

Science.gov (United States)

Erk, Susanne; Meyer-Lindenberg, Andreas; Schnell, Knut; Opitz von Boberfeld, Carola; Esslinger, Christine; Kirsch, Peter; Grimm, Oliver; Arnold, Claudia; Haddad, Leila; Witt, Stephanie H; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Walter, Henrik

2010-08-01

The neural abnormalities underlying genetic risk for bipolar disorder, a severe, common, and highly heritable psychiatric condition, are largely unknown. An opportunity to define these mechanisms is provided by the recent discovery, through genome-wide association, of a single-nucleotide polymorphism (rs1006737) strongly associated with bipolar disorder within the CACNA1C gene, encoding the alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2. To determine whether the genetic risk associated with rs1006737 is mediated through hippocampal function. Functional magnetic resonance imaging study. University hospital. A total of 110 healthy volunteers of both sexes and of German descent in the Hardy-Weinberg equilibrium for rs1006737. Blood oxygen level-dependent signal during an episodic memory task and behavioral and psychopathological measures. Using an intermediate phenotype approach, we show that healthy carriers of the CACNA1C risk variant exhibit a pronounced reduction of bilateral hippocampal activation during episodic memory recall and diminished functional coupling between left and right hippocampal regions. Furthermore, risk allele carriers exhibit activation deficits of the subgenual anterior cingulate cortex, a region repeatedly associated with affective disorders and the mediation of adaptive stress-related responses. The relevance of these findings for affective disorders is supported by significantly higher psychopathology scores for depression, anxiety, obsessive-compulsive thoughts, interpersonal sensitivity, and neuroticism in risk allele carriers, correlating negatively with the observed regional brain activation. Our data demonstrate that rs1006737 or genetic variants in linkage disequilibrium with it are functional in the human brain and provide a neurogenetic risk mechanism for bipolar disorder backed by genome-wide evidence.

Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome

NARCIS (Netherlands)

Sharp, Andrew J.; Hansen, Sierra; Selzer, Rebecca R.; Cheng, Ze; Regan, Regina; Hurst, Jane A.; Stewart, Helen; Price, Sue M.; Blair, Edward; Hennekam, Raoul C.; Fitzpatrick, Carrie A.; Segraves, Rick; Richmond, Todd A.; Guiver, Cheryl; Albertson, Donna G.; Pinkel, Daniel; Eis, Peggy S.; Schwartz, Stuart; Knight, Samantha J. L.; Eichler, Evan E.

2006-01-01

Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic

Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions

International Nuclear Information System (INIS)

Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.

2003-01-01

Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive

SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.

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Jason Liang

2018-03-01

Full Text Available Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO. Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.

Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development.

Science.gov (United States)

Koga, Tomoyuki; Li, Bin; Figueroa, Javier M; Ren, Bing; Chen, Clark C; Carter, Bob S; Furnari, Frank B

2018-04-12

Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear. We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

Science.gov (United States)

Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

2008-11-07

The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

Exceptional Complex Chromosomal Rearrangements in Three Generations

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Hannie Kartapradja

2015-01-01

Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.

Stress-induced rearrangement of Fusarium retrotransposon sequences.

Science.gov (United States)

Anaya, N; Roncero, M I

1996-11-27

Rearrangement of fusarium oxysporum retrotransposon skippy was induced by growth in the presence of potassium chlorate. Three fungal strains, one sensitive to chlorate (Co60) and two resistant to chlorate and deficient for nitrate reductase (Co65 and Co94), were studied by Southern analysis of their genomic DNA. Polymorphism was detected in their hybridization banding pattern, relative to the wild type grown in the absence of chlorate, using various enzymes with or without restriction sites within the retrotransposon. Results were consistent with the assumption that three different events had occurred in strain Co60: genomic amplification of skippy yielding tandem arrays of the element, generation of new skippy sequences, and deletion of skippy sequences. Amplification of Co60 genomic DNA using the polymerase chain reaction and divergent primers derived from the retrotransposon generated a new band, corresponding to one long terminal repeat plus flanking sequences, that was not present in the wild-type strain. Molecular analysis of nitrate reductase-deficient mutants showed that generation and deletion of skippy sequences, but not genomic amplification in tandem repeats, had occurred in their genomes.

Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

Science.gov (United States)

Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

2018-02-01

Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (Phit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular

The mitochondrial genome of Frankliniella intonsa: insights into the evolution of mitochondrial genomes at lower taxonomic levels in Thysanoptera.

Science.gov (United States)

Yan, Dankan; Tang, Yunxia; Hu, Min; Liu, Fengquan; Zhang, Dongfang; Fan, Jiaqin

2014-10-01

Thrips is an ideal group for studying the evolution of mitochondrial (mt) genomes in the genus and family due to independent rearrangements within this order. The complete sequence of the mitochondrial DNA (mtDNA) of the flower thrips Frankliniella intonsa has been completed and annotated in this study. The circular genome is 15,215bp in length with an A+T content of 75.9% and contains the typical 37 genes and it has triplicate putative control regions. Nucleotide composition is A+T biased, and the majority of the protein-coding genes present opposite CG skew which is reflected by the nucleotide composition, codon and amino acid usage. Although the known thrips have massive gene rearrangements, it showed no reversal of strand asymmetry. Gene rearrangements have been found in the lower taxonomic levels of thrips. Three tRNA genes were translocated in the genus Frankliniella and eight tRNA genes in the family Thripidae. Although the gene arrangements of mt genomes of all three thrips species differ massively from the ancestral insect, they are all very similar to each other, indicating that there was a large rearrangement somewhere before the most recent common ancestor of these three species and very little genomic evolution or rearrangements after then. The extremely similar sequences among the CRs suggest that they are ongoing concerted evolution. Analyses of the up and downstream sequence of CRs reveal that the CR2 is actually the ancestral CR. The three CRs are in the same spot in each of the three thrips mt genomes which have the identical inverted genes. These characteristics might be obtained from the most recent common ancestor of this three thrips. Above observations suggest that the mt genomes of the three thrips keep a single massive rearrangement from the common ancestor and have low evolutionary rates among them. Copyright © 2014 Elsevier Inc. All rights reserved.

Chromosome rearrangements, recombination suppression, and limited segregation distortion in hybrids between Yellowstone cutthroat trout (Oncorhynchus clarkii bouvieri) and rainbow trout (O. mykiss)

Science.gov (United States)

2013-01-01

Background Introgressive hybridization is an important evolutionary process that can lead to the creation of novel genome structures and thus potentially new genetic variation for selection to act upon. On the other hand, hybridization with introduced species can threaten native species, such as cutthroat trout (Oncorhynchus clarkii) following the introduction of rainbow trout (O. mykiss). Neither the evolutionary consequences nor conservation implications of rainbow trout introgression in cutthroat trout is well understood. Therefore, we generated a genetic linkage map for rainbow-Yellowstone cutthroat trout (O. clarkii bouvieri) hybrids to evaluate genome processes that may help explain how introgression affects hybrid genome evolution. Results The hybrid map closely aligned with the rainbow trout map (a cutthroat trout map does not exist), sharing all but one linkage group. This linkage group (RYHyb20) represented a fusion between an acrocentric (Omy28) and a metacentric chromosome (Omy20) in rainbow trout. Additional mapping in Yellowstone cutthroat trout indicated the two rainbow trout homologues were fused in the Yellowstone genome. Variation in the number of hybrid linkage groups (28 or 29) likely depended on a Robertsonian rearrangement polymorphism within the rainbow trout stock. Comparison between the female-merged F1 map and a female consensus rainbow trout map revealed that introgression suppressed recombination across large genomic regions in 5 hybrid linkage groups. Two of these linkage groups (RYHyb20 and RYHyb25_29) contained confirmed chromosome rearrangements between rainbow and Yellowstone cutthroat trout indicating that rearrangements may suppress recombination. The frequency of allelic and genotypic segregation distortion varied among parents and families, suggesting few incompatibilities exist between rainbow and Yellowstone cutthroat trout genomes. Conclusions Chromosome rearrangements suppressed recombination in the hybrids. This result

Short and long-term genome stability analysis of prokaryotic genomes.

Science.gov (United States)

Brilli, Matteo; Liò, Pietro; Lacroix, Vincent; Sagot, Marie-France

2013-05-08

Gene organization dynamics is actively studied because it provides useful evolutionary information, makes functional annotation easier and often enables to characterize pathogens. There is therefore a strong interest in understanding the variability of this trait and the possible correlations with life-style. Two kinds of events affect genome organization: on one hand translocations and recombinations change the relative position of genes shared by two genomes (i.e. the backbone gene order); on the other, insertions and deletions leave the backbone gene order unchanged but they alter the gene neighborhoods by breaking the syntenic regions. A complete picture about genome organization evolution therefore requires to account for both kinds of events. We developed an approach where we model chromosomes as graphs on which we compute different stability estimators; we consider genome rearrangements as well as the effect of gene insertions and deletions. In a first part of the paper, we fit a measure of backbone gene order conservation (hereinafter called backbone stability) against phylogenetic distance for over 3000 genome comparisons, improving existing models for the divergence in time of backbone stability. Intra- and inter-specific comparisons were treated separately to focus on different time-scales. The use of multiple genomes of a same species allowed to identify genomes with diverging gene order with respect to their conspecific. The inter-species analysis indicates that pathogens are more often unstable with respect to non-pathogens. In a second part of the text, we show that in pathogens, gene content dynamics (insertions and deletions) have a much more dramatic effect on genome organization stability than backbone rearrangements. In this work, we studied genome organization divergence taking into account the contribution of both genome order rearrangements and genome content dynamics. By studying species with multiple sequenced genomes available, we were

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing

OpenAIRE

Kauffman, Tia L.; Wilfond, Benjamin S.; Jarvik, Gail P.; Leo, Michael C.; Lynch, Frances L.; Reiss, Jacob A.; Richards, C. Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O.; Goddard, Katrina A.B.

2016-01-01

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results...

Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia

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M.M. Sales

2005-05-01

Full Text Available We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

The mitochondrial genome of Phallusia mammillata and Phallusia fumigata (Tunicata, Ascidiacea: high genome plasticity at intra-genus level

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Pesole Graziano

2007-08-01

Full Text Available Abstract Background Within Chordata, the subphyla Vertebrata and Cephalochordata (lancelets are characterized by a remarkable stability of the mitochondrial (mt genome, with constancy of gene content and almost invariant gene order, whereas the limited mitochondrial data on the subphylum Tunicata suggest frequent and extensive gene rearrangements, observed also within ascidians of the same genus. Results To confirm this evolutionary trend and to better understand the evolutionary dynamics of the mitochondrial genome in Tunicata Ascidiacea, we have sequenced and characterized the complete mt genome of two congeneric ascidian species, Phallusia mammillata and Phallusia fumigata (Phlebobranchiata, Ascidiidae. The two mtDNAs are surprisingly rearranged, both with respect to one another and relative to those of other tunicates and chordates, with gene rearrangements affecting both protein-coding and tRNA genes. The new data highlight the extraordinary variability of ascidian mt genome in base composition, tRNA secondary structure, tRNA gene content, and non-coding regions (number, size, sequence and location. Indeed, both Phallusia genomes lack the trnD gene, show loss/acquisition of DHU-arm in two tRNAs, and have a G+C content two-fold higher than other ascidians. Moreover, the mt genome of P. fumigata presents two identical copies of trnI, an extra tRNA gene with uncertain amino acid specificity, and four almost identical sequence regions. In addition, a truncated cytochrome b, lacking a C-terminal tail that commonly protrudes into the mt matrix, has been identified as a new mt feature probably shared by all tunicates. Conclusion The frequent occurrence of major gene order rearrangements in ascidians both at high taxonomic level and within the same genus makes this taxon an excellent model to study the mechanisms of gene rearrangement, and renders the mt genome an invaluable phylogenetic marker to investigate molecular biodiversity and speciation

[Genome Rearrangements in Azospirillum brasilense Sp7 with the Involvement of the Plasmid pRhico and the Prophage phiAb-Cd].

Science.gov (United States)

Katsy, E I; Petrova, L P

2015-12-01

Alphaproteobacteria of the species Azospirillum brasilense have a multicomponent genome that undergoes frequent spontaneous rearrangements, yielding changes in the plasmid profiles of strains. Specifically, variants (Cd, Sp7.K2, Sp7.1, Sp7.4, Sp7.8, etc.) of the type strainA. brasilense Sp7 that had lost a 115-MDa plasmid were previously selected. In many of them, the molecular weight of a 90-MDa plasmid (p90 or pRhico), which is a kind of "depot" for glycopolymer biosynthesis genes, increased. In this study, a collection of primers was designed to the plasmid pRhico and to the DNA of prophage phiAb-Cd integrated in it. The use ofthese primers in polymerase chain reactions allowed the detection of the probable excision of phiAb-Cd phage from the DNA of A. brasilense variants Sp7.4 and Sp7.8 and other alterations of the pRhico structure in A. brasilense strains Cd, Sp7.K2, and Sp7.8. The developed primers and PCR conditions may be recoin mended for primary analysis of spontaneous plasmid rearrangements in A. brasilense Sp7 and related strains.

Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

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Antoine Marmignon

2014-08-01

Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium

Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

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Emanuel, Beverly S.

2008-01-01

Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

Genome sequences of seven foot-and-mouth disease virus isolates collected from serial samples from one persistently infected carrier cow in Vietnam

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Several FMDV carrier cattle were identified in Vietnam by recovery of infectious virus from oropharyngeal fluid. This report contains the first near-complete genome sequences of seven viruses isolated from a single carrier animal over the course of one year. Understanding within-host viral evolution...

Remembrance of things past retrieved from the Paramecium genome.

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Sperling, Linda

2011-01-01

Paramecium and other ciliates are the only unicellular eukaryotes that separate germinal and somatic functions. A germline micronucleus transmits the genetic information to sexual progeny, while a somatic macronucleus expresses the genetic information during vegetative growth to determine the phenotype. At each sexual generation, a new macronucleus develops from the zygotic nucleus through programmed rearrangements of the germline genome. Paramecium tetraurelia somatic genome sequencing, reviewed here, has provided insight into the organization and evolution of the genome. A series of at least 3 whole genome duplications was detected in the Paramecium lineage and selective pressures that determine the fate of the gene duplicates analyzed. Variability in the somatic DNA was characterized and could be attributed to the genome rearrangement processes. Since, in Paramecium, alternative genome rearrangement patterns can be inherited across sexual generations by homology-dependent epigenetic mechanisms and can affect phenotype, I discuss the possibility that ciliate nuclear dimorphism buffers genetic variation hidden in the germline. Copyright © 2011 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia

International Nuclear Information System (INIS)

Perl, A.; Wang, N.; Williams, J.M.; Hunt, M.J.; Rosenfeld, S.I.; Condemi, J.J.; Packman, C.H.; Abraham, G.N.

1987-01-01

The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic, 32 P-labelled, DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the genes. BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with two of the probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation

GAAP: Genome-organization-framework-Assisted Assembly Pipeline for prokaryotic genomes.

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Yuan, Lina; Yu, Yang; Zhu, Yanmin; Li, Yulai; Li, Changqing; Li, Rujiao; Ma, Qin; Siu, Gilman Kit-Hang; Yu, Jun; Jiang, Taijiao; Xiao, Jingfa; Kang, Yu

2017-01-25

Next-generation sequencing (NGS) technologies have greatly promoted the genomic study of prokaryotes. However, highly fragmented assemblies due to short reads from NGS are still a limiting factor in gaining insights into the genome biology. Reference-assisted tools are promising in genome assembly, but tend to result in false assembly when the assigned reference has extensive rearrangements. Herein, we present GAAP, a genome assembly pipeline for scaffolding based on core-gene-defined Genome Organizational Framework (cGOF) described in our previous study. Instead of assigning references, we use the multiple-reference-derived cGOFs as indexes to assist in order and orientation of the scaffolds and build a skeleton structure, and then use read pairs to extend scaffolds, called local scaffolding, and distinguish between true and chimeric adjacencies in the scaffolds. In our performance tests using both empirical and simulated data of 15 genomes in six species with diverse genome size, complexity, and all three categories of cGOFs, GAAP outcompetes or achieves comparable results when compared to three other reference-assisted programs, AlignGraph, Ragout and MeDuSa. GAAP uses both cGOF and pair-end reads to create assemblies in genomic scale, and performs better than the currently available reference-assisted assembly tools as it recovers more assemblies and makes fewer false locations, especially for species with extensive rearranged genomes. Our method is a promising solution for reconstruction of genome sequence from short reads of NGS.

Genomic rearrangement in radiation-induced murine myeloid leukemia

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Ishihara, Hiroshi

1994-01-01

After whole body irradiation of 3Gy X ray to C3H/He male mice, acute myeloid leukemia is induced at an incidence of 20 to 30% within 2 years. We have studied the mechanism of occurrence of this radiation-induced murine myeloid leukemia. Detection and isolation of genomic structural aberration which may be accumulated accompanied with leukemogenesis are helpful in analyzing the complicated molecular process from radiation damage to leukemogenesis. So, our research work was done in three phases. First, structures of previously characterized oncogenes and cytokine-related genes were analyzed, and abnormal structures of fms(protooncogene encoding M-CSF receptor gene)-related and myc-related genes were found in several leukemia cells. Additionally, genomic structural aberration of IL-3 gene was observed in some leukemia cells, so that construction of genomic libraries and cloning of the abnormal IL-3 genomic DNAs were performed to characterize the structure. Secondly, because the breakage of chromosome 2 that is frequently observed in myeloid leukemia locates in proximal position of IL-1 gene cluster in some cases, the copy number of IL-1 gene was determined and the gene was cloned. Lastly, the abnormal genome of leukemia cell was cloned by in-gel competence reassociation method. We discussed these findings and evaluated the analysis of the molecular process of leukemogenesis using these cloned genomic fragments. (author)

An Atypical Human Induced Pluripotent Stem Cell Line With a Complex, Stable, and Balanced Genomic Rearrangement Including a Large De Novo 1q Uniparental Disomy

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Steichen, Clara; Maluenda, Jérôme; Tosca, Lucie; Luce, Eléanor; Pineau, Dominique; Dianat, Noushin; Hannoun, Zara; Tachdjian, Gérard; Melki, Judith

2015-01-01

Human induced pluripotent stem cells (hiPSCs) hold great promise for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts. PMID:25650439

Sequencing and characterisation of rearrangements in three S. pastorianus strains reveals the presence of chimeric genes and gives evidence of breakpoint reuse.

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Sarah K Hewitt

Full Text Available Gross chromosomal rearrangements have the potential to be evolutionarily advantageous to an adapting organism. The generation of a hybrid species increases opportunity for recombination by bringing together two homologous genomes. We sought to define the location of genomic rearrangements in three strains of Saccharomyces pastorianus, a natural lager-brewing yeast hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus, using whole genome shotgun sequencing. Each strain of S. pastorianus has lost species-specific portions of its genome and has undergone extensive recombination, producing chimeric chromosomes. We predicted 30 breakpoints that we confirmed at the single nucleotide level by designing species-specific primers that flank each breakpoint, and then sequencing the PCR product. These rearrangements are the result of recombination between areas of homology between the two subgenomes, rather than repetitive elements such as transposons or tRNAs. Interestingly, 28/30 S. cerevisiae-S. eubayanus recombination breakpoints are located within genic regions, generating chimeric genes. Furthermore we show evidence for the reuse of two breakpoints, located in HSP82 and KEM1, in strains of proposed independent origin.

Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation

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Pasqual, Nicolas; Gallagher, Maighréad; Aude-Garcia, Catherine; Loiodice, Mélanie; Thuderoz, Florence; Demongeot, Jacques; Ceredig, Rod; Marche, Patrice Noël; Jouvin-Marche, Evelyne

2002-01-01

Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR α chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR α repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3′ side than 5′ end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR α repertoire size and suggest a scenario for V usage during differentiation. PMID:12417627

Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells

International Nuclear Information System (INIS)

Moore, Stephen R.; Papworth, David; Grosovsky, Andrew J.

2006-01-01

Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p < 0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p < 0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p = 0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms

Molecular rearrangements of superelectrophiles

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Douglas A. Klumpp

2011-03-01

Full Text Available Superelectrophiles are multiply charged cationic species (dications, trications, etc. which are characterized by their reactions with weak nucleophiles. These reactive intermediates may also undergo a wide variety of rearrangement-type reactions. Superelectrophilic rearrangements are often driven by charge–charge repulsive effects, as these densely charged ions react so as to maximize the distances between charge centers. These rearrangements involve reaction steps similar to monocationic rearrangements, such as alkyl group shifts, Wagner–Meerwein shifts, hydride shifts, ring opening reactions, and other skeletal rearrangements. This review will describe these types of superelectrophilic reactions.

Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast.

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Lanthaler, Karin; Bilsland, Elizabeth; Dobson, Paul D; Moss, Harry J; Pir, Pınar; Kell, Douglas B; Oliver, Stephen G

2011-10-24

The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

Discovery of global genomic re-organization based on comparison of two newly sequenced rice mitochondrial genomes with cytoplasmic male sterility-related genes

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Yamada Mari

2010-03-01

Full Text Available Abstract Background Plant mitochondrial genomes are known for their complexity, and there is abundant evidence demonstrating that this organelle is important for plant sexual reproduction. Cytoplasmic male sterility (CMS is a phenomenon caused by incompatibility between the nucleus and mitochondria that has been discovered in various plant species. As the exact sequence of steps leading to CMS has not yet been revealed, efforts should be made to elucidate the factors underlying the mechanism of this important trait for crop breeding. Results Two CMS mitochondrial genomes, LD-CMS, derived from Oryza sativa L. ssp. indica (434,735 bp, and CW-CMS, derived from Oryza rufipogon Griff. (559,045 bp, were newly sequenced in this study. Compared to the previously sequenced Nipponbare (Oryza sativa L. ssp. japonica mitochondrial genome, the presence of 54 out of 56 protein-encoding genes (including pseudo-genes, 22 tRNA genes (including pseudo-tRNAs, and three rRNA genes was conserved. Two other genes were not present in the CW-CMS mitochondrial genome, and one of them was present as part of the newly identified chimeric ORF, CW-orf307. At least 12 genomic recombination events were predicted between the LD-CMS mitochondrial genome and Nipponbare, and 15 between the CW-CMS genome and Nipponbare, and novel genetic structures were formed by these genomic rearrangements in the two CMS lines. At least one of the genomic rearrangements was completely unique to each CMS line and not present in 69 rice cultivars or 9 accessions of O. rufipogon. Conclusion Our results demonstrate novel mitochondrial genomic rearrangements that are unique in CMS cytoplasm, and one of the genes that is unique in the CW mitochondrial genome, CW-orf307, appeared to be the candidate most likely responsible for the CW-CMS event. Genomic rearrangements were dynamic in the CMS lines in comparison with those of rice cultivars, suggesting that 'death' and possible 'birth' processes of the

Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

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Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

2007-10-01

Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

Rearrangements in ground and excited states

CERN Document Server

de Mayo, Paul

1980-01-01

Rearrangements in Ground and Excited States, Volume 2 covers essays on the theoretical approach of rearrangements; the rearrangements involving boron; and the molecular rearrangements of organosilicon compounds. The book also includes essays on the polytopal rearrangement at phosphorus; the rearrangement in coordination complexes; and the reversible thermal intramolecular rearrangements of metal carbonyls. Chemists and people involved in the study of rearrangements will find the book invaluable.

Complete chloroplast genome of Trachelium caeruleum: extensiverearrangements are associated with repeats and tRNAs

Energy Technology Data Exchange (ETDEWEB)

Haberle, Rosemarie C.; Fourcade, Matthew L.; Boore, Jeffrey L.; Jansen, Robert K.

2006-01-09

Chloroplast genome structure, gene order and content arehighly conserved in land plants. We sequenced the complete chloroplastgenome sequence of Trachelium caeruleum (Campanulaceae) a member of anangiosperm family known for highly rearranged chloroplast genomes. Thetotal genome size is 162,321 bp with an IR of 27,273 bp, LSC of 100,113bp and SSC of 7,661 bp. The genome encodes 115 unique genes, with 19duplicated in the IR, a tRNA (trnI-CAU) duplicated once in the LSC and aprotein coding gene (psbJ) duplicated twice, for a total of 137 genes.Four genes (ycf15, rpl23, infA and accD) are truncated and likelynonfunctional; three others (clpP, ycf1 and ycf2) are so highly divergedthat they may now be pseudogenes. The most conspicuous feature of theTrachelium genome is the presence of eighteen internally unrearrangedblocks of genes that have been inverted or relocated within the genome,relative to the typical gene order of most angiosperm chloroplastgenomes. Recombination between repeats or tRNAs has been suggested as twomeans of chloroplast genome rearrangements. We compared the relativenumber of repeats in Trachelium to eight other angiosperm chloroplastgenomes, and evaluated the location of repeats and tRNAs in relation torearrangements. Trachelium has the highest number and largest repeats,which are concentrated near inversion endpoints or other rearrangements.tRNAs occur at many but not all inversion endpoints. There is likely nosingle mechanism responsible for the remarkable number of alterations inthis genome, but both repeats and tRNAs are clearly associated with theserearrangements. Land plant chloroplast genomes are highly conserved instructure, gene order and content. The chloroplast genomes of ferns, thegymnosperm Ginkgo, and most angiosperms are nearly collinear, reflectingthe gene order in lineages that diverged from lycopsids and the ancestralchloroplast gene order over 350 million years ago (Raubeson and Jansen,1992). Although earlier mapping studies

A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

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Gyorgy Petrovics

2015-12-01

Full Text Available Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA and Caucasian American (CA CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients. Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.

Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

DEFF Research Database (Denmark)

Buysse, Karen; Crepel, An; Menten, Björn

2008-01-01

these rearrangements. METHODS: We analysed a series of patients with breakpoints clustering within chromosome band 5q35. Using high density arrays and subsequent quantitative polymerase chain reaction (qPCR), we characterised the breakpoints of four interstitial deletions (including one associated with an unbalanced...

FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

Energy Technology Data Exchange (ETDEWEB)

Jinks-Robertson, Sue

2002-02-01

The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

Rearrangements in ground and excited states

CERN Document Server

de Mayo, Paul

1980-01-01

Rearrangements in Ground and Excited States, Volume 3 presents essays on the chemical generation of excited states; the cis-trans isomerization of olefins; and the photochemical rearrangements in trienes. The book also includes essays on the zimmerman rearrangements; the photochemical rearrangements of enones; the photochemical rearrangements of conjugated cyclic dienones; and the rearrangements of the benzene ring. Essays on the photo rearrangements via biradicals of simple carbonyl compounds; the photochemical rearrangements involving three-membered rings or five-membered ring heterocycles;

Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

International Nuclear Information System (INIS)

Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

2011-01-01

During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

Genome aliquoting with double cut and join

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Sankoff David

2008-01-01

Full Text Available Abstract Background The genome aliquoting probem is, given an observed genome A with n copies of each gene, presumed to descend from an n-way polyploidization event from an ordinary diploid genome B, followed by a history of chromosomal rearrangements, to reconstruct the identity of the original genome B'. The idea is to construct B', containing exactly one copy of each gene, so as to minimize the number of rearrangements d(A, B' ⊕ B' ⊕ ... ⊕ B' necessary to convert the observed genome B' ⊕ B' ⊕ ... ⊕ B' into A. Results In this paper we make the first attempt to define and solve the genome aliquoting problem. We present a heuristic algorithm for the problem as well the data from our experiments demonstrating its validity. Conclusion The heuristic performs well, consistently giving a non-trivial result. The question as to the existence or non-existence of an exact solution to this problem remains open.

Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series.

Science.gov (United States)

Shwan, Nzar A A; Louzada, Sandra; Yang, Fengtang; Armour, John A L

2017-05-01

The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1. © 2017 WILEY PERIODICALS, INC.

Rearrangements of Cycloalkenyl Aryl Ethers

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Mercedesz Törincsi

2016-04-01

Full Text Available Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed.

CSAR-web: a web server of contig scaffolding using algebraic rearrangements.

Science.gov (United States)

Chen, Kun-Tze; Lu, Chin Lung

2018-05-04

CSAR-web is a web-based tool that allows the users to efficiently and accurately scaffold (i.e. order and orient) the contigs of a target draft genome based on a complete or incomplete reference genome from a related organism. It takes as input a target genome in multi-FASTA format and a reference genome in FASTA or multi-FASTA format, depending on whether the reference genome is complete or incomplete, respectively. In addition, it requires the users to choose either 'NUCmer on nucleotides' or 'PROmer on translated amino acids' for CSAR-web to identify conserved genomic markers (i.e. matched sequence regions) between the target and reference genomes, which are used by the rearrangement-based scaffolding algorithm in CSAR-web to order and orient the contigs of the target genome based on the reference genome. In the output page, CSAR-web displays its scaffolding result in a graphical mode (i.e. scalable dotplot) allowing the users to visually validate the correctness of scaffolded contigs and in a tabular mode allowing the users to view the details of scaffolds. CSAR-web is available online at http://genome.cs.nthu.edu.tw/CSAR-web.

Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes.

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Sun, Yan-Bo; Xiong, Zi-Jun; Xiang, Xue-Yan; Liu, Shi-Ping; Zhou, Wei-Wei; Tu, Xiao-Long; Zhong, Li; Wang, Lu; Wu, Dong-Dong; Zhang, Bao-Lin; Zhu, Chun-Ling; Yang, Min-Min; Chen, Hong-Man; Li, Fang; Zhou, Long; Feng, Shao-Hong; Huang, Chao; Zhang, Guo-Jie; Irwin, David; Hillis, David M; Murphy, Robert W; Yang, Huan-Ming; Che, Jing; Wang, Jun; Zhang, Ya-Ping

2015-03-17

The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.

Branchio-otic syndrome caused by a genomic rearrangement: clinical findings and molecular cytogenetic studies in a patient with a pericentric inversion of chromosome 8.

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Schmidt, T; Bierhals, T; Kortüm, F; Bartels, I; Liehr, T; Burfeind, P; Shoukier, M; Frank, V; Bergmann, C; Kutsche, K

2014-01-01

Branchio-oto-renal (BOR) syndrome is an autosomal dominantly inherited developmental disorder, which is characterized by anomalies of the ears, the branchial arches and the kidneys. It is caused by mutations in the genes EYA1,SIX1 and SIX5. Genomic rearrangements of chromosome 8 affecting the EYA1 gene have also been described. Owing to this fact, methods for the identification of abnormal copy numbers such as multiplex ligation-dependent probe amplification (MLPA) have been introduced as routine laboratory techniques for molecular diagnostics of BOR syndrome. The advantages of these techniques are clear compared to standard cytogenetic and array approaches as well as Southern blot. MLPA detects deletions or duplications of a part or the entire gene of interest, but not balanced structural aberrations such as inversions and translocations. Consequently, disruption of a gene by a genomic rearrangement may escape detection by a molecular genetic analysis, although this gene interruption results in haploinsufficiency and, therefore, causes the disease. In a patient with clinical features of BOR syndrome, such as hearing loss, preauricular fistulas and facial dysmorphisms, but no renal anomalies, neither sequencing of the 3 genes linked to BOR syndrome nor array comparative genomic hybridization and MLPA were able to uncover a causative mutation. By routine cytogenetic analysis, we finally identified a pericentric inversion of chromosome 8 in the affected female. High-resolution multicolor banding confirmed the chromosome 8 inversion and narrowed down the karyotype to 46,XX,inv(8)(p22q13). By applying fluorescence in situ hybridization, we narrowed down both breakpoints on chromosome 8 and found the EYA1 gene in q13.3 to be directly disrupted. We conclude that standard karyotyping should not be neglected in the genetic diagnostics of BOR syndrome or other Mendelian disorders, particularly when molecular testing failed to detect any causative alteration in patients with

Genomic rearrangements of PTEN in prostate cancer

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Sopheap ePhin

2013-09-01

Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

Extensive structural variations between mitochondrial genomes of CMS and normal peppers (Capsicum annuum L.) revealed by complete nucleotide sequencing.

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Jo, Yeong Deuk; Choi, Yoomi; Kim, Dong-Hwan; Kim, Byung-Dong; Kang, Byoung-Cheorl

2014-07-04

Cytoplasmic male sterility (CMS) is an inability to produce functional pollen that is caused by mutation of the mitochondrial genome. Comparative analyses of mitochondrial genomes of lines with and without CMS in several species have revealed structural differences between genomes, including extensive rearrangements caused by recombination. However, the mitochondrial genome structure and the DNA rearrangements that may be related to CMS have not been characterized in Capsicum spp. We obtained the complete mitochondrial genome sequences of the pepper CMS line FS4401 (507,452 bp) and the fertile line Jeju (511,530 bp). Comparative analysis between mitochondrial genomes of peppers and tobacco that are included in Solanaceae revealed extensive DNA rearrangements and poor conservation in non-coding DNA. In comparison between pepper lines, FS4401 and Jeju mitochondrial DNAs contained the same complement of protein coding genes except for one additional copy of an atp6 gene (ψatp6-2) in FS4401. In terms of genome structure, we found eighteen syntenic blocks in the two mitochondrial genomes, which have been rearranged in each genome. By contrast, sequences between syntenic blocks, which were specific to each line, accounted for 30,380 and 17,847 bp in FS4401 and Jeju, respectively. The previously-reported CMS candidate genes, orf507 and ψatp6-2, were located on the edges of the largest sequence segments that were specific to FS4401. In this region, large number of small sequence segments which were absent or found on different locations in Jeju mitochondrial genome were combined together. The incorporation of repeats and overlapping of connected sequence segments by a few nucleotides implied that extensive rearrangements by homologous recombination might be involved in evolution of this region. Further analysis using mtDNA pairs from other plant species revealed common features of DNA regions around CMS-associated genes. Although large portion of sequence context was

Genome Organization Drives Chromosome Fragility.

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Canela, Andres; Maman, Yaakov; Jung, Seolkyoung; Wong, Nancy; Callen, Elsa; Day, Amanda; Kieffer-Kwon, Kyong-Rim; Pekowska, Aleksandra; Zhang, Hongliang; Rao, Suhas S P; Huang, Su-Chen; Mckinnon, Peter J; Aplan, Peter D; Pommier, Yves; Aiden, Erez Lieberman; Casellas, Rafael; Nussenzweig, André

2017-07-27

In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT. Published by Elsevier Inc.

Decoding Synteny Blocks and Large-Scale Duplications in Mammalian and Plant Genomes

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Peng, Qian; Alekseyev, Max A.; Tesler, Glenn; Pevzner, Pavel A.

The existing synteny block reconstruction algorithms use anchors (e.g., orthologous genes) shared over all genomes to construct the synteny blocks for multiple genomes. This approach, while efficient for a few genomes, cannot be scaled to address the need to construct synteny blocks in many mammalian genomes that are currently being sequenced. The problem is that the number of anchors shared among all genomes quickly decreases with the increase in the number of genomes. Another problem is that many genomes (plant genomes in particular) had extensive duplications, which makes decoding of genomic architecture and rearrangement analysis in plants difficult. The existing synteny block generation algorithms in plants do not address the issue of generating non-overlapping synteny blocks suitable for analyzing rearrangements and evolution history of duplications. We present a new algorithm based on the A-Bruijn graph framework that overcomes these difficulties and provides a unified approach to synteny block reconstruction for multiple genomes, and for genomes with large duplications.

Genome engineering in Vibrio cholerae

DEFF Research Database (Denmark)

Val, Marie-Eve; Skovgaard, Ole; Ducos-Galand, Magaly

2012-01-01

Although bacteria with multipartite genomes are prevalent, our knowledge of the mechanisms maintaining their genome is very limited, and much remains to be learned about the structural and functional interrelationships of multiple chromosomes. Owing to its bi-chromosomal genome architecture and its....... This difficulty was surmounted using a unique and powerful strategy based on massive rearrangement of prokaryotic genomes. We developed a site-specific recombination-based engineering tool, which allows targeted, oriented, and reciprocal DNA exchanges. Using this genetic tool, we obtained a panel of V. cholerae...

Three-dimensional genome architecture influences partner selection for chromosomal translocations in human disease.

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Jesse M Engreitz

Full Text Available Chromosomal translocations are frequent features of cancer genomes that contribute to disease progression. These rearrangements result from formation and illegitimate repair of DNA double-strand breaks (DSBs, a process that requires spatial colocalization of chromosomal breakpoints. The "contact first" hypothesis suggests that translocation partners colocalize in the nuclei of normal cells, prior to rearrangement. It is unclear, however, the extent to which spatial interactions based on three-dimensional genome architecture contribute to chromosomal rearrangements in human disease. Here we intersect Hi-C maps of three-dimensional chromosome conformation with collections of 1,533 chromosomal translocations from cancer and germline genomes. We show that many translocation-prone pairs of regions genome-wide, including the cancer translocation partners BCR-ABL and MYC-IGH, display elevated Hi-C contact frequencies in normal human cells. Considering tissue specificity, we find that translocation breakpoints reported in human hematologic malignancies have higher Hi-C contact frequencies in lymphoid cells than those reported in sarcomas and epithelial tumors. However, translocations from multiple tissue types show significant correlation with Hi-C contact frequencies, suggesting that both tissue-specific and universal features of chromatin structure contribute to chromosomal alterations. Our results demonstrate that three-dimensional genome architecture shapes the landscape of rearrangements directly observed in human disease and establish Hi-C as a key method for dissecting these effects.

Evolution of gastropod mitochondrial genome arrangements

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Zardoya Rafael

2008-02-01

Full Text Available Abstract Background Gastropod mitochondrial genomes exhibit an unusually great variety of gene orders compared to other metazoan mitochondrial genome such as e.g those of vertebrates. Hence, gastropod mitochondrial genomes constitute a good model system to study patterns, rates, and mechanisms of mitochondrial genome rearrangement. However, this kind of evolutionary comparative analysis requires a robust phylogenetic framework of the group under study, which has been elusive so far for gastropods in spite of the efforts carried out during the last two decades. Here, we report the complete nucleotide sequence of five mitochondrial genomes of gastropods (Pyramidella dolabrata, Ascobulla fragilis, Siphonaria pectinata, Onchidella celtica, and Myosotella myosotis, and we analyze them together with another ten complete mitochondrial genomes of gastropods currently available in molecular databases in order to reconstruct the phylogenetic relationships among the main lineages of gastropods. Results Comparative analyses with other mollusk mitochondrial genomes allowed us to describe molecular features and general trends in the evolution of mitochondrial genome organization in gastropods. Phylogenetic reconstruction with commonly used methods of phylogenetic inference (ME, MP, ML, BI arrived at a single topology, which was used to reconstruct the evolution of mitochondrial gene rearrangements in the group. Conclusion Four main lineages were identified within gastropods: Caenogastropoda, Vetigastropoda, Patellogastropoda, and Heterobranchia. Caenogastropoda and Vetigastropoda are sister taxa, as well as, Patellogastropoda and Heterobranchia. This result rejects the validity of the derived clade Apogastropoda (Caenogastropoda + Heterobranchia. The position of Patellogastropoda remains unclear likely due to long-branch attraction biases. Within Heterobranchia, the most heterogeneous group of gastropods, neither Euthyneura (because of the inclusion of P

Recent Developments in the Reformatsky-Claisen Rearrangement

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Susumi Hatakeyama

2012-11-01

Full Text Available The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

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Küssau, Tanja; Flipo, Marion; Van Wyk, Niel; Viljoen, Albertus; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël

2018-05-01

In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP + -bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP + -bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

Putative interchromosomal rearrangements in the hexaploid wheat (Triticum aestivum L.) genotype 'Chinese Spring' revealed by gene locations on homoeologous chromosomes

Czech Academy of Sciences Publication Activity Database

Ma, J.; Stiller, J.; Zheng, Z.; Wei, Y.M.; Zheng, Y.L.; Yan, G.J.; Doležel, Jaroslav; Liu, C.

2015-01-01

Roč. 15, MAR 11 2015 (2015) ISSN 1471-2148 Institutional support: RVO:61389030 Keywords : Interchromosomal rearrangements * Wheat genome * Translocation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.406, year: 2015

Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients.

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Page, Elyse C; Heatley, Susan L; Yeung, David T; Thomas, Paul Q; White, Deborah L

2018-06-04

Breakthrough studies over the past decade have uncovered unique gene fusions implicated in acute lymphoblastic leukaemia (ALL). The critical gene, cytokine receptor-like factor 2 (CRLF2), is rearranged in 5-16% of B-ALL, comprising 50% of Philadelphia-like ALL and cooperates with genomic lesions in the Jak, Mapk and Ras signalling pathways. Children with Down Syndrome (DS) have a predisposition to developing CRLF2 rearranged-ALL which is observed in 60% of DS-ALL patients. These patients experience a poor survival outcome. Mutations of genes involved in epigenetic regulation are more prevalent in DS-ALL patients than non-DS ALL patients, highlighting the potential for alternative treatment strategies. DS-ALL patients also suffer greater treatment-related toxicity from current ALL treatment regimens compared to non-DS-ALL patients. An increased gene dosage of critical genes on chromosome 21 which have roles in purine synthesis and folate transport may contribute. As the genomic landscape of DS-ALL patients is different to non-DS-ALL patients, targeted therapies for individual lesions may improve outcomes. Therapeutically targeting each rearrangement with targeted or combination therapy that will perturb the transforming signalling pathways will likely improve the poor survival rates of this subset of patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Media Access Time-Rearrangement of Wireless LAN for a Multi-Radio Collocated Platform

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Shin, Sang-Heon; Kim, Chul; Park, Sang Kyu

With the advent of new Radio Access Technologies (RATs), it is inevitable that several RATs will co-exist, especially in the license-exempt band. In this letter, we present an in-depth adaptation of the proactive time-rearrangement (PATRA) scheme for IEEE 802.11 WLAN. The PATRA is a time division approach for reducing interference from a multi-radio device. Because IEEE 802.11 is based on carrier sensing and contention mechanism, it is the most suitable candidate to adapt the PATRA.

Complete sequences of the highly rearranged molluscan mitochondrial genomes of the scaphopod graptacme eborea and the bivalve mytilus edulis

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Boore, Jeffrey L.; Medina, Monica; Rosenberg, Lewis A.

2004-01-31

We have determined the complete sequence of the mitochondrial genome of the scaphopod mollusk Graptacme eborea (Conrad, 1846) (14,492 nts) and completed the sequence of the mitochondrial genome of the bivalve mollusk Mytilus edulis Linnaeus, 1758 (16,740 nts). (The name Graptacme eborea is a revision of the species formerly known as Dentalium eboreum.) G. eborea mtDNA contains the 37 genes that are typically found and has the genes divided about evenly between the two strands, but M. edulis contains an extra trnM and is missing atp8, and has all genes on the same strand. Each has a highly rearranged gene order relative to each other and to all other studied mtDNAs. G. eborea mtDNA has almost no strand skew, but the coding strand of M. edulis mtDNA is very rich in G and T. This is reflected in differential codon usage patterns and even in amino acid compositions. G. eborea mtDNA has fewer non-coding nucleotides than any other mtDNA studied to date, with the largest non-coding region being only 24 nt long. Phylogenetic analysis using 2,420 aligned amino acid positions of concatenated proteins weakly supports an association of the scaphopod with gastropods to the exclusion of Bivalvia, Cephalopoda, and Polyplacophora, but is generally unable to convincingly resolve the relationships among major groups of the Lophotrochozoa, in contrast to the good resolution seen for several other major metazoan groups.

Suppression of gross chromosomal rearrangements by a new alternative replication factor C complex

International Nuclear Information System (INIS)

Banerjee, Soma; Sikdar, Nilabja; Myung, Kyungjae

2007-01-01

Defects in DNA replication fidelity lead to genomic instability. Gross chromosomal rearrangement (GCR), a type of genomic instability, is highly enhanced by various initial mutations affecting DNA replication. Frequent observations of GCRs in many cancers strongly argue the importance of maintaining high fidelity of DNA replication to suppress carcinogenesis. Recent genome wide screens in Saccharomyces cerevisiae identified a new GCR suppressor gene, ELG1, enhanced level of genome instability gene 1. Its physical interaction with proliferating cell nuclear antigen (PCNA) and complex formation with Rfc2-5p proteins suggest that Elg1 functions to load/unload PCNA onto DNA during a certain DNA metabolism. High level of DNA damage accumulation and enhanced phenotypes with mutations in genes involved in cell cycle checkpoints, homologous recombination (HR), or chromatin assembly in the elg1 strain suggest that Elg1p-Rfc2-5p functions in a fundamental DNA metabolism to suppress genomic instability

Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

DEFF Research Database (Denmark)

Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben

2015-01-01

Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B...... frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus....

Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid

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Seow Hoon Saw

2016-09-01

Full Text Available Background Meningitis is a major cause of mortality in tuberculosis (TB. It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb might have genetic traits associated with neurotropism. Methods In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF of patients presenting with tuberculous meningitis (TBM in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. Results Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate/PPE (proline-proline-glutamate, transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. Discussion The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB

Comparative scaffolding and gap filling of ancient bacterial genomes applied to two ancient Yersinia pestis genomes

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Doerr, Daniel; Chauve, Cedric

2017-01-01

Yersinia pestis is the causative agent of the bubonic plague, a disease responsible for several dramatic historical pandemics. Progress in ancient DNA (aDNA) sequencing rendered possible the sequencing of whole genomes of important human pathogens, including the ancient Y. pestis strains responsible for outbreaks of the bubonic plague in London in the 14th century and in Marseille in the 18th century, among others. However, aDNA sequencing data are still characterized by short reads and non-uniform coverage, so assembling ancient pathogen genomes remains challenging and often prevents a detailed study of genome rearrangements. It has recently been shown that comparative scaffolding approaches can improve the assembly of ancient Y. pestis genomes at a chromosome level. In the present work, we address the last step of genome assembly, the gap-filling stage. We describe an optimization-based method AGapEs (ancestral gap estimation) to fill in inter-contig gaps using a combination of a template obtained from related extant genomes and aDNA reads. We show how this approach can be used to refine comparative scaffolding by selecting contig adjacencies supported by a mix of unassembled aDNA reads and comparative signal. We applied our method to two Y. pestis data sets from the London and Marseilles outbreaks, for which we obtained highly improved genome assemblies for both genomes, comprised of, respectively, five and six scaffolds with 95 % of the assemblies supported by ancient reads. We analysed the genome evolution between both ancient genomes in terms of genome rearrangements, and observed a high level of synteny conservation between these strains. PMID:29114402

Whole-genome sequencing of a laboratory-evolved yeast strain

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Dunham Maitreya J

2010-02-01

Full Text Available Abstract Background Experimental evolution of microbial populations provides a unique opportunity to study evolutionary adaptation in response to controlled selective pressures. However, until recently it has been difficult to identify the precise genetic changes underlying adaptation at a genome-wide scale. New DNA sequencing technologies now allow the genome of parental and evolved strains of microorganisms to be rapidly determined. Results We sequenced >93.5% of the genome of a laboratory-evolved strain of the yeast Saccharomyces cerevisiae and its ancestor at >28× depth. Both single nucleotide polymorphisms and copy number amplifications were found, with specific gains over array-based methodologies previously used to analyze these genomes. Applying a segmentation algorithm to quantify structural changes, we determined the approximate genomic boundaries of a 5× gene amplification. These boundaries guided the recovery of breakpoint sequences, which provide insights into the nature of a complex genomic rearrangement. Conclusions This study suggests that whole-genome sequencing can provide a rapid approach to uncover the genetic basis of evolutionary adaptations, with further applications in the study of laboratory selections and mutagenesis screens. In addition, we show how single-end, short read sequencing data can provide detailed information about structural rearrangements, and generate predictions about the genomic features and processes that underlie genome plasticity.

Complete chloroplast genome sequence of a tree fern Alsophila spinulosa: insights into evolutionary changes in fern chloroplast genomes.

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Gao, Lei; Yi, Xuan; Yang, Yong-Xia; Su, Ying-Juan; Wang, Ting

2009-06-11

Ferns have generally been neglected in studies of chloroplast genomics. Before this study, only one polypod and two basal ferns had their complete chloroplast (cp) genome reported. Tree ferns represent an ancient fern lineage that first occurred in the Late Triassic. In recent phylogenetic analyses, tree ferns were shown to be the sister group of polypods, the most diverse group of living ferns. Availability of cp genome sequence from a tree fern will facilitate interpretation of the evolutionary changes of fern cp genomes. Here we have sequenced the complete cp genome of a scaly tree fern Alsophila spinulosa (Cyatheaceae). The Alsophila cp genome is 156,661 base pairs (bp) in size, and has a typical quadripartite structure with the large (LSC, 86,308 bp) and small single copy (SSC, 21,623 bp) regions separated by two copies of an inverted repeat (IRs, 24,365 bp each). This genome contains 117 different genes encoding 85 proteins, 4 rRNAs and 28 tRNAs. Pseudogenes of ycf66 and trnT-UGU are also detected in this genome. A unique trnR-UCG gene (derived from trnR-CCG) is found between rbcL and accD. The Alsophila cp genome shares some unusual characteristics with the previously sequenced cp genome of the polypod fern Adiantum capillus-veneris, including the absence of 5 tRNA genes that exist in most other cp genomes. The genome shows a high degree of synteny with that of Adiantum, but differs considerably from two basal ferns (Angiopteris evecta and Psilotum nudum). At one endpoint of an ancient inversion we detected a highly repeated 565-bp-region that is absent from the Adiantum cp genome. An additional minor inversion of the trnD-GUC, which is possibly shared by all ferns, was identified by comparison between the fern and other land plant cp genomes. By comparing four fern cp genome sequences it was confirmed that two major rearrangements distinguish higher leptosporangiate ferns from basal fern lineages. The Alsophila cp genome is very similar to that of the

Complete chloroplast genome sequence of a tree fern Alsophila spinulosa: insights into evolutionary changes in fern chloroplast genomes

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Yang Yong-Xia

2009-06-01

Full Text Available Abstract Background Ferns have generally been neglected in studies of chloroplast genomics. Before this study, only one polypod and two basal ferns had their complete chloroplast (cp genome reported. Tree ferns represent an ancient fern lineage that first occurred in the Late Triassic. In recent phylogenetic analyses, tree ferns were shown to be the sister group of polypods, the most diverse group of living ferns. Availability of cp genome sequence from a tree fern will facilitate interpretation of the evolutionary changes of fern cp genomes. Here we have sequenced the complete cp genome of a scaly tree fern Alsophila spinulosa (Cyatheaceae. Results The Alsophila cp genome is 156,661 base pairs (bp in size, and has a typical quadripartite structure with the large (LSC, 86,308 bp and small single copy (SSC, 21,623 bp regions separated by two copies of an inverted repeat (IRs, 24,365 bp each. This genome contains 117 different genes encoding 85 proteins, 4 rRNAs and 28 tRNAs. Pseudogenes of ycf66 and trnT-UGU are also detected in this genome. A unique trnR-UCG gene (derived from trnR-CCG is found between rbcL and accD. The Alsophila cp genome shares some unusual characteristics with the previously sequenced cp genome of the polypod fern Adiantum capillus-veneris, including the absence of 5 tRNA genes that exist in most other cp genomes. The genome shows a high degree of synteny with that of Adiantum, but differs considerably from two basal ferns (Angiopteris evecta and Psilotum nudum. At one endpoint of an ancient inversion we detected a highly repeated 565-bp-region that is absent from the Adiantum cp genome. An additional minor inversion of the trnD-GUC, which is possibly shared by all ferns, was identified by comparison between the fern and other land plant cp genomes. Conclusion By comparing four fern cp genome sequences it was confirmed that two major rearrangements distinguish higher leptosporangiate ferns from basal fern lineages. The

The complete mitochondrial genome of Sesarmops sinensis reveals gene rearrangements and phylogenetic relationships in Brachyura.

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Tang, Bo-Ping; Xin, Zhao-Zhe; Liu, Yu; Zhang, Dai-Zhen; Wang, Zheng-Fei; Zhang, Hua-Bin; Chai, Xin-Yue; Zhou, Chun-Lin; Liu, Qiu-Ning

2017-01-01

Mitochondrial genome (mitogenome) is very important to understand molecular evolution and phylogenetics. Herein, in this study, the complete mitogenome of Sesarmops sinensis was reported. The mitogenome was 15,905 bp in size, and contained 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region (CR). The AT skew and the GC skew are both negative in the mitogenomes of S. sinensis. The nucleotide composition of the S. sinensis mitogenome was also biased toward A + T nucleotides (75.7%). All tRNA genes displayed a typical mitochondrial tRNA cloverleaf structure, except for the trnS1 gene, which lacked a dihydroxyuridine arm. S. sinensis exhibits a novel rearrangement compared with the Pancrustacean ground pattern and other Brachyura species. Based on the 13 PCGs, the phylogenetic analysis showed that S. sinensis and Sesarma neglectum were clustered on one branch with high nodal support values, indicating that S. sinensis and S. neglectum have a sister group relationship. The group (S. sinensis + S. neglectum) was sister to (Parasesarmops tripectinis + Metopaulias depressus), suggesting that S. sinensis belongs to Grapsoidea, Sesarmidae. Phylogenetic trees based on amino acid sequences and nucleotide sequences of mitochondrial 13 PCGs using BI and ML respectively indicate that section Eubrachyura consists of four groups clearly. The resulting phylogeny supports the establishment of a separate subsection Potamoida. These four groups correspond to four subsections of Raninoida, Heterotremata, Potamoida, and Thoracotremata.

Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

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Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

2008-01-01

Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

Divergence of RNA polymerase ? subunits in angiosperm plastid genomes is mediated by genomic rearrangement

OpenAIRE

Blazier, J. Chris; Ruhlman, Tracey A.; Weng, Mao-Lun; Rehman, Sumaiyah K.; Sabir, Jamal S. M.; Jansen, Robert K.

2016-01-01

Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP ? subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled an...

Exploration of the Germline Genome of the Ciliate Chilodonella uncinata through Single-Cell Omics (Transcriptomics and Genomics

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Xyrus X. Maurer-Alcalá

2018-01-01

Full Text Available Separate germline and somatic genomes are found in numerous lineages across the eukaryotic tree of life, often separated into distinct tissues (e.g., in plants, animals, and fungi or distinct nuclei sharing a common cytoplasm (e.g., in ciliates and some foraminifera. In ciliates, germline-limited (i.e., micronuclear-specific DNA is eliminated during the development of a new somatic (i.e., macronuclear genome in a process that is tightly linked to large-scale genome rearrangements, such as deletions and reordering of protein-coding sequences. Most studies of germline genome architecture in ciliates have focused on the model ciliates Oxytricha trifallax, Paramecium tetraurelia, and Tetrahymena thermophila, for which the complete germline genome sequences are known. Outside of these model taxa, only a few dozen germline loci have been characterized from a limited number of cultivable species, which is likely due to difficulties in obtaining sufficient quantities of “purified” germline DNA in these taxa. Combining single-cell transcriptomics and genomics, we have overcome these limitations and provide the first insights into the structure of the germline genome of the ciliate Chilodonella uncinata, a member of the understudied class Phyllopharyngea. Our analyses reveal the following: (i large gene families contain a disproportionate number of genes from scrambled germline loci; (ii germline-soma boundaries in the germline genome are demarcated by substantial shifts in GC content; (iii single-cell omics techniques provide large-scale quality germline genome data with limited effort, at least for ciliates with extensively fragmented somatic genomes. Our approach provides an efficient means to understand better the evolution of genome rearrangements between germline and soma in ciliates.

Fast and accurate phylogenetic reconstruction from high-resolution whole-genome data and a novel robustness estimator.

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Lin, Y; Rajan, V; Moret, B M E

2011-09-01

The rapid accumulation of whole-genome data has renewed interest in the study of genomic rearrangements. Comparative genomics, evolutionary biology, and cancer research all require models and algorithms to elucidate the mechanisms, history, and consequences of these rearrangements. However, even simple models lead to NP-hard problems, particularly in the area of phylogenetic analysis. Current approaches are limited to small collections of genomes and low-resolution data (typically a few hundred syntenic blocks). Moreover, whereas phylogenetic analyses from sequence data are deemed incomplete unless bootstrapping scores (a measure of confidence) are given for each tree edge, no equivalent to bootstrapping exists for rearrangement-based phylogenetic analysis. We describe a fast and accurate algorithm for rearrangement analysis that scales up, in both time and accuracy, to modern high-resolution genomic data. We also describe a novel approach to estimate the robustness of results-an equivalent to the bootstrapping analysis used in sequence-based phylogenetic reconstruction. We present the results of extensive testing on both simulated and real data showing that our algorithm returns very accurate results, while scaling linearly with the size of the genomes and cubically with their number. We also present extensive experimental results showing that our approach to robustness testing provides excellent estimates of confidence, which, moreover, can be tuned to trade off thresholds between false positives and false negatives. Together, these two novel approaches enable us to attack heretofore intractable problems, such as phylogenetic inference for high-resolution vertebrate genomes, as we demonstrate on a set of six vertebrate genomes with 8,380 syntenic blocks. A copy of the software is available on demand.

Local effect of enhancer of zeste-like reveals cooperation of epigenetic and cis-acting determinants for zygotic genome rearrangements.

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Maoussi Lhuillier-Akakpo

2014-09-01

Full Text Available In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3 displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.

New progress in snake mitochondrial gene rearrangement.

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Chen, Nian; Zhao, Shujin

2009-08-01

To further understand the evolution of snake mitochondrial genomes, the complete mitochondrial DNA (mtDNA) sequences were determined for representative species from two snake families: the Many-banded krait, the Banded krait, the Chinese cobra, the King cobra, the Hundred-pace viper, the Short-tailed mamushi, and the Chain viper. Thirteen protein-coding genes, 22-23 tRNA genes, 2 rRNA genes, and 2 control regions were identified in these mtDNAs. Duplication of the control region and translocation of the tRNAPro gene were two notable features of the snake mtDNAs. These results from the gene rearrangement comparisons confirm the correctness of traditional classification schemes and validate the utility of comparing complete mtDNA sequences for snake phylogeny reconstruction.

Analysis of horse genomes provides insight into the diversification and adaptive evolution of karyotype.

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Huang, Jinlong; Zhao, Yiping; Shiraigol, Wunierfu; Li, Bei; Bai, Dongyi; Ye, Weixing; Daidiikhuu, Dorjsuren; Yang, Lihua; Jin, Burenqiqige; Zhao, Qinan; Gao, Yahan; Wu, Jing; Bao, Wuyundalai; Li, Anaer; Zhang, Yuhong; Han, Haige; Bai, Haitang; Bao, Yanqing; Zhao, Lele; Zhai, Zhengxiao; Zhao, Wenjing; Sun, Zikui; Zhang, Yan; Meng, He; Dugarjaviin, Manglai

2014-05-14

Karyotypic diversification is more prominent in Equus species than in other mammals. Here, using next generation sequencing technology, we generated and de novo assembled quality genomes sequences for a male wild horse (Przewalski's horse) and a male domestic horse (Mongolian horse), with about 93-fold and 91-fold coverage, respectively. Portion of Y chromosome from wild horse assemblies (3 M bp) and Mongolian horse (2 M bp) were also sequenced and de novo assembled. We confirmed a Robertsonian translocation event through the wild horse's chromosomes 23 and 24, which contained sequences that were highly homologous with those on the domestic horse's chromosome 5. The four main types of rearrangement, insertion of unknown origin, inserted duplication, inversion, and relocation, are not evenly distributed on all the chromosomes, and some chromosomes, such as the X chromosome, contain more rearrangements than others, and the number of inversions is far less than the number of insertions and relocations in the horse genome. Furthermore, we discovered the percentages of LINE_L1 and LTR_ERV1 are significantly increased in rearrangement regions. The analysis results of the two representative Equus species genomes improved our knowledge of Equus chromosome rearrangement and karyotype evolution.

Degradations and Rearrangement Reactions

Science.gov (United States)

Zhang, Jianbo

This section deals with recent reports concerning degradation and rearrangement reactions of free sugars as well as some glycosides. The transformations are classified in chemical and enzymatic ways. In addition, the Maillard reaction will be discussed as an example of degradation and rearrangement transformation and its application in current research in the fields of chemistry and biology.

Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

International Nuclear Information System (INIS)

Ritchie, K.A.

1986-01-01

Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

Chromosome Evolution in the Free-Living Flatworms: First Evidence of Intrachromosomal Rearrangements in Karyotype Evolution of Macrostomum lignano (Platyhelminthes, Macrostomida)

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Zadesenets, Kira S.; Ershov, Nikita I.; Berezikov, Eugene; Rubtsov, Nikolay B.

2017-01-01

The free-living flatworm Macrostomum lignano is a hidden tetraploid. Its genome was formed by a recent whole genome duplication followed by chromosome fusions. Its karyotype (2n = 8) consists of a pair of large chromosomes (MLI1), which contain regions of all other chromosomes, and three pairs of small metacentric chromosomes. Comparison of MLI1 with metacentrics was performed by painting with microdissected DNA probes and fluorescent in situ hybridization of unique DNA fragments. Regions of MLI1 homologous to small metacentrics appeared to be contiguous. Besides the loss of DNA repeat clusters (pericentromeric and telomeric repeats and the 5S rDNA cluster) from MLI1, the difference between small metacentrics MLI2 and MLI4 and regions homologous to them in MLI1 were revealed. Abnormal karyotypes found in the inbred DV1/10 subline were analyzed, and structurally rearranged chromosomes were described with the painting technique, suggesting the mechanism of their origin. The revealed chromosomal rearrangements generate additional diversity, opening the way toward massive loss of duplicated genes from a duplicated genome. Our findings suggest that the karyotype of M. lignano is in the early stage of genome diploidization after whole genome duplication, and further studies on M. lignano and closely related species can address many questions about karyotype evolution in animals. PMID:29084138

The infinite sites model of genome evolution.

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Ma, Jian; Ratan, Aakrosh; Raney, Brian J; Suh, Bernard B; Miller, Webb; Haussler, David

2008-09-23

We formalize the problem of recovering the evolutionary history of a set of genomes that are related to an unseen common ancestor genome by operations of speciation, deletion, insertion, duplication, and rearrangement of segments of bases. The problem is examined in the limit as the number of bases in each genome goes to infinity. In this limit, the chromosomes are represented by continuous circles or line segments. For such an infinite-sites model, we present a polynomial-time algorithm to find the most parsimonious evolutionary history of any set of related present-day genomes.

How resilient is the soybean genome? Insights from fast neutron mutagenesis

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Previously, we described the development of a fast neutron mutant population resource in soybean and identified mutations of interest through phenotypic screening. Here, we consider the resiliency of the soybean genome by examining genomic rearrangements and mutations that arise from fast neutron ra...

SIS: a program to generate draft genome sequence scaffolds for prokaryotes

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Dias Zanoni

2012-05-01

Full Text Available Abstract Background Decreasing costs of DNA sequencing have made prokaryotic draft genome sequences increasingly common. A contig scaffold is an ordering of contigs in the correct orientation. A scaffold can help genome comparisons and guide gap closure efforts. One popular technique for obtaining contig scaffolds is to map contigs onto a reference genome. However, rearrangements that may exist between the query and reference genomes may result in incorrect scaffolds, if these rearrangements are not taken into account. Large-scale inversions are common rearrangement events in prokaryotic genomes. Even in draft genomes it is possible to detect the presence of inversions given sufficient sequencing coverage and a sufficiently close reference genome. Results We present a linear-time algorithm that can generate a set of contig scaffolds for a draft genome sequence represented in contigs given a reference genome. The algorithm is aimed at prokaryotic genomes and relies on the presence of matching sequence patterns between the query and reference genomes that can be interpreted as the result of large-scale inversions; we call these patterns inversion signatures. Our algorithm is capable of correctly generating a scaffold if at least one member of every inversion signature pair is present in contigs and no inversion signatures have been overwritten in evolution. The algorithm is also capable of generating scaffolds in the presence of any kind of inversion, even though in this general case there is no guarantee that all scaffolds in the scaffold set will be correct. We compare the performance of sis, the program that implements the algorithm, to seven other scaffold-generating programs. The results of our tests show that sis has overall better performance. Conclusions sis is a new easy-to-use tool to generate contig scaffolds, available both as stand-alone and as a web server. The good performance of sis in our tests adds evidence that large

Extensive Pericentric Rearrangements in the Bread Wheat (Triticum aestivum L.) Genotype "Chinese Spring" Revealed from Chromosome Shotgun Sequence Data

Czech Academy of Sciences Publication Activity Database

Ma, J.; Stiller, J.; Wei, Y.M.; Zheng, Y.L.; Devos, K. M.; Doležel, Jaroslav; Liu, C.L.

2014-01-01

Roč. 6, č. 11 (2014), s. 3039-3048 ISSN 1759-6653 R&D Projects: GA ČR GBP501/12/G090 Institutional support: RVO:61389030 Keywords : chromosomal rearrangement * comparative genomics * pericentric inversion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.229, year: 2014

Analysis of TCRAD gene recombination: radio-induct rearrangement and signal joint structure

International Nuclear Information System (INIS)

Touvrey, C.

2005-09-01

We have shown that irradiation of pre-TCR-deficient CD3ε -/- mice restores thymocyte differentiation, by a p53-dependent and by a p53-independent pathway. Events normally associated during normal thymocyte development are dissociated in response to radiation exposure. Both of these pathways require LAT expression. Therefore, radiation exposure activates pre-TCR-like signals. TCRA gene rearrangement is induced following radiation exposure. The signal joints resulting from TCRA gene rearrangement have the same structure than those found in wild type mice. All signal joint analyzed in un-manipulated wild type mice do exhibit junctional diversity. This diversity results mainly from TdT activity. We present evidences that proteins involved in DNA repair and genomic stability participated in SJ formation. We propose that signal joint diversity is not an aberrant process but is a key feature of V(D)J recombination. All our work increases our understanding of molecular events associated with V(D)J recombination. (author)

Claisen thermally rearranged (CTR) polymers

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Tena, Alberto; Rangou, Sofia; Shishatskiy, Sergey; Filiz, Volkan; Abetz, Volker

2016-01-01

Thermally rearranged (TR) polymers, which are considered the next-generation of membrane materials because of their excellent transport properties and high thermal and chemical stability, are proven to have significant drawbacks because of the high temperature required for the rearrangement and low degree of conversion during this process. We demonstrate that using a [3,3]-sigmatropic rearrangement, the temperature required for the rearrangement of a solid glassy polymer was reduced by 200°C. Conversions of functionalized polyimide to polybenzoxazole of more than 97% were achieved. These highly mechanically stable polymers were almost five times more permeable and had more than two times higher degrees of conversion than the reference polymer treated under the same conditions. Properties of these second-generation TR polymers provide the possibility of preparing efficient polymer membranes in a form of, for example, thin-film composite membranes for various gas and liquid membrane separation applications. PMID:27482538

Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Denny, C.T.; Shah, N.P.; Ogden, S.; Willman, C.; McConnell, T.; Crist, W.; Carroll, A.; Witte, O.N.

1989-01-01

The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. The authors have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. They have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

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Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215 (United States); Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States); Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States)

2017-03-15

Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

International Nuclear Information System (INIS)

Nishino, Mizuki; Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra; Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto; Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin

2017-01-01

Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

Rearrangements of organic peroxides and related processes

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Ivan A. Yaremenko

2016-08-01

Full Text Available This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O–O-bond cleavage. Detailed information about the Baeyer−Villiger, Criegee, Hock, Kornblum−DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately.

The Brassica oleracea genome reveals the asymmetrical evolution of polyploid genomes

Science.gov (United States)

Liu, Shengyi; Liu, Yumei; Yang, Xinhua; Tong, Chaobo; Edwards, David; Parkin, Isobel A. P.; Zhao, Meixia; Ma, Jianxin; Yu, Jingyin; Huang, Shunmou; Wang, Xiyin; Wang, Junyi; Lu, Kun; Fang, Zhiyuan; Bancroft, Ian; Yang, Tae-Jin; Hu, Qiong; Wang, Xinfa; Yue, Zhen; Li, Haojie; Yang, Linfeng; Wu, Jian; Zhou, Qing; Wang, Wanxin; King, Graham J; Pires, J. Chris; Lu, Changxin; Wu, Zhangyan; Sampath, Perumal; Wang, Zhuo; Guo, Hui; Pan, Shengkai; Yang, Limei; Min, Jiumeng; Zhang, Dong; Jin, Dianchuan; Li, Wanshun; Belcram, Harry; Tu, Jinxing; Guan, Mei; Qi, Cunkou; Du, Dezhi; Li, Jiana; Jiang, Liangcai; Batley, Jacqueline; Sharpe, Andrew G; Park, Beom-Seok; Ruperao, Pradeep; Cheng, Feng; Waminal, Nomar Espinosa; Huang, Yin; Dong, Caihua; Wang, Li; Li, Jingping; Hu, Zhiyong; Zhuang, Mu; Huang, Yi; Huang, Junyan; Shi, Jiaqin; Mei, Desheng; Liu, Jing; Lee, Tae-Ho; Wang, Jinpeng; Jin, Huizhe; Li, Zaiyun; Li, Xun; Zhang, Jiefu; Xiao, Lu; Zhou, Yongming; Liu, Zhongsong; Liu, Xuequn; Qin, Rui; Tang, Xu; Liu, Wenbin; Wang, Yupeng; Zhang, Yangyong; Lee, Jonghoon; Kim, Hyun Hee; Denoeud, France; Xu, Xun; Liang, Xinming; Hua, Wei; Wang, Xiaowu; Wang, Jun; Chalhoub, Boulos; Paterson, Andrew H

2014-01-01

Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear. Brassica is an ideal model to increase knowledge of polyploid evolution. Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes. Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B. oleracea. This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus. PMID:24852848

Fragile genomic sites are associated with origins of replication.

Science.gov (United States)

Di Rienzi, Sara C; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

2009-09-09

Genome rearrangements are mediators of evolution and disease. Such rearrangements are frequently bounded by transfer RNAs (tRNAs), transposable elements, and other repeated elements, suggesting a functional role for these elements in creating or repairing breakpoints. Though not well explored, there is evidence that origins of replication also colocalize with breakpoints. To investigate a potential correlation between breakpoints and origins, we analyzed evolutionary breakpoints defined between Saccharomyces cerevisiae and Kluyveromyces waltii and S. cerevisiae and a hypothetical ancestor of both yeasts, as well as breakpoints reported in the experimental literature. We find that origins correlate strongly with both evolutionary breakpoints and those described in the literature. Specifically, we find that origins firing earlier in S phase are more strongly correlated with breakpoints than are later-firing origins. Despite origins being located in genomic regions also bearing tRNAs and Ty elements, the correlation we observe between origins and breakpoints appears to be independent of these genomic features. This study lays the groundwork for understanding the mechanisms by which origins of replication may impact genome architecture and disease.

A tandem cross-metathesis/semipinacol rearrangement reaction.

Science.gov (United States)

Plummer, Christopher W; Soheili, Arash; Leighton, James L

2012-05-18

An efficient and (E)-selective synthesis of a 6-alkylidenebicyclo[3.2.1]octan-8-one has been developed. The key step is a tandem cross-metathesis/semipinacol rearrangement reaction, wherein the Hoveyda-Grubbs II catalyst, or more likely a derivative thereof, serves as the Lewis acid for the rearrangement. Despite the fact that both the starting alkene and the cross-metathesis product are viable rearrangement substrates, only the latter rearranges, suggesting that the Lewis acidic species is generated only after the cross-metathesis reaction is complete.

Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci.

Science.gov (United States)

Rother, Magdalena B; Palstra, Robert-Jan; Jhunjhunwala, Suchit; van Kester, Kevin A M; van IJcken, Wilfred F J; Hendriks, Rudi W; van Dongen, Jacques J M; Murre, Cornelis; van Zelm, Menno C

2016-01-08

Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igκ remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Sequence analysis of 17 NRXN1 deletions

DEFF Research Database (Denmark)

Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés

2014-01-01

into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism...

Child Development and Structural Variation in the Human Genome

Science.gov (United States)

Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

2013-01-01

Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

Keeping it complicated: Mitochondrial genome plasticity across diplonemids.

Science.gov (United States)

Valach, Matus; Moreira, Sandrine; Hoffmann, Steve; Stadler, Peter F; Burger, Gertraud

2017-10-26

Chromosome rearrangements are important drivers in genome and gene evolution, with implications ranging from speciation to development to disease. In the flagellate Diplonema papillatum (Euglenozoa), mitochondrial genome rearrangements have resulted in nearly hundred chromosomes and a systematic dispersal of gene fragments across the multipartite genome. Maturation into functional RNAs involves separate transcription of gene pieces, joining of precursor RNAs via trans-splicing, and RNA editing by substitution and uridine additions both reconstituting crucial coding sequence. How widespread these unusual features are across diplonemids is unclear. We have analyzed the mitochondrial genomes and transcriptomes of four species from the Diplonema/Rhynchopus clade, revealing a considerable genomic plasticity. Although gene breakpoints, and thus the total number of gene pieces (~80), are essentially conserved across this group, the number of distinct chromosomes varies by a factor of two, with certain chromosomes combining up to eight unrelated gene fragments. Several internal protein-coding gene pieces overlap substantially, resulting, for example, in a stretch of 22 identical amino acids in cytochrome c oxidase subunit 1 and NADH dehydrogenase subunit 5. Finally, the variation of post-transcriptional editing patterns across diplonemids indicates compensation of two adverse trends: rapid sequence evolution and loss of genetic information through unequal chromosome segregation.

Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

Directory of Open Access Journals (Sweden)

Tomaiuolo Anna

2011-04-01

Full Text Available Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.

The mitochondrial genomes of the barklice, Lepinotus reticulatus and Dorypteryx domestica (Psocodea: Trogiomorpha): Insight into phylogeny of the order Psocodea.

Science.gov (United States)

Feng, Shiqian; Stejskal, Václav; Wang, Yannan; Li, Zhihong

2018-05-05

The order Psocodea which has incorporated the two former orders Psocoptera (barklice and booklice) and Phthiraptera (parasitic lice) attracts much attention for its unusual mitochondrial (mt) genome rearrangements. Available phylogenetic analysis for Psocodea is subjected to partial taxa and a complete one is needed. To further explore the genome rearrangement and phylogeny in Psocodea, we sequenced the mt genomes of two barklice, Lepinotus reticulatus (collected from China) and Dorypteryx domestica (collected from Czech Republic). Both of newly sequenced barklice had typical one-chromosome mt genomes and the same mt gene arrangement with the reported Lepidopsocidae sp. The mt genomes of L. reticulatus and D. domestica contained 37 genes typical of bilateral animals. In contrast with the recent report mt genome of D. domestica, our strain was found with many single nucleotide polymorphisms in intra-specific difference. Phylogenetic relationships were inferred from all available mt genomes of Psocodea data using Maximum Likelihood and Bayesian methods. The mt genome of L. reticulatus is the first representative with complete sequences of the family Trogiidae and our D. domestica data enriched the family Psyllipsocidae, which will contribute to the further study of mt gene rearrangement and phylogeny of Psocodea. Copyright © 2018 Elsevier B.V. All rights reserved.

Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Wang, Xianshu; Pankratz, V. Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D. P.; Ponder, Bruce A. J.; Dunning, Alison M.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B. L.; Hooning, Maartje J.; Ligtenberg, Marjolijn J.; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Singer, Christian F.; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I.; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N.; Hunter, David J.; Chanock, Stephen J.; Easton, Douglas F.; Antoniou, Antonis C.; Couch, Fergus J.; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick; Cole, Trevor; McKeown, Carole; Taylor, Amy; Donaldson, Alan; Paterson, Joan; Murray, Alexandra; Rogers, Mark; McCann, Emma; Kennedy, John; Barton, David; Porteous, Mary; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; Davidson, Rosemarie; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Izatt, Louise; Pichert, Gabriella; Langman, Caroline; Dorkins, Huw; Barwell, Julian; Chu, Carol; Bishop, Tim; Miller, Julie; Ellis, Ian; Evans, D. Gareth; Lalloo, Fiona; Holt, Felicity; Male, Alison; Robinson, Anne; Gardiner, Carol; Douglas, Fiona; Claber, Oonagh; Walker, Lisa; McLeod, Diane; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Mitra, Anita; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; Hodgson, Shirley; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eccles, Diana; Lucassen, Anneke; Crawford, Gillian; Tyler, Emma; McBride, Donna; Bérard, Léon; Sinilnikova, Olga; Barjhoux, Laure; Giraud, Sophie; Léone, Mélanie; Gauthier-Villars, Marion; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrde, Véronique; Caron, Olivier; Lenoir, Gilbert; Bignon, Yves-Jean; Uhrhammer, Nancy; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Bourdon, Violaine; Eisinger, Françoise; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Payrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Longy, Michel; Sevenet, Nicolas; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélèn; Rebischung, Christine; Cassini, Cécile; Olivier-Faivre, Laurence; Prieur, Fabienne; Ferrer, Sandra Fert; Frénay, Marc; Vénat-Bouvet, Laurence; Lynch, Henry T.; Hogervorst, Frans; Vernhoef, Senno; Pijpe, Anouk; van 't Veer, Laura; van Leeuwen, Flora; Rookus, Matti; Collée, Margriet; van den Ouweland, Ans; Kriege, Mieke; Schutte, Mieke; Hooning, Maartje; Seynaeve, Caroline; van Asperen, Christi; Wijnen, Juul; Vreeswijk, Maaike; Tollenaar, Rob; Devilee, Peter; Ligtenberg, Marjolijn; Hoogerbrugge, Nicoline; Ausems, Margreet; van der Luijt, Rob; Aalfs, Cora; van Os, Theo; Gille, Hans; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Gomez-Garcia, Encarna; van Roozendaal, Kees; Blok, Marinus; Oosterwijk, Jan; van der Hout, Annemieke; Mourits, Marian; Vasen, Hans; Szabo, Csilla; Pohlreich, Petr; Kleibl, Zdenek; Machackova, Eva; Lukesova, Miroslava; de Leeneer, Kim; Poppe, Bruce; de Paepe, Anne

2010-01-01

Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs),

The complete chloroplast genome sequence of Pelargonium xhortorum: Or ganization and evolution of the largest and most highlyrearranged chloroplast genome of land plants

Energy Technology Data Exchange (ETDEWEB)

Chumley, Timothy W.; Palmer, Jeffrey D.; Mower, Jeffrey P.; Fourcade, H. Matthew; Calie, Patrick J.; Boore, Jeffrey L.; Jansen,Robert K.

2006-01-20

The chloroplast genome of Pelargonium e hortorum has beencompletely sequenced. It maps as a circular molecule of 217,942 bp, andis both the largest and most rearranged land plant chloroplast genome yetsequenced. It features two copies of a greatly expanded inverted repeat(IR) of 75,741 bp each, and consequently diminished single copy regionsof 59,710 bp and 6,750 bp. It also contains two different associations ofrepeated elements that contribute about 10 percent to the overall sizeand account for the majority of repeats found in the genome. Theyrepresent hotspots for rearrangements and gene duplications and include alarge number of pseudogenes. We propose simple models that account forthe major rearrangements with a minimum of eight IR boundary changes and12 inversions in addition to a several insertions of duplicated sequence.The major processes at work (duplication, IR expansion, and inversion)have disrupted at least one and possibly two or three transcriptionaloperons, and the genes involved in these disruptions form the core of thetwo major repeat associations. Despite the vast increase in size andcomplexity of the genome, the gene content is similar to that of otherangiosperms, with the exceptions of a large number of pseudogenes as partof the repeat associations, the recognition of two open reading frames(ORF56 and ORF42) in the trnA intron with similarities to previouslyidentified mitochondrial products (ACRS and pvs-trnA), the loss of accDand trnT-GGU, and in particular, the lack of a recognizably functionalrpoA. One or all of three similar open reading frames may possibly encodethe latter, however.

Circumambulatory rearrangements of cyclopolyenes containing element-centred migrants

International Nuclear Information System (INIS)

Minkin, Vladimir I; Mikhailov, Igor E; Dushenko, Galina A; Zschunke, Adolf

2003-01-01

Data on circumambulatory rearrangements caused by rapid migrations of substituents formed by Group 13-17 elements around three- to nine-membered cyclopolyenes are generalised and systematised. Depending on the ring size, the nature of the migrating group, substituents in the ring and the medium, the rate constants of circumambulatory rearrangements vary over a wide range from 10 6 to 10 -8 s -1 at room temperature. Particular attention is given to analysis of the mechanisms of these rearrangements ([1, j]-, [2,3]- and [3,3]-sigmatropic shifts, haptotropic rearrangements and ionisation-recombination) and to the correlation of these mechanisms with the structural characteristics of the compounds that undergo rearrangements.

Reconstruction of Ancestral Genomes in Presence of Gene Gain and Loss.

Science.gov (United States)

Avdeyev, Pavel; Jiang, Shuai; Aganezov, Sergey; Hu, Fei; Alekseyev, Max A

2016-03-01

Since most dramatic genomic changes are caused by genome rearrangements as well as gene duplications and gain/loss events, it becomes crucial to understand their mechanisms and reconstruct ancestral genomes of the given genomes. This problem was shown to be NP-complete even in the "simplest" case of three genomes, thus calling for heuristic rather than exact algorithmic solutions. At the same time, a larger number of input genomes may actually simplify the problem in practice as it was earlier illustrated with MGRA, a state-of-the-art software tool for reconstruction of ancestral genomes of multiple genomes. One of the key obstacles for MGRA and other similar tools is presence of breakpoint reuses when the same breakpoint region is broken by several different genome rearrangements in the course of evolution. Furthermore, such tools are often limited to genomes composed of the same genes with each gene present in a single copy in every genome. This limitation makes these tools inapplicable for many biological datasets and degrades the resolution of ancestral reconstructions in diverse datasets. We address these deficiencies by extending the MGRA algorithm to genomes with unequal gene contents. The developed next-generation tool MGRA2 can handle gene gain/loss events and shares the ability of MGRA to reconstruct ancestral genomes uniquely in the case of limited breakpoint reuse. Furthermore, MGRA2 employs a number of novel heuristics to cope with higher breakpoint reuse and process datasets inaccessible for MGRA. In practical experiments, MGRA2 shows superior performance for simulated and real genomes as compared to other ancestral genome reconstruction tools.

Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

Science.gov (United States)

Singh, Param Priya; Arora, Jatin; Isambert, Hervé

2015-07-01

Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

Science.gov (United States)

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma

Radical Smiles Rearrangement: An Update

Directory of Open Access Journals (Sweden)

Ingrid Allart-Simon

2016-07-01

Full Text Available Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of this approach, especially if it is incorporated into a domino process, for the preparation of polyfunctionalized complex molecules.

Variation of minority charge carrier lifetime in high-resistance p-type silicon under irradiation

International Nuclear Information System (INIS)

Basheleishvili, Z.V.; Garnyk, V.S.; Gorin, S.N.; Pagava, T.A.

1984-01-01

The minority carrier lifetime (tau) variation was studied in the process of p-type silicon bombardment with fast 8 MeV electrons. The irradiation and all measurements were carried out at room temperature. The tau quantity was measured by the photoconductivity attenuation method at a low injection level 20% measurement error; the resistivity was measured by the four-probe method (10% error). The resistivity and minority charge carrier lifetime tau are shown to increase with the exposure dose. It is supposed that as radiation dose increases, the rearrangement of the centres responsible for reducing the lifetime occurs and results in a tau increase in the material being irradiated, however the tau value observed in the original samples is not attained. The restoration of the minority carrier lifetime in p-type high-resistance silicon with a growing exposure dose might proceed due to reduction in the free carrier concentration

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

DEFF Research Database (Denmark)

Loviglio, M N; Leleu, M; Männik, K

2017-01-01

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phen...

Gene order data from a model amphibian (Ambystoma: new perspectives on vertebrate genome structure and evolution

Directory of Open Access Journals (Sweden)

Voss S Randal

2006-08-01

Full Text Available Abstract Background Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates. Results Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian species but similar to that of chicken and fish. Overall, we found greater conservation of genome structure between Ambystoma and tetrapod vertebrates, nevertheless, 57% of Ambystoma-fish orthologs are found in conserved syntenies of four or more genes. Comparisons between Ambystoma and amniotes reveal extensive conservation of segmental homology for 57% of the presumptive Ambystoma-amniote orthologs. Conclusion Our analyses suggest relatively constant interchromosomal rearrangement rates from the euteleost ancestor to the origin of mammals and illustrate the utility of amphibian mapping data in establishing ancestral amniote and tetrapod gene orders. Comparisons between Ambystoma and amniotes reveal some of the key events that have structured the human genome since diversification of the ancestral amniote lineage.

Somatic DNA recombination yielding circular DNA and deletion of a genomic region in embryonic brain

International Nuclear Information System (INIS)

Maeda, Toyoki; Chijiiwa, Yoshiharu; Tsuji, Hideo; Sakoda, Saburo; Tani, Kenzaburo; Suzuki, Tomokazu

2004-01-01

In this study, a mouse genomic region is identified that undergoes DNA rearrangement and yields circular DNA in brain during embryogenesis. External region-directed inverse polymerase chain reaction on circular DNA extracted from late embryonic brain tissue repeatedly detected DNA of this region containing recombination joints. Wide-range genomic PCR and digestion-circularization PCR analysis showed this region underwent recombination accompanied with deletion of intervening sequences, including the circularized regions. This region was mapped by fluorescence in situ hybridization to C1 on mouse chromosome 16, where no gene and no physiological DNA rearrangement had been identified. DNA sequence in the region has segmental homology to an orthologous region on human chromosome 3q.13. These observations demonstrated somatic DNA recombination yielding genomic deletions in brain during embryogenesis

Biotransformation and Rearrangement of Laromustine.

Science.gov (United States)

Nassar, Alaa-Eldin F; Wisnewski, Adam V; King, Ivan

2016-08-01

This review highlights the recent research into the biotransformations and rearrangement of the sulfonylhydrazine-alkylating agent laromustine. Incubation of [(14)C]laromustine with rat, dog, monkey, and human liver microsomes produced eight radioactive components (C-1 to C-8). There was little difference in the metabolite profile among the species examined, partly because NADPH was not required for the formation of most components, which instead involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Liquid chromatography-multistage mass spectrometry (LC-MS(n)) studies determined that collision-induced dissociation, and not biotransformation or enzyme catalysis, produced the unique mass spectral rearrangement. Accurate mass measurements performed with a Fourier-transform ion cyclotron resonance mass spectrometer (FTICR-MS) significantly aided determination of the elemental compositions of the fragments and in the case of laromustine revealed the possibility of rearrangement. Further, collision-induced dissociation produced the loss of nitrogen (N2) and methylsulfonyl and methyl isocyanate moieties. The rearrangement, metabolite/decomposition products, and conjugation reactions were analyzed utilizing hydrogen-deuterium exchange, exact mass, (13)C-labeled laromustine, nuclear magnetic resonance spectroscopy (NMR), and LC-MS(n) experiments to assist with the assignments of these fragments and possible mechanistic rearrangement. Such techniques produced valuable insights into these functions: 1) Cytochrome P450 is involved in C-7 formation but plays little or no role in the conversion of [(14)C]laromustine to C-1 through C-6 and C-8; 2) the relative abundance of individual degradation/metabolite products was not species-dependent; and 3) laromustine produces several reactive intermediates that may produce the toxicities seen in the clinical trials. Copyright © 2016 by The American Society for

Genome engineering in human cells.

Science.gov (United States)

Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

2014-01-01

Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

Complete Chloroplast Genome of Pinus massoniana (Pinaceae): Gene Rearrangements, Loss of ndh Genes, and Short Inverted Repeats Contraction, Expansion.

Science.gov (United States)

Ni, ZhouXian; Ye, YouJu; Bai, Tiandao; Xu, Meng; Xu, Li-An

2017-09-11

The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. massoniana CPG has a typical quadripartite structure that includes large single copy (LSC) (65,563 bp), small single copy (SSC) (53,230 bp) and two IRs (IRa and IRb, 485 bp). The 108 unique genes were identified, including 73 protein-coding genes, 31 tRNAs, and 4 rRNAs. Most of the 81 simple sequence repeats (SSRs) identified in CPG were mononucleotides motifs of A/T types and located in non-coding regions. Comparisons with related species revealed an inversion (21,556 bp) in the LSC region; P. massoniana CPG lacks all 11 intact ndh genes (four ndh genes lost completely; the five remained truncated as pseudogenes; and the other two ndh genes remain as pseudogenes because of short insertions or deletions). A pair of short IRs was found instead of large IRs, and size variations among pine species were observed, which resulted from short insertions or deletions and non-synchronized variations between "IRa" and "IRb". The results of phylogenetic analyses based on whole CPG sequences of 16 conifers indicated that the whole CPG sequences could be used as a powerful tool in phylogenetic analyses.

Chromosomal rearrangements in Tourette syndrome

DEFF Research Database (Denmark)

Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E

2013-01-01

, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...... been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS...

The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9 gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia.

Science.gov (United States)

Fonseca, Ana Carolina S; Bonaldi, Adriano; Bertola, Débora R; Kim, Chong A; Otto, Paulo A; Vianna-Morgante, Angela M

2013-05-07

The association of balanced rearrangements with breakpoints near SOX9 [SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences. We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17;20)(q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917-855 kb and 601-585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932-789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601-585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517-595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development. These two novel translocations illustrate the clinical variability in carriers of balanced

Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria

OpenAIRE

Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

2017-01-01

A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compen...

Cattle genomics and its implications for future nutritional strategies for dairy cattle.

Science.gov (United States)

Seo, S; Larkin, D M; Loor, J J

2013-03-01

The recently sequenced cattle (Bos taurus) genome unraveled the unique genomic features of the species and provided the molecular basis for applying a systemic approach to systematically link genomic information to metabolic traits. Comparative analysis has identified a variety of evolutionary adaptive features in the cattle genome, such as an expansion of the gene families related to the rumen function, large number of chromosomal rearrangements affecting regulation of genes for lactation, and chromosomal rearrangements that are associated with segmental duplications and copy number variations. Metabolic reconstruction of the cattle genome has revealed that core metabolic pathways are highly conserved among mammals although five metabolic genes are deleted or highly diverged and seven metabolic genes are present in duplicate in the cattle genome compared to their human counter parts. The evolutionary loss and gain of metabolic genes in the cattle genome may reflect metabolic adaptations of cattle. Metabolic reconstruction also provides a platform for better understanding of metabolic regulation in cattle and ruminants. A substantial body of transcriptomics data from dairy and beef cattle under different nutritional management and across different stages of growth and lactation are already available and will aid in linking the genome with metabolism and nutritional physiology of cattle. Application of cattle genomics has great potential for future development of nutritional strategies to improve efficiency and sustainability of beef and milk production. One of the biggest challenges is to integrate genomic and phenotypic data and interpret them in a biological and practical platform. Systems biology, a holistic and systemic approach, will be very useful in overcoming this challenge.

System for the detection of chromosomal rearrangements using Sordaria macrospora

Energy Technology Data Exchange (ETDEWEB)

Arnaise, S.; Leblon, G.; Lares, L. (Paris-11 Univ., 91 - Orsay (France). Lab. de Biologie Cellulaire et Genetique)

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS.

Science.gov (United States)

Kondo, Yukiko; Saitsu, Hirotomo; Miyamoto, Toshinobu; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Ryoo, Na-Kyung; Kim, Jeong Hun; Yu, Young Suk; Matsumoto, Naomichi

2012-03-01

Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.

Insertion Sequence-Caused Large Scale-Rearrangements in the Genome of Escherichia coli

Science.gov (United States)

2016-07-18

affordable ap- proach to genome-wide characterization of genetic varia - tion in bacterial and eukaryotic genomes (1–3). In addition to small-scale...Paired-End Reads), that uses a graph-based al- gorithm (27) capable of detecting most large-scale varia - tion involving repetitive regions, including novel...Avila,P., Grinsted,J. and De La Cruz,F. (1988) Analysis of the variable endpoints generated by one-ended transposition of Tn21.. J. Bacteriol., 170

Comparative genomics of Serratia spp.: two paths towards endosymbiotic life.

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Alejandro Manzano-Marín

Full Text Available Symbiosis is a widespread phenomenon in nature, in which insects show a great number of these associations. Buchnera aphidicola, the obligate endosymbiont of aphids, coexists in some species with another intracellular bacterium, Serratia symbiotica. Of particular interest is the case of the cedar aphid Cinara cedri, where B. aphidicola BCc and S. symbiotica SCc need each other to fulfil their symbiotic role with the insect. Moreover, various features seem to indicate that S. symbiotica SCc is closer to an obligate endosymbiont than to other facultative S. symbiotica, such as the one described for the aphid Acirthosyphon pisum (S. symbiotica SAp. This work is based on the comparative genomics of five strains of Serratia, three free-living and two endosymbiotic ones (one facultative and one obligate which should allow us to dissect the genome reduction taking place in the adaptive process to an intracellular life-style. Using a pan-genome approach, we have identified shared and strain-specific genes from both endosymbiotic strains and gained insight into the different genetic reduction both S. symbiotica have undergone. We have identified both retained and reduced functional categories in S. symbiotica compared to the Free-Living Serratia (FLS that seem to be related with its endosymbiotic role in their specific host-symbiont systems. By means of a phylogenomic reconstruction we have solved the position of both endosymbionts with confidence, established the probable insect-pathogen origin of the symbiotic clade as well as the high amino-acid substitution rate in S. symbiotica SCc. Finally, we were able to quantify the minimal number of rearrangements suffered in the endosymbiotic lineages and reconstruct a minimal rearrangement phylogeny. All these findings provide important evidence for the existence of at least two distinctive S. symbiotica lineages that are characterized by different rearrangements, gene content, genome size and branch lengths.

Faithful One-way Trip Deterministic Secure Quantum Communication Scheme Against Collective Rotating Noise Based on Order Rearrangement of Photon Pairs

Science.gov (United States)

Yuan, Hao; Zhang, Qin; Hong, Liang; Yin, Wen-jie; Xu, Dong

2014-08-01

We present a novel scheme for deterministic secure quantum communication (DSQC) over collective rotating noisy channel. Four special two-qubit states are found can constitute a noise-free subspaces, and so are utilized as quantum information carriers. In this scheme, the information carriers transmite over the quantum channel only one time, which can effectively reduce the influence of other noise existing in quantum channel. The information receiver need only perform two single-photon collective measurements to decode the secret messages, which can make the present scheme more convenient in practical application. It will be showed that our scheme has a relatively high information capacity and intrisic efficiency. Foremostly, the decoy photon pair checking technique and the order rearrangement of photon pairs technique guarantee that the present scheme is unconditionally secure.

Whole genome PCR scanning reveals the syntenic genome structure of toxigenic Vibrio cholerae strains in the O1/O139 population.

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Bo Pang

Full Text Available Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+ strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes.

Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy

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Juan-Mateu Jonàs

2012-10-01

Full Text Available Abstract Background Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy. Methods We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females. Results Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found. Conclusions Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene.

The Ultrafast Wolff Rearrangement in the Gas Phase

Science.gov (United States)

Steinbacher, Andreas; Roeding, Sebastian; Brixner, Tobias; Nuernberger, Patrick

The Wolff rearrangement of gas-phase 5-diazo Meldrum's acid is disclosed with femtosecond ion spectroscopy. Distinct differences are found for 267 nm and 200 nm excitation, the latter leading to even two ultrafast rearrangement reactions.

Punctuated evolution of prostate cancer genomes.

Science.gov (United States)

Baca, Sylvan C; Prandi, Davide; Lawrence, Michael S; Mosquera, Juan Miguel; Romanel, Alessandro; Drier, Yotam; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V; Sboner, Andrea; Theurillat, Jean-Philippe; Soong, T David; Nickerson, Elizabeth; Auclair, Daniel; Tewari, Ashutosh; Beltran, Himisha; Onofrio, Robert C; Boysen, Gunther; Guiducci, Candace; Barbieri, Christopher E; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Kantoff, Philip W; Berger, Michael F; Gabriel, Stacey B; Golub, Todd R; Meyerson, Matthew; Lander, Eric S; Elemento, Olivier; Getz, Gad; Demichelis, Francesca; Rubin, Mark A; Garraway, Levi A

2013-04-25

The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Array-CGH in patients with Kabuki-like phenotype: identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration.

Science.gov (United States)

Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

2008-04-11

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

Science.gov (United States)

2016-05-01

COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer 5b. GRANT NUMBER W81XWH...that result from gene rearrangements given their high frequency relative to somatic point mutations. Gene rearrangements can yield novel chimeric

Comprehensive Analysis of Genome Rearrangements in Eight Human Malignant Tumor Tissues.

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Stefanie Marczok

Full Text Available Carcinogenesis is a complex multifactorial, multistage process, but the precise mechanisms are not well understood. In this study, we performed a genome-wide analysis of the copy number variation (CNV, breakpoint region (BPR and fragile sites in 2,737 tumor samples from eight tumor entities and in 432 normal samples. CNV detection and BPR identification revealed that BPRs tended to accumulate in specific genomic regions in tumor samples whereas being dispersed genome-wide in the normal samples. Hotspots were observed, at which segments with similar alteration in copy number were overlapped along with BPRs adjacently clustered. Evaluation of BPR occurrence frequency showed that at least one was detected in about and more than 15% of samples for each tumor entity while BPRs were maximal in 12% of the normal samples. 127 of 2,716 tumor-relevant BPRs (termed 'common BPRs' exhibited also a noticeable occurrence frequency in the normal samples. Colocalization assessment identified 20,077 CNV-affecting genes and 169 of these being known tumor-related genes. The most noteworthy genes are KIAA0513 important for immunologic, synaptic and apoptotic signal pathways, intergenic non-coding RNA RP11-115C21.2 possibly acting as oncogene or tumor suppressor by changing the structure of chromatin, and ADAM32 likely importance in cancer cell proliferation and progression by ectodomain-shedding of diverse growth factors, and the well-known tumor suppressor gene p53. The BPR distributions indicate that CNV mutations are likely non-random in tumor genomes. The marked recurrence of BPRs at specific regions supports common progression mechanisms in tumors. The presence of hotspots together with common BPRs, despite its small group size, imply a relation between fragile sites and cancer-gene alteration. Our data further suggest that both protein-coding and non-coding genes possessing a range of biological functions might play a causative or functional role in tumor

Comparative mitogenomics of Braconidae (Insecta: Hymenoptera) and the phylogenetic utility of mitochondrial genomes with special reference to Holometabolous insects

Science.gov (United States)

2010-01-01

Background Animal mitochondrial genomes are potential models for molecular evolution and markers for phylogenetic and population studies. Previous research has shown interesting features in hymenopteran mitochondrial genomes. Here, we conducted a comparative study of mitochondrial genomes of the family Braconidae, one of the largest families of Hymenoptera, and assessed the utility of mitochondrial genomic data for phylogenetic inference at three different hierarchical levels, i.e., Braconidae, Hymenoptera, and Holometabola. Results Seven mitochondrial genomes from seven subfamilies of Braconidae were sequenced. Three of the four sequenced A+T-rich regions are shown to be inverted. Furthermore, all species showed reversal of strand asymmetry, suggesting that inversion of the A+T-rich region might be a synapomorphy of the Braconidae. Gene rearrangement events occurred in all braconid species, but gene rearrangement rates were not taxonomically correlated. Most rearranged genes were tRNAs, except those of Cotesia vestalis, in which 13 protein-coding genes and 14 tRNA genes changed positions or/and directions through three kinds of gene rearrangement events. Remote inversion is posited to be the result of two independent recombination events. Evolutionary rates were lower in species of the cyclostome group than those of noncyclostomes. Phylogenetic analyses based on complete mitochondrial genomes and secondary structure of rrnS supported a sister-group relationship between Aphidiinae and cyclostomes. Many well accepted relationships within Hymenoptera, such as paraphyly of Symphyta and Evaniomorpha, a sister-group relationship between Orussoidea and Apocrita, and monophyly of Proctotrupomorpha, Ichneumonoidea and Aculeata were robustly confirmed. New hypotheses, such as a sister-group relationship between Evanioidea and Aculeata, were generated. Among holometabolous insects, Hymenoptera was shown to be the sister to all other orders. Mecoptera was recovered as the

Comparative mitogenomics of Braconidae (Insecta: Hymenoptera and the phylogenetic utility of mitochondrial genomes with special reference to Holometabolous insects

Directory of Open Access Journals (Sweden)

Shi Min

2010-06-01

Full Text Available Abstract Background Animal mitochondrial genomes are potential models for molecular evolution and markers for phylogenetic and population studies. Previous research has shown interesting features in hymenopteran mitochondrial genomes. Here, we conducted a comparative study of mitochondrial genomes of the family Braconidae, one of the largest families of Hymenoptera, and assessed the utility of mitochondrial genomic data for phylogenetic inference at three different hierarchical levels, i.e., Braconidae, Hymenoptera, and Holometabola. Results Seven mitochondrial genomes from seven subfamilies of Braconidae were sequenced. Three of the four sequenced A+T-rich regions are shown to be inverted. Furthermore, all species showed reversal of strand asymmetry, suggesting that inversion of the A+T-rich region might be a synapomorphy of the Braconidae. Gene rearrangement events occurred in all braconid species, but gene rearrangement rates were not taxonomically correlated. Most rearranged genes were tRNAs, except those of Cotesia vestalis, in which 13 protein-coding genes and 14 tRNA genes changed positions or/and directions through three kinds of gene rearrangement events. Remote inversion is posited to be the result of two independent recombination events. Evolutionary rates were lower in species of the cyclostome group than those of noncyclostomes. Phylogenetic analyses based on complete mitochondrial genomes and secondary structure of rrnS supported a sister-group relationship between Aphidiinae and cyclostomes. Many well accepted relationships within Hymenoptera, such as paraphyly of Symphyta and Evaniomorpha, a sister-group relationship between Orussoidea and Apocrita, and monophyly of Proctotrupomorpha, Ichneumonoidea and Aculeata were robustly confirmed. New hypotheses, such as a sister-group relationship between Evanioidea and Aculeata, were generated. Among holometabolous insects, Hymenoptera was shown to be the sister to all other orders

Third International E. coli genome meeting

Energy Technology Data Exchange (ETDEWEB)

NONE

1994-12-31

Proceedings of the Third E. Coli Genome Meeting are provided. Presentations were divided into sessions entitled (1) Large Scale Sequencing, Sequence Analysis; (2) Databases; (3) Sequence Analysis; (4) Sequence Divergence in E. coli Strains; (5) Repeated Sequences and Regulatory Motifs; (6) Mutations, Rearrangements and Stress Responses; and (7) Origins of New Genes. The document provides a collection of abstracts of oral and poster presentations.

Transcription as a Threat to Genome Integrity.

Science.gov (United States)

Gaillard, Hélène; Aguilera, Andrés

2016-06-02

Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant.

Rearrangement moves on rooted phylogenetic networks.

Science.gov (United States)

Gambette, Philippe; van Iersel, Leo; Jones, Mark; Lafond, Manuel; Pardi, Fabio; Scornavacca, Celine

2017-08-01

Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide a solid basis for

Rearrangement moves on rooted phylogenetic networks.

Directory of Open Access Journals (Sweden)

Philippe Gambette

2017-08-01

Full Text Available Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide

Whole genome comparisons of Fragaria, Prunus and Malus reveal different modes of evolution between Rosaceous subfamilies.

Science.gov (United States)

Jung, Sook; Cestaro, Alessandro; Troggio, Michela; Main, Dorrie; Zheng, Ping; Cho, Ilhyung; Folta, Kevin M; Sosinski, Bryon; Abbott, Albert; Celton, Jean-Marc; Arús, Pere; Shulaev, Vladimir; Verde, Ignazio; Morgante, Michele; Rokhsar, Daniel; Velasco, Riccardo; Sargent, Daniel James

2012-04-04

Rosaceae include numerous economically important and morphologically diverse species. Comparative mapping between the member species in Rosaceae have indicated some level of synteny. Recently the whole genome of three crop species, peach, apple and strawberry, which belong to different genera of the Rosaceae family, have been sequenced, allowing in-depth comparison of these genomes. Our analysis using the whole genome sequences of peach, apple and strawberry identified 1399 orthologous regions between the three genomes, with a mean length of around 100 kb. Each peach chromosome showed major orthology mostly to one strawberry chromosome, but to more than two apple chromosomes, suggesting that the apple genome went through more chromosomal fissions in addition to the whole genome duplication after the divergence of the three genera. However, the distribution of contiguous ancestral regions, identified using the multiple genome rearrangements and ancestors (MGRA) algorithm, suggested that the Fragaria genome went through a greater number of small scale rearrangements compared to the other genomes since they diverged from a common ancestor. Using the contiguous ancestral regions, we reconstructed a hypothetical ancestral genome for the Rosaceae 7 composed of nine chromosomes and propose the evolutionary steps from the ancestral genome to the extant Fragaria, Prunus and Malus genomes. Our analysis shows that different modes of evolution may have played major roles in different subfamilies of Rosaceae. The hypothetical ancestral genome of Rosaceae and the evolutionary steps that lead to three different lineages of Rosaceae will facilitate our understanding of plant genome evolution as well as have a practical impact on knowledge transfer among member species of Rosaceae.

Comparison of 26 sphingomonad genomes reveals diverse environmental adaptations and biodegradative capabilities

DEFF Research Database (Denmark)

Aylward, Frank O.; McDonald, Bradon R.; Adams, Sandra M.

2013-01-01

to the genus Sphingobium. Our pan-genomic analysis of sphingomonads reveals numerous species-specific open reading frames (ORFs) but few signatures of genus-specific cores. The organization and coding potential of the sphingomonad genomes appear to be highly variable, and plasmid-mediated gene transfer...... and chromosome-plasmid recombination, together with prophage- and transposon-mediated rearrangements, appear to play prominent roles in the genome evolution of this group. We find that many of the sphingomonad genomes encode numerous oxygenases and glycoside hydrolases, which are likely responsible...... a basis for understanding the ecological strategies employed by sphingomonads and their role in environmental nutrient cycling....

High-resolution characterization of a hepatocellular carcinoma genome.

Science.gov (United States)

Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

2011-05-01

Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

Multiple independent structural dynamic events in the evolution of snake mitochondrial genomes.

Science.gov (United States)

Qian, Lifu; Wang, Hui; Yan, Jie; Pan, Tao; Jiang, Shanqun; Rao, Dingqi; Zhang, Baowei

2018-05-10

Mitochondrial DNA sequences have long been used in phylogenetic studies. However, little attention has been paid to the changes in gene arrangement patterns in the snake's mitogenome. Here, we analyzed the complete mitogenome sequences and structures of 65 snake species from 14 families and examined their structural patterns, organization and evolution. Our purpose was to further investigate the evolutionary implications and possible rearrangement mechanisms of the mitogenome within snakes. In total, eleven types of mitochondrial gene arrangement patterns were detected (Type I, II, III, III-A, III-B, III-B1, III-C, III-D, III-E, III-F, III-G), with mitochondrial genome rearrangements being a major trend in snakes, especially in Alethinophidia. In snake mitogenomes, the rearrangements mainly involved three processes, gene loss, translocation and duplication. Within Scolecophidia, the O L was lost several times in Typhlopidae and Leptotyphlopidae, but persisted as a plesiomorphy in the Alethinophidia. Duplication of the control region and translocation of the tRNA Leu gene are two visible features in Alethinophidian mitochondrial genomes. Independently and stochastically, the duplication of pseudo-Pro (P*) emerged in seven different lineages of unequal size in three families, indicating that the presence of P* was a polytopic event in the mitogenome. The WANCY tRNA gene cluster and the control regions and their adjacent segments were hotspots for mitogenome rearrangement. Maintenance of duplicate control regions may be the source for snake mitogenome structural diversity.

A system for the detection of chromosomal rearrangements using Sordaria macrospora

International Nuclear Information System (INIS)

Arnaise, S.; Leblon, G.; Lares, L.

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine. (orig.)

A system for the detection of chromosomal rearrangements using Sordaria macrospora.

Science.gov (United States)

Arnaise, S; Leblon, G; Lares, L

1984-01-01

A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

Science.gov (United States)

Morris, Lydia P; Conley, Andrew B; Degtyareva, Natalya; Jordan, I King; Doetsch, Paul W

2017-11-01

The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Algorithms for sorting unsigned linear genomes by the DCJ operations.

Science.gov (United States)

Jiang, Haitao; Zhu, Binhai; Zhu, Daming

2011-02-01

The double cut and join operation (abbreviated as DCJ) has been extensively used for genomic rearrangement. Although the DCJ distance between signed genomes with both linear and circular (uni- and multi-) chromosomes is well studied, the only known result for the NP-complete unsigned DCJ distance problem is an approximation algorithm for unsigned linear unichromosomal genomes. In this article, we study the problem of computing the DCJ distance on two unsigned linear multichromosomal genomes (abbreviated as UDCJ). We devise a 1.5-approximation algorithm for UDCJ by exploiting the distance formula for signed genomes. In addition, we show that UDCJ admits a weak kernel of size 2k and hence an FPT algorithm running in O(2(2k)n) time.

Genomic rearrangements and functional diversification of lecA and lecB lectin-coding regions impacting the efficacy of glycomimetics directed against Pseudomonas aeruginosa

Directory of Open Access Journals (Sweden)

Amine M Boukerb

2016-05-01

Full Text Available LecA and LecB tetrameric lectins take part in oligosaccharide-mediated adhesion-processes of Pseudomonas aeruginosa. Glycomimetics have been designed to block these interactions. The great versatility of P. aeruginosa suggests that the range of application of these glycomimetics could be restricted to genotypes with particular lectin types. The likelihood of having genomic and genetic changes impacting LecA and LecB interactions with glycomimetics such as galactosylated and fucosylated calix[4]arene was investigated over a collection of strains from the main clades of P. aeruginosa. Lectin types were defined, and their ligand specificities were inferred. These analyses showed a loss of lecA among the PA7 clade. Genomic changes impacting lec loci were thus assessed using strains of this clade, and by making comparisons with the PAO1 genome. The lecA regions were found challenged by phage attacks and PAGI-2 (genomic island integrations. A prophage was linked to the loss of lecA. The lecB regions were found less impacted by such rearrangements but greater lecB than lecA genetic divergences were recorded. Sixteen combinations of LecA and LecB types were observed. Amino acid variations were mapped on PAO1 crystal structures. Most significant changes were observed on LecBPA7, and found close to the fucose binding site. Glycan array analyses were performed with purified LecBPA7. LecBPA7 was found less specific for fucosylated oligosaccharides than LecBPAO1, with a preference for H type 2 rather than type 1, and Lewisa rather than Lewisx. Comparison of the crystal structures of LecBPA7 and LecBPAO1 in complex with Lewisa showed these changes in specificity to have resulted from a modification of the water network between the lectin, galactose and GlcNAc residues. Incidence of these modifications on the interactions with calix[4]arene glycomimetics at the cell level was investigated. An aggregation test was used to establish the efficacy of these ligands

Elucidating the triplicated ancestral genome structure of radish based on chromosome-level comparison with the Brassica genomes.

Science.gov (United States)

Jeong, Young-Min; Kim, Namshin; Ahn, Byung Ohg; Oh, Mijin; Chung, Won-Hyong; Chung, Hee; Jeong, Seongmun; Lim, Ki-Byung; Hwang, Yoon-Jung; Kim, Goon-Bo; Baek, Seunghoon; Choi, Sang-Bong; Hyung, Dae-Jin; Lee, Seung-Won; Sohn, Seong-Han; Kwon, Soo-Jin; Jin, Mina; Seol, Young-Joo; Chae, Won Byoung; Choi, Keun Jin; Park, Beom-Seok; Yu, Hee-Ju; Mun, Jeong-Hwan

2016-07-01

This study presents a chromosome-scale draft genome sequence of radish that is assembled into nine chromosomal pseudomolecules. A comprehensive comparative genome analysis with the Brassica genomes provides genomic evidences on the evolution of the mesohexaploid radish genome. Radish (Raphanus sativus L.) is an agronomically important root vegetable crop and its origin and phylogenetic position in the tribe Brassiceae is controversial. Here we present a comprehensive analysis of the radish genome based on the chromosome sequences of R. sativus cv. WK10039. The radish genome was sequenced and assembled into 426.2 Mb spanning >98 % of the gene space, of which 344.0 Mb were integrated into nine chromosome pseudomolecules. Approximately 36 % of the genome was repetitive sequences and 46,514 protein-coding genes were predicted and annotated. Comparative mapping of the tPCK-like ancestral genome revealed that the radish genome has intermediate characteristics between the Brassica A/C and B genomes in the triplicated segments, suggesting an internal origin from the genus Brassica. The evolutionary characteristics shared between radish and other Brassica species provided genomic evidences that the current form of nine chromosomes in radish was rearranged from the chromosomes of hexaploid progenitor. Overall, this study provides a chromosome-scale draft genome sequence of radish as well as novel insight into evolution of the mesohexaploid genomes in the tribe Brassiceae.

Quantum concept of the rearrangement of a crystal lattice

International Nuclear Information System (INIS)

Gureev, M.D.; Mednikov, S.I.

1995-01-01

Using quantum considerations based on the concept of lattice rearrangement waves, we carried out an analysis of processes of rearrangement of a crystal lattice occurring on a moving front (interface) of crystal rearrangement. For the introduction and quantization of these waves we use the method of acoustomechanical analogy and the Sommerfeld quantum conditions. We calculate the energies and the propagation velocities of the lattice rearrangement waves. Along with quanta having a certain momentum, quanta that have a certain angular momentum are introduced into consideration. On the basis of the concepts developed, we suggest a new expression for calculating the probability of thermofluctuational processes in a crystal. We perform a numerical analysis of the rate of growth of the γ-phase in iron in the process of α-γ-conversion. Satisfactory agreement with experiment is obtained. We discuss the limitations and prospects of further development of the concept suggested. For direct experimental verification of the concept we propose to investigate the diffraction of electrons and other particles on the lattice rearrangement waves, i.e., in the process of phase conversions or disintegration of crystals

Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States

NARCIS (Netherlands)

F. Kastrinos (Fay); E.M. Stoffel (Elena); J. Balmana (Judith); E.W. Steyerberg (Ewout); R. Mercado (Rowena); S. Syngal (Sapna)

2008-01-01

textabstractBackground and Aims: Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic expression. Methods: This is a

Genome Sequence of the Palaeopolyploid soybean

Energy Technology Data Exchange (ETDEWEB)

Schmutz, Jeremy; Cannon, Steven B.; Schlueter, Jessica; Ma, Jianxin; Mitros, Therese; Nelson, William; Hyten, David L.; Song, Qijian; Thelen, Jay J.; Cheng, Jianlin; Xu, Dong; Hellsten, Uffe; May, Gregory D.; Yu, Yeisoo; Sakura, Tetsuya; Umezawa, Taishi; Bhattacharyya, Madan K.; Sandhu, Devinder; Valliyodan, Babu; Lindquist, Erika; Peto, Myron; Grant, David; Shu, Shengqiang; Goodstein, David; Barry, Kerrie; Futrell-Griggs, Montona; Abernathy, Brian; Du, Jianchang; Tian, Zhixi; Zhu, Liucun; Gill, Navdeep; Joshi, Trupti; Libault, Marc; Sethuraman, Anand; Zhang, Xue-Cheng; Shinozaki, Kazuo; Nguyen, Henry T.; Wing, Rod A.; Cregan, Perry; Specht, James; Grimwood, Jane; Rokhsar, Dan; Stacey, Gary; Shoemaker, Randy C.; Jackson, Scott A.

2009-08-03

Soybean (Glycine max) is one of the most important crop plants for seed protein and oil content, and for its capacity to fix atmospheric nitrogen through symbioses with soil-borne microorganisms. We sequenced the 1.1-gigabase genome by a whole-genome shotgun approach and integrated it with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly. We predict 46,430 protein-coding genes, 70percent more than Arabidopsis and similar to the poplar genome which, like soybean, is an ancient polyploid (palaeopolyploid). About 78percent of the predicted genes occur in chromosome ends, which comprise less than one-half of the genome but account for nearly all of the genetic recombination. Genome duplications occurred at approximately 59 and 13 million years ago, resulting in a highly duplicated genome with nearly 75percent of the genes present in multiple copies. The two duplication events were followed by gene diversification and loss, and numerous chromosome rearrangements. An accurate soybean genome sequence will facilitate the identification of the genetic basis of many soybean traits, and accelerate the creation of improved soybean varieties.

Constituent rearrangement model and large transverse momentum reactions

International Nuclear Information System (INIS)

Igarashi, Yuji; Imachi, Masahiro; Matsuoka, Takeo; Otsuki, Shoichiro; Sawada, Shoji.

1978-01-01

In this chapter, two models based on the constituent rearrangement picture for large p sub( t) phenomena are summarized. One is the quark-junction model, and the other is the correlating quark rearrangement model. Counting rules of the models apply to both two-body reactions and hadron productions. (author)

Árni Magnússon's rearrangement of paper manuscripts

DEFF Research Database (Denmark)

Stegmann, Beeke

Árni Magnússon’s rearrangement of paper manuscripts draws attention to the early history of Árni Magnússon’s (1663-1730) manuscript collection. The thesis examines Árni’s extensive rearrangement of paper manuscripts, showing that he repeatedly altered the physical composition of codices in his...

Evolutionary restoration of fertility in an interspecies hybrid yeast, by whole-genome duplication after a failed mating-type switch.

Directory of Open Access Journals (Sweden)

Raúl A Ortiz-Merino

2017-05-01

Full Text Available Many interspecies hybrids have been discovered in yeasts, but most of these hybrids are asexual and can replicate only mitotically. Whole-genome duplication has been proposed as a mechanism by which interspecies hybrids can regain fertility, restoring their ability to perform meiosis and sporulate. Here, we show that this process occurred naturally during the evolution of Zygosaccharomyces parabailii, an interspecies hybrid that was formed by mating between 2 parents that differed by 7% in genome sequence and by many interchromosomal rearrangements. Surprisingly, Z. parabailii has a full sexual cycle and is genetically haploid. It goes through mating-type switching and autodiploidization, followed by immediate sporulation. We identified the key evolutionary event that enabled Z. parabailii to regain fertility, which was breakage of 1 of the 2 homeologous copies of the mating-type (MAT locus in the hybrid, resulting in a chromosomal rearrangement and irreparable damage to 1 MAT locus. This rearrangement was caused by HO endonuclease, which normally functions in mating-type switching. With 1 copy of MAT inactivated, the interspecies hybrid now behaves as a haploid. Our results provide the first demonstration that MAT locus damage is a naturally occurring evolutionary mechanism for whole-genome duplication and restoration of fertility to interspecies hybrids. The events that occurred in Z. parabailii strongly resemble those postulated to have caused ancient whole-genome duplication in an ancestor of Saccharomyces cerevisiae.

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Energy Technology Data Exchange (ETDEWEB)

Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

2012-03-14

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

DEFF Research Database (Denmark)

Staaf, Johan; Törngren, Therese; Rambech, Eva

2008-01-01

deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

The complete genome sequencing of Prevotella intermedia strain OMA14 and a subsequent fine-scale, intra-species genomic comparison reveal an unusual amplification of conjugative and mobile transposons and identify a novel Prevotella-lineage-specific repeat.

Science.gov (United States)

Naito, Mariko; Ogura, Yoshitoshi; Itoh, Takehiko; Shoji, Mikio; Okamoto, Masaaki; Hayashi, Tetsuya; Nakayama, Koji

2016-02-01

Prevotella intermedia is a pathogenic bacterium involved in periodontal diseases. Here, we present the complete genome sequence of a clinical strain, OMA14, of this bacterium along with the results of comparative genome analysis with strain 17 of the same species whose genome has also been sequenced, but not fully analysed yet. The genomes of both strains consist of two circular chromosomes: the larger chromosomes are similar in size and exhibit a high overall linearity of gene organizations, whereas the smaller chromosomes show a significant size variation and have undergone remarkable genome rearrangements. Unique features of the Pre. intermedia genomes are the presence of a remarkable number of essential genes on the second chromosomes and the abundance of conjugative and mobilizable transposons (CTns and MTns). The CTns/MTns are particularly abundant in the second chromosomes, involved in its extensive genome rearrangement, and have introduced a number of strain-specific genes into each strain. We also found a novel 188-bp repeat sequence that has been highly amplified in Pre. intermedia and are specifically distributed among the Pre. intermedia-related species. These findings expand our understanding of the genetic features of Pre. intermedia and the roles of CTns and MTns in the evolution of bacteria. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Genome-wide alterations of the DNA replication program during tumor progression

Science.gov (United States)

Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.

2016-08-01

Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.

Analysis Of Segmental Duplications In The Pig Genome Based On Next-Generation Sequencing

DEFF Research Database (Denmark)

Fadista, João; Bendixen, Christian

Segmental duplications are >1kb segments of duplicated DNA present in a genome with high sequence identity (>90%). They are associated with genomic rearrangements and provide a significant source of gene and genome evolution within mammalian genomes. Although segmental duplications have been...... extensively studied in other organisms, its analysis in pig has been hampered by the lack of a complete pig genome assembly. By measuring the depth of coverage of Illumina whole-genome shotgun sequencing reads of the Tabasco animal aligned to the latest pig genome assembly (Sus scrofa 10 – based also...... and their associated copy number alterations, focusing on the global organization of these segments and their possible functional significance in porcine phenotypes. This work provides insights into mammalian genome evolution and generates a valuable resource for porcine genomics research...

Reference genome sequence of the model plant Setaria.

Science.gov (United States)

Bennetzen, Jeffrey L; Schmutz, Jeremy; Wang, Hao; Percifield, Ryan; Hawkins, Jennifer; Pontaroli, Ana C; Estep, Matt; Feng, Liang; Vaughn, Justin N; Grimwood, Jane; Jenkins, Jerry; Barry, Kerrie; Lindquist, Erika; Hellsten, Uffe; Deshpande, Shweta; Wang, Xuewen; Wu, Xiaomei; Mitros, Therese; Triplett, Jimmy; Yang, Xiaohan; Ye, Chu-Yu; Mauro-Herrera, Margarita; Wang, Lin; Li, Pinghua; Sharma, Manoj; Sharma, Rita; Ronald, Pamela C; Panaud, Olivier; Kellogg, Elizabeth A; Brutnell, Thomas P; Doust, Andrew N; Tuskan, Gerald A; Rokhsar, Daniel; Devos, Katrien M

2012-05-13

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The ∼400-Mb assembly covers ∼80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).

Reference genome sequence of the model plant Setaria

Energy Technology Data Exchange (ETDEWEB)

Bennetzen, Jeffrey L [ORNL; Schmutz, Jeremy [Hudson Alpha Institute of Biotechnology; Wang, Hao [University of Georgia, Athens, GA; Percifield, Ryan [University of Georgia, Athens, GA; Hawkins, Jennifer [University of Georgia, Athens, GA; Pontaroli, Ana C. [University of Georgia, Athens, GA; Estep, Matt [University of Georgia, Athens, GA; Feng, Liang [University of Georgia, Athens, GA; Vaughn, Justin N [ORNL; Grimwood, Jane [Hudson Alpha Institute of Biotechnology; Jenkins, Jerry [Hudson Alpha Institute of Biotechnology; Barry, Kerrie [U.S. Department of Energy, Joint Genome Institute; Lindquist, Erika [U.S. Department of Energy, Joint Genome Institute; Hellsten, Uffe [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Wang, Xuewen [University of Georgia, Athens, GA; Wu, Xiaomei [University of Georgia, Athens, GA; Mitros, Therese [University of California, Berkeley; Triplett, Jimmy [University of Missouri, St. Louis; Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Mauro-Herrera, Margarita [Oklahoma State University; Wang, Lin [Cornell University; Li, Pinghua [Cornell University; Sharma, Manoj [University of California, Davis; Sharma, Rita [University of California, Davis; Ronald, Pamela [University of California, Davis; Panaud, Olivier [Universite de Perpignan, Perpignan, France; Kellogg, Elizabeth A. [University of Missouri, St. Louis; Brutnell, Thomas P. [Cornell University; Doust, Andrew N. [Oklahoma State University; Tuskan, Gerald A [ORNL; Rokhsar, Daniel [U.S. Department of Energy, Joint Genome Institute; Devos, Katrien M [ORNL

2012-01-01

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The ~400-Mb assembly covers ~80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).

Reference genome sequence of the model plant Setaria

Energy Technology Data Exchange (ETDEWEB)

Bennetzen, Jeffrey L [ORNL; Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Tuskan, Gerald A [ORNL

2012-01-01

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The {approx}400-Mb assembly covers {approx}80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).

Mitochondrial genome evolution in the Saccharomyces sensu stricto complex.

Science.gov (United States)

Ruan, Jiangxing; Cheng, Jian; Zhang, Tongcun; Jiang, Huifeng

2017-01-01

Exploring the evolutionary patterns of mitochondrial genomes is important for our understanding of the Saccharomyces sensu stricto (SSS) group, which is a model system for genomic evolution and ecological analysis. In this study, we first obtained the complete mitochondrial sequences of two important species, Saccharomyces mikatae and Saccharomyces kudriavzevii. We then compared the mitochondrial genomes in the SSS group with those of close relatives, and found that the non-coding regions evolved rapidly, including dramatic expansion of intergenic regions, fast evolution of introns and almost 20-fold higher rearrangement rates than those of the nuclear genomes. However, the coding regions, and especially the protein-coding genes, are more conserved than those in the nuclear genomes of the SSS group. The different evolutionary patterns of coding and non-coding regions in the mitochondrial and nuclear genomes may be related to the origin of the aerobic fermentation lifestyle in this group. Our analysis thus provides novel insights into the evolution of mitochondrial genomes.

Whole genome comparisons of Fragaria, Prunus and Malus reveal different modes of evolution between Rosaceous subfamilies

Directory of Open Access Journals (Sweden)

Jung Sook

2012-04-01

Full Text Available Abstract Background Rosaceae include numerous economically important and morphologically diverse species. Comparative mapping between the member species in Rosaceae have indicated some level of synteny. Recently the whole genome of three crop species, peach, apple and strawberry, which belong to different genera of the Rosaceae family, have been sequenced, allowing in-depth comparison of these genomes. Results Our analysis using the whole genome sequences of peach, apple and strawberry identified 1399 orthologous regions between the three genomes, with a mean length of around 100 kb. Each peach chromosome showed major orthology mostly to one strawberry chromosome, but to more than two apple chromosomes, suggesting that the apple genome went through more chromosomal fissions in addition to the whole genome duplication after the divergence of the three genera. However, the distribution of contiguous ancestral regions, identified using the multiple genome rearrangements and ancestors (MGRA algorithm, suggested that the Fragaria genome went through a greater number of small scale rearrangements compared to the other genomes since they diverged from a common ancestor. Using the contiguous ancestral regions, we reconstructed a hypothetical ancestral genome for the Rosaceae 7 composed of nine chromosomes and propose the evolutionary steps from the ancestral genome to the extant Fragaria, Prunus and Malus genomes. Conclusion Our analysis shows that different modes of evolution may have played major roles in different subfamilies of Rosaceae. The hypothetical ancestral genome of Rosaceae and the evolutionary steps that lead to three different lineages of Rosaceae will facilitate our understanding of plant genome evolution as well as have a practical impact on knowledge transfer among member species of Rosaceae.

Whole genomes redefine the mutational landscape of pancreatic cancer.

Science.gov (United States)

Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K; Kassahn, Karin S; Bailey, Peter; Johns, Amber L; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C J; Robertson, Alan J; Fadlullah, Muhammad Z H; Bruxner, Tim J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen H; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Lee, Hong C; Jones, Marc D; Nagrial, Adnan M; Humphris, Jeremy; Chantrill, Lorraine A; Chin, Venessa; Steinmann, Angela M; Mawson, Amanda; Humphrey, Emily S; Colvin, Emily K; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Pettitt, Jessica A; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; Graham, Janet S; Niclou, Simone P; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A; Gill, Anthony J; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Pearson, John V; Biankin, Andrew V; Grimmond, Sean M

2015-02-26

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Whole genomes redefine the mutational landscape of pancreatic cancer

Science.gov (United States)

Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

2015-01-01

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.

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Jian Li

Full Text Available The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR mediated by low-copy repeats (LCRs. Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.

Myc-dependent genome instability and lifespan in Drosophila.

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Christina Greer

Full Text Available The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs. In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.

Reorganization of wheat and rye genomes in octoploid triticale (× Triticosecale).

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Kalinka, Anna; Achrem, Magdalena

2018-04-01

The analysis of early generations of triticale showed numerous rearrangements of the genome. Complexed transformation included loss of chromosomes, t-heterochromatin content changes and the emergence of retrotransposons in new locations. This study investigated certain aspects of genomic transformations in the early generations (F5 and F8) of the primary octoploid triticale derived from the cross of hexaploid wheat with the diploid rye. Most of the plants tested were hypoploid; among eliminated chromosomes were rye chromosomes 4R and 5R and variable number of wheat chromosomes. Wheat chromosomes were eliminated to a higher extent. The lower content of telomeric heterochromatin was also found in rye chromosomes in comparison with parental rye. Studying the location of selected retrotransposons from Ty1-copia and Ty3-gypsy families using fluorescence in situ hybridization revealed additional locations of these retrotransposons that were not present in chromosomes of parental species. ISSR, IRAP and REMAP analyses showed significant changes at the level of specific DNA nucleotide sequences. In most cases, the disappearance of certain types of bands was observed, less frequently new types of bands appeared, not present in parental species. This demonstrates the scale of genome rearrangement and, above all, the elimination of wheat and rye sequences, largely due to the reduction of chromosome number. With regard to the proportion of wheat to rye genome, the rye genome was more affected by the changes, thus this study was focused more on the rye genome. Observations suggest that genome reorganization is not finished in the F5 generation but is still ongoing in the F8 generation.

A Dense Brown Trout (Salmo trutta) Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

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Leitwein, Maeva; Guinand, Bruno; Pouzadoux, Juliette; Desmarais, Erick; Berrebi, Patrick; Gagnaire, Pierre-Alexandre

2017-01-01

High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta), a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π) was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout. PMID:28235829

A Dense Brown Trout (Salmo trutta Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

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Maeva Leitwein

2017-04-01

Full Text Available High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta, a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout.

Comparing Mycobacterium tuberculosis genomes using genome topology networks.

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Jiang, Jianping; Gu, Jianlei; Zhang, Liang; Zhang, Chenyi; Deng, Xiao; Dou, Tonghai; Zhao, Guoping; Zhou, Yan

2015-02-14

Over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. Several findings have revealed that genomic structural variations (SVs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by SVs may extend our knowledge of the relationships between SVs and phenotypes in microbes, especially in pathogenic bacteria. In this work, we introduce a 'Genome Topology Network' (GTN) method based on gene homology and gene locations to analyze genomic SVs and perform phylogenetic analysis. Furthermore, the concept of 'unfixed ortholog' has been proposed, whose members are affected by SVs in genome topology among close species. To improve the precision of 'unfixed ortholog' recognition, a strategy to detect annotation differences and complete gene annotation was applied. To assess the GTN method, a set of thirteen complete M. tuberculosis genomes was analyzed as a case study. GTNs with two different gene homology-assigning methods were built, the Clusters of Orthologous Groups (COG) method and the orthoMCL clustering method, and two phylogenetic trees were constructed accordingly, which may provide additional insights into whole genome-based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most members were related to immunogenicity and drug resistance, such as PPE-repeat proteins (COG5651) and transcriptional regulator TetR gene family members (COG1309). The GTN method has been implemented in PERL and released on our website. The tool can be downloaded from http://homepage.fudan.edu.cn/zhouyan/gtn/ , and allows re-annotating the 'lost' genes among closely related genomes, analyzing genes affected by SVs, and performing phylogenetic analysis. With this tool, many immunogenic-related and drug resistance-related genes

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

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Stephanie R. Hare

2016-02-01

Full Text Available This review describes unexpected dynamical behaviors of rearranging carbocations and the modern computational methods used to elucidate these aspects of reaction mechanisms. Unique potential energy surface topologies associated with these rearrangements have been discovered in recent years that are not only of fundamental interest, but also provide insight into the way Nature manipulates chemical space to accomplish specific chemical transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout.

Maximum likelihood phylogenetic reconstruction from high-resolution whole-genome data and a tree of 68 eukaryotes.

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Lin, Yu; Hu, Fei; Tang, Jijun; Moret, Bernard M E

2013-01-01

The rapid accumulation of whole-genome data has renewed interest in the study of the evolution of genomic architecture, under such events as rearrangements, duplications, losses. Comparative genomics, evolutionary biology, and cancer research all require tools to elucidate the mechanisms, history, and consequences of those evolutionary events, while phylogenetics could use whole-genome data to enhance its picture of the Tree of Life. Current approaches in the area of phylogenetic analysis are limited to very small collections of closely related genomes using low-resolution data (typically a few hundred syntenic blocks); moreover, these approaches typically do not include duplication and loss events. We describe a maximum likelihood (ML) approach for phylogenetic analysis that takes into account genome rearrangements as well as duplications, insertions, and losses. Our approach can handle high-resolution genomes (with 40,000 or more markers) and can use in the same analysis genomes with very different numbers of markers. Because our approach uses a standard ML reconstruction program (RAxML), it scales up to large trees. We present the results of extensive testing on both simulated and real data showing that our approach returns very accurate results very quickly. In particular, we analyze a dataset of 68 high-resolution eukaryotic genomes, with from 3,000 to 42,000 genes, from the eGOB database; the analysis, including bootstrapping, takes just 3 hours on a desktop system and returns a tree in agreement with all well supported branches, while also suggesting resolutions for some disputed placements.

Reproductive Incompatibility Involving Senegalese Aedes aegypti (L Is Associated with Chromosome Rearrangements.

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Laura B Dickson

2016-04-01

Full Text Available Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf, has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane's rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL. Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane's rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI

Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

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Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

2016-01-01

Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa) is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf), has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae) failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane’s rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL). Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane’s rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH) experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI staining

Heterogeneity of BCR-ABL rearrangement in patients with chronic myeloid leukemia in Pakistan.

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Tabassum, Najia; Saboor, Mohammad; Ghani, Rubina; Moinuddin, Moinuddin

2014-07-01

Breakpoint cluster region-Abelson (BCR-ABL) rearrangement or Philadelphia (Ph) chromosome in Chronic Myeloid Leukemia (CML) is derived from a reciprocal chromosomal translocation between ABL gene on chromosome 9 and BCR gene on chromosome 22. This chimeric protein has various sizes and therefore different clinical behaviour. The purpose of this study was to determine the heterogeneity of BCR-ABL rearrangement in patients with Ph(+)CML in Pakistan. The study was conducted at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed to identify various BCR-ABL transcripts. All 25 samples showed BCR-ABL rearrangements. Out of these, 24 (96%) patients expressed p210 BCR-ABL rearrangements i.e. 60% (n=15) had b3a2 and 32% (n=8) had b2a2 rearrangements. Co-expression of b3a2 /b2a2 rearrangement and p190 (e1a3) rearrangement was also identified in two patients. It is apparent that majority of the patients had p210 BCR-ABL rearrangements. Frequency of co-expression and rare fusion transcripts was very low.

Analyses of charophyte chloroplast genomes help characterize the ancestral chloroplast genome of land plants.

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Civaň, Peter; Foster, Peter G; Embley, Martin T; Séneca, Ana; Cox, Cymon J

2014-04-01

Despite the significance of the relationships between embryophytes and their charophyte algal ancestors in deciphering the origin and evolutionary success of land plants, few chloroplast genomes of the charophyte algae have been reconstructed to date. Here, we present new data for three chloroplast genomes of the freshwater charophytes Klebsormidium flaccidum (Klebsormidiophyceae), Mesotaenium endlicherianum (Zygnematophyceae), and Roya anglica (Zygnematophyceae). The chloroplast genome of Klebsormidium has a quadripartite organization with exceptionally large inverted repeat (IR) regions and, uniquely among streptophytes, has lost the rrn5 and rrn4.5 genes from the ribosomal RNA (rRNA) gene cluster operon. The chloroplast genome of Roya differs from other zygnematophycean chloroplasts, including the newly sequenced Mesotaenium, by having a quadripartite structure that is typical of other streptophytes. On the basis of the improbability of the novel gain of IR regions, we infer that the quadripartite structure has likely been lost independently in at least three zygnematophycean lineages, although the absence of the usual rRNA operonic synteny in the IR regions of Roya may indicate their de novo origin. Significantly, all zygnematophycean chloroplast genomes have undergone substantial genomic rearrangement, which may be the result of ancient retroelement activity evidenced by the presence of integrase-like and reverse transcriptase-like elements in the Roya chloroplast genome. Our results corroborate the close phylogenetic relationship between Zygnematophyceae and land plants and identify 89 protein-coding genes and 22 introns present in the chloroplast genome at the time of the evolutionary transition of plants to land, all of which can be found in the chloroplast genomes of extant charophytes.

Comprehensive preimplantation genetic screening and sperm deoxyribonucleic acid fragmentation from three males carrying balanced chromosome rearrangements.

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Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima

2015-09-01

To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.

CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

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Abhishek Nag

Full Text Available Tourette syndrome (TS is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179 have a significant excess (P = 0.006 of large CNV (>500 kb calls compared to controls (N = 234. Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

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Nag, Abhishek; Bochukova, Elena G; Kremeyer, Barbara; Campbell, Desmond D; Muller, Heike; Valencia-Duarte, Ana V; Cardona, Julio; Rivas, Isabel C; Mesa, Sandra C; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D; Romero, Roxana; Fournier, Eduardo; Reus, Victor I; Lowe, Thomas L; Farooqi, I Sadaf; Mathews, Carol A; McGrath, Lauren M; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M; Pauls, David L; Freimer, Nelson B; Plagnol, Vincent; Ruiz-Linares, Andrés

2013-01-01

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

Reconstruction of chromosome rearrangements between the two most ancestral duckweed species Spirodela polyrhiza and S. intermedia.

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Hoang, Phuong T N; Schubert, Ingo

2017-12-01

The monophyletic duckweeds comprising five genera within the monocot order Alismatales are neotenic, free-floating, aquatic organisms with fast vegetative propagation. Some species are considered for efficient biomass production, for life stock feeding, and for (simultaneous) wastewater phytoremediation. The ancestral genus Spirodela consists of only two species, Spirodela polyrhiza and Spirodela intermedia, both with a similar small genome (~160 Mbp/1C). Reference genome drafts and a physical map of 96 BACs on the 20 chromosome pairs of S. polyrhiza strain 7498 are available and provide useful tools for further evolutionary studies within and between duckweed genera. Here we applied sequential comparative multicolor fluorescence in situ hybridization (mcFISH) to address homeologous chromosomes in S. intermedia (2n = 36), to detect chromosome rearrangements between both species and to elucidate the mechanisms which may have led to the chromosome number alteration after their evolutionary separation. Ten chromosome pairs proved to be conserved between S. polyrhiza and S. intermedia, the remaining ones experienced, depending on the assumed direction of evolution, translocations, inversion, and fissions, respectively. These results represent a first step to unravel karyotype evolution among duckweeds and are anchor points for future genome assembly of S. intermedia.

A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

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Asia, Saba; Vaziri Nasab, Hamed; Sabbaghian, Marjan; Kalantari, Hamid; Zari Moradi, Shabnam; Gourabi, Hamid; Mohseni Meybodi, Anahita

2014-01-01

Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

Phylogeny Inference of Closely Related Bacterial Genomes: Combining the Features of Both Overlapping Genes and Collinear Genomic Regions

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Zhang, Yan-Cong; Lin, Kui

2015-01-01

Overlapping genes (OGs) represent one type of widespread genomic feature in bacterial genomes and have been used as rare genomic markers in phylogeny inference of closely related bacterial species. However, the inference may experience a decrease in performance for phylogenomic analysis of too closely or too distantly related genomes. Another drawback of OGs as phylogenetic markers is that they usually take little account of the effects of genomic rearrangement on the similarity estimation, such as intra-chromosome/genome translocations, horizontal gene transfer, and gene losses. To explore such effects on the accuracy of phylogeny reconstruction, we combine phylogenetic signals of OGs with collinear genomic regions, here called locally collinear blocks (LCBs). By putting these together, we refine our previous metric of pairwise similarity between two closely related bacterial genomes. As a case study, we used this new method to reconstruct the phylogenies of 88 Enterobacteriale genomes of the class Gammaproteobacteria. Our results demonstrated that the topological accuracy of the inferred phylogeny was improved when both OGs and LCBs were simultaneously considered, suggesting that combining these two phylogenetic markers may reduce, to some extent, the influence of gene loss on phylogeny inference. Such phylogenomic studies, we believe, will help us to explore a more effective approach to increasing the robustness of phylogeny reconstruction of closely related bacterial organisms. PMID:26715828

Genetic rearrangements of six wheat-agropyron cristatum 6P addition lines revealed by molecular markers.

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Haiming Han

Full Text Available Agropyron cristatum (L. Gaertn. (2n = 4x = 28, PPPP not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH, SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering.

Mitochondrial genome sequencing helps show the evolutionary mechanism of mitochondrial genome formation in Brassica

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2011-01-01

Background Angiosperm mitochondrial genomes are more complex than those of other organisms. Analyses of the mitochondrial genome sequences of at least 11 angiosperm species have showed several common properties; these cannot easily explain, however, how the diverse mitotypes evolved within each genus or species. We analyzed the evolutionary relationships of Brassica mitotypes by sequencing. Results We sequenced the mitotypes of cam (Brassica rapa), ole (B. oleracea), jun (B. juncea), and car (B. carinata) and analyzed them together with two previously sequenced mitotypes of B. napus (pol and nap). The sizes of whole single circular genomes of cam, jun, ole, and car are 219,747 bp, 219,766 bp, 360,271 bp, and 232,241 bp, respectively. The mitochondrial genome of ole is largest as a resulting of the duplication of a 141.8 kb segment. The jun mitotype is the result of an inherited cam mitotype, and pol is also derived from the cam mitotype with evolutionary modifications. Genes with known functions are conserved in all mitotypes, but clear variation in open reading frames (ORFs) with unknown functions among the six mitotypes was observed. Sequence relationship analysis showed that there has been genome compaction and inheritance in the course of Brassica mitotype evolution. Conclusions We have sequenced four Brassica mitotypes, compared six Brassica mitotypes and suggested a mechanism for mitochondrial genome formation in Brassica, including evolutionary events such as inheritance, duplication, rearrangement, genome compaction, and mutation. PMID:21988783

Expression of the hepatitis B virus genome in chronic hepatitis B carriers and patients with hepatocellular carcinoma

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Bowyer, S.M.; Dusheiko, G.M.; Schoub, B.D.; Kew, M.C.

1987-01-01

The authors examined the methylation status of CCGG sites in hepatitis B virus (HBV) DNA to determine whether methylation could be responsible for the selective expression of the HBV surface gene in chronic hepatitis B infection and hepatocellular carcinoma. Infected liver tissue from patients with low levels of viral replication was analyzed for HBV DNA copy number per haploid cell genome. Total cellular DNA, with sufficient HBV DNA, was digested with the restriction endonucleases Msp I and Hpa II, to determine whether the HBV DNA was methylated, or HindIII, to determine whether the HBV DNA was integrated or episomal. The cleavage fragments were analyzed by Southern blotting and hybridization to 32 P-labeled HBV DNA. In replicative chronic hepatitis B, hypomethylation of the HBV genome correlated with HBV expression in both virions and infected tissue. In carriers with nonreplicative infection, it was difficult to ascertain the role of methylation as copy number was low. HBV DNA copy number was also low in 17 out of 29 of the rumor tissues tested and as many as 14 out of 16 of the adjacent non-neoplastic tissues tested. Integrated sequences were hypermethylated in the PLC/PRF/5 cell line and in six of the tumor tissues suggesting that methylation plays a role in HBV gene repression. However, since DNA from five other tumors was hypomethylated, the belief that methylation per se is an absolute determinant of HBV core gene repression does not hold for human hepatocellular carcinoma tissue

The hardness of train rearrangements

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Eggermont, C.E.J.; Hurkens, C.A.J.; Modelski, M.S.; Woeginger, G.J.

2009-01-01

We derive several results on the computational complexity of train rearrangement problems in railway optimization. Our main result states that arranging a departing train in a depot is NP-complete, even if each track in the depot contains only two cars.

Initiation of MLL-rearranged AML is dependent on C/EBPα

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Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton

2014-01-01

have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

Mind the gap; seven reasons to close fragmented genome assemblies.

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Thomma, Bart P H J; Seidl, Michael F; Shi-Kunne, Xiaoqian; Cook, David E; Bolton, Melvin D; van Kan, Jan A L; Faino, Luigi

2016-05-01

Like other domains of life, research into the biology of filamentous microbes has greatly benefited from the advent of whole-genome sequencing. Next-generation sequencing (NGS) technologies have revolutionized sequencing, making genomic sciences accessible to many academic laboratories including those that study non-model organisms. Thus, hundreds of fungal genomes have been sequenced and are publically available today, although these initiatives have typically yielded considerably fragmented genome assemblies that often lack large contiguous genomic regions. Many important genomic features are contained in intergenic DNA that is often missing in current genome assemblies, and recent studies underscore the significance of non-coding regions and repetitive elements for the life style, adaptability and evolution of many organisms. The study of particular types of genetic elements, such as telomeres, centromeres, repetitive elements, effectors, and clusters of co-regulated genes, but also of phenomena such as structural rearrangements, genome compartmentalization and epigenetics, greatly benefits from having a contiguous and high-quality, preferably even complete and gapless, genome assembly. Here we discuss a number of important reasons to produce gapless, finished, genome assemblies to help answer important biological questions. Copyright © 2015 Elsevier Inc. All rights reserved.

Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.

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Catelain, Cyril; Pailler, Emma; Oulhen, Marianne; Faugeroux, Vincent; Pommier, Anne-Laure; Farace, Françoise

2017-01-01

Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.

Conserved microstructure of the Brassica B Genome of Brassica nigra in relation to homologous regions of Arabidopsis thaliana, B. rapa and B. oleracea

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2013-01-01

Background The Brassica B genome is known to carry several important traits, yet there has been limited analyses of its underlying genome structure, especially in comparison to the closely related A and C genomes. A bacterial artificial chromosome (BAC) library of Brassica nigra was developed and screened with 17 genes from a 222 kb region of A. thaliana that had been well characterised in both the Brassica A and C genomes. Results Fingerprinting of 483 apparently non-redundant clones defined physical contigs for the corresponding regions in B. nigra. The target region is duplicated in A. thaliana and six homologous contigs were found in B. nigra resulting from the whole genome triplication event shared by the Brassiceae tribe. BACs representative of each region were sequenced to elucidate the level of microscale rearrangements across the Brassica species divide. Conclusions Although the B genome species separated from the A/C lineage some 6 Mya, comparisons between the three paleopolyploid Brassica genomes revealed extensive conservation of gene content and sequence identity. The level of fractionation or gene loss varied across genomes and genomic regions; however, the greatest loss of genes was observed to be common to all three genomes. One large-scale chromosomal rearrangement differentiated the B genome suggesting such events could contribute to the lack of recombination observed between B genome species and those of the closely related A/C lineage. PMID:23586706

Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

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Marcus Sokolowski

Full Text Available Suicidal behavior (SB has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs, as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA in offspring as main outcome (n = 660 trios. We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (100 kb CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having

The chloroplast genome sequence of the green alga Leptosira terrestris: multiple losses of the inverted repeat and extensive genome rearrangements within the Trebouxiophyceae

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Turmel Monique

2007-07-01

Full Text Available Abstract Background In the Chlorophyta – the green algal phylum comprising the classes Prasinophyceae, Ulvophyceae, Trebouxiophyceae and Chlorophyceae – the chloroplast genome displays a highly variable architecture. While chlorophycean chloroplast DNAs (cpDNAs deviate considerably from the ancestral pattern described for the prasinophyte Nephroselmis olivacea, the degree of remodelling sustained by the two ulvophyte cpDNAs completely sequenced to date is intermediate relative to those observed for chlorophycean and trebouxiophyte cpDNAs. Chlorella vulgaris (Chlorellales is currently the only photosynthetic trebouxiophyte whose complete cpDNA sequence has been reported. To gain insights into the evolutionary trends of the chloroplast genome in the Trebouxiophyceae, we sequenced cpDNA from the filamentous alga Leptosira terrestris (Ctenocladales. Results The 195,081-bp Leptosira chloroplast genome resembles the 150,613-bp Chlorella genome in lacking a large inverted repeat (IR but differs greatly in gene order. Six of the conserved genes present in Chlorella cpDNA are missing from the Leptosira gene repertoire. The 106 conserved genes, four introns and 11 free standing open reading frames (ORFs account for 48.3% of the genome sequence. This is the lowest gene density yet observed among chlorophyte cpDNAs. Contrary to the situation in Chlorella but similar to that in the chlorophycean Scenedesmus obliquus, the gene distribution is highly biased over the two DNA strands in Leptosira. Nine genes, compared to only three in Chlorella, have significantly expanded coding regions relative to their homologues in ancestral-type green algal cpDNAs. As observed in chlorophycean genomes, the rpoB gene is fragmented into two ORFs. Short repeats account for 5.1% of the Leptosira genome sequence and are present mainly in intergenic regions. Conclusion Our results highlight the great plasticity of the chloroplast genome in the Trebouxiophyceae and indicate

Rearrangement of cluster structure during fission processes

DEFF Research Database (Denmark)

Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Andrey V.

2004-01-01

Results of molecular dynamics simulations of fission reactions $Na_10^2+ -->Na_7^++ Na_3^+ and Na_18^2+--> 2Na_9^+ are presented. The dependence of the fission barriers on the isomer structure of the parent cluster is analysed. It is demonstrated that the energy necessary for removing homothetic...... groups of atoms from the parent cluster is largely independent of the isomer form of the parent cluster. The importance of rearrangement of the cluster structure during the fission process is elucidated. This rearrangement may include transition to another isomer state of the parent cluster before actual...

TALENs: customizable molecular DNA scissors for genome engineering of plants.

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Chen, Kunling; Gao, Caixia

2013-06-20

Precise genome modification with engineered nucleases is a powerful tool for studying basic biology and applied biotechnology. Transcription activator-like effector nucleases (TALENs), consisting of an engineered specific (TALE) DNA binding domain and a Fok I cleavage domain, are newly developed versatile reagents for genome engineering in different organisms. Because of the simplicity of the DNA recognition code and their modular assembly, TALENs can act as customizable molecular DNA scissors inducing double-strand breaks (DSBs) at given genomic location. Thus, they provide a valuable approach to targeted genome modifications such as mutations, insertions, replacements or chromosome rearrangements. In this article, we review the development of TALENs, and summarize the principles and tools for TALEN-mediated gene targeting in plant cells, as well as current and potential strategies for use in plant research and crop improvement. Copyright © 2013. Published by Elsevier Ltd.

The complete chloroplast genome sequences of Lychnis wilfordii and Silene capitata and comparative analyses with other Caryophyllaceae genomes.

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Kang, Jong-Soo; Lee, Byoung Yoon; Kwak, Myounghai

2017-01-01

The complete chloroplast genomes of Lychnis wilfordii and Silene capitata were determined and compared with ten previously reported Caryophyllaceae chloroplast genomes. The chloroplast genome sequences of L. wilfordii and S. capitata contain 152,320 bp and 150,224 bp, respectively. The gene contents and orders among 12 Caryophyllaceae species are consistent, but several microstructural changes have occurred. Expansion of the inverted repeat (IR) regions at the large single copy (LSC)/IRb and small single copy (SSC)/IR boundaries led to partial or entire gene duplications. Additionally, rearrangements of the LSC region were caused by gene inversions and/or transpositions. The 18 kb inversions, which occurred three times in different lineages of tribe Sileneae, were thought to be facilitated by the intermolecular duplicated sequences. Sequence analyses of the L. wilfordii and S. capitata genomes revealed 39 and 43 repeats, respectively, including forward, palindromic, and reverse repeats. In addition, a total of 67 and 56 simple sequence repeats were discovered in the L. wilfordii and S. capitata chloroplast genomes, respectively. Finally, we constructed phylogenetic trees of the 12 Caryophyllaceae species and two Amaranthaceae species based on 73 protein-coding genes using both maximum parsimony and likelihood methods.

The somatic genomic landscape of chromophobe renal cell carcinoma.

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Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

2014-09-08

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. Copyright © 2014 Elsevier Inc. All rights reserved.

Genome landscape and evolutionary plasticity of chromosomes in malaria mosquitoes.

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Ai Xia

2010-05-01

Full Text Available Nonrandom distribution of rearrangements is a common feature of eukaryotic chromosomes that is not well understood in terms of genome organization and evolution. In the major African malaria vector Anopheles gambiae, polymorphic inversions are highly nonuniformly distributed among five chromosomal arms and are associated with epidemiologically important adaptations. However, it is not clear whether the genomic content of the chromosomal arms is associated with inversion polymorphism and fixation rates.To better understand the evolutionary dynamics of chromosomal inversions, we created a physical map for an Asian malaria mosquito, Anopheles stephensi, and compared it with the genome of An. gambiae. We also developed and deployed novel Bayesian statistical models to analyze genome landscapes in individual chromosomal arms An. gambiae. Here, we demonstrate that, despite the paucity of inversion polymorphisms on the X chromosome, this chromosome has the fastest rate of inversion fixation and the highest density of transposable elements, simple DNA repeats, and GC content. The highly polymorphic and rapidly evolving autosomal 2R arm had overrepresentation of genes involved in cellular response to stress supporting the role of natural selection in maintaining adaptive polymorphic inversions. In addition, the 2R arm had the highest density of regions involved in segmental duplications that clustered in the breakpoint-rich zone of the arm. In contrast, the slower evolving 2L, 3R, and 3L, arms were enriched with matrix-attachment regions that potentially contribute to chromosome stability in the cell nucleus.These results highlight fundamental differences in evolutionary dynamics of the sex chromosome and autosomes and revealed the strong association between characteristics of the genome landscape and rates of chromosomal evolution. We conclude that a unique combination of various classes of genes and repetitive DNA in each arm, rather than a single type

Genome analysis and comparative genomics of a Giardia intestinalis assemblage E isolate

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Andersson Jan O

2010-10-01

Full Text Available Abstract Background Giardia intestinalis is a protozoan parasite that causes diarrhea in a wide range of mammalian species. To further understand the genetic diversity between the Giardia intestinalis species, we have performed genome sequencing and analysis of a wild-type Giardia intestinalis sample from the assemblage E group, isolated from a pig. Results We identified 5012 protein coding genes, the majority of which are conserved compared to the previously sequenced genomes of the WB and GS strains in terms of microsynteny and sequence identity. Despite this, there is an unexpectedly large number of chromosomal rearrangements and several smaller structural changes that are present in all chromosomes. Novel members of the VSP, NEK Kinase and HCMP gene families were identified, which may reveal possible mechanisms for host specificity and new avenues for antigenic variation. We used comparative genomics of the three diverse Giardia intestinalis isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes. Extensive analyses of polymorphisms in the core proteome of Giardia revealed differential rates of divergence among cellular processes. Conclusions Our results indicate that despite a well conserved core of genes there is significant genome variation between Giardia isolates, both in terms of gene content, gene polymorphisms, structural chromosomal variations and surface molecule repertoires. This study improves the annotation of the Giardia genomes and enables the identification of functionally important variation.

The genome of the polar eukaryotic microalga Coccomyxa subellipsoidea reveals traits of cold adaptation

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Blanc, Guillaume; Agarkova, Irina; Grimwood, Jane; Kuo, Alan; Brueggeman, Andrew; Dunigan, David D.; Gurnon, James; Ladunga, Istvan; Lindquist, Erika; Lucas, Susan; Pangilinan, Jasmyn; Proschold, Thomas; Salamov, Asaf; Schmutz, Jeremy; Weeks, Donald; Tamada, Takashi; Lomsadze, Alexandre; Borodovsky, Mark; Claverie, Jean-Michel; Grigoriev, Igor V.; Van Etten, James L.

2012-02-13

Background Little is known about the mechanisms of adaptation of life to the extreme environmental conditions encountered in polar regions. Here we present the genome sequence of a unicellular green alga from the division chlorophyta, Coccomyxa subellipsoidea C-169, which we will hereafter refer to as C-169. This is the first eukaryotic microorganism from a polar environment to have its genome sequenced. Results The 48.8 Mb genome contained in 20 chromosomes exhibits significant synteny conservation with the chromosomes of its relatives Chlorella variabilis and Chlamydomonas reinhardtii. The order of the genes is highly reshuffled within synteny blocks, suggesting that intra-chromosomal rearrangements were more prevalent than inter-chromosomal rearrangements. Remarkably, Zepp retrotransposons occur in clusters of nested elements with strictly one cluster per chromosome probably residing at the centromere. Several protein families overrepresented in C. subellipsoidae include proteins involved in lipid metabolism, transporters, cellulose synthases and short alcohol dehydrogenases. Conversely, C-169 lacks proteins that exist in all other sequenced chlorophytes, including components of the glycosyl phosphatidyl inositol anchoring system, pyruvate phosphate dikinase and the photosystem 1 reaction center subunit N (PsaN). Conclusions We suggest that some of these gene losses and gains could have contributed to adaptation to low temperatures. Comparison of these genomic features with the adaptive strategies of psychrophilic microbes suggests that prokaryotes and eukaryotes followed comparable evolutionary routes to adapt to cold environments.

High-resolution comparative mapping among man, cattle and mouse suggests a role for repeat sequences in mammalian genome evolution

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Rodolphe François

2006-08-01

Full Text Available Abstract Background Comparative mapping provides new insights into the evolutionary history of genomes. In particular, recent studies in mammals have suggested a role for segmental duplication in genome evolution. In some species such as Drosophila or maize, transposable elements (TEs have been shown to be involved in chromosomal rearrangements. In this work, we have explored the presence of interspersed repeats in regions of chromosomal rearrangements, using an updated high-resolution integrated comparative map among cattle, man and mouse. Results The bovine, human and mouse comparative autosomal map has been constructed using data from bovine genetic and physical maps and from FISH-mapping studies. We confirm most previous results but also reveal some discrepancies. A total of 211 conserved segments have been identified between cattle and man, of which 33 are new segments and 72 correspond to extended, previously known segments. The resulting map covers 91% and 90% of the human and bovine genomes, respectively. Analysis of breakpoint regions revealed a high density of species-specific interspersed repeats in the human and mouse genomes. Conclusion Analysis of the breakpoint regions has revealed specific repeat density patterns, suggesting that TEs may have played a significant role in chromosome evolution and genome plasticity. However, we cannot rule out that repeats and breakpoints accumulate independently in the few same regions where modifications are better tolerated. Likewise, we cannot ascertain whether increased TE density is the cause or the consequence of chromosome rearrangements. Nevertheless, the identification of high density repeat clusters combined with a well-documented repeat phylogeny should highlight probable breakpoints, and permit their precise dating. Combining new statistical models taking the present information into account should help reconstruct ancestral karyotypes.

Approximating the edit distance for genomes with duplicate genes under DCJ, insertion and deletion

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Shao Mingfu

2012-12-01

Full Text Available Abstract Computing the edit distance between two genomes under certain operations is a basic problem in the study of genome evolution. The double-cut-and-join (DCJ model has formed the basis for most algorithmic research on rearrangements over the last few years. The edit distance under the DCJ model can be easily computed for genomes without duplicate genes. In this paper, we study the edit distance for genomes with duplicate genes under a model that includes DCJ operations, insertions and deletions. We prove that computing the edit distance is equivalent to finding the optimal cycle decomposition of the corresponding adjacency graph, and give an approximation algorithm with an approximation ratio of 1.5 + ∈.

Insights into bilaterian evolution from three spiralian genomes

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Simakov, Oleg; Marletaz, Ferdinand; Cho, Sung-Jin; Edsinger-Gonzales, Eric; Havlak, Paul; Hellsten, Uffe; Kuo, Dian-Han; Larsson, Tomas; Lv, Jie; Arendt, Detlev; Savage, Robert; Osoegawa, Kazutoyo; de Jong, Pieter; Grimwood, Jane; Chapman, Jarrod A.; Shapiro, Harris; Otillar, Robert P.; Terry, Astrid Y.; Boore, Jeffrey L.; Grigoriev, Igor V.; Lindberg, David R.; Seaver, Elaine C.; Weisblat, David A.; Putnam, Nicholas H.; Rokhsar, Daniel S.; Aerts, Andrea

2012-01-07

Current genomic perspectives on animal diversity neglect two prominent phyla, the molluscs and annelids, that together account for nearly one-third of known marine species and are important both ecologically and as experimental systems in classical embryology1, 2, 3. Here we describe the draft genomes of the owl limpet (Lottia gigantea), a marine polychaete (Capitella teleta) and a freshwater leech (Helobdella robusta), and compare them with other animal genomes to investigate the origin and diversification of bilaterians from a genomic perspective. We find that the genome organization, gene structure and functional content of these species are more similar to those of some invertebrate deuterostome genomes (for example, amphioxus and sea urchin) than those of other protostomes that have been sequenced to date (flies, nematodes and flatworms). The conservation of these genomic features enables us to expand the inventory of genes present in the last common bilaterian ancestor, establish the tripartite diversification of bilaterians using multiple genomic characteristics and identify ancient conserved long- and short-range genetic linkages across metazoans. Superimposed on this broadly conserved pan-bilaterian background we find examples of lineage-specific genome evolution, including varying rates of rearrangement, intron gain and loss, expansions and contractions of gene families, and the evolution of clade-specific genes that produce the unique content of each genome.

Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

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Kyung Park

2010-07-01

Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

Comparative mapping of Brassica juncea and Arabidopsis thaliana using Intron Polymorphism (IP markers: homoeologous relationships, diversification and evolution of the A, B and C Brassica genomes

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Gupta Vibha

2008-03-01

Full Text Available Abstract Background Extensive mapping efforts are currently underway for the establishment of comparative genomics between the model plant, Arabidopsis thaliana and various Brassica species. Most of these studies have deployed RFLP markers, the use of which is a laborious and time-consuming process. We therefore tested the efficacy of PCR-based Intron Polymorphism (IP markers to analyze genome-wide synteny between the oilseed crop, Brassica juncea (AABB genome and A. thaliana and analyzed the arrangement of 24 (previously described genomic block segments in the A, B and C Brassica genomes to study the evolutionary events contributing to karyotype variations in the three diploid Brassica genomes. Results IP markers were highly efficient and generated easily discernable polymorphisms on agarose gels. Comparative analysis of the segmental organization of the A and B genomes of B. juncea (present study with the A and B genomes of B. napus and B. nigra respectively (described earlier, revealed a high degree of colinearity suggesting minimal macro-level changes after polyploidization. The ancestral block arrangements that remained unaltered during evolution and the karyotype rearrangements that originated in the Oleracea lineage after its divergence from Rapa lineage were identified. Genomic rearrangements leading to the gain or loss of one chromosome each between the A-B and A-C lineages were deciphered. Complete homoeology in terms of block organization was found between three linkage groups (LG each for the A-B and A-C genomes. Based on the homoeology shared between the A, B and C genomes, a new nomenclature for the B genome LGs was assigned to establish uniformity in the international Brassica LG nomenclature code. Conclusion IP markers were highly effective in generating comparative relationships between Arabidopsis and various Brassica species. Comparative genomics between the three Brassica lineages established the major rearrangements

PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

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Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

2006-01-01

Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

Differential genomic arrangements in Caryophyllales through deep transcriptome sequencing of A. hypochondriacus.

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Meeta Sunil

Full Text Available Genome duplication event in edible dicots under the orders Rosid and Asterid, common during the oligocene period, is missing for species under the order Caryophyllales. Despite this, grain amaranths not only survived this period but display many desirable traits missing in species under rosids and asterids. For example, grain amaranths display traits like C4 photosynthesis, high-lysine seeds, high-yield, drought resistance, tolerance to infection and resilience to stress. It is, therefore, of interest to look for minor genome rearrangements with potential functional implications that are unique to grain amaranths. Here, by deep sequencing and assembly of 16 transcriptomes (86.8 billion bases we have interrogated differential genome rearrangement unique to Amaranthus hypochondriacus with potential links to these phenotypes. We have predicted 125,581 non-redundant transcripts including 44,529 protein coding transcripts identified based on homology to known proteins and 13,529 predicted as novel/amaranth specific coding transcripts. Of the protein coding de novo assembled transcripts, we have identified 1810 chimeric transcripts. More than 30% and 19% of the gene pairs within the chimeric transcripts are found within the same loci in the genomes of A. hypochondriacus and Beta vulgaris respectively and are considered real positives. Interestingly, one of the chimeric transcripts comprises two important genes, namely DHDPS1, a key enzyme implicated in the biosynthesis of lysine, and alpha-glucosidase, an enzyme involved in sucrose catabolism, in close proximity to each other separated by a distance of 612 bases in the genome of A. hypochondriacus in a convergent configuration. We have experimentally validated that transcripts of these two genes are also overlapping in the 3' UTR with their expression negatively correlated from bud to mature seed, suggesting a potential link between the high seed lysine trait and unique genome organization.

How life changes itself: the Read-Write (RW) genome.

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Shapiro, James A

2013-09-01

The genome has traditionally been treated as a Read-Only Memory (ROM) subject to change by copying errors and accidents. In this review, I propose that we need to change that perspective and understand the genome as an intricately formatted Read-Write (RW) data storage system constantly subject to cellular modifications and inscriptions. Cells operate under changing conditions and are continually modifying themselves by genome inscriptions. These inscriptions occur over three distinct time-scales (cell reproduction, multicellular development and evolutionary change) and involve a variety of different processes at each time scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA sequence structure). Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences. © 2013 Elsevier B.V. All rights reserved.

Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency.

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Bhargava, Ragini; Carson, Caree R; Lee, Gabriella; Stark, Jeremy M

2017-01-24

A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation. We developed a reporter in mouse cells for a 0.4-Mbp deletion rearrangement that is formed by EJ between two DSBs induced by the Cas9 endonuclease. We found that disruption of the ATM kinase causes an increase in the frequency of the rearrangement as well as a shift toward rearrangement junctions that show hallmarks of C-NHEJ. Furthermore, ATM suppresses rearrangement formation in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expression of the 3' exonuclease Trex2). Finally, several C-NHEJ factors are required for the increase in rearrangement frequency caused by inhibition of the ATM kinase. We also examined ATM effectors and found that H2AX shows a similar influence as ATM, whereas the influence of ATM on this rearrangement seems independent of 53BP1. We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rearrangement is enhanced in ATM-deficient cells.

Ionization-induced rearrangement of defects in silicon

International Nuclear Information System (INIS)

Vinetskij, V.L.; Manojlo, M.A.; Matvijchuk, A.S.; Strikha, V.I.; Kholodar', G.A.

1988-01-01

Ionizing factor effect on defect rearrangement in silicon including centers with deep local electron levels in the p-n-transition region is considered. Deep center parameters were determined using non-steady-state capacity spectroscopy of deep levels (NCDLS) method. NCDLS spectrum measurement was performed using source p + -n - diodes and after their irradiation with 15 keV energy electrons or laser pulses. It is ascertained that in silicon samples containing point defect clusters defect rearrangement under ionizing factor effect takes place, i.e. deep level spectra are changed. This mechanism is efficient in case of silicon irradiation with subthreshold energy photons and electrons and can cause degradation of silicon semiconducting structures

Second generation sequencing of the mesothelioma tumor genome.

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Raphael Bueno

2010-05-01

Full Text Available The current paradigm for elucidating the molecular etiology of cancers relies on the interrogation of small numbers of genes, which limits the scope of investigation. Emerging second-generation massively parallel DNA sequencing technologies have enabled more precise definition of the cancer genome on a global scale. We examined the genome of a human primary malignant pleural mesothelioma (MPM tumor and matched normal tissue by using a combination of sequencing-by-synthesis and pyrosequencing methodologies to a 9.6X depth of coverage. Read density analysis uncovered significant aneuploidy and numerous rearrangements. Method-dependent informatics rules, which combined the results of different sequencing platforms, were developed to identify and validate candidate mutations of multiple types. Many more tumor-specific rearrangements than point mutations were uncovered at this depth of sequencing, resulting in novel, large-scale, inter- and intra-chromosomal deletions, inversions, and translocations. Nearly all candidate point mutations appeared to be previously unknown SNPs. Thirty tumor-specific fusions/translocations were independently validated with PCR and Sanger sequencing. Of these, 15 represented disrupted gene-encoding regions, including kinases, transcription factors, and growth factors. One large deletion in DPP10 resulted in altered transcription and expression of DPP10 transcripts in a set of 53 additional MPM tumors correlated with survival. Additionally, three point mutations were observed in the coding regions of NKX6-2, a transcription regulator, and NFRKB, a DNA-binding protein involved in modulating NFKB1. Several regions containing genes such as PCBD2 and DHFR, which are involved in growth factor signaling and nucleotide synthesis, respectively, were selectively amplified in the tumor. Second-generation sequencing uncovered all types of mutations in this MPM tumor, with DNA rearrangements representing the dominant type.

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

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Sebastian Krüger

2014-01-01

Full Text Available This review summarizes the application of the divinylcyclopropane–cycloheptadiene rearrangement in synthetic organic chemistry. A brief overview of the new mechanistic insights concerning the title reaction is provided as well as a condensed account on the biological relevance of the topic. Heteroatom variants of this rearrangement are covered briefly.

A second generation genetic map of the bumblebee Bombus terrestris (Linnaeus, 1758 reveals slow genome and chromosome evolution in the Apidae

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Kube Michael

2011-01-01

Full Text Available Abstract Background The bumblebee Bombus terrestris is an ecologically and economically important pollinator and has become an important biological model system. To study fundamental evolutionary questions at the genomic level, a high resolution genetic linkage map is an essential tool for analyses ranging from quantitative trait loci (QTL mapping to genome assembly and comparative genomics. We here present a saturated linkage map and match it with the Apis mellifera genome using homologous markers. This genome-wide comparison allows insights into structural conservations and rearrangements and thus the evolution on a chromosomal level. Results The high density linkage map covers ~ 93% of the B. terrestris genome on 18 linkage groups (LGs and has a length of 2'047 cM with an average marker distance of 4.02 cM. Based on a genome size of ~ 430 Mb, the recombination rate estimate is 4.76 cM/Mb. Sequence homologies of 242 homologous markers allowed to match 15 B. terrestris with A. mellifera LGs, five of them as composites. Comparing marker orders between both genomes we detect over 14% of the genome to be organized in synteny and 21% in rearranged blocks on the same homologous LG. Conclusions This study demonstrates that, despite the very high recombination rates of both A. mellifera and B. terrestris and a long divergence time of about 100 million years, the genomes' genetic architecture is highly conserved. This reflects a slow genome evolution in these bees. We show that data on genome organization and conserved molecular markers can be used as a powerful tool for comparative genomics and evolutionary studies, opening up new avenues of research in the Apidae.

Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

DEFF Research Database (Denmark)

Richards, Stephen; Liu, Yue; Bettencourt, Brian R.

2005-01-01

years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences......We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each...... between the species-but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence...

Identification of mitochondrial carriers in Saccharomyces cerevisiae by transport assay of reconstituted recombinant proteins.

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Palmieri, Ferdinando; Agrimi, Gennaro; Blanco, Emanuela; Castegna, Alessandra; Di Noia, Maria A; Iacobazzi, Vito; Lasorsa, Francesco M; Marobbio, Carlo M T; Palmieri, Luigi; Scarcia, Pasquale; Todisco, Simona; Vozza, Angelo; Walker, John

2006-01-01

The inner membranes of mitochondria contain a family of carrier proteins that are responsible for the transport in and out of the mitochondrial matrix of substrates, products, co-factors and biosynthetic precursors that are essential for the function and activities of the organelle. This family of proteins is characterized by containing three tandem homologous sequence repeats of approximately 100 amino acids, each folded into two transmembrane alpha-helices linked by an extensive polar loop. Each repeat contains a characteristic conserved sequence. These features have been used to determine the extent of the family in genome sequences. The genome of Saccharomyces cerevisiae contains 34 members of the family. The identity of five of them was known before the determination of the genome sequence, but the functions of the remaining family members were not. This review describes how the functions of 15 of these previously unknown transport proteins have been determined by a strategy that consists of expressing the genes in Escherichia coli or Saccharomyces cerevisiae, reconstituting the gene products into liposomes and establishing their functions by transport assay. Genetic and biochemical evidence as well as phylogenetic considerations have guided the choice of substrates that were tested in the transport assays. The physiological roles of these carriers have been verified by genetic experiments. Various pieces of evidence point to the functions of six additional members of the family, but these proposals await confirmation by transport assay. The sequences of many of the newly identified yeast carriers have been used to characterize orthologs in other species, and in man five diseases are presently known to be caused by defects in specific mitochondrial carrier genes. The roles of eight yeast mitochondrial carriers remain to be established.

Comparative analysis of the mitochondrial genomes in gastropods

International Nuclear Information System (INIS)

Arquez, Moises; Uribe, Juan Esteban; Castro, Lyda Raquel

2012-01-01

In this work we presented a comparative analysis of the mitochondrial genomes in gastropods. Nucleotide and amino acids composition was calculated and a comparative visual analysis of the start and termination codons was performed. The organization of the genome was compared calculating the number of intergenic sequences, the location of the genes and the number of reorganized genes (breakpoints) in comparison with the sequence that is presumed to be ancestral for the group. In order to calculate variations in the rates of molecular evolution within the group, the relative rate test was performed. In spite of the differences in the size of the genomes, the amino acids number is conserved. The nucleotide and amino acid composition is similar between Vetigastropoda, Ceanogastropoda and Neritimorpha in comparison to Heterobranchia and Patellogastropoda. The mitochondrial genomes of the group are very compact with few intergenic sequences, the only exception is the genome of Patellogastropoda with 26,828 bp. Start codons of the Heterobranchia and Patellogastropoda are very variable and there is also an increase in genome rearrangements for these two groups. Generally, the hypothesis of constant rates of molecular evolution between the groups is rejected, except when the genomes of Caenogastropoda and Vetigastropoda are compared.

Telomere Length Dynamics and the Evolution of Cancer Genome Architecture

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Kez Cleal

2018-02-01

Full Text Available Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci. The consequences of telomere fusions in promoting genome instability have long been appreciated through the breakage–fusion–bridge (BFB cycle mechanism, although recent studies using high-throughput sequencing technologies have uncovered evidence of involvement in a wider spectrum of genomic rearrangements including chromothripsis. A critical step in cancer progression is the transition of a clone to immortality, through the stabilisation of the telomere repeat array. This can be achieved via the reactivation of telomerase, or the induction of the alternative lengthening of telomeres (ALT pathway. Whilst telomere dysfunction may promote genome instability and tumour progression, by limiting the replicative potential of a cell and enforcing senescence, telomere shortening can act as a tumour suppressor mechanism. However, the burden of senescent cells has also been implicated as a driver of ageing and age-related pathology, and in the promotion of cancer through inflammatory signalling. Considering the critical role of telomere length in governing cancer biology, we review questions related to the prognostic value of studying the dynamics of telomere shortening and fusion, and discuss mechanisms and consequences of telomere-induced genome rearrangements.

Gene arrangement and sequence of mitochondrial genomes yield insights into the phylogeny and evolution of bees and sphecid wasps (Hymenoptera: Apoidea).

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Zheng, Bo-Ying; Cao, Li-Jun; Tang, Pu; van Achterberg, Kees; Hoffmann, Ary A; Chen, Hua-Yan; Chen, Xue-Xin; Wei, Shu-Jun

2018-07-01

The Apoidea represent a large and common superfamily of the Hymenoptera including the bees and sphecid wasps. A robust phylogenetic tree is essential to understanding the diversity, taxonomy and evolution of the Apoidea. In this study, features of apoid mitochondrial genomes were used to reconstruct phylogenetic relationships. Twelve apoid mitochondrial genomes were newly sequenced, representing six families and nine subfamilies. Gene rearrangement events have occurred in all apoid mitochondrial genomes sequenced to date. Sphecid wasps have both tRNA and protein-coding gene rearrangements in 5 of 8 species. In bees, the only rearranged genes are tRNAs; long-tongued bees (Apidae + Megachilidae) are characterized by movement of trnA to the trnI-trnQ-trnM tRNA cluster. Phylogenetic analyses of mitochondrial gene sequences support the known paraphyly of sphecid wasps, with bees nested within this clade. The Ampulicidae is sister to the remaining Apoidea. Crabronidae is paraphyletic, split into Crabronidae s.s. and Philanthidae, with the latter group a sister clade to bees. The monophyletic bees are either classified into two clades, long-tongued bees (Apidae + Megachilidae) and short-tongued bees (Andrenidae + Halictidae + Colletidae + Melitidae), or three groups with the Melitidae sister to the other bees. Our study showed that both gene sequences and arrangements provide information on the phylogeny of apoid families. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamic Evolution of the Chloroplast Genome in the Green Algal Classes Pedinophyceae and Trebouxiophyceae.

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Turmel, Monique; Otis, Christian; Lemieux, Claude

2015-07-01

Previous studies of trebouxiophycean chloroplast genomes revealed little information regarding the evolutionary dynamics of this genome because taxon sampling was too sparse and the relationships between the sampled taxa were unknown. We recently sequenced the chloroplast genomes of 27 trebouxiophycean and 2 pedinophycean green algae to resolve the relationships among the main lineages recognized for the Trebouxiophyceae. These taxa and the previously sampled members of the Pedinophyceae and Trebouxiophyceae are included in the comparative chloroplast genome analysis we report here. The 38 genomes examined display considerable variability at all levels, except gene content. Our results highlight the high propensity of the rDNA-containing large inverted repeat (IR) to vary in size, gene content and gene order as well as the repeated losses it experienced during trebouxiophycean evolution. Of the seven predicted IR losses, one event demarcates a superclade of 11 taxa representing 5 late-diverging lineages. IR expansions/contractions account not only for changes in gene content in this region but also for changes in gene order and gene duplications. Inversions also led to gene rearrangements within the IR, including the reversal or disruption of the rDNA operon in some lineages. Most of the 20 IR-less genomes are more rearranged compared with their IR-containing homologs and tend to show an accelerated rate of sequence evolution. In the IR-less superclade, several ancestral operons were disrupted, a few genes were fragmented, and a subgroup of taxa features a G+C-biased nucleotide composition. Our analyses also unveiled putative cases of gene acquisitions through horizontal transfer. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

[Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement].

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Caliez, J; Monnet, I; Pujals, A; Rousseau-Bussac, G; Jabot, L; Boudjemaa, A; Leroy, K; Chouaid, C

2017-05-01

Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly. A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later. The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI. Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Short-term genome evolution of Listeria monocytogenes in a non-controlled environment

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Ivy Reid A

2008-11-01

Full Text Available Abstract Background While increasing data on bacterial evolution in controlled environments are available, our understanding of bacterial genome evolution in natural environments is limited. We thus performed full genome analyses on four Listeria monocytogenes, including human and food isolates from both a 1988 case of sporadic listeriosis and a 2000 listeriosis outbreak, which had been linked to contaminated food from a single processing facility. All four isolates had been shown to have identical subtypes, suggesting that a specific L. monocytogenes strain persisted in this processing plant over at least 12 years. While a genome sequence for the 1988 food isolate has been reported, we sequenced the genomes of the 1988 human isolate as well as a human and a food isolate from the 2000 outbreak to allow for comparative genome analyses. Results The two L. monocytogenes isolates from 1988 and the two isolates from 2000 had highly similar genome backbone sequences with very few single nucleotide (nt polymorphisms (1 – 8 SNPs/isolate; confirmed by re-sequencing. While no genome rearrangements were identified in the backbone genome of the four isolates, a 42 kb prophage inserted in the chromosomal comK gene showed evidence for major genome rearrangements. The human-food isolate pair from each 1988 and 2000 had identical prophage sequence; however, there were significant differences in the prophage sequences between the 1988 and 2000 isolates. Diversification of this prophage appears to have been caused by multiple homologous recombination events or possibly prophage replacement. In addition, only the 2000 human isolate contained a plasmid, suggesting plasmid loss or acquisition events. Surprisingly, besides the polymorphisms found in the comK prophage, a single SNP in the tRNA Thr-4 prophage represents the only SNP that differentiates the 1988 isolates from the 2000 isolates. Conclusion Our data support the hypothesis that the 2000 human listeriosis

The He+H¯→He p¯+e+ rearrangement

Science.gov (United States)

Todd, Allan C.; Armour, Edward A. G.

2006-06-01

In this paper, we present a summary of our work in progress on calculating cross sections for the He+H¯→He p¯+e+ rearrangement process in He H¯ scattering. This has involved a study of the system He p¯ within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H¯ entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049].

The He+H-bar → Hep-bar +e+ rearrangement

International Nuclear Information System (INIS)

Todd, Allan C.; Armour, Edward A.G.

2006-01-01

In this paper, we present a summary of our work in progress on calculating cross sections for the He+H-bar ->Hep-bar +e + rearrangement process in HeH-bar scattering. This has involved a study of the system Hep-bar within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H-bar entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049

Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

1987-01-01

The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

Triisobutylaluminium (TIBAL Promoted Rearrangement of C-glycosides

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P. Sinay

2005-08-01

Full Text Available Triisobutylaluminium-promoted rearrangement of unsaturated glycosides containing electron-donating aglycons, such as C-aryl glycosides, provides direct access to highly functionalised cyclohexane derivatives.

Complete mitochondrial genome of the monogonont rotifer, Brachionus koreanus (Rotifera, Brachionidae).

Science.gov (United States)

Hwang, Dae-Sik; Suga, Koushirou; Sakakura, Yoshitaka; Park, Heum Gi; Hagiwara, Atsushi; Rhee, Jae-Sung; Lee, Jae-Seong

2014-02-01

The complete mitochondrial genome was obtained from the assembled genome data sequenced by next generation sequencing (NGS) technology from the monogonont rotifer Brachionus koreanus. The mitochondrial genome of B. koreanus was composed of two circular chromosomes designated as mtDNA-I (10,421 bp) and mtDNA-II (11,923 bp). The gene contents of B. koreanus were identical with previously reported B. plicatilis mitochondrial genomes. However, gene orders of B. koreanus showed one rearrangement between the two species. Of 12 protein-coding genes (PCGs), 3 genes (ATP6, ND1, and ND3) had an incomplete stop codon. The A + T base composition of B. koreanus mitochondrial genome was high (68.81%). They also showed anti-G bias (12.03% and 10.97%) on the second and third position of PCGs as well as slight anti-C bias (15.96% and 14.31%) on the first and third position of PCGs.

Quantifying stretching and rearrangement in epithelial sheet migration

International Nuclear Information System (INIS)

Lee, Rachel M; Nordstrom, Kerstin N; Losert, Wolfgang; Kelley, Douglas H; Ouellette, Nicholas T

2013-01-01

Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a finite-time Lyapunov exponent (FTLE) analysis, we find that—in spite of large fluctuations—the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e. positive FTLE) is localized at the leading edge of migration and increases when the cells are more highly stimulated. By decomposing the motion of the cells into affine and non-affine components using the metric D m in 2 , we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearrangements with increasing density. (paper)

Complete Genome Sequence of the Soybean Symbiont Bradyrhizobium japonicum Strain USDA6T

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Nobukazu Uchiike

2011-10-01

Full Text Available The complete nucleotide sequence of the genome of the soybean symbiont Bradyrhizobium japonicum strain USDA6T was determined. The genome of USDA6T is a single circular chromosome of 9,207,384 bp. The genome size is similar to that of the genome of another soybean symbiont, B. japonicum USDA110 (9,105,828 bp. Comparison of the whole-genome sequences of USDA6T and USDA110 showed colinearity of major regions in the two genomes, although a large inversion exists between them. A significantly high level of sequence conservation was detected in three regions on each genome. The gene constitution and nucleotide sequence features in these three regions indicate that they may have been derived from a symbiosis island. An ancestral, large symbiosis island, approximately 860 kb in total size, appears to have been split into these three regions by unknown large-scale genome rearrangements. The two integration events responsible for this appear to have taken place independently, but through comparable mechanisms, in both genomes.

Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes.

Science.gov (United States)

Mignon-Ravix, Cécile; Cacciagli, Pierre; Choucair, Nancy; Popovici, Cornel; Missirian, Chantal; Milh, Mathieu; Mégarbané, André; Busa, Tiffany; Julia, Sophie; Girard, Nadine; Badens, Catherine; Sigaudy, Sabine; Philip, Nicole; Villard, Laurent

2014-08-01

High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the identification of new disease genes. We report on the analysis of 54 male patients presenting with intellectual deficiency (ID) and a family history suggesting X-linked (XL) inheritance or maternal skewed X-chromosome inactivation (XCI), using a home-made X-chromosome-specific microarray covering the whole human X-chromosome at high resolution. The majority of patients had whole genome array-CGH prior to the selection and we did not include large rearrangements such as MECP2 and FMR1 duplications. We identified four rearrangements considered as causative or potentially pathogenic, corresponding to a detection rate of 8%. Two CNVs affected known XLID genes and were therefore considered as causative (IL1RAPL1 and OPHN1 intragenic deletions). Two new CNVs were considered as potentially pathogenic as they affected interesting candidates for ID. The first CNV is a deletion of the first exon of the TRPC5 gene, encoding a cation channel implicated in dendrite growth and patterning, in a child presenting with ID and an autism spectrum disorder (ASD). The second CNV is a partial deletion of KLHL15, in a patient with severe ID, epilepsy, and anomalies of cortical development. In both cases, in spite of strong arguments for clinical relevance, we were not able at this stage to confirm pathogenicity of the mutations, and the causality of the variants identified in XLID remains to be confirmed. © 2014 Wiley Periodicals, Inc.

Nothing in Evolution Makes Sense Except in the Light of Genomics: Read–Write Genome Evolution as an Active Biological Process

Directory of Open Access Journals (Sweden)

James A. Shapiro

2016-06-01

Full Text Available The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess “Read–Write Genomes” they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.

Improved de novo genomic assembly for the domestic donkey

Science.gov (United States)

Newton, Richard; Paillot, Romain; Bryant, Neil; Vaudin, Mark

2018-01-01

Donkeys and horses share a common ancestor dating back to about 4 million years ago. Although a high-quality genome assembly at the chromosomal level is available for the horse, current assemblies available for the donkey are limited to moderately sized scaffolds. The absence of a better-quality assembly for the donkey has hampered studies involving the characterization of patterns of genetic variation at the genome-wide scale. These range from the application of genomic tools to selective breeding and conservation to the more fundamental characterization of the genomic loci underlying speciation and domestication. We present a new high-quality donkey genome assembly obtained using the Chicago HiRise assembly technology, providing scaffolds of subchromosomal size. We make use of this new assembly to obtain more accurate measures of heterozygosity for equine species other than the horse, both genome-wide and locally, and to detect runs of homozygosity potentially pertaining to positive selection in domestic donkeys. Finally, this new assembly allowed us to identify fine-scale chromosomal rearrangements between the horse and the donkey that likely played an active role in their divergence and, ultimately, speciation. PMID:29740610

Comparative genomic analysis by microbial COGs self-attraction rate.

Science.gov (United States)

Santoni, Daniele; Romano-Spica, Vincenzo

2009-06-21

Whole genome analysis provides new perspectives to determine phylogenetic relationships among microorganisms. The availability of whole nucleotide sequences allows different levels of comparison among genomes by several approaches. In this work, self-attraction rates were considered for each cluster of orthologous groups of proteins (COGs) class in order to analyse gene aggregation levels in physical maps. Phylogenetic relationships among microorganisms were obtained by comparing self-attraction coefficients. Eighteen-dimensional vectors were computed for a set of 168 completely sequenced microbial genomes (19 archea, 149 bacteria). The components of the vector represent the aggregation rate of the genes belonging to each of 18 COGs classes. Genes involved in nonessential functions or related to environmental conditions showed the highest aggregation rates. On the contrary genes involved in basic cellular tasks showed a more uniform distribution along the genome, except for translation genes. Self-attraction clustering approach allowed classification of Proteobacteria, Bacilli and other species belonging to Firmicutes. Rearrangement and Lateral Gene Transfer events may influence divergences from classical taxonomy. Each set of COG classes' aggregation values represents an intrinsic property of the microbial genome. This novel approach provides a new point of view for whole genome analysis and bacterial characterization.

Improved de novo genomic assembly for the domestic donkey.

Science.gov (United States)

Renaud, Gabriel; Petersen, Bent; Seguin-Orlando, Andaine; Bertelsen, Mads Frost; Waller, Andrew; Newton, Richard; Paillot, Romain; Bryant, Neil; Vaudin, Mark; Librado, Pablo; Orlando, Ludovic

2018-04-01

Donkeys and horses share a common ancestor dating back to about 4 million years ago. Although a high-quality genome assembly at the chromosomal level is available for the horse, current assemblies available for the donkey are limited to moderately sized scaffolds. The absence of a better-quality assembly for the donkey has hampered studies involving the characterization of patterns of genetic variation at the genome-wide scale. These range from the application of genomic tools to selective breeding and conservation to the more fundamental characterization of the genomic loci underlying speciation and domestication. We present a new high-quality donkey genome assembly obtained using the Chicago HiRise assembly technology, providing scaffolds of subchromosomal size. We make use of this new assembly to obtain more accurate measures of heterozygosity for equine species other than the horse, both genome-wide and locally, and to detect runs of homozygosity potentially pertaining to positive selection in domestic donkeys. Finally, this new assembly allowed us to identify fine-scale chromosomal rearrangements between the horse and the donkey that likely played an active role in their divergence and, ultimately, speciation.

Input-output rearrangement of isolated converters

DEFF Research Database (Denmark)

Madsen, Mickey Pierre; Kovacevic, Milovan; Mønster, Jakob Døllner

2015-01-01

This paper presents a new way of rearranging the input and output of isolated converters. The new arrangement posses several advantages, as increased voltage range, higher power handling capabilities, reduced voltage stress and improved efficiency, for applications where galvanic isolation...

Behavior of restriction–modification systems as selfish mobile elements and their impact on genome evolution

Science.gov (United States)

Kobayashi, Ichizo

2001-01-01

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

Science.gov (United States)

Kobayashi, I

2001-09-15

Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and

Understanding the direction of evolution in Burkholderia glumae through comparative genomics.

Science.gov (United States)

Lee, Hyun-Hee; Park, Jungwook; Kim, Jinnyun; Park, Inmyoung; Seo, Young-Su

2016-02-01

Members of the genus Burkholderia occupy remarkably diverse niches, with genome sizes ranging from ~3.75 to 11.29 Mbp. The genome of Burkholderia glumae ranges in size from ~5.81 to 7.89 Mbp. Unlike other plant pathogenic bacteria, B. glumae can infect a wide range of monocot and dicot plants. Comparative genome analysis of B. glumae strains can provide insight into genome variation as well as differential features of whole metabolism or pathways between multiple strains of B. glumae infecting the same host. Comparative analysis of complete genomes among B. glumae BGR1, B. glumae LMG 2196, and B. glumae PG1 revealed the largest departmentalization of genes onto separate replicons in B. glumae BGR1 and considerable downsizing of the genome in B. glumae LMG 2196. In addition, the presence of large-scale evolutionary events such as rearrangement and inversion and the development of highly specialized systems were found to be related to virulence-associated features in the three B. glumae strains. This connection may explain why this bacterium broadens its host range and reinforces its interaction with hosts.

Generalization of the quark rearrangement model

International Nuclear Information System (INIS)

Fields, T.; Chen, C.K.

1976-01-01

An extension and generalization of the quark rearrangement model of baryon annihilation is described which can be applied to all annihilation reactions and which incorporates some of the features of the highly successful quark parton model. Some p anti-p interactions are discussed

The Complete Sequence of the Mitochondrial Genome of the Chamberednautilus (Mollusca: Cephalopoda)

Energy Technology Data Exchange (ETDEWEB)

Boore, Jeffrey L.

2005-12-01

Background: Mitochondria contain small genomes that arephysically separate from those of nuclei. Their comparison serves as amodel system for understanding the processes of genome evolution.Although complete mitochondrial genome sequences have been reported formore than 600 animals, the taxonomic sampling is highly biased towardvertebrates and arthropods, leaving much of the diversity yetuncharacterized. Results: The mitochondrial genome of a cephalopodmollusk, the Chambered Nautilus, is 16,258 nts in length and 59.5 percentA+T, both values that are typical of animal mitochondrial genomes. Itcontains the 37 genes that are typical for animal mtDNAs, with 15 on oneDNA strand and 22 on the other. The arrangement of these genes can bederived from that of the distantly related Katharina tunicata (Mollusca:Polyplacophora) by a switch in position of two large blocks of genes andtranspositions of four tRNA genes. There is strong skew in thedistribution of nucleotides between the two strands. There are an unusualnumber of non-coding regions and their function, if any, is not known;however, several of these demark abrupt shifts in nucleotide skew,suggesting that they may play roles in transcription and/or replication.One of the non-coding regions contains multiple repeats of a tRNA-likesequence. Some of the tRNA genes appear to overlap on the same strand,but this could be resolved if the polycistron were cleaved at thebeginning of the downstream gene, followed by polyadenylation of theproduct of the upstream gene to form a fully paired structure.Conclusions: Nautilus sp. mtDNA contains an expected gene content thathas experienced few rearrangements since the evolutionary split betweencephalopods and polyplacophorans. It contains an unusual number ofnon-coding regions, especially considering that these otherwise often aregenerated by the same processes that produce gene rearrangements. Thisappears to be yet another case where polyadenylation of mitochondrialtRNAs restores

Hexose rearrangements upon fragmentation of N-glycopeptides and reductively aminated N-glycans.

Science.gov (United States)

Wuhrer, Manfred; Koeleman, Carolien A M; Deelder, André M

2009-06-01

Tandem mass spectrometry of glycans and glycoconjugates in protonated form is known to result in rearrangement reactions leading to internal residue loss. Here we studied the occurrence of hexose rearrangements in tandem mass spectrometry of N-glycopeptides and reductively aminated N-glycans by MALDI-TOF/TOF-MS/MS and ESI-ion trap-MS/MS. Fragmentation of proton adducts of oligomannosidic N-glycans of ribonuclease B that were labeled with 2-aminobenzamide and 2-aminobenzoic acid resulted in transfer of one to five hexose residues to the fluorescently tagged innermost N-acetylglucosamine. Glycopeptides from various biological sources with oligomannosidic glycans were likewise shown to undergo hexose rearrangement reactions, resulting in chitobiose cleavage products that have acquired one or two hexose moieties. Tryptic immunoglobulin G Fc-glycopeptides with biantennary N-glycans likewise showed hexose rearrangements resulting in hexose transfer to the peptide moiety retaining the innermost N-acetylglucosamine. Thus, as a general phenomenon, tandem mass spectrometry of reductively aminated glycans as well as glycopeptides may result in hexose rearrangements. This characteristic of glycopeptide MS/MS has to be considered when developing tools for de novo glycopeptide structural analysis.

Looking for Broken TAD Boundaries and Changes on DNA Interactions: Clinical Guide to 3D Chromatin Change Analysis in Complex Chromosomal Rearrangements and Chromothripsis.

Science.gov (United States)

Yauy, Kevin; Gatinois, Vincent; Guignard, Thomas; Sati, Satish; Puechberty, Jacques; Gaillard, Jean Baptiste; Schneider, Anouck; Pellestor, Franck

2018-01-01

Apparition of next-generation sequencing (NGS) was a breakthrough on knowledge of genome structure. Bioinformatic tools are a key point to analyze this huge amount of data from NGS and characterize the three-dimensional organization of chromosomes. This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. Their pathogenic impact on clinical phenotype and gene misexpression can also be evaluated with annotated databases.

The complete mitochondrial genome of the enigmatic bigheadedturtle (Platysternon): description of unusual genomic features and thereconciliation of phylogenetic hypotheses based on mitochondrial andnuclear DNA

Energy Technology Data Exchange (ETDEWEB)

Parham, James F.; Feldman, Chris R.; Boore, Jeffrey L.

2005-12-28

The big-headed turtle (Platysternon megacephalum) from east Asia is the sole living representative of a poorly-studied turtle lineage (Platysternidae). It has no close living relatives, and its phylogenetic position within turtles is one of the outstanding controversies in turtle systematics. Platysternon was traditionally considered to be close to snapping turtles (Chelydridae) based on some studies of its morphology and mitochondrial (mt) DNA, however, other studies of morphology and nuclear (nu) DNA do not support that hypothesis. We sequenced the complete mt genome of Platysternon and the nearly complete mt genomes of two other relevant turtles and compared them to turtle mt genomes from the literature to form the largest molecular dataset used to date to address this issue. The resulting phylogeny robustly rejects the placement of Platysternon with Chelydridae, but instead shows that it is a member of the Testudinoidea, a diverse, nearly globally-distributed group that includes pond turtles and tortoises. We also discovered that Platysternon mtDNA has large-scale gene rearrangements and possesses two, nearly identical, control regions, features that distinguish it from all other studied turtles. Our study robustly determines the phylogenetic placement of Platysternon and provides a well-resolved outline of major turtle lineages, while demonstrating the significantly greater resolving power of comparing large amounts of mt sequence over that of short fragments. Earlier phylogenies placing Platysternon with chelydrids required a temporal gap in the fossil record that is now unnecessary. The duplicated control regions and gene rearrangements of the Platysternon mt DNA probably resulted from the duplication of part of the genome and then the subsequent loss of redundant genes. Although it is possible that having two control regions may provide some advantage, explaining why the control regions would be maintained while some of the duplicated genes were eroded

Whole genomes redefine the mutational landscape of pancreatic cancer

OpenAIRE

Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.

2015-01-01

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (...

A Prediction Model for ROS1-Rearranged Lung Adenocarcinomas based on Histologic Features

OpenAIRE

Zhou, Jianya; Zhao, Jing; Zheng, Jing; Kong, Mei; Sun, Ke; Wang, Bo; Chen, Xi; Ding, Wei; Zhou, Jianying

2016-01-01

Aims To identify the clinical and histological characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) and build a prediction model to prescreen suitable patients for molecular testing. Methods and Results We identified 27 cases of ROS1-rearranged lung adenocarcinomas in 1165 patients with NSCLCs confirmed by real-time PCR and FISH and performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement and finally developed predi...

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

OpenAIRE

Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Shen, Joseph; Li, Chumei; Roeder, Elizabeth; Cox, Sarah; Karaviti, Lefkothea; Pearson, Margret; Kang, Sung-Hae L; Sahoo, Trilochan; Lalani, Seema R; Stankiewicz, Pawel; Sutton, V Reid; Cheung, Sau Wai

2009-01-01

Deletions in chromosome 17q12 encompassing the HNF1β gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with a...

Study on the effect of paclitaxel nanostructure lipid carrier cooperated with radiation on the KB Cells

International Nuclear Information System (INIS)

Liu Min; Li Zhihui; Xu Yujie

2011-01-01

Objective: To investigate the cytotoxicity effect of paclitaxel nanostructure lipid carrier (TAX-NLC) cooperated with radiation treatment on the KB cells. Methods: The cytotoxicity effect of TAX-NLC compared with free paclitaxel (TAX) on the KB cells was measured by MTT assay, and the cell cycle distribution was analyzed by flow cytometry. Results: The cytotoxicity effect of TAX-NLC was stronger than that of the free TAX. And the cooperative effect between the TAX-NLC and ionized radiation were observed, the cooperative effect of TAX-NLC was stronger than that of the free TAX. Flow cytometric analysis indicated that the rearrangement of cell cycle in KB cells were induced by TAX-NLC. The more G2/M phase cells were observed in KB cells treated by TAX-NLC compared with free TAX. The effect of TAX-NLC in the rearrangement of cell cycle was stronger than that of the free TAX. Conclusion: The cytotoxicity effect of TAX-NLC is stronger than that of the free TAX. And the cooperative effect of TAX-NLC is stronger than that of the free TAX. (authors)

A multi-platform draft de novo genome assembly and comparative analysis for the Scarlet Macaw (Ara macao.

Directory of Open Access Journals (Sweden)

Christopher M Seabury

Full Text Available Data deposition to NCBI Genomes: This Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession AMXX00000000 (SMACv1.0, unscaffolded genome assembly. The version described in this paper is the first version (AMXX01000000. The scaffolded assembly (SMACv1.1 has been deposited at DDBJ/EMBL/GenBank under the accession AOUJ00000000, and is also the first version (AOUJ01000000. Strong biological interest in traits such as the acquisition and utilization of speech, cognitive abilities, and longevity catalyzed the utilization of two next-generation sequencing platforms to provide the first-draft de novo genome assembly for the large, new world parrot Ara macao (Scarlet Macaw. Despite the challenges associated with genome assembly for an outbred avian species, including 951,507 high-quality putative single nucleotide polymorphisms, the final genome assembly (>1.035 Gb includes more than 997 Mb of unambiguous sequence data (excluding N's. Cytogenetic analyses including ZooFISH revealed complex rearrangements associated with two scarlet macaw macrochromosomes (AMA6, AMA7, which supports the hypothesis that translocations, fusions, and intragenomic rearrangements are key factors associated with karyotype evolution among parrots. In silico annotation of the scarlet macaw genome provided robust evidence for 14,405 nuclear gene annotation models, their predicted transcripts and proteins, and a complete mitochondrial genome. Comparative analyses involving the scarlet macaw, chicken, and zebra finch genomes revealed high levels of nucleotide-based conservation as well as evidence for overall genome stability among the three highly divergent species. Application of a new whole-genome analysis of divergence involving all three species yielded prioritized candidate genes and noncoding regions for parrot traits of interest (i.e., speech, intelligence, longevity which were independently supported by the results of previous human GWAS

Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

Energy Technology Data Exchange (ETDEWEB)

O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

2010-08-19

Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds.

Science.gov (United States)

Dudchenko, Olga; Batra, Sanjit S; Omer, Arina D; Nyquist, Sarah K; Hoeger, Marie; Durand, Neva C; Shamim, Muhammad S; Machol, Ido; Lander, Eric S; Aiden, Aviva Presser; Aiden, Erez Lieberman

2017-04-07

The Zika outbreak, spread by the Aedes aegypti mosquito, highlights the need to create high-quality assemblies of large genomes in a rapid and cost-effective way. Here we combine Hi-C data with existing draft assemblies to generate chromosome-length scaffolds. We validate this method by assembling a human genome, de novo, from short reads alone (67× coverage). We then combine our method with draft sequences to create genome assemblies of the mosquito disease vectors Ae aegypti and Culex quinquefasciatus , each consisting of three scaffolds corresponding to the three chromosomes in each species. These assemblies indicate that almost all genomic rearrangements among these species occur within, rather than between, chromosome arms. The genome assembly procedure we describe is fast, inexpensive, and accurate, and can be applied to many species. Copyright © 2017, American Association for the Advancement of Science.

Impact of Lateral Transfers on the Genomes of Lepidoptera

Directory of Open Access Journals (Sweden)

Jean-Michel Drezen

2017-11-01

Full Text Available Transfer of DNA sequences between species regardless of their evolutionary distance is very common in bacteria, but evidence that horizontal gene transfer (HGT also occurs in multicellular organisms has been accumulating in the past few years. The actual extent of this phenomenon is underestimated due to frequent sequence filtering of “alien” DNA before genome assembly. However, recent studies based on genome sequencing have revealed, and experimentally verified, the presence of foreign DNA sequences in the genetic material of several species of Lepidoptera. Large DNA viruses, such as baculoviruses and the symbiotic viruses of parasitic wasps (bracoviruses, have the potential to mediate these transfers in Lepidoptera. In particular, using ultra-deep sequencing, newly integrated transposons have been identified within baculovirus genomes. Bacterial genes have also been acquired by genomes of Lepidoptera, as in other insects and nematodes. In addition, insertions of bracovirus sequences were present in the genomes of certain moth and butterfly lineages, that were likely corresponding to rearrangements of ancient integrations. The viral genes present in these sequences, sometimes of hymenopteran origin, have been co-opted by lepidopteran species to confer some protection against pathogens.

Endogenous retroviruses in fish genomes: from relics of past infections to evolutionary innovations?

Directory of Open Access Journals (Sweden)

Magali Naville

2016-08-01

Full Text Available The increasing availability of fish genome sequences has allowed to gain new insights into the diversity and host distribution of retroviruses in fish and other vertebrates. This distribution can be assessed through the identification and analysis of endogenous retroviruses, which are proviral remnants of past infections integrated in genomes. Retroviral sequences are probably important for evolution through their ability to induce rearrangements and to contribute regulatory and coding sequences; they may also protect their host against new infections. We argue that the current mass of genome sequences will soon strongly improve our understanding of retrovirus diversity and evolution in aquatic animals, with the identification of new/re-emerging elements and host resistance genes that restrict their infectivity.

Chromosomal Speciation in the Genomics Era: Disentangling Phylogenetic Evolution of Rock-wallabies.

Science.gov (United States)

Potter, Sally; Bragg, Jason G; Blom, Mozes P K; Deakin, Janine E; Kirkpatrick, Mark; Eldridge, Mark D B; Moritz, Craig

2017-01-01

The association of chromosome rearrangements (CRs) with speciation is well established, and there is a long history of theory and evidence relating to "chromosomal speciation." Genomic sequencing has the potential to provide new insights into how reorganization of genome structure promotes divergence, and in model systems has demonstrated reduced gene flow in rearranged segments. However, there are limits to what we can understand from a small number of model systems, which each only tell us about one episode of chromosomal speciation. Progressing from patterns of association between chromosome (and genic) change, to understanding processes of speciation requires both comparative studies across diverse systems and integration of genome-scale sequence comparisons with other lines of evidence. Here, we showcase a promising example of chromosomal speciation in a non-model organism, the endemic Australian marsupial genus Petrogale . We present initial phylogenetic results from exon-capture that resolve a history of divergence associated with extensive and repeated CRs. Yet it remains challenging to disentangle gene tree heterogeneity caused by recent divergence and gene flow in this and other such recent radiations. We outline a way forward for better integration of comparative genomic sequence data with evidence from molecular cytogenetics, and analyses of shifts in the recombination landscape and potential disruption of meiotic segregation and epigenetic programming. In all likelihood, CRs impact multiple cellular processes and these effects need to be considered together, along with effects of genic divergence. Understanding the effects of CRs together with genic divergence will require development of more integrative theory and inference methods. Together, new data and analysis tools will combine to shed light on long standing questions of how chromosome and genic divergence promote speciation.

Characterisation and expression of the mitochondrial genome of a new type of cytoplasmic male-sterile sunflower

NARCIS (Netherlands)

Spassova, Mariana; Moneger, Françoise; Leaver, Christopher J.; Petrov, Peter; Atanassov, Atanas; Nijkamp, H. John J.; Hille, Jacques

1994-01-01

A new cytoplasmic male sterile sunflower, CMS3, was characterised in relation to the Petiolaris (PET1) cytoplasmic male-sterile sunflower, CMS89. Southern blot analysis showed that the mitochondrial genome of CMS3 contains unique rearrangements in at least five loci (atp6, atp9, atpA, nad1 + 5 and

RECG maintains plastid and mitochondrial genome stability by suppressing extensive recombination between short dispersed repeats.

Directory of Open Access Journals (Sweden)

Masaki Odahara

2015-03-01

Full Text Available Maintenance of plastid and mitochondrial genome stability is crucial for photosynthesis and respiration, respectively. Recently, we have reported that RECA1 maintains mitochondrial genome stability by suppressing gross rearrangements induced by aberrant recombination between short dispersed repeats in the moss Physcomitrella patens. In this study, we studied a newly identified P. patens homolog of bacterial RecG helicase, RECG, some of which is localized in both plastid and mitochondrial nucleoids. RECG partially complements recG deficiency in Escherichia coli cells. A knockout (KO mutation of RECG caused characteristic phenotypes including growth delay and developmental and mitochondrial defects, which are similar to those of the RECA1 KO mutant. The RECG KO cells showed heterogeneity in these phenotypes. Analyses of RECG KO plants showed that mitochondrial genome was destabilized due to a recombination between 8-79 bp repeats and the pattern of the recombination partly differed from that observed in the RECA1 KO mutants. The mitochondrial DNA (mtDNA instability was greater in severe phenotypic RECG KO cells than that in mild phenotypic ones. This result suggests that mitochondrial genomic instability is responsible for the defective phenotypes of RECG KO plants. Some of the induced recombination caused efficient genomic rearrangements in RECG KO mitochondria. Such loci were sometimes associated with a decrease in the levels of normal mtDNA and significant decrease in the number of transcripts derived from the loci. In addition, the RECG KO mutation caused remarkable plastid abnormalities and induced recombination between short repeats (12-63 bp in the plastid DNA. These results suggest that RECG plays a role in the maintenance of both plastid and mitochondrial genome stability by suppressing aberrant recombination between dispersed short repeats; this role is crucial for plastid and mitochondrial functions.

Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

Science.gov (United States)

Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

2010-12-01

Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

Distribution of the various radiation-induced chromosomal rearrangements in relation to the dose and sampling time

International Nuclear Information System (INIS)

Dutrillaux, B.; Viegas-Pequignot, E.; Prod'homme, M.; Sportes, M.

1985-01-01

The quantitative analysis of the chromosome rearrangements detected in 2128 R-banded metaphases, obtained from γ-irradiated human lymphocytes after 48 to 96 h in culture is reported. Depending on the culture time, and possibly on the dose of radiation (from 1 to 3 Gy), the most frequent type of rearrangement was either dicentrics or reciprocal translocations. In first generation mitoses, the frequency of cells without rearrangement ranged from 0.66 to 0.18, and the mean number of rearranged chromosomes per cell from 0.79 to 3.28. The dose-response curve follows a quadratic function for dicentric aberration yields, but not for other rearrangements. (Auth.)

Long span DNA paired-end-tag (DNA-PET sequencing strategy for the interrogation of genomic structural mutations and fusion-point-guided reconstruction of amplicons.

Directory of Open Access Journals (Sweden)

Fei Yao

Full Text Available Structural variations (SVs contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET sequencing is an attractive approach to identify genomic SVs, the current application of PET sequencing with short insert size DNA can be insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We employed a recently developed procedure to generate PET sequencing data using large DNA inserts of 10-20 kb and compared their characteristics with short insert (1 kb libraries for their ability to identify SVs. Our results suggest that although short insert libraries bear an advantage in identifying small deletions, they do not provide significantly better breakpoint resolution. In contrast, large inserts are superior to short inserts in providing higher physical genome coverage for the same sequencing cost and achieve greater sensitivity, in practice, for the identification of several classes of SVs, such as copy number neutral and complex events. Furthermore, our results confirm that large insert libraries allow for the identification of SVs within repetitive sequences, which cannot be spanned by short inserts. This provides a key advantage in studying rearrangements in cancer, and we show how it can be used in a fusion-point-guided-concatenation algorithm to study focally amplified regions in cancer.

Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds

Directory of Open Access Journals (Sweden)

Janusz Nowicki

2000-08-01

Full Text Available A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrangements, sequential ("tandem" sigmatropic rearrangements and the "ene" reaction in the syntheses of flavour and fragrance compounds is presented.

Aligning the unalignable: bacteriophage whole genome alignments.

Science.gov (United States)

Bérard, Sèverine; Chateau, Annie; Pompidor, Nicolas; Guertin, Paul; Bergeron, Anne; Swenson, Krister M

2016-01-13

In recent years, many studies focused on the description and comparison of large sets of related bacteriophage genomes. Due to the peculiar mosaic structure of these genomes, few informative approaches for comparing whole genomes exist: dot plots diagrams give a mostly qualitative assessment of the similarity/dissimilarity between two or more genomes, and clustering techniques are used to classify genomes. Multiple alignments are conspicuously absent from this scene. Indeed, whole genome aligners interpret lack of similarity between sequences as an indication of rearrangements, insertions, or losses. This behavior makes them ill-prepared to align bacteriophage genomes, where even closely related strains can accomplish the same biological function with highly dissimilar sequences. In this paper, we propose a multiple alignment strategy that exploits functional collinearity shared by related strains of bacteriophages, and uses partial orders to capture mosaicism of sets of genomes. As classical alignments do, the computed alignments can be used to predict that genes have the same biological function, even in the absence of detectable similarity. The Alpha aligner implements these ideas in visual interactive displays, and is used to compute several examples of alignments of Staphylococcus aureus and Mycobacterium bacteriophages, involving up to 29 genomes. Using these datasets, we prove that Alpha alignments are at least as good as those computed by standard aligners. Comparison with the progressive Mauve aligner - which implements a partial order strategy, but whose alignments are linearized - shows a greatly improved interactive graphic display, while avoiding misalignments. Multiple alignments of whole bacteriophage genomes work, and will become an important conceptual and visual tool in comparative genomics of sets of related strains. A python implementation of Alpha, along with installation instructions for Ubuntu and OSX, is available on bitbucket (https://bitbucket.org/thekswenson/alpha).

Pyrophosphate as a central energy carrier in the hydrogen-producing extremely thermophilic Caldicellulosiruptor saccharolyticus

NARCIS (Netherlands)

Bielen, A.A.M.; Willquist, K.; Engman, J.; Oost, van der J.; Niel, van E.W.J.; Kengen, S.W.M.

2010-01-01

The role of inorganic pyrophosphate (PPi) as an energy carrier in the central metabolism of the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was investigated. In agreement with its annotated genome sequence, cell extracts were shown to exhibit PPi-dependent

Nuclear structure in cold rearrangement processes in fission and fusion

Energy Technology Data Exchange (ETDEWEB)

Armbruster, P.

1998-11-01

In fission and fusion of heavy nuclei large numbers of nucleons are rearranged at a scale of excitation energy very small compared to the binding energy of the nuclei. The energies involved are less than 40 MeV at nuclear temperatures below 1.5 MeV. The shapes of the configurations in the rearrangement of a binary system into a monosystem in fusion, or vice versa in fission, change their elongations by as much as 8 fm, the radius of the monosystem. The dynamics of the reactions macroscopically described by a potential energy surface, inertia parameters, dissipation, and a collision energy is strongly modified by the nuclear structure of the participating nuclei. Experiments showing nuclear structure effects in fusion and fission of the heaviest nuclei are reviewed. The reaction kinematics and the multitude of isotopes involved are investigated by detector techniques and by recoil spectrometers. The advancement of the latter allows to find very small reaction branches in the range of 10{sup -5} to 10{sup -10}. The experiments reveal nuclear structure effects in all stages of the rearrangement processes. These are discussed pointing to analogies in fusion and fission on the microscopic scale, notwithstanding that both processes macroscopically are irreversible. Heavy clusters, as 132Sn, 208Pb, nuclei with closed shell configurations N=82,126, Z=50,82 survive in large parts of the nuclear rearrangement. They determine the asymmetry in the mass distribution of low energy fission, and they allow to synthesise superheavy elements, until now up to element 112. Experiments on the cold rearrangement in fission and fusion are presented. Here, in the range of excitation energies below 12 MeV the phenomena are observed most convincingly. (orig.)

RTEL1 maintains genomic stability by suppressing homologous recombination.

Science.gov (United States)

Barber, Louise J; Youds, Jillian L; Ward, Jordan D; McIlwraith, Michael J; O'Neil, Nigel J; Petalcorin, Mark I R; Martin, Julie S; Collis, Spencer J; Cantor, Sharon B; Auclair, Melissa; Tissenbaum, Heidi; West, Stephen C; Rose, Ann M; Boulton, Simon J

2008-10-17

Homologous recombination (HR) is an important conserved process for DNA repair and ensures maintenance of genome integrity. Inappropriate HR causes gross chromosomal rearrangements and tumorigenesis in mammals. In yeast, the Srs2 helicase eliminates inappropriate recombination events, but the functional equivalent of Srs2 in higher eukaryotes has been elusive. Here, we identify C. elegans RTEL-1 as a functional analog of Srs2 and describe its vertebrate counterpart, RTEL1, which is required for genome stability and tumor avoidance. We find that rtel-1 mutant worms and RTEL1-depleted human cells share characteristic phenotypes with yeast srs2 mutants: lethality upon deletion of the sgs1/BLM homolog, hyperrecombination, and DNA damage sensitivity. In vitro, purified human RTEL1 antagonizes HR by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis. We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.

Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer.

Science.gov (United States)

Pailler, Emma; Adam, Julien; Barthélémy, Amélie; Oulhen, Marianne; Auger, Nathalie; Valent, Alexander; Borget, Isabelle; Planchard, David; Taylor, Melissa; André, Fabrice; Soria, Jean Charles; Vielh, Philippe; Besse, Benjamin; Farace, Françoise

2013-06-20

The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3'5') split pattern, and heterogeneous patterns (3'5', only 3') of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

Serendipitous discovery of Wolbachia genomes in multiple Drosophila species.

Science.gov (United States)

Salzberg, Steven L; Dunning Hotopp, Julie C; Delcher, Arthur L; Pop, Mihai; Smith, Douglas R; Eisen, Michael B; Nelson, William C

2005-01-01

The Trace Archive is a repository for the raw, unanalyzed data generated by large-scale genome sequencing projects. The existence of this data offers scientists the possibility of discovering additional genomic sequences beyond those originally sequenced. In particular, if the source DNA for a sequencing project came from a species that was colonized by another organism, then the project may yield substantial amounts of genomic DNA, including near-complete genomes, from the symbiotic or parasitic organism. By searching the publicly available repository of DNA sequencing trace data, we discovered three new species of the bacterial endosymbiont Wolbachia pipientis in three different species of fruit fly: Drosophila ananassae, D. simulans, and D. mojavensis. We extracted all sequences with partial matches to a previously sequenced Wolbachia strain and assembled those sequences using customized software. For one of the three new species, the data recovered were sufficient to produce an assembly that covers more than 95% of the genome; for a second species the data produce the equivalent of a 'light shotgun' sampling of the genome, covering an estimated 75-80% of the genome; and for the third species the data cover approximately 6-7% of the genome. The results of this study reveal an unexpected benefit of depositing raw data in a central genome sequence repository: new species can be discovered within this data. The differences between these three new Wolbachia genomes and the previously sequenced strain revealed numerous rearrangements and insertions within each lineage and hundreds of novel genes. The three new genomes, with annotation, have been deposited in GenBank.

Chromosome-specific staining to detect genetic rearrangements

Energy Technology Data Exchange (ETDEWEB)

Gray, Joe W.; Pinkel, Daniel; Tkachuk, Douglas; Westbrook, Carol

2013-04-09

Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

The molecular genetic makeup of acute lymphoblastic leukemia | Office of Cancer Genomics

Science.gov (United States)

Abstract: Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention.

Cytoplasmic male sterility-associated chimeric open reading frames identified by mitochondrial genome sequencing of four Cajanus genotypes.

Science.gov (United States)

Tuteja, Reetu; Saxena, Rachit K; Davila, Jaime; Shah, Trushar; Chen, Wenbin; Xiao, Yong-Li; Fan, Guangyi; Saxena, K B; Alverson, Andrew J; Spillane, Charles; Town, Christopher; Varshney, Rajeev K

2013-10-01

The hybrid pigeonpea (Cajanus cajan) breeding technology based on cytoplasmic male sterility (CMS) is currently unique among legumes and displays major potential for yield increase. CMS is defined as a condition in which a plant is unable to produce functional pollen grains. The novel chimeric open reading frames (ORFs) produced as a results of mitochondrial genome rearrangements are considered to be the main cause of CMS. To identify these CMS-related ORFs in pigeonpea, we sequenced the mitochondrial genomes of three C. cajan lines (the male-sterile line ICPA 2039, the maintainer line ICPB 2039, and the hybrid line ICPH 2433) and of the wild relative (Cajanus cajanifolius ICPW 29). A single, circular-mapping molecule of length 545.7 kb was assembled and annotated for the ICPA 2039 line. Sequence annotation predicted 51 genes, including 34 protein-coding and 17 RNA genes. Comparison of the mitochondrial genomes from different Cajanus genotypes identified 31 ORFs, which differ between lines within which CMS is present or absent. Among these chimeric ORFs, 13 were identified by comparison of the related male-sterile and maintainer lines. These ORFs display features that are known to trigger CMS in other plant species and to represent the most promising candidates for CMS-related mitochondrial rearrangements in pigeonpea.

Fine-tiling array CGH to improve diagnostics for alpha- and beta-thalassemia rearrangements

NARCIS (Netherlands)

Phylipsen, M.; Chaibunruang, A.; Vogelaar, I.P.; Balak, J.R.; Schaap, R.A.; Ariyurek, Y.; Fucharoen, S.; den Dunnen, J.T.; Giordano, P.C.; Bakker, E.; Harteveld, C.L.

2012-01-01

Implementation of multiplex ligation-dependent probe amplification (MLPA) for thalassemia causing deletions has lead to the detection of new rearrangements. Knowledge of the exact breakpoint sequences should give more insight into the molecular mechanisms underlying these rearrangements, and would

Classic theory for chromosome rearrangements with spatially restricted volume for broken ends interaction

International Nuclear Information System (INIS)

Omel'yanchuk, L.V.

1997-01-01

D. Lea classic theory for chromosomal rearrangements formation was modified to account for local interaction of broken chromosome ends. This assumption makes it possible to drastically improve coincidence of the theory and experiment in the case of complex rearrangements

CrusView: a Java-based visualization platform for comparative genomics analyses in Brassicaceae species.

Science.gov (United States)

Chen, Hao; Wang, Xiangfeng

2013-09-01

In plants and animals, chromosomal breakage and fusion events based on conserved syntenic genomic blocks lead to conserved patterns of karyotype evolution among species of the same family. However, karyotype information has not been well utilized in genomic comparison studies. We present CrusView, a Java-based bioinformatic application utilizing Standard Widget Toolkit/Swing graphics libraries and a SQLite database for performing visualized analyses of comparative genomics data in Brassicaceae (crucifer) plants. Compared with similar software and databases, one of the unique features of CrusView is its integration of karyotype information when comparing two genomes. This feature allows users to perform karyotype-based genome assembly and karyotype-assisted genome synteny analyses with preset karyotype patterns of the Brassicaceae genomes. Additionally, CrusView is a local program, which gives its users high flexibility when analyzing unpublished genomes and allows users to upload self-defined genomic information so that they can visually study the associations between genome structural variations and genetic elements, including chromosomal rearrangements, genomic macrosynteny, gene families, high-frequency recombination sites, and tandem and segmental duplications between related species. This tool will greatly facilitate karyotype, chromosome, and genome evolution studies using visualized comparative genomics approaches in Brassicaceae species. CrusView is freely available at http://www.cmbb.arizona.edu/CrusView/.

High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Science.gov (United States)

Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

2015-07-01

Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

Protein Dynamics in Mammalian Genome Maintenance

NARCIS (Netherlands)

A. Zotter (Angelika)

2008-01-01

textabstractThe integrity of the genome, carrier of the blueprint for each organism, is under constant attack from environmental as well as endogenous DNA damaging agents. An agent with substantial impact on our DNA is the UV-fraction of sunlight. It inflicts bulky DNA lesions, which can interfere

Nearly complete mitogenome of hairy sawfly, Corynis lateralis (Brullé, 1832) (Hymenoptera: Cimbicidae): rearrangements in the IQM and ARNS1EF gene clusters.

Science.gov (United States)

Doğan, Özgül; Korkmaz, E Mahir

2017-10-01

The Cimbicidae is a small family of the primitive and relatively less diverse suborder Symphyta (Hymenoptera). Here, nearly complete mitochondrial genome (mitogenome) of hairy sawfly, Corynis lateralis (Hymenoptera: Cimbicidae) was sequenced using next generation sequencing and comparatively analysed with the mitogenome of Trichiosoma anthracinum. The sequenced length of C. lateralis mitogenome was 14,899 bp with an A+T content of 80.60%. All protein coding genes (PCGs) are initiated by ATN codons and all are terminated with TAR or T- stop codon. All tRNA genes preferred usual anticodons. Compared with the inferred insect ancestral mitogenome, two tRNA rearrangements were observed in the IQM and ARNS1EF gene clusters, representing a new event not previously reported in Symphyta. An illicit priming of replication and/or intra/inter-mitochondrial recombination and TDRL seem to be responsible mechanisms for the rearrangement events in these gene clusters. Phylogenetic analyses confirmed the position of Corynis within Cimbicidae and recovered a relationship of Tenthredinoidea + (Cephoidea + Orussoidea) in Symphyta.

Selenium-mediated synthesis of biaryls through rearrangement.

Science.gov (United States)

Shahzad, Sohail A; Vivant, Clotilde; Wirth, Thomas

2010-03-19

A new cyclization of beta-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

Science.gov (United States)

Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Armstrong, Georgina N.; Shete, Sanjay; Lau, Ching C.; Bainbridge, Matthew N.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Houlston, Richard S.; Schildkraut, Joellen; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert B.; Lachance, Daniel H.; Wrensch, Margaret; Davis, Faith G.; Merrell, Ryan; Johansen, Christoffer; Sadetzki, Siegal; Bondy, Melissa L.; Melin, Beatrice S.; Adatto, Phyllis; Morice, Fabian; Payen, Sam; McQuinn, Lacey; McGaha, Rebecca; Guerra, Sandra; Paith, Leslie; Roth, Katherine; Zeng, Dong; Zhang, Hui; Yung, Alfred; Aldape, Kenneth; Gilbert, Mark; Weinberger, Jeffrey; Colman, Howard; Conrad, Charles; de Groot, John; Forman, Arthur; Groves, Morris; Levin, Victor; Loghin, Monica; Puduvalli, Vinay; Sawaya, Raymond; Heimberger, Amy; Lang, Frederick; Levine, Nicholas; Tolentino, Lori; Saunders, Kate; Thach, Thu-Trang; Iacono, Donna Dello; Sloan, Andrew; Gerson, Stanton; Selman, Warren; Bambakidis, Nicholas; Hart, David; Miller, Jonathan; Hoffer, Alan; Cohen, Mark; Rogers, Lisa; Nock, Charles J; Wolinsky, Yingli; Devine, Karen; Fulop, Jordonna; Barrett, Wendi; Shimmel, Kristen; Ostrom, Quinn; Barnett, Gene; Rosenfeld, Steven; Vogelbaum, Michael; Weil, Robert; Ahluwalia, Manmeet; Peereboom, David; Staugaitis, Susan; Schilero, Cathy; Brewer, Cathy; Smolenski, Kathy; McGraw, Mary; Naska, Theresa; Rosenfeld, Steven; Ram, Zvi; Blumenthal, Deborah T.; Bokstein, Felix; Umansky, Felix; Zaaroor, Menashe; Cohen, Avi; Tzuk-Shina, Tzeela; Voldby, Bo; Laursen, René; Andersen, Claus; Brennum, Jannick; Henriksen, Matilde Bille; Marzouk, Maya; Davis, Mary Elizabeth; Boland, Eamon; Smith, Marcel; Eze, Ogechukwu; Way, Mahalia; Lada, Pat; Miedzianowski, Nancy; Frechette, Michelle; Paleologos, Nina; Byström, Gudrun; Svedberg, Eva; Huggert, Sara; Kimdal, Mikael; Sandström, Monica; Brännström, Nikolina; Hayat, Amina; Tihan, Tarik; Zheng, Shichun; Berger, Mitchel; Butowski, Nicholas; Chang, Susan; Clarke, Jennifer; Prados, Michael; Rice, Terri; Sison, Jeannette; Kivett, Valerie; Duo, Xiaoqin; Hansen, Helen; Hsuang, George; Lamela, Rosito; Ramos, Christian; Patoka, Joe; Wagenman, Katherine; Zhou, Mi; Klein, Adam; McGee, Nora; Pfefferle, Jon; Wilson, Callie; Morris, Pagan; Hughes, Mary; Britt-Williams, Marlin; Foft, Jessica; Madsen, Julia; Polony, Csaba; McCarthy, Bridget; Zahora, Candice; Villano, John; Engelhard, Herbert; Borg, Ake; Chanock, Stephen K; Collins, Peter; Elston, Robert; Kleihues, Paul; Kruchko, Carol; Petersen, Gloria; Plon, Sharon; Thompson, Patricia; Johansen, C.; Sadetzki, S.; Melin, B.; Bondy, Melissa L.; Lau, Ching C.; Scheurer, Michael E.; Armstrong, Georgina N.; Liu, Yanhong; Shete, Sanjay; Yu, Robert K.; Aldape, Kenneth D.; Gilbert, Mark R.; Weinberg, Jeffrey; Houlston, Richard S.; Hosking, Fay J.; Robertson, Lindsay; Papaemmanuil, Elli; Claus, Elizabeth B.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Sloan, Andrew E.; Barnett, Gene; Devine, Karen; Wolinsky, Yingli; Lai, Rose; McKean-Cowdin, Roberta; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Yechezkel, Galit Hirsh; Bruchim, Revital Bar-Sade; Aslanov, Lili; Sadetzki, Siegal; Johansen, Christoffer; Kosteljanetz, Michael; Broholm, Helle; Bernstein, Jonine L.; Olson, Sara H.; Schubert, Erica; DeAngelis, Lisa; Jenkins, Robert B.; Yang, Ping; Rynearson, Amanda; Andersson, Ulrika; Wibom, Carl; Henriksson, Roger; Melin, Beatrice S.; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Merrell, Ryan; Lada, Patricia; Wrensch, Margaret; Wiencke, John; Wiemels, Joe; McCoy, Lucie; McCarthy, Bridget J.; Davis, Faith G.

2014-01-01

Background Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. PMID:24723567

The Somatic Genomic Landscape of Glioblastoma

Science.gov (United States)

Brennan, Cameron W.; Verhaak, Roel G.W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary; Berman, Samuel H.; Beroukhim, Rameen; Bernard, Brady; Wu, Chang-Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz-Sloan, Jill; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A.; Ciriello, Giovanni; Yung, WK; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D.; Van Meir, Erwin G.; Prados, Michael; Sloan, Andrew; Black, Keith L.; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William; Andrews, David W.; Guha, Abhijit; Iacocca, Mary; O’Neill, Brian P.; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J.; Penny, Robert; Kucherlapati, Raju; Perou, Charles M.; Hayes, D. Neil; Gibbs, Richard; Marra, Marco; Mills, Gordon B.; Lander, Eric; Spellman, Paul; Wilson, Richard; Sander, Chris; Weinstein, John; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W.; Haussler, David; Getz, Gad; Chin, Lynda

2013-01-01

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer. PMID:24120142

The solute carrier 6 family of transporters

DEFF Research Database (Denmark)

Bröer, Stefan; Gether, Ulrik

2012-01-01

of these transporters is associated with a variety of diseases. Pharmacological inhibition of the neurotransmitter transporters in this family is an important strategy in the management of neurological and psychiatric disorders. This review provides an overview of the biochemical and pharmacological properties......The solute carrier 6 (SLC6) family of the human genome comprises transporters for neurotransmitters, amino acids, osmolytes and energy metabolites. Members of this family play critical roles in neurotransmission, cellular and whole body homeostasis. Malfunction or altered expression...... of the SLC6 family transporters....

Inversion variants in human and primate genomes.

Science.gov (United States)

Catacchio, Claudia Rita; Maggiolini, Flavia Angela Maria; D'Addabbo, Pietro; Bitonto, Miriana; Capozzi, Oronzo; Signorile, Martina Lepore; Miroballo, Mattia; Archidiacono, Nicoletta; Eichler, Evan E; Ventura, Mario; Antonacci, Francesca

2018-05-18

For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates. © 2018 Catacchio et al.; Published by Cold Spring Harbor Laboratory Press.

Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine.

Science.gov (United States)

Chen, Weibin; Wu, Huifang; Bernard, Denzil; Metcalf, Matthew D; Deschamps, Jeffrey R; Flippen-Anderson, Judith L; MacKerell, Alexander D; Coop, Andrew

2003-03-07

Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.

A genomic point-of-view on environmental factors influencing the human brain methylome.

Science.gov (United States)

LaSalle, Janine M

2011-07-01

The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental, and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, non-mutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.

Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS) line and its maintainer line.

Science.gov (United States)

Liu, Huitao; Cui, Peng; Zhan, Kehui; Lin, Qiang; Zhuo, Guoyin; Guo, Xiaoli; Ding, Feng; Yang, Wenlong; Liu, Dongcheng; Hu, Songnian; Yu, Jun; Zhang, Aimin

2011-03-29

Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS), a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line. The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi) CMS line, Ks3, was assembled into a master circle (MC) molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs), and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38%) and repeats (> 100 bp, 29 units) as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs) in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants. The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of its maintainer line Km3, especially in non

Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS line and its maintainer line

Directory of Open Access Journals (Sweden)

Liu Dongcheng

2011-03-01

Full Text Available Abstract Background Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS, a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA, and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line. Results The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi CMS line, Ks3, was assembled into a master circle (MC molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs, and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38% and repeats (> 100 bp, 29 units as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants. Conclusion The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of

Mapping the pericentric heterochromatin by comparative genomic hybridization analysis and chromosome deletions in Drosophila melanogaster

OpenAIRE

He, Bing; Caudy, Amy; Parsons, Lance; Rosebrock, Adam; Pane, Attilio; Raj, Sandeep; Wieschaus, Eric

2012-01-01

Heterochromatin represents a significant portion of eukaryotic genomes and has essential structural and regulatory functions. Its molecular organization is largely unknown due to difficulties in sequencing through and assembling repetitive sequences enriched in the heterochromatin. Here we developed a novel strategy using chromosomal rearrangements and embryonic phenotypes to position unmapped Drosophila melanogaster heterochromatic sequence to specific chromosomal regions. By excluding seque...

Genome sequence of the lager brewing yeast, an interspecies hybrid.

Science.gov (United States)

Nakao, Yoshihiro; Kanamori, Takeshi; Itoh, Takehiko; Kodama, Yukiko; Rainieri, Sandra; Nakamura, Norihisa; Shimonaga, Tomoko; Hattori, Masahira; Ashikari, Toshihiko

2009-04-01

This work presents the genome sequencing of the lager brewing yeast (Saccharomyces pastorianus) Weihenstephan 34/70, a strain widely used in lager beer brewing. The 25 Mb genome comprises two nuclear sub-genomes originating from Saccharomyces cerevisiae and Saccharomyces bayanus and one circular mitochondrial genome originating from S. bayanus. Thirty-six different types of chromosomes were found including eight chromosomes with translocations between the two sub-genomes, whose breakpoints are within the orthologous open reading frames. Several gene loci responsible for typical lager brewing yeast characteristics such as maltotriose uptake and sulfite production have been increased in number by chromosomal rearrangements. Despite an overall high degree of conservation of the synteny with S. cerevisiae and S. bayanus, the syntenies were not well conserved in the sub-telomeric regions that contain lager brewing yeast characteristic and specific genes. Deletion of larger chromosomal regions, a massive unilateral decrease of the ribosomal DNA cluster and bilateral truncations of over 60 genes reflect a post-hybridization evolution process. Truncations and deletions of less efficient maltose and maltotriose uptake genes may indicate the result of adaptation to brewing. The genome sequence of this interspecies hybrid yeast provides a new tool for better understanding of lager brewing yeast behavior in industrial beer production.

Mechanisms of Low Dose Radio-Suppression of Genomic Instability

Energy Technology Data Exchange (ETDEWEB)

Engelward, Bevin P. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

2009-09-16

The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

Internal flow inside droplets within a concentrated emulsion during droplet rearrangement

Science.gov (United States)

Leong, Chia Min; Gai, Ya; Tang, Sindy K. Y.

2018-03-01

Droplet microfluidics, in which each droplet serves as a micro-reactor, has found widespread use in high-throughput biochemical screening applications. These droplets are often concentrated at various steps to form a concentrated emulsion. As part of a serial interrogation and sorting process, such concentrated emulsions are typically injected into a tapered channel leading to a constriction that fits one drop at a time for the probing of droplet content in a serial manner. The flow physics inside the droplets under these flow conditions are not well understood but are critical for predicting and controlling the mixing of reagents inside the droplets as reactors. Here we investigate the flow field inside droplets of a concentrated emulsion flowing through a tapered microchannel using micro-particle image velocimetry. The confining geometry of the channel forces the number of rows of drops to reduce by one at specific and uniformly spaced streamwise locations, which are referred to as droplet rearrangement zones. Within each rearrangement zone, the phase-averaged velocity results show that the motion of the droplets involved in the rearrangement process, also known as a T1 event, creates vortical structures inside themselves and their adjacent droplets. These flow structures increase the circulation inside droplets up to 2.5 times the circulation in droplets at the constriction. The structures weaken outside of the rearrangement zones suggesting that the flow patterns created by the T1 process are transient. The time scale of circulation is approximately the same as the time scale of a T1 event. Outside of the rearrangement zones, flow patterns in the droplets are determined by the relative velocity between the continuous and disperse phases.

Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

DEFF Research Database (Denmark)

Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren

2007-01-01

Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

Synthesis of fused tricyclic systems by thermal Cope rearrangement of furan-substituted vinyl cyclopropanes.

Science.gov (United States)

Klaus, Verena; Wittmann, Stéphane; Senn, Hans M; Clark, J Stephen

2018-05-15

A novel method for the stereoselective construction of hexahydroazuleno[4,5-b]furans from simple precursors has been developed. The route involves the use of our recently developed Brønsted acid catalysed cyclisation reaction of acyclic ynenones to prepare fused 1-furanyl-2-alkenylcyclopropanes that undergo highly stereoselective thermal Cope rearrangement to produce fused tricyclic products. Substrates possessing an E-alkene undergo smooth Cope rearrangement at 40 °C, whereas the corresponding Z-isomers do not react at this temperature. Computational studies have been performed to explain the difference in behaviour of the E- and Z-isomers in the Cope rearrangement reaction. The hexahydroazuleno[4,5-b]furans produced by Cope rearrangement have potential as advanced intermediates for the synthesis of members of the guaianolide family of natural products.

Efficient propagation of archetype JC polyomavirus in COS-7 cells: evaluation of rearrangements within the NCCR structural organization after transfection.

Science.gov (United States)

Prezioso, Carla; Scribano, Daniela; Bellizzi, Anna; Anzivino, Elena; Rodio, Donatella Maria; Trancassini, Maria; Palamara, Anna Teresa; Pietropaolo, Valeria

2017-12-01

John Cunningham virus (JCPyV) is an ubiquitous human pathogen that causes disease in immunocompromised patients. The JCPyV genome is composed of an early region and a late region, which are physically separated by the non-coding control region (NCCR). The DNA sequence of the NCCR distinguishes two forms of JCPyV, the designated archetype and the prototype, which resulted from a rearrangement of the archetype sequence. To date, the cell culture systems for propagating JCPyV archetype have been very limited in their availability and robustness. Prior to this study, it was demonstrated that JCPyV archetype DNA replicates in COS-7 simian kidney cells expressing SV40 TAg and COS-7 cells expressing HIV-1 Tat. Based on these observations, the present study was conducted to reproduce an in vitro model in COS-7 cells transfected with the JCPyV archetype strain in order to study JCPyV DNA replication and analyze NCCR rearrangements during the viral life cycle. The efficiency of JCPyV replication was evaluated by quantitative PCR (Q-PCR) and by hemagglutination (HA) assay after transfection. In parallel, sequence analysis of JCPyV NCCR was performed. JCPyV efficiently replicated in kidney-derived COS-7 cells, as demonstrated by a progressive increase in viral load and virion particle production after transfection. The archetypal structure of NCCR was maintained during the viral cycle, but two characteristic point mutations were detected 28 days after transfection. This model is a useful tool for analyzing NCCR rearrangements during in vitro replication in cells that are sites of viral persistence, such as tubular epithelial cells of the kidney.

A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

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Karen M Chisholm

Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

Legionella pneumophila secretes a mitochondrial carrier protein during infection.

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Pavel Dolezal

2012-01-01

Full Text Available The Mitochondrial Carrier Family (MCF is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionellanucleotide carrier Protein (LncP, encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms.

CrusView: A Java-Based Visualization Platform for Comparative Genomics Analyses in Brassicaceae Species[OPEN

Science.gov (United States)

Chen, Hao; Wang, Xiangfeng

2013-01-01

In plants and animals, chromosomal breakage and fusion events based on conserved syntenic genomic blocks lead to conserved patterns of karyotype evolution among species of the same family. However, karyotype information has not been well utilized in genomic comparison studies. We present CrusView, a Java-based bioinformatic application utilizing Standard Widget Toolkit/Swing graphics libraries and a SQLite database for performing visualized analyses of comparative genomics data in Brassicaceae (crucifer) plants. Compared with similar software and databases, one of the unique features of CrusView is its integration of karyotype information when comparing two genomes. This feature allows users to perform karyotype-based genome assembly and karyotype-assisted genome synteny analyses with preset karyotype patterns of the Brassicaceae genomes. Additionally, CrusView is a local program, which gives its users high flexibility when analyzing unpublished genomes and allows users to upload self-defined genomic information so that they can visually study the associations between genome structural variations and genetic elements, including chromosomal rearrangements, genomic macrosynteny, gene families, high-frequency recombination sites, and tandem and segmental duplications between related species. This tool will greatly facilitate karyotype, chromosome, and genome evolution studies using visualized comparative genomics approaches in Brassicaceae species. CrusView is freely available at http://www.cmbb.arizona.edu/CrusView/. PMID:23898041

Genome Sequences of the Oxytetracycline Production Strain Streptomyces rimosus R6-500 and Two Mutants with Chromosomal Rearrangements

KAUST Repository

Baranasic, Damir

2014-07-17

The genome sequence of Streptomyces rimosus R6-500, an industrially improved strain which produces high titers of the important antibiotic oxytetracycline, is reported, as well as the genome sequences of two derivatives arising due to the genetic instability of the strain.

Genome Sequences of the Oxytetracycline Production Strain Streptomyces rimosus R6-500 and Two Mutants with Chromosomal Rearrangements

KAUST Repository

Baranasic, Damir; Zucko, Jurica; Nair, Mridul; Pain, Arnab; Long, Paul F.; Hranueli, Daslav; Cullum, John; Starcevic, Antonio

2014-01-01

The genome sequence of Streptomyces rimosus R6-500, an industrially improved strain which produces high titers of the important antibiotic oxytetracycline, is reported, as well as the genome sequences of two derivatives arising due to the genetic instability of the strain.

Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics.

Science.gov (United States)

Bowden, Katherine E; Weigand, Michael R; Peng, Yanhui; Cassiday, Pamela K; Sammons, Scott; Knipe, Kristen; Rowe, Lori A; Loparev, Vladimir; Sheth, Mili; Weening, Keeley; Tondella, M Lucia; Williams, Margaret M

2016-01-01

During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome structural

PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development

Directory of Open Access Journals (Sweden)

Zhuo Sun

2014-03-01

Full Text Available Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here, we describe a knockin mouse model of a nonsense mutation that results in the deletion of the entire Pten C-terminal region, referred to as PtenΔC. Mice heterozygous for PtenΔC develop multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C-terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 promotes metastasis without influencing the initiation of tumors, suggesting that p53 mainly suppresses tumor progression. Our data highlight the essential role of the PTEN C terminus in the maintenance of genomic stability and suppression of tumorigenesis.

Loss of Heterozygosity at an Unlinked Genomic Locus Is Responsible for the Phenotype of a Candida albicans sap4Δ sap5Δ sap6Δ Mutant ▿

OpenAIRE

Dunkel, Nico; Morschhäuser, Joachim

2011-01-01

The diploid genome of the pathogenic yeast Candida albicans exhibits a high degree of heterozygosity. Genomic alterations that result in a loss of heterozygosity at specific loci may affect phenotypes and confer a selective advantage under certain conditions. Such genomic rearrangements can also occur during the construction of C. albicans mutants and remain undetected. The SAP2 gene on chromosome R encodes a secreted aspartic protease that is induced and required for growth of C. albicans wh...

A web-based multi-genome synteny viewer for customized data

Directory of Open Access Journals (Sweden)

Revanna Kashi V

2012-08-01

Full Text Available Abstract Background Web-based synteny visualization tools are important for sharing data and revealing patterns of complicated genome conservation and rearrangements. Such tools should allow biologists to upload genomic data for their own analysis. This requirement is critical because individual biologists are generating large amounts of genomic sequences that quickly overwhelm any centralized web resources to collect and display all those data. Recently, we published a web-based synteny viewer, GSV, which was designed to satisfy the above requirement. However, GSV can only compare two genomes at a given time. Extending the functionality of GSV to visualize multiple genomes is important to meet the increasing demand of the research community. Results We have developed a multi-Genome Synteny Viewer (mGSV. Similar to GSV, mGSV is a web-based tool that allows users to upload their own genomic data files for visualization. Multiple genomes can be presented in a single integrated view with an enhanced user interface. Users can navigate through all the selected genomes in either pairwise or multiple viewing mode to examine conserved genomic regions as well as the accompanying genome annotations. Besides serving users who manually interact with the web server, mGSV also provides Web Services for machine-to-machine communication to accept data sent by other remote resources. The entire mGSV package can also be downloaded for easy local installation. Conclusions mGSV significantly enhances the original functionalities of GSV. A web server hosting mGSV is provided at http://cas-bioinfo.cas.unt.edu/mgsv.

MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

Directory of Open Access Journals (Sweden)

Fen Zhu

Full Text Available INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19 resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC, and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC. The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001 and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively. Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023 or disease-free survival (p = 0.027 as well as correlation between FLT1 and overall survival (p = 0.009. CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity.

Science.gov (United States)

Zhang, Jin; Ruhlman, Tracey A; Sabir, Jamal S M; Blazier, John Chris; Weng, Mao-Lun; Park, Seongjun; Jansen, Robert K

2016-02-17

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Amplification of pico-scale DNA mediated by bacterial carrier DNA for small-cell-number transcription factor ChIP-seq

DEFF Research Database (Denmark)

Jakobsen, Janus S; Bagger, Frederik O; Hasemann, Marie S

2015-01-01

BACKGROUND: Chromatin-Immunoprecipitation coupled with deep sequencing (ChIP-seq) is used to map transcription factor occupancy and generate epigenetic profiles genome-wide. The requirement of nano-scale ChIP DNA for generation of sequencing libraries has impeded ChIP-seq on in vivo tissues of low...... transcription factor (CEBPA) and histone mark (H3K4me3) ChIP. We further demonstrate that genomic profiles are highly resilient to changes in carrier DNA to ChIP DNA ratios. CONCLUSIONS: This represents a significant advance compared to existing technologies, which involve either complex steps of pre...... cell numbers. RESULTS: We describe a robust, simple and scalable methodology for ChIP-seq of low-abundant cell populations, verified down to 10,000 cells. By employing non-mammalian genome mapping bacterial carrier DNA during amplification, we reliably amplify down to 50 pg of ChIP DNA from...

Catalytic synthesis of amides via aldoximes rearrangement.

Science.gov (United States)

Crochet, Pascale; Cadierno, Victorio

2015-02-14

Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

The Genomic and Transcriptomic Landscape of a HeLa Cell Line

Science.gov (United States)

Landry, Jonathan J. M.; Pyl, Paul Theodor; Rausch, Tobias; Zichner, Thomas; Tekkedil, Manu M.; Stütz, Adrian M.; Jauch, Anna; Aiyar, Raeka S.; Pau, Gregoire; Delhomme, Nicolas; Gagneur, Julien; Korbel, Jan O.; Huber, Wolfgang; Steinmetz, Lars M.

2013-01-01

HeLa is the most widely used model cell line for studying human cellular and molecular biology. To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome. Effective design and interpretation of molecular genetic studies performed using HeLa cells require accurate genomic information. Here we present a detailed genomic and transcriptomic characterization of a HeLa cell line. We performed DNA and RNA sequencing of a HeLa Kyoto cell line and analyzed its mutational portfolio and gene expression profile. Segmentation of the genome according to copy number revealed a remarkably high level of aneuploidy and numerous large structural variants at unprecedented resolution. Some of the extensive genomic rearrangements are indicative of catastrophic chromosome shattering, known as chromothripsis. Our analysis of the HeLa gene expression profile revealed that several pathways, including cell cycle and DNA repair, exhibit significantly different expression patterns from those in normal human tissues. Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins. This study underscores the importance of accounting for the strikingly aberrant characteristics of HeLa cells when designing and interpreting experiments, and has implications for the use of HeLa as a model of human biology. PMID:23550136

A complete mitochondrial genome sequence of Ogura-type male-sterile cytoplasm and its comparative analysis with that of normal cytoplasm in radish (Raphanus sativus L.

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Tanaka Yoshiyuki

2012-07-01

Full Text Available Abstract Background Plant mitochondrial genome has unique features such as large size, frequent recombination and incorporation of foreign DNA. Cytoplasmic male sterility (CMS is caused by rearrangement of the mitochondrial genome, and a novel chimeric open reading frame (ORF created by shuffling of endogenous sequences is often responsible for CMS. The Ogura-type male-sterile cytoplasm is one of the most extensively studied cytoplasms in Brassicaceae. Although the gene orf138 has been isolated as a determinant of Ogura-type CMS, no homologous sequence to orf138 has been found in public databases. Therefore, how orf138 sequence was created is a mystery. In this study, we determined the complete nucleotide sequence of two radish mitochondrial genomes, namely, Ogura- and normal-type genomes, and analyzed them to reveal the origin of the gene orf138. Results Ogura- and normal-type mitochondrial genomes were assembled to 258,426-bp and 244,036-bp circular sequences, respectively. Normal-type mitochondrial genome contained 33 protein-coding and three rRNA genes, which are well conserved with the reported mitochondrial genome of rapeseed. Ogura-type genomes contained same genes and additional atp9. As for tRNA, normal-type contained 17 tRNAs, while Ogura-type contained 17 tRNAs and one additional trnfM. The gene orf138 was specific to Ogura-type mitochondrial genome, and no sequence homologous to it was found in normal-type genome. Comparative analysis of the two genomes revealed that radish mitochondrial genome consists of 11 syntenic regions (length >3 kb, similarity >99.9%. It was shown that short repeats and overlapped repeats present in the edge of syntenic regions were involved in recombination events during evolution to interconvert two types of mitochondrial genome. Ogura-type mitochondrial genome has four unique regions (2,803 bp, 1,601 bp, 451 bp and 15,255 bp in size that are non-syntenic to normal-type genome, and the gene orf138

Relationship between mitochondrial gene rearrangements and stability of the origin of light strand replication

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Miguel M. Fonseca

2008-01-01

Full Text Available Mitochondrial gene rearrangements are much more frequent in vertebrates than initially thought. It has been suggested that the origin of light strand replication could have an important role in the process of gene rearrangements, but this hypothesis has never been tested before. We used amphibians to test the correlation between light-strand replication origin thermodynamic stability and the occurrence of gene rearrangements. The two variables were correlated in a non-phylogenetic approach, but when tested in a phylogenetically based comparative method the correlation was not significant, although species with unstable light-strand replication origins were much more likely to have undergone gene rearrangements. This indicates that within amphibians there are stable and unstable phylogenetic groups regarding mitochondrial gene order. The species analyzed showed variability in the thermodynamic stability of the secondary structure, in the length of its stem and loop, and several species did not present the 5’-GCCGG-3’ motif reported to be necessary for efficient mitochondrial DNA replication. Future studies should focus on the role of the light-strand replication origin in mitochondrial DNA replication and gene rearrangements mechanisms.

Spatially Rearranged Object Parts Can Facilitate Perception of Intact Whole Objects

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Laura eCacciamani

2014-05-01

Full Text Available The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively. We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime’s border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

Spatially rearranged object parts can facilitate perception of intact whole objects.

Science.gov (United States)

Cacciamani, Laura; Ayars, Alisabeth A; Peterson, Mary A

2014-01-01

The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively). We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime's border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

The Genome Biology of Effector Gene Evolution in Filamentous Plant Pathogens.

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Sánchez-Vallet, Andrea; Fouché, Simone; Fudal, Isabelle; Hartmann, Fanny E; Soyer, Jessica L; Tellier, Aurélien; Croll, Daniel

2018-05-16

Filamentous pathogens, including fungi and oomycetes, pose major threats to global food security. Crop pathogens cause damage by secreting effectors that manipulate the host to the pathogen's advantage. Genes encoding such effectors are among the most rapidly evolving genes in pathogen genomes. Here, we review how the major characteristics of the emergence, function, and regulation of effector genes are tightly linked to the genomic compartments where these genes are located in pathogen genomes. The presence of repetitive elements in these compartments is associated with elevated rates of point mutations and sequence rearrangements with a major impact on effector diversification. The expression of many effectors converges on an epigenetic control mediated by the presence of repetitive elements. Population genomics analyses showed that rapidly evolving pathogens show high rates of turnover at effector loci and display a mosaic in effector presence-absence polymorphism among strains. We conclude that effective pathogen containment strategies require a thorough understanding of the effector genome biology and the pathogen's potential for rapid adaptation. Expected final online publication date for the Annual Review of Phytopathology Volume 56 is August 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Genome-wide identification of blood DNA methylation patterns associated with early-onset hepatocellular carcinoma development in hepatitis B carriers.

Science.gov (United States)

Kao, Wei-Yi; Yang, Shu-Han; Liu, Wen-Jie; Yeh, Meng-Yin; Lin, Chih-Lin; Liu, Chun-Jen; Huang, Chi-Jung; Lin, Shi-Ming; Lee, Shou-Dong; Chen, Pei-Jer; Yu, Ming-Whei

2017-02-01

The etiology of early-onset hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) carriers remains unclear. DNA methylation levels in peripheral leukocytes have been associated with different environmental exposures and immune or inflammatory response. We aimed to identify methylation signatures of peripheral leukocytes that could track hepatitis B progression to HCC, especially for early-onset HCC. We first performed an epigenome-wide association analysis on 48 matched case-control pairs in a nested case-control study within a 22-yr follow-up cohort of HBV carriers. Through this analysis we found that progression to early-onset HCC involved methylation variable positions across the genome, in which a substantial proportion displayed significant variation due to HBV viral load, chronic hepatitis status, and/or leukocyte subtype composition, and these associations were significantly enriched among genes in immune pathways. Methylation at probes cg00300879, cg06872964, and cg07080864, that are located within the proximal promoter of CNKSR1, IFI44L, and PENK, respectively, was validated by bisulfite pyrosequencing and findings were replicated in a case-sibling study of early-onset HCC (134 cases vs. 174 sibling controls). Furthermore, a high methylation score, constructed using the three probes, was predictive for the risk of early-onset HCC in two datasets (adjusted-odds ratios = 0.21-0.32, P ≤ 0.0206). This association was also observed for late-onset HCC (adjusted-odds ratio = 0.42-0.47, P ≤ 0.0194) in a nested case-control study (120 cases vs. 178 controls). In prospective analysis, change in the score was detected 5-9 yr before HCC onset. Blood-based methylation profiling provides new insights into the complexity of virus-host interaction underlying HBV-related HCC, holding promise for the disease risk management. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Complete nucleotide sequence and gene rearrangement of the ...

Indian Academy of Sciences (India)

3Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People's Republic of China ... of these rearrangements involve tRNA genes, ND5 gene and ... ncbi.nlm.nih.gov/projects/Sequin/download/seq_win_download.

Non-Random Inversion Landscapes in Prokaryotic Genomes Are Shaped by Heterogeneous Selection Pressures.

Science.gov (United States)

Repar, Jelena; Warnecke, Tobias

2017-08-01

Inversions are a major contributor to structural genome evolution in prokaryotes. Here, using a novel alignment-based method, we systematically compare 1,651 bacterial and 98 archaeal genomes to show that inversion landscapes are frequently biased toward (symmetric) inversions around the origin-terminus axis. However, symmetric inversion bias is not a universal feature of prokaryotic genome evolution but varies considerably across clades. At the extremes, inversion landscapes in Bacillus-Clostridium and Actinobacteria are dominated by symmetric inversions, while there is little or no systematic bias favoring symmetric rearrangements in archaea with a single origin of replication. Within clades, we find strong but clade-specific relationships between symmetric inversion bias and different features of adaptive genome architecture, including the distance of essential genes to the origin of replication and the preferential localization of genes on the leading strand. We suggest that heterogeneous selection pressures have converged to produce similar patterns of structural genome evolution across prokaryotes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Performance Evaluation of NIPT in Detection of Chromosomal Copy Number Variants Using Low-Coverage Whole-Genome Sequencing of Plasma DNA

DEFF Research Database (Denmark)

Liu, Hongtai; Gao, Ya; Hu, Zhiyang

2016-01-01

, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis...

Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome.

Science.gov (United States)

Rouleau, Etienne; Lefol, Cédrick; Bourdon, Violaine; Coulet, Florence; Noguchi, Tetsuro; Soubrier, Florent; Bièche, Ivan; Olschwang, Sylviane; Sobol, Hagay; Lidereau, Rosette

2009-06-01

Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called "quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM)," which combines qPCR and HRM to obtain a rapid and cost-effective method suitable for testing a large series of samples. We designed PCR amplicons to scan the MLH1 gene using qPCR HRM. Seventy-six patients were fully scanned in replicate, including 14 wild-type patients and 62 patients with known mutations (57 point mutations and five rearrangements). To validate the detected mutations, we used sequencing and/or hybridization on a dedicated MLH1 array-comparative genomic hybridization (array-CGH). All point mutations and rearrangements detected by denaturing high-performance liquid chromatography (dHPLC)+multiplex ligation-dependent probe amplification (MLPA) were successfully detected by qPCR HRM. Three large rearrangements were characterized with the dedicated MLH1 array-CGH. One variant was detected with qPCR HRM in a wild-type patient and was located within the reverse primer. One variant was not detected with qPCR HRM or with dHPLC due to its proximity to a T-stretch. With qPCR HRM, prescreening for point mutations and large rearrangements are performed in one tube and in one step with a single machine, without the need for any automated sequencer in the prescreening process. In replicate, its reagent cost, sensitivity, and specificity are comparable to those of dHPLC+MLPA techniques. However, qPCR HRM outperformed the other techniques in terms of its rapidity and amount of data provided.

Crossing the LINE toward genomic instability: LINE-1 retrotransposition in cancer

Science.gov (United States)

Kemp, Jacqueline; Longworth, Michelle

2015-12-01

Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises approximately 17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

DEFF Research Database (Denmark)

Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

2014-01-01

In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

On colour rearrangement in hadronic W+W- events

International Nuclear Information System (INIS)

Sjoestrand, T.; Khoze, V.A.

1994-01-01

We discuss the possibility of colour rearrangement in e + e - →W + W - →q 1 anti q 2 q 3 anti q 4 events, i.e. that the original colour singlets q 1 anti q 2 and q 3 anti q 4 may be transmuted, for instance, into new singlets q 1 anti q 4 and q 3 anti q 2 . The effects on event properties could be quite large if such a rearrangement would occur instantaneously, so that gluon emission would be restricted to each of the new singlets separately. We argue that such a scenario is unlikely for two reasons. Firstly, the W + and W - usually decay at separate times after the W + W - production, which leads to large relative phases for energetic radiation off the two constituents of a rearranged system, and a corresponding dampening of the QCD cascades. Secondly, within the perturbative scenario the colour transmutation appears only in order α s 2 and is colour-suppressed. Colour reconnection at longer time scales is quite feasible, however, and may affect the fragmentation phase. If so, the nature of non-perturbative QCD can be probed in a new way. We formulate several alternative toy models and use these to estimate the colour reconnection probability as a function of the event kinematics. Possible consequences for LEP 2 events are illustrated, with special attention to systematic errors in W mass determinations. (orig.)

Adiabatic Rearrangement of Hollow PV Towers

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Eric A Hendricks

2010-10-01

Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

Electron beam-induced Fries rearrangement of arylsulfonamides and arylsulfonates in the crystalline state

International Nuclear Information System (INIS)

Kato, Jun; Yuasa, Kanako; Yamashita, Takashi; Maekawa, Yasunari; Yoshida, Masaru

2003-01-01

Electron beam (EB)-induced reactions of organic crystals containing a carbonyl or a sulfonyl group have been investigated. The EB irradiation of benzenesulfonanilide (BSA) in the crystalline state induced the Fries rearrangement to yield o- and p-aminodiphenylsulfones as the major and minor products, respectively. Several BSA derivatives also had the same reactivity, while benzanilide as the corresponding carbonyl compound did not rearrange under the same conditions. These results showed that the S-N bond could be cleaved selectively by EB irradiation but the C-N bond couldn't, which could take place only by the use of EB. The EB irradiation of phenyl p-toluenesulfonate (PTS) crystals gave not only Fries-type products but also the oxidation product. By comparing with the reactivity of liquid phenyl benzenesulfonate, the EB-induced Fries rearrangement was suggested to proceed under crystalline lattice restrictions. The G-values of arylsulfonamides and arylsulfonates were in the range of ca. 1-2 molecules per 100 eV of absorbed energy. This is the first Fries rearrangement via direct excitation by EB irradiation. (author)