WorldWideScience

Sample records for lef-2 deletion temporal

  1. Interstitial deletion of chromosome 4p associated with mild mental retardation, epilepsy and polymicrogyria of the left temporal lobe

    DEFF Research Database (Denmark)

    Møller, R S; Hansen, C P; Jackson, G D

    2007-01-01

    In this study, we present a 38-year-old woman with an interstitial deletion of 4p15.1-15.3, mild mental retardation, epilepsy and polymicrogyria adjacent to an arachnoid cyst of the left temporal lobe. The deletion was ascertained through array-comparative genome hybridization screening of patien...

  2. Deletion of mTOR in Reactive Astrocytes Suppresses Chronic Seizures in a Mouse Model of Temporal Lobe Epilepsy.

    Science.gov (United States)

    Wang, Xueqin; Sha, Longze; Sun, Nannan; Shen, Yan; Xu, Qi

    2017-01-01

    Germline and somatic mutations in key genes of the mammalian target of rapamycin (mTOR) pathway have been identified in seizure-associated disorders. mTOR mutations lead to aberrant activation of mTOR signaling, and, although affected neurons are critical for epileptogenesis, the role of mTOR activation in glial cells remains poorly understood. We previously reported a consistent activation of the mTOR pathway in astrocytes in the epileptic foci of temporal lobe epilepsy. In this study, it was demonstrated that mTOR deletion from reactive astrocytes prevents increases in seizure frequency over the disease course. By using a tamoxifen-inducible mTOR conditional knockout system and kainic acid, a model was developed that allowed astrocyte-specific mTOR gene deletion in mice with chronic epilepsy. Animals in which mTOR was deleted from 44 % of the astrocyte population exhibited a lower seizure frequency compared with controls. Down-regulation of mTOR significantly ameliorated astrogliosis in the sclerotic hippocampus but did not rescue mossy fiber sprouting. In cultured astrocytes, the mTOR pathway modulated the stability of the astroglial glutamate transporter 1 (Glt1) and influenced the ability of astrocytes to remove extracellular glutamate. Taken together, these data indicate that astrocytes with activated mTOR signaling may provide conditions that are favorable for spontaneous recurrent seizures.

  3. Temporal Lobe Anatomy and Psychiatric Symptoms in Velocardiofacial Syndrome (22Q11.2 Deletion Syndrome)

    Science.gov (United States)

    Kates, Wendy R.; Miller, Adam M.; Abdulsabur, Nuria; Antshel, Kevin M.; Conchelos, Jena; Fremont, Wanda; Roizen, Nancy

    2006-01-01

    Objective: To investigate the association between mesial temporal lobe morphology, ratios of prefrontal cortex to amygdala and hippocampus volumes, and psychiatric symptomatology in children and adolescents with velocardiofacial syndrome (VCFS). Method: Scores on behavioral rating scales and volumetric measures of the amygdala, hippocampus, and…

  4. Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

    NARCIS (Netherlands)

    Thuijl, H.F. van; Scheinin, I.; Sie, D.; Alentorn, A.; Essen, H.F. van; Cordes, M.; Fleischeuer, R.; Gijtenbeek, A.; Beute, G.; Brink, W.A. van den; Meijer, G.A.; Havenith, M.; Idbaih, A.; Hoang-Xuan, K.; Mokhtari, K.; Verhaak, R.; Valk, P. van der; Wiel, M.A. van de; Heimans, J.J.; Aronica, E.; Reijneveld, J.C.; Wesseling, P.; Ylstra, B.

    2014-01-01

    BackgroundThe disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative

  5. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...... frequently seen in proximal 11q deletions involving 11q21. Telomeric staining using the PRINS technique demonstrated normal telomeric sequences in the deleted chromosome 11....

  6. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

  7. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  8. Quantum deletion: Beyond the no-deletion principle

    International Nuclear Information System (INIS)

    Adhikari, Satyabrata

    2005-01-01

    Suppose we are given two identical copies of an unknown quantum state and we wish to delete one copy from among the given two copies. The quantum no-deletion principle restricts us from perfectly deleting a copy but it does not prohibit us from deleting a copy approximately. Here we construct two types of a 'universal quantum deletion machine' which approximately deletes a copy such that the fidelity of deletion does not depend on the input state. The two types of universal quantum deletion machines are (1) a conventional deletion machine described by one unitary operator and (2) a modified deletion machine described by two unitary operators. Here it is shown that the modified deletion machine deletes a qubit with fidelity 3/4, which is the maximum limit for deleting an unknown quantum state. In addition to this we also show that the modified deletion machine retains the qubit in the first mode with average fidelity 0.77 (approx.) which is slightly greater than the fidelity of measurement for two given identical states, showing how precisely one can determine its state [S. Massar and S. Popescu, Phys. Rev. Lett. 74, 1259 (1995)]. We also show that the deletion machine itself is input state independent, i.e., the information is not hidden in the deleting machine, and hence we can delete the information completely from the deletion machine

  9. (AJST) GENERALISED DELETION DESIGNS

    African Journals Online (AJOL)

    th row if the t-th level is deleted from factor Fj in the preliminary design d-p to obtain d and xss j is an s x s permutation matrix with 1 in the aj - th column of the o-th row. We shall also write j j a j j. * a. cDPDc d j j. ′. ′= (3.2) where cj is a contrast ...

  10. Deletions of the mitochondrial genome.

    Science.gov (United States)

    Harding, A E; Hammans, S R

    1992-01-01

    Single large deletions of mitochondrial DNA are found in the muscle of about 40% of patients with mitochondrial myopathies, and are detectable in both blood and muscle in Pearson syndrome. In mitochondrial myopathies, there is a close association between the presence of deletions and involvement of extra-ocular muscles, together with other features of the Kearns-Sayre syndrome. Deletions appear to arise as fresh mutations in the vast majority of patients and are often flanked by direct repeats up to 13 nucleotides in length. They should affect translation of all mitochondrially encoded components of the respiratory chain, but there is evidence to suggest that intramitochondrial complementation occurs in some cases.

  11. Strategies for state-dependent quantum deleting

    International Nuclear Information System (INIS)

    Song Wei; Yang Ming; Cao Zhuoliang

    2004-01-01

    A quantum state-dependent quantum deleting machine is constructed. We obtain a upper bound of the global fidelity on N-to-M quantum deleting from a set of K non-orthogonal states. Quantum networks are constructed for the above state-dependent quantum deleting machine when K=2. Our deleting protocol only involves a unitary interaction among the initial copies, with no ancilla. We also present some analogies between quantum cloning and deleting

  12. 76 FR 9555 - Procurement List; Proposed Deletions

    Science.gov (United States)

    2011-02-18

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed deletions from the Procurement...'Day Act (41 U.S.C. 46- 48c) in connection with the products proposed for deletion from the Procurement...

  13. 78 FR 56679 - Procurement List; Deletions

    Science.gov (United States)

    2013-09-13

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the Procurement List. SUMMARY: This action deletes products from the Procurement List previously furnished by nonprofit agencies employing...

  14. Project Temporalities

    DEFF Research Database (Denmark)

    Tryggestad, Kjell; Justesen, Lise; Mouritsen, Jan

    2013-01-01

    into account. Design/methodology/approach – The paper is based on a qualitative case study of a project in the building industry. The authors use actor-network theory (ANT) to analyze the emergence of animal stakeholders, stakes and temporalities. Findings – The study shows how project temporalities can...... into account. This may require investments in new project management technologies. Originality/value – This paper adds to the literatures on project temporalities and stakeholder theory by connecting them to the question of non-human stakeholders and to project management technologies.......Purpose – The purpose of this paper is to explore how animals can become stakeholders in interaction with project management technologies and what happens with project temporalities when new and surprising stakeholders become part of a project and a recognized matter of concern to be taken...

  15. Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome

    DEFF Research Database (Denmark)

    Larsen, Kit Melissa; Mørup, Morten; Birknow, Michelle Rosgaard

    2018-01-01

    11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison....... Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia......-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q...

  16. 1p36 deletion syndrome: an update

    Directory of Open Access Journals (Sweden)

    Jordan VK

    2015-08-01

    Full Text Available Valerie K Jordan,1 Hitisha P Zaveri,2 Daryl A Scott1,2 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA; 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Abstract: Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are the most common terminal deletions in humans. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, distinctive facial features, brain anomalies, orofacial clefting, congenital heart defects, cardiomyopathy, and renal anomalies. Although 1p36 deletion syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. This variation is due, at least in part, to the genetic heterogeneity seen in 1p36 deletions which include terminal and interstitial deletions of varying lengths located throughout the 30 Mb of DNA that comprise chromosome 1p36. Array-based copy number variant analysis can easily identify genomic regions of 1p36 that are deleted in an affected individual. However, predicting the phenotype of an individual based solely on the location and extent of their 1p36 deletion remains a challenge since most of the genes that contribute to 1p36-related phenotypes have yet to be identified. In addition, haploinsufficiency of more than one gene may contribute to some phenotypes. In this article, we review recent successes in the effort to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes. In particular, we highlight evidence implicating MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1 in various 1p36 deletion phenotypes. Keywords: chromosome 1p36, chromosome deletion, 1p36 deletion syndrome, monosomy 1p36

  17. 78 FR 68823 - Procurement List Deletions

    Science.gov (United States)

    2013-11-15

    ...'Day Act (41 U.S.C. 8501-8506) in connection with the products and services deleted from the... Center, Chicago, IL. Service Type/Location: Janitorial/Custodial Service, Gamelin USARC, 10 Asylum Road... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Deletions...

  18. Seven gene deletions in seven days

    DEFF Research Database (Denmark)

    Ingemann Jensen, Sheila; Lennen, Rebecca; Herrgard, Markus

    2015-01-01

    genes and a rhamnose inducible flippase recombinase was constructed to facilitate fast marker-free deletions. To further speed up the procedure, we integrated the arabinose inducible lambda Red recombineering genes and the rhamnose inducible FLP into the genome of E. coli K-12 MG1655. This system...... in which four to seven genes were deleted in E. coli W and E. coli K-12. The growth rate of an E. coli K-12 quintuple deletion strain was significantly improved in the presence of high concentrations of acetate and NaCl. In conclusion, we have generated a method that enables efficient and simultaneous...... deletion of multiple genes in several E. coli variants. The method enables deletion of up to seven genes in as little as seven days....

  19. Probabilistic cloning and deleting of quantum states

    International Nuclear Information System (INIS)

    Feng Yuan; Zhang Shengyu; Ying Mingsheng

    2002-01-01

    We construct a probabilistic cloning and deleting machine which, taking several copies of an input quantum state, can output a linear superposition of multiple cloning and deleting states. Since the machine can perform cloning and deleting in a single unitary evolution, the probabilistic cloning and other cloning machines proposed in the previous literature can be thought of as special cases of our machine. A sufficient and necessary condition for successful cloning and deleting is presented, and it requires that the copies of an arbitrarily presumed number of the input states are linearly independent. This simply generalizes some results for cloning. We also derive an upper bound for the success probability of the cloning and deleting machine

  20. Genetics Home Reference: distal 18q deletion syndrome

    Science.gov (United States)

    ... Health Conditions Distal 18q deletion syndrome Distal 18q deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Distal 18q deletion syndrome is a chromosomal condition that occurs when ...

  1. Genetics Home Reference: proximal 18q deletion syndrome

    Science.gov (United States)

    ... Health Conditions Proximal 18q deletion syndrome Proximal 18q deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Proximal 18q deletion syndrome is a chromosomal condition that occurs when ...

  2. Eating in the absence of hunger but not loss of control behaviors are associated with 16p11.2 deletions.

    Science.gov (United States)

    Gill, Richard; Chen, Qixuan; D'Angelo, Debra; Chung, Wendy K

    2014-12-01

    The ∼600-kb BP4-BP5 16p11.2 deletion has been consistently associated with obesity. We studied two heritable disinhibited eating behaviors, eating in the absence of hunger (EAH) and loss of control (LOC), to better characterize the relationship between the deletion and obesity. Our study population included ninety-three 16p11.2 CNV carriers (64 with deletions and 29 with duplications) and their families. We performed analyses using linear mixed models and focused on deletion carriers. We confirmed previous associations between the 16p11.2 deletion and obesity (P affect. Conditioning BMI on the 16p11.2 deletion and each EAH behavior did not abolish the association between the deletion and obesity. LOC was underrepresented and not associated with the deletion. We report evidence that the 16p11.2 deletion may influence specific obesity-associated disinhibited eating behaviors: EAH due to external trigger and EAH due to boredom. Prospective studies are needed to confirm the temporal order of EAH behaviors and obesity related to the deletion. © 2014 The Obesity Society.

  3. Temporal naturalism

    Science.gov (United States)

    Smolin, Lee

    2015-11-01

    Two people may claim both to be naturalists, but have divergent conceptions of basic elements of the natural world which lead them to mean different things when they talk about laws of nature, or states, or the role of mathematics in physics. These disagreements do not much affect the ordinary practice of science which is about small subsystems of the universe, described or explained against a background, idealized to be fixed. But these issues become crucial when we consider including the whole universe within our system, for then there is no fixed background to reference observables to. I argue here that the key issue responsible for divergent versions of naturalism and divergent approaches to cosmology is the conception of time. One version, which I call temporal naturalism, holds that time, in the sense of the succession of present moments, is real, and that laws of nature evolve in that time. This is contrasted with timeless naturalism, which holds that laws are immutable and the present moment and its passage are illusions. I argue that temporal naturalism is empirically more adequate than the alternatives, because it offers testable explanations for puzzles its rivals cannot address, and is likely a better basis for solving major puzzles that presently face cosmology and physics. This essay also addresses the problem of qualia and experience within naturalism and argues that only temporal naturalism can make a place for qualia as intrinsic qualities of matter.

  4. Temporal contingency.

    Science.gov (United States)

    Gallistel, C R; Craig, Andrew R; Shahan, Timothy A

    2014-01-01

    Contingency, and more particularly temporal contingency, has often figured in thinking about the nature of learning. However, it has never been formally defined in such a way as to make it a measure that can be applied to most animal learning protocols. We use elementary information theory to define contingency in such a way as to make it a measurable property of almost any conditioning protocol. We discuss how making it a measurable construct enables the exploration of the role of different contingencies in the acquisition and performance of classically and operantly conditioned behavior. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. 19 CFR 142.49 - Deletion of C-4 Code.

    Science.gov (United States)

    2010-04-01

    .... Entry filers may delete C-4 Codes from Line Release by notifying the port director in writing on a Deletion Data Loading Sheet. Such notification shall state the C-4 Code which is to be deleted, the port... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A port...

  6. 78 FR 17641 - Procurement List; Proposed Addition and Deletion

    Science.gov (United States)

    2013-03-22

    ... Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add a..., Washington, DC Deletion The following product is proposed for deletion from the Procurement List: Product...

  7. 46 CFR 67.171 - Deletion; requirement and procedure.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Deletion; requirement and procedure. 67.171 Section 67...; Requirement for Exchange, Replacement, Deletion, Cancellation § 67.171 Deletion; requirement and procedure. (a... provided in § 67.161, and the vessel is subject to deletion from the roll of actively documented vessels...

  8. 78 FR 54871 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2013-09-06

    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to and deletions from the Procurement List. SUMMARY: The Committee is proposing to add... by the Defense Commissary Agency. Deletion The following product is proposed for deletion from the...

  9. Rapid deletion production in fungi via Agrobacterium mediated transformation of OSCAR deletion contructs.

    Science.gov (United States)

    Precise deletion of gene(s) of interest, while leaving the rest of the genome unchanged, provides the ideal product to determine that particular gene’s function in the living organism. In this protocol we describe the OSCAR method of precise and rapid deletion plasmid construction. OSCAR relies on t...

  10. Temporal Glare

    DEFF Research Database (Denmark)

    Ritschel, Tobias; Ihrke, Matthias; Frisvad, Jeppe Revall

    2009-01-01

    and attractive renderings of bright light sources. Based on the anatomy of the human eye, we propose a model that enables real-time simulation of dynamic glare on a GPU. This allows an improved depiction of HDR images on LDR media for interactive applications like games, feature films, or even by adding movement......Glare is a consequence of light scattered within the human eye when looking at bright light sources. This effect can be exploited for tone mapping since adding glare to the depiction of high-dynamic range (HDR) imagery on a low-dynamic range (LDR) medium can dramatically increase perceived contrast....... Even though most, if not all, subjects report perceiving glare as a bright pattern that fluctuates in time, up to now it has only been modeled as a static phenomenon. We argue that the temporal properties of glare are a strong means to increase perceived brightness and to produce realistic...

  11. Somatic mosaicism for a DMD gene deletion

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Kayoko; Ikeya, Kiyoko; Kondo, Eri [Tokyo Women`s Medical College (Japan)] [and others

    1995-03-13

    Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocytochemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5{prime} end containing both muscle and brain promoters. As the patient`s mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent from the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin-positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5{prime} end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed genotypic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation. 34 refs., 7 figs.

  12. 9q22 Deletion - First Familial Case

    Directory of Open Access Journals (Sweden)

    Yamamoto Toshiyuki

    2011-06-01

    Full Text Available Abstract Background Only 29 cases of constitutional 9q22 deletions have been published and all have been sporadic. Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400 due to haploinsufficiency of the PTCH1 gene (MIM *601309. Methods and Results We report two mentally retarded female siblings and their cognitively normal father, all carrying a similar 5.3 Mb microdeletion at 9q22.2q22.32, detected by array CGH (244 K. The deletion does not involve the PTCH1 gene, but instead 30 other gene,s including the ROR2 gene (MIM *602337 which causing both brachydactyly type 1 (MIM #113000 and Robinow syndrome (MIM #268310, and the immunologically active SYK gene (MIM *600085. The deletion in the father was de novo and FISH analysis of blood lymphocytes did not suggest mosaicism. All three patients share similar mild dysmorphic features with downslanting palpebral fissures, narrow, high bridged nose with small nares, long, deeply grooved philtrum, ears with broad helix and uplifted lobuli, and small toenails. All have significant dysarthria and suffer from continuous middle ear and upper respiratory infections. The father also has a funnel chest and unilateral hypoplastic kidney but the daughters have no malformations. Conclusions This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the PTCH1 gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.

  13. Deletion 22q13.3 syndrome

    Directory of Open Access Journals (Sweden)

    Phelan Mary C

    2008-05-01

    Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

  14. Some analogies between quantum cloning and quantum deleting

    International Nuclear Information System (INIS)

    Qiu Daowen

    2002-01-01

    We further verify the impossibility of deleting an arbitrary unknown quantum state, and also show it is impossible to delete two nonorthogonal quantum states as a consequence of unitarity of quantum mechanics. A quantum approximate (deterministic) deleting machine and a probabilistic (exact) deleting machine are constructed. The estimation for the global fidelity characterizing the efficiency of the quantum approximate deleting is given. We then demonstrate that unknown nonorthogonal states chosen from a set with their multiple copies can evolve into a linear superposition of multiple deletions and failure branches by a unitary process if and only if the states are linearly independent. It is notable that the proof for necessity is somewhat different from Pati's [Phys. Rev. Lett. 83, 2849 (1999)]. Another deleting machine for the input states that are unnecessarily linearly independent is also presented. The bounds on the success probabilities of these deleting machines are derived. So we expound some preliminary analogies between quantum cloning and deleting

  15. Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Crowley, Blaine; Ruffner, Melanie; McDonald McGinn, Donna M; Sullivan, Kathleen E

    2018-01-17

    The clinical features of 22q11.2 deletion syndrome include virtually every organ of the body. This review will focus on the immune system and the differences related to deletion breakpoints. A hypoplastic thymus was one of the first features described in this syndrome and low T cell counts, as a consequence of thymic hypoplasia, are the most commonly described immunologic feature. These are most prominently seen in early childhood and can be associated with increased persistence of viruses. Later in life, evidence of T cell exhaustion may be seen and secondary deficiencies of antibody function have been described. The relationship of the immunodeficiency to the deletion breakpoints has been understudied due to the infrequent analysis of people carrying smaller deletions. This manuscript will review the immune deficiency in 22q11.2 deletion syndrome and describe differences in the T cell counts related to the deletion breakpoints. Distal, non-TBX1 inclusive deletions, were found to be associated with better T cell counts. Another new finding is the relative preservation of T cell counts in those patients with a 22q11.2 duplication. © 2018 Wiley Periodicals, Inc.

  16. Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Larsen, Kit Melissa; Mørup, Morten; Birknow, Michelle Rosgaard; Fischer, Elvira; Hulme, Oliver; Vangkilde, Anders; Schmock, Henriette; Baaré, William Frans Christiaan; Didriksen, Michael; Olsen, Line; Werge, Thomas; Siebner, Hartwig R; Garrido, Marta I

    2018-01-30

    22q11.2 deletion syndrome (22q11.2DS) is one of the most common copy number variants and confers a markedly increased risk for schizophrenia. As such, 22q11.2DS is a homogeneous genetic liability model which enables studies to delineate functional abnormalities that may precede disease onset. Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia relative to healthy controls in MMN tasks. In the search for early risk-markers for schizophrenia we investigated the neural basis of change detection in a group with 22q11.2DS. We recorded high-density EEG from 19 young non-psychotic 22q11.2 deletion carriers, as well as from 27 healthy non-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison. We discuss these findings in terms of reduced adaptation and a general increased sensitivity to tones in 22q11.2DS. Copyright © 2018. Published by Elsevier B.V.

  17. Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects.

    Science.gov (United States)

    Varela, Monica Castro; Kok, Fernando; Otto, Paulo Alberto; Koiffmann, Celia Priszkulnik

    2004-12-01

    Angelman syndrome (AS) can result from either a 15q11-q13 deletion (del), paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. Here, we describe the phenotypic and behavioral variability detected in 49 patients with different classes of deletions and nine patients with UPD. Diagnosis was made by methylation pattern analysis of exon 1 of the SNRPN-SNURF gene and by microsatellite profiling of loci within and outside the 15q11-q13 region. There were no major phenotypic differences between the two main classes (BP1-BP3; BP2-BP3) of AS deletion patients, except for the absence of vocalization, more prevalent in patients with BP1-BP3 deletions, and for the age of sitting without support, which was lower in patients with BP2-BP3 deletions. Our data suggest that gene deletions (NIPA1, NIPA2, CYF1P1, GCP5) mapped to the region between breakpoints BP1 and BP2 may be involved in the severity of speech impairment, since all BP1-BP3 deletion patients showed complete absence of vocalization, while 38.1% of the BP2-BP3 deletion patients were able to pronounce syllabic sounds, with doubtful meaning. Compared to UPD patients, deletion patients presented a higher incidence of swallowing disorders (73.9% del x 22.2% UPD) and hypotonia (73.3% del x 28.57% UPD). In addition, children with UPD showed better physical growth, fewer or no seizures, a lower incidence of microcephaly, less ataxia and higher cognitive skills. As a consequence of their milder or less typical phenotype, AS may remain undiagnosed, leading to an overall underdiagnosis of the disease.

  18. Nature of frequent deletions in CEBPA.

    Science.gov (United States)

    Fuchs, Ota; Kostecka, Arnost; Provaznikova, Dana; Krasna, Blazena; Brezinova, Jana; Filkukova, Jitka; Kotlin, Roman; Kouba, Michal; Kobylka, Petr; Neuwirtova, Radana; Jonasova, Anna; Caniga, Miroslav; Schwarz, Jiri; Markova, Jana; Maaloufova, Jacqueline; Sponerova, Dana; Novakova, Ludmila; Cermak, Jaroslav

    2009-01-01

    C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.

  19. Obtaining a Proportional Allocation by Deleting Items

    NARCIS (Netherlands)

    Dorn, B.; de Haan, R.; Schlotter, I.; Röthe, J.

    2017-01-01

    We consider the following control problem on fair allocation of indivisible goods. Given a set I of items and a set of agents, each having strict linear preference over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the

  20. 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A S; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2015-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of

  1. 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...

  2. Union-Find with Constant Time Deletions

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Thorup, Mikkel; Gørtz, Inge Li

    2014-01-01

    operations performed, and α_M/N_(n) is a functional inverse of Ackermann’s function. They left open the question whether delete operations can be implemented more efficiently than find operations, for example, in o(log n) worst-case time. We resolve this open problem by presenting a relatively simple...

  3. Delayed chromosomal instability caused by large deletion

    International Nuclear Information System (INIS)

    Ojima, M.; Suzuki, K.; Kodama, S.; Watanabe, M.

    2003-01-01

    Full text: There is accumulating evidence that genomic instability, manifested by the expression of delayed phenotypes, is induced by X-irradiation but not by ultraviolet (UV) light. It is well known that ionizing radiation, such as X-rays, induces DNA double strand breaks, but UV-light mainly causes base damage like pyrimidine dimers and (6-4) photoproducts. Although the mechanism of radiation-induced genomic instability has not been thoroughly explained, it is suggested that DNA double strand breaks contribute the induction of genomic instability. We examined here whether X-ray induced gene deletion at the hprt locus induces delayed instability in chromosome X. SV40-immortalized normal human fibroblasts, GM638, were irradiated with X-rays (3, 6 Gy), and the hprt mutants were isolated in the presence of 6-thioguanine (6-TG). A 2-fold and a 60-fold increase in mutation frequency were found by 3 Gy and 6 Gy irradiation, respectively. The molecular structure of the hprt mutations was determined by multiplex polymerase chain reaction of nine exons. Approximately 60% of 3 Gy mutants lost a part or the entire hprt gene, and the other mutants showed point mutations like spontaneous mutants. All 6 Gy mutants show total gene deletion. The chromosomes of the hprt mutants were analyzed by Whole Human Chromosome X Paint FISH or Xq telomere FISH. None of the point or partial gene deletion mutants showed aberrations of X-chromosome, however total gene deletion mutants induced translocations and dicentrics involving chromosome X. These results suggest that large deletion caused by DNA double strand breaks destabilizes chromosome structure, which may be involved in an induction of radiation-induced genomic instability

  4. Quantum Temporal Imaging

    OpenAIRE

    Tsang, Mankei; Psaltis, Demetri

    2006-01-01

    The concept of quantum temporal imaging is proposed to manipulate the temporal correlation of entangled photons. In particular, we show that time correlation and anticorrelation can be converted to each other using quantum temporal imaging.

  5. 78 FR 29119 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2013-05-17

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and Deletion from the Procurement List. SUMMARY: This action adds products and services to the... Activity: Washington Headquarters Services (WHS), Acquisition Directorate, Washington, DC. Deletion On 4/5...

  6. 75 FR 41451 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2010-07-16

    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to and deletion from the Procurement List. SUMMARY: The Committee is proposing to add..., Mission and Installation Contracting Command--Carlisle Barracks, Carlisle, PA. Deletion Regulatory...

  7. Genetics Home Reference: 2q37 deletion syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions 2q37 deletion syndrome 2q37 deletion syndrome Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description 2q37 deletion syndrome is a condition that can affect many ...

  8. Genetics Home Reference: 1p36 deletion syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions 1p36 deletion syndrome 1p36 deletion syndrome Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description 1p36 deletion syndrome is a disorder that typically causes severe ...

  9. 5 CFR 1631.17 - Deletion of exempted information.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Deletion of exempted information. 1631.17... Deletion of exempted information. Where requested records contain matters which are exempted under 5 U.S.C... disclosed by the Board with deletions. To each such record, the Board shall attach a written justification...

  10. 75 FR 56995 - Procurement List Proposed Additions and Deletion

    Science.gov (United States)

    2010-09-17

    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and Deletion From the Procurement List. SUMMARY: The Committee is proposing to add... aggregated by the Defense Logistics Agency Troop Support, Philadelphia, PA. Deletion Regulatory Flexibility...

  11. 5 CFR 2502.18 - Deletion of exempted information.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Deletion of exempted information. 2502.18... Charges for Search and Reproduction § 2502.18 Deletion of exempted information. Where requested records... the remainder of the records, they shall be disclosed by the Office with deletions. To each such...

  12. 78 FR 75912 - Procurement List; Addition and Deletion

    Science.gov (United States)

    2013-12-13

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Addition to and deletion from the Procurement List. SUMMARY: This action adds a service to the Procurement...: General Services Administration, Fort Worth, TX Deletion On 11/1/2013 (78 FR 65618), the Committee for...

  13. 78 FR 27369 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2013-05-10

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and Deletion from the Procurement List. SUMMARY: This action adds products to the Procurement..., Philadelphia, PA. Deletion On 4/5/2013 (78 FR 20622-20623), the Committee for Purchase From People Who Are...

  14. Genetics Home Reference: 22q11.2 deletion syndrome

    Science.gov (United States)

    ... Health Conditions 22q11.2 deletion syndrome 22q11.2 deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description 22q11.2 deletion syndrome (which is also known by several other ...

  15. 75 FR 7450 - Procurement List: Proposed Addition and Deletion

    Science.gov (United States)

    2010-02-19

    ... Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed addition to and deletion from Procurement List. SUMMARY: The Committee is proposing to add to the... W6BA ACA, FT CARSON, COLORADO. Deletion Regulatory Flexibility Act Certification I certify that the...

  16. 77 FR 20795 - Procurement List Proposed Addition and Deletion

    Science.gov (United States)

    2012-04-06

    ... Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add a.... Deletion Regulatory Flexibility Act Certification I certify that the following action will not have a...

  17. 36 CFR 1275.58 - Deletion of restricted portions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Deletion of restricted... HISTORICAL MATERIALS OF THE NIXON ADMINISTRATION Access by the Public § 1275.58 Deletion of restricted... materials after the deletion of the portions which are restricted under this § 1275.50 or § 1275.52. ...

  18. Characterization of five partial deletions of the factor VIII gene

    International Nuclear Information System (INIS)

    Youssoufian, H.; Antonarakis, S.E.; Aronis, S.; Tsiftis, G.; Phillips, D.G.; Kazazian, H.H. Jr.

    1987-01-01

    Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, the authors have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes

  19. 75 FR 69638 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2010-11-15

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds products and a service to the...), DENVER, CO. Deletion On 9/17/2010 (75 FR 56995-56996), the Committee for Purchase From People Who Are...

  20. 76 FR 60810 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2011-09-30

    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add... Activity: Department of Energy, Idaho Operations Office, Idaho Falls, ID. DELETION Regulatory Flexibility...

  1. 44 CFR 5.27 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Deletion of identifying... Availability of General Agency Information, Rules, Orders, Policies, and Similar Material § 5.27 Deletion of..., interpretation, or staff manual or instruction. However, the justification for each deletion will be explained...

  2. 29 CFR 1610.20 - Deletion of exempted matters.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Deletion of exempted matters. 1610.20 Section 1610.20 Labor... Production or Disclosure Under 5 U.S.C. 552 § 1610.20 Deletion of exempted matters. Where requested records... the remainder of the records, they shall be disclosed by the Commission with deletions. To each such...

  3. 75 FR 41449 - Procurement List Additions and Deletion

    Science.gov (United States)

    2010-07-16

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds products and services to the... of the Air Force, FA6643 HQ AFRES LGC, Robins AFB, GA Deletion On 5/28/2010 (75 FR 29994-29995), the...

  4. 49 CFR 7.6 - Deletion of identifying detail.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Deletion of identifying detail. 7.6 Section 7.6... To Be Made Public by DOT § 7.6 Deletion of identifying detail. Whenever it is determined to be... the deletion will accompany the record published or made available for inspection. ...

  5. 76 FR 5142 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2011-01-28

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds services to the Procurement.... Contracting Activity: Department of Transportation, Federal Aviation Administration, Jamaica, NY. Deletion On...

  6. Genetics Home Reference: 22q13.3 deletion syndrome

    Science.gov (United States)

    ... Health Conditions 22q13.3 deletion syndrome 22q13.3 deletion syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description 22q13.3 deletion syndrome , which is also commonly known as Phelan- ...

  7. Probabilistic phylogenetic inference with insertions and deletions.

    Directory of Open Access Journals (Sweden)

    Elena Rivas

    2008-09-01

    Full Text Available A fundamental task in sequence analysis is to calculate the probability of a multiple alignment given a phylogenetic tree relating the sequences and an evolutionary model describing how sequences change over time. However, the most widely used phylogenetic models only account for residue substitution events. We describe a probabilistic model of a multiple sequence alignment that accounts for insertion and deletion events in addition to substitutions, given a phylogenetic tree, using a rate matrix augmented by the gap character. Starting from a continuous Markov process, we construct a non-reversible generative (birth-death evolutionary model for insertions and deletions. The model assumes that insertion and deletion events occur one residue at a time. We apply this model to phylogenetic tree inference by extending the program dnaml in phylip. Using standard benchmarking methods on simulated data and a new "concordance test" benchmark on real ribosomal RNA alignments, we show that the extended program dnamlepsilon improves accuracy relative to the usual approach of ignoring gaps, while retaining the computational efficiency of the Felsenstein peeling algorithm.

  8. Cognitive Temporal Document Priors

    NARCIS (Netherlands)

    Peetz, M.H.; de Rijke, M.

    2013-01-01

    Temporal information retrieval exploits temporal features of document collections and queries. Temporal document priors are used to adjust the score of a document based on its publication time. We consider a class of temporal document priors that is inspired by retention functions considered in

  9. Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

    OpenAIRE

    Tomescu MI Rihs TA Becker R Britz J Custo A Grouiller F Schneider M Debbané M Eliez S Miche

    2014-01-01

    Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS) known to have a 30 fold increased risk to develop schizophrenia already show deviant EEG microstates. If this is the case temporal alterations of EEG microstates in 22q11DS individuals could be considered as potential biomarkers for schizophrenia. We used high density...

  10. Submicroscopic deletions at 22q11.2: Variability of the clinical picture and delineation of a commonly deleted region

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Shaffer, L.G.; Greenberg, F. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-03-27

    DiGeorge anomaly (DGA) and velo-cardio-facial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The test probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1. Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region. 24 refs., 2 figs., 2 tabs.

  11. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E

    2008-01-01

    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

  12. Targeted gene deletion in Zygosaccharomyces bailii.

    Science.gov (United States)

    Mollapour, M; Piper, P

    2001-01-30

    Yeasts of the genus Zygosaccharomyces are notable agents of large-scale food spoilage. Despite the economic importance of these organisms, little is known about the stress adaptations whereby they adapt to many of the more severe conditions of food preservation. In this study it was shown that genes of Z. bailii, a yeast notable for its high resistances to food preservatives and ethanol, can be isolated by complementation of the corresponding mutant strains of Saccharomyces cerevisiae. It was also discovered that the acquisition by S. cerevisiae of a single small Z. bailii gene (ZbYME2) was sufficient for the former yeast to acquire the ability to degrade two major food preservatives, benzoic acid and sorbic acid. Using DNA cassettes containing dominant selectable markers and methods originally developed for performing gene deletions in S. cerevisiae, the two copies of ZbYME2 in the Z. bailii genome were sequentially deleted. The resulting Zbyme2/Zbyme2 homozygous deletant strain had lost any ability to utilize benzoate as sole carbon source and was more sensitive to weak acid preservatives during growth on glucose. Thus, ZbYME2, probably the nuclear gene for a mitochondrial mono-oxygenase function, is essential for Z. bailii to degrade food preservatives. This ability to catabolize weak acid preservatives is a significant factor contributing to the preservative resistance of Z. bailii under aerobic conditions. This study is the first to demonstrate that it is possible to delete in Z. bailii genes that are suspected as being important for growth of this organism in preserved foods and beverages. With the construction of further mutant of Z. bailii strains, a clearer picture should emerge of how this yeast adapts to the conditions of food preservation. This information will, in turn, allow the design of new preservation strategies. GenBank Accession Nos: ZbURA3 (AF279259), ZbTIM9 (AF279260), ZbYME2 (AF279261), ZbTRP1 (AF279262), ZbHHT1(AF296170). Copyright 2000 John

  13. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

    Science.gov (United States)

    2012-01-01

    Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone

  14. Method for introducing unidirectional nested deletions

    Science.gov (United States)

    Dunn, J.J.; Quesada, M.A.; Randesi, M.

    1999-07-27

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector. The cloning vector has an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe. 1 fig.

  15. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  16. Are there ethnic differences in deletions in the dystrophin gene?

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, M.; Verma, I.C. [All India Inst. of Medical Sciences, New Delhi (India)

    1997-01-20

    We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene. 38 refs., 2 figs., 3 tabs.

  17. Managing Temporal Knowledge in Port Management Systems

    Directory of Open Access Journals (Sweden)

    Anita Gudelj

    2006-05-01

    Full Text Available Large ports need to deal with a number of disparate activities:the movement of ships, containers and other cargo, theloading and unloading of ships and containers, customs activities.As well as human resources, anchorages, channels, lighters,tugs, berths, warehouse and other storage spaces have to beallocated and released. The efficient management of a port involvesmanaging these activities and resources, managing theflows of money involved between the agents providing and usingthese resources, and providing management information.Many information systems will be involved.Many applications have to deal with a large amount of datawhich not only represent the perceived state of the real world atpresent, but also past and/or future states. These applicationsare not served adequately by today's computer managementand database systems. In particular, deletions and updates insuch systems have destructive semantics. This means that previousdatabase contents (representing previous perceived statesof the real world cannot be accessed anymore.A review of how define temporal data models, based ongeneralizing a non-temporal data model in to a temporal one toimprove port management is presented. This paper describes apractical experiment which supports managing temporal dataalong with the corresponding prototype implementations.

  18. Temporal bone imaging

    International Nuclear Information System (INIS)

    Shaffer, K.A.

    1987-01-01

    Although pluridirectional tomography had been the standard method to evaluate the temporal bone, computed tomography has replaced it for nearly all applications. Magnetic resonance imaging can demonstrate nonosseous temporal bone structures as well

  19. Multiple causes of apnea in 1p36 deletion syndrome include seizures.

    Science.gov (United States)

    Kanabar, Gorande; Boyd, Stewart; Schugal, Anna; Bhate, Sanjay

    2012-06-01

    Apneic episodes have not previously been described in children with 1p36 deletion syndrome with seizures. Having encountered one such patient, we reviewed our experience of breathing difficulties in this syndrome, with particular attention to evidence of ictal apnea. We describe four children with 1p36 deletion syndrome, seizures and apneic episodes. Retrospective analysis of clinical features, seizure semiology and video-EEG data. All patients showed characteristic craniofacial features, mental retardation, and diffuse hypotonia and apnea. Seizure semiology included focal motor, ± secondary generalized tonic clonic and tonic events. All had histories of status epilepticus; three showed clustering of their habitual seizures. Assessment of apnea was complicated by the presence of multiple other potential causes including obesity, reflux, respiratory, and cardiac problems Epileptic apneas were confirmed in one child by video-telemetry. In three other children, an epileptic basis for apneas was inferred from their clinical histories and treatment response supported by EEG findings. In three children, epileptiform discharges occurred over fronto-centro-temporal regions. Epileptic apnea is a feature of 1p36 deletion syndrome, though episodic apnea is multifactorial in these children, and may need repeated re-appraisal. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Clival encephalocele and 5q15 deletion: a case report.

    Science.gov (United States)

    Puvabanditsin, Surasak; Malik, Imran; Garrow, Eugene; Francois, Lissa; Mehta, Rajeev

    2015-03-01

    A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion. © The Author(s) 2014.

  1. Panchromatic cooperative hyperspectral adaptive wide band deletion repair method

    Science.gov (United States)

    Jiang, Bitao; Shi, Chunyu

    2018-02-01

    In the hyperspectral data, the phenomenon of stripe deletion often occurs, which seriously affects the efficiency and accuracy of data analysis and application. Narrow band deletion can be directly repaired by interpolation, and this method is not ideal for wide band deletion repair. In this paper, an adaptive spectral wide band missing restoration method based on panchromatic information is proposed, and the effectiveness of the algorithm is verified by experiments.

  2. NPL deletion policy for RCRA-regulated TSD facilities finalized

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Under a new policy published by EPA on March 20, 1995, certain sites may be deleted from the National Priorities List (NPL) and deferred to RCRA corrective action. To be deleted from the NPL, a site must (1) be regulated under RCRA as a treatment, storage, or disposal (TSD) facility and (2) meet the four criteria specified by EPA. The new NPL deletion policy, which does not pertain to federal TSD facilities, became effective on April 19, 1995. 1 tab

  3. Mesial temporal sclerosis

    African Journals Online (AJOL)

    Kurt

    2005-07-29

    Jul 29, 2005 ... tail of the hippocampus were involved, with associated poor grey- white matter differentiation. In addi- tion, there was atrophy of the hip- pocampus and fornix, with dilatation of the temporal horn (Figs 1 - 4). Discussion. Mesial temporal sclerosis (MTS) is the commonest cause of temporal lobe epilepsy.

  4. A Comparative Study of Quantum and Classical Deletion

    International Nuclear Information System (INIS)

    Shen Yao; Hao Liang; Long Guilu

    2010-01-01

    Here in this letter, we study the difference between quantum and classical deletion. We point out that the linear mapping deletion operation used in the impossibility proof for quantum systems applies also to classical system. The general classical deletion operation is a combined operation of measurement and transformation, i.e., first read the state and then transfer the state to the standard blank state. Though both quantum information and classical information can be deleted in an open system, quantum information cannot be recovered while classical information can be recovered. (general)

  5. Memory for temporally dynamic scenes.

    Science.gov (United States)

    Ferguson, Ryan; Homa, Donald; Ellis, Derek

    2017-07-01

    Recognition memory was investigated for individual frames extracted from temporally continuous, visually rich film segments of 5-15 min. Participants viewed a short clip from a film in either a coherent or a jumbled order, followed by a recognition test of studied frames. Foils came either from an earlier or a later part of the film (Experiment 1) or from deleted segments selected from random cuts of varying duration (0.5 to 30 s) within the film itself (Experiment 2). When the foils came from an earlier or later part of the film (Experiment 1), recognition was excellent, with the hit rate far exceeding the false-alarm rate (.78 vs. 18). In Experiment 2, recognition was far worse, with the hit rate (.76) exceeding the false-alarm rate only for foils drawn from the longest cuts (15 and 30 s) and matching the false-alarm rate for the 5 s segments. When the foils were drawn from the briefest cuts (0.5 and 1.0 s), the false-alarm rate exceeded the hit rate. Unexpectedly, jumbling had no effect on recognition in either experiment. These results are consistent with the view that memory for complex visually temporal events is excellent, with the integrity unperturbed by disruption of the global structure of the visual stream. Disruption of memory was observed only when foils were drawn from embedded segments of duration less than 5 s, an outcome consistent with the view that memory at these shortest durations are consolidated with expectations drawn from the previous stream.

  6. Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways.

    Science.gov (United States)

    Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong; Fu, Xiaoying; Zhang, Zhiqian; Dong, Eric N; Hao, Zhao-Zhe; Dong, Jin-Tang

    2014-11-01

    Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer. Histologic analysis demonstrated that when one Pten allele was deleted, which causes mouse prostatic intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth, increased cell proliferation, and caused more severe morphologic and molecular alterations. Homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Pten deletion alone expanded basal cell population in a tumor as reported, Klf5 deletion in the Pten-null background clearly reduced basal cell population while expanding luminal cell population. Global gene expression profiling, pathway analysis, and experimental validation indicate that multiple mechanisms could mediate the tumor-promoting effect of Klf5 deletion, including the up-regulation of epidermal growth factor and its downstream signaling molecules AKT and ERK and the inactivation of the p15 cell cycle inhibitor. KLF5 also appears to cooperate with several transcription factors, including CREB1, Sp1, Myc, ER and AR, to regulate gene expression. These findings validate the tumor suppressor function of KLF5. They also yield a mouse model that shares two common genetic alterations with human prostate cancer-mutation/deletion of Pten and deletion of Klf5.

  7. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    Science.gov (United States)

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical circuits.

    Directory of Open Access Journals (Sweden)

    Shui-Wang Ying

    Full Text Available Hyperpolarization-activated, cyclic nucleotide-gated (HCN channels generate the pacemaking current, I(h, which regulates neuronal excitability, burst firing activity, rhythmogenesis, and synaptic integration. The physiological consequence of HCN activation depends on regulation of channel gating by endogenous modulators and stabilization of the channel complex formed by principal and ancillary subunits. KCNE2 is a voltage-gated potassium channel ancillary subunit that also regulates heterologously expressed HCN channels; whether KCNE2 regulates neuronal HCN channel function is unknown.We investigated the effects of Kcne2 gene deletion on I(h properties and excitability in ventrobasal (VB and cortical layer 6 pyramidal neurons using brain slices prepared from Kcne2(+/+ and Kcne2(-/- mice. Kcne2 deletion shifted the voltage-dependence of I(h activation to more hyperpolarized potentials, slowed gating kinetics, and decreased I(h density. Kcne2 deletion was associated with a reduction in whole-brain expression of both HCN1 and HCN2 (but not HCN4, although co-immunoprecipitation from whole-brain lysates failed to detect interaction of KCNE2 with HCN1 or 2. Kcne2 deletion also increased input resistance and temporal summation of subthreshold voltage responses; this increased intrinsic excitability enhanced burst firing in response to 4-aminopyridine. Burst duration increased in corticothalamic, but not thalamocortical, neurons, suggesting enhanced cortical excitatory input to the thalamus; such augmented excitability did not result from changes in glutamate release machinery since miniature EPSC frequency was unaltered in Kcne2(-/- neurons.Loss of KCNE2 leads to downregulation of HCN channel function associated with increased excitability in neurons in the cortico-thalamo-cortical loop. Such findings further our understanding of the normal physiology of brain circuitry critically involved in cognition and have implications for our understanding of

  9. "I feel stupid I can't delete..."::a study of users' cloud deletion practices and coping strategies

    OpenAIRE

    Ramokapane, Kopo Marvin; Rashid, Awais; Such, Jose

    2017-01-01

    Deletion of data from cloud storage and services is an important aspect of privacy and security. But how easy or simple a task is it for users to complete? Cloud users' deletion practices, challenges and coping strategies have not been well studied to date. We undertook an exploratory study to better understand this issue. Through in-depth semi-structured interviews and use of deletion scenarios with 26 subjects, we explored several key questions: why and when cloud users would like to delete...

  10. Neuro-behavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood

    International Nuclear Information System (INIS)

    Philippe, A.; Malan, V.; De Blois, M.C.; Colleaux, L.; Munnich, A.; Philippe, A.; De Blois, M.C.; Colleaux, L.; Munnich, A.; Boddaert, N.; Vaivre-Douret, L.; Robel, L.; Golse, B.; Vaivre-Douret, L.; Vaivre-Douret, L.; Danon-Boileau, L.; Heron, D.

    2008-01-01

    The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neuro-developmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains under-diagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neuro-behavioral phenotype and brain abnormalities of this micro-deletional syndrome. We assessed neuro-motor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion. Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages similar to 3 to 5 years; sensory processing dysfunction; and neuro-motor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion. The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely under-diagnosed condition. (authors)

  11. Neuro-behavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, A.; Malan, V.; De Blois, M.C.; Colleaux, L.; Munnich, A. [Hop Necker Enfants Malad, Assistance Publ Hop Paris, Natl Inst Hlth and Med Res, Paris (France); Philippe, A.; De Blois, M.C.; Colleaux, L.; Munnich, A. [HopNecker Enfants Malad, Assistance Publ Hop Paris, Dept Genet, Paris (France); Boddaert, N. [Natl Inst Hlth and Med Res, Mixed Unit Res 0205, Orsay (France); Vaivre-Douret, L.; Robel, L.; Golse, B. [Hop Necker Enfants Malad, Assistance Publ Hop Paris, Dept Psychiat, Paris (France); Vaivre-Douret, L. [Univ Paris 10, Mixed Unit Res S0669, Univ Paris 05, Univ Paris 11, Paris 10 (France); Vaivre-Douret, L. [Assistance Publ Hop Paris, Dept Obstet et Gynaecol, Paris (France); Danon-Boileau, L. [Natl Ctr Sci Res, Mixed Unit Res 7114, Paris (France); Heron, D. [Hop La Pitie Salpetriere, Assistance Publ HopParis, Dept Genet, Paris (France)

    2008-07-01

    The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neuro-developmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains under-diagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neuro-behavioral phenotype and brain abnormalities of this micro-deletional syndrome. We assessed neuro-motor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion. Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages similar to 3 to 5 years; sensory processing dysfunction; and neuro-motor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion. The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely under-diagnosed condition. (authors)

  12. AZFc deletion detected in a newborn with prenatally diagnosed Yq deletion.

    Science.gov (United States)

    Tóth, A; Tardy, E P; Gombos, S; Hajdu, K; Bátorfi, J; Krausz, C

    2001-04-01

    A case of prenatally diagnosed Yq deletion is described. Fluorescence in situ hybridisation (FISH) was used to identify the abnormal chromosome and to exclude mosaicism. Based on the cytogenetic result and the ultrasound investigation the pregnancy was continued. A newborn with normal male genitalia was delivered. Microdeletion analysis of the Yq showed the absence of the AZFc region. This type of deletion has been described as being associated with azoospermia or oligozoospermia with a progressive decrease of sperm number over time. Long-term andrological follow-up of the newborn will be necessary with eventual cryoconservation of sperm at early adulthood. The present report proposes that AZF analysis combined with FISH has an important role in accurate genetic counselling in sex chromosome anomalies. Copyright 2001 John Wiley & Sons, Ltd.

  13. Linguistic and Psychomotor Development in Children with Chromosome 14 Deletions

    Science.gov (United States)

    Zampini, Laura; D'Odorico, Laura; Zanchi, Paola; Zollino, Marcella; Neri, Giovanni

    2012-01-01

    The present study focussed on a specific type of rare genetic condition: chromosome 14 deletions. Children with this genetic condition often show developmental delays and brain and neurological problems, although the type and severity of symptoms varies depending on the size and location of the deleted genetic material. The specific aim of the…

  14. Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis.

    Science.gov (United States)

    Fromenty, B; Grimbert, S; Mansouri, A; Beaugrand, M; Erlinger, S; Rötig, A; Pessayre, D

    1995-01-01

    Alcohol abuse may lead to microvesicular steatosis, a lesion ascribed to impaired mitochondrial function. Because alcohol abuse leads to reactive oxygen species in the hepatic mitochondria, it may damage mitochondrial DNA. The aim of this study was to look for the presence of the "common" 4977-base pair deletion in the hepatic mitochondrial DNA of alcoholic patients and age-matched, nonalcoholic controls. Hepatic DNA was subjected to two polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively. The deletion was found in 6 of 10 alcoholics with microvesicular steatosis, 2 of 17 alcoholic patients with macrovacuolar steatosis, but in none of 12 patients with acute alcoholic hepatitis, 11 patients with alcoholic cirrhosis, or 62 nonalcoholic patients of comparable ages with various other liver diseases or normal liver histology. In all patients with the deletion, restriction fragments of deleted mitochondrial DNA co-migrated with those of reference Pearson bone marrow-pancreas syndrome patients with the common mitochondrial DNA deletion. The common deletion is frequent in the hepatic DNA of alcoholic patients with microvesicular steatosis. Alcohol-induced mitochondrial DNA damage may contribute to the occurrence of this lesion in some alcoholics.

  15. Lack of association of insertion/deletion polymorphism in ...

    African Journals Online (AJOL)

    In the present preliminary study the insertion/deletion polymorphism within angiotensin converting enzyme gene is not likely to be associated with nephropathy in type 2 diabetic patients of Punjabi population of Pakistan. Key words: Angiotensin converting enzymes, insertion/deletion polymorphism, albuminuria and type 2 ...

  16. Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder

    Science.gov (United States)

    Günes, Serkan; Ekinci, Özalp; Ekinci, Nuran; Toros, Fevziye

    2017-01-01

    Deletion or duplication of the short arm of chromosome 9 may lead to a variety of clinical conditions including craniofacial and limb abnormalities, skeletal malformations, mental retardation, and autism spectrum disorder. Here, we present a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum disorder.

  17. Mitochondrial DNA deletions in patients with chronic suppurative otitis media.

    Science.gov (United States)

    Tatar, Arzu; Tasdemir, Sener; Sahin, Ibrahim; Bozoglu, Ceyda; Erdem, Haktan Bagis; Yoruk, Ozgur; Tatar, Abdulgani

    2016-09-01

    The aim of this study was to investigate the 4977 and 7400 bp deletions of mitochondrial DNA in patients with chronic suppurative otitis media and to indicate the possible association of mitochondrial DNA deletions with chronic suppurative otitis media. Thirty-six patients with chronic suppurative otitis media were randomly selected to assess the mitochondrial DNA deletions. Tympanomastoidectomy was applied for the treatment of chronic suppurative otitis media, and the curettage materials including middle ear tissues were collected. The 4977 and 7400 bp deletion regions and two control regions of mitochondrial DNA were assessed by using the four pair primers. DNA was extracted from middle ear tissues and peripheral blood samples of the patients, and then polymerase chain reactions (PCRs) were performed. PCR products were separated in 2 % agarose gel. Seventeen of 36 patients had the heterozygote 4977 bp deletion in the middle ear tissue but not in peripheral blood. There wasn't any patient who had the 7400 bp deletion in mtDNA of their middle ear tissue or peripheral blood tissue. The patients with the 4977 bp deletion had a longer duration of chronic suppurative otitis media and a higher level of hearing loss than the others (p otitis media and the reactive oxygen species can cause the mitochondrial DNA deletions and this may be a predisposing factor to sensorineural hearing loss in chronic suppurative otitis media. An antioxidant drug as a scavenger agent may be used in long-term chronic suppurative otitis media.

  18. Phosphatase and tensin homologue deleted on chromosome 10 ...

    African Journals Online (AJOL)

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene deleted or mutated in many human cancers such as glioblastoma, spinal tumors, prostate, bladder, adrenals, thyroid, breast, endometrium, and colon cancers. They result from loss of heterozygosity (LOH) for the PTEN ...

  19. Generalised deletion designs | Gachii | African Journal of Science ...

    African Journals Online (AJOL)

    In this paper asymmetrical single replicate factorial designs are constructed from symmetrical single replicate factorial designs using the deletion technique. The study is along the lines of Voss(1986), Chauhan(1989) and Gachii and Odhiambo(1997). We give results for the general order deletion designs of the form sn-m1(s ...

  20. 24 CFR 990.155 - Addition and deletion of units.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Addition and deletion of units. 990.155 Section 990.155 Housing and Urban Development Regulations Relating to Housing and Urban...; Computation of Eligible Unit Months § 990.155 Addition and deletion of units. (a) Changes in public housing...

  1. 4977-bp mitochondrial DNA deletion in infertile patients with varicocele.

    Science.gov (United States)

    Gashti, N G; Salehi, Z; Madani, A H; Dalivandan, S T

    2014-04-01

    Varicocele is the abnormal inflexion and distension of veins of the pampiniform plexus within spermatic cord and is one of the amendable causes of male infertility. It can increase reactive oxygen species (ROS) production in semen and cause oxidative stress. The purpose of this study was to analyse spermatozoa mtDNA 4977-bp deletion in infertile men with varicocele. To detect 4977-bp deletion in spermatozoa mtDNA, semen samples of 60 infertile patients with clinical varicocele and 90 normal men from northern Iran were prepared. After extraction of spermatozoa total DNA, Gap polymerase chain reaction (Gap PCR) was performed. 4977-bp deletion was observed in 81.66% of patients with varicocele, while approximately 15.55% of controls had this deletion. As spermatozoa from patients with varicocele had a high frequency of occurrence of 4977-bp deletion in mtDNA [OR = 24.18, 95% confidence interval (CI) = 10.15-57.57, P deletion in spermatozoa and cause infertility in north Iranian men. However, to determine the relation between sperm mtDNA 4977-bp deletion and varicocele-induced infertility, larger population-based studies are needed. It is concluded that there is an association between sperm mtDNA 4977-bp deletion and varicocele-induced infertility in the population studied. © 2013 Blackwell Verlag GmbH.

  2. 34 CFR 5.16 - Deletion of identifying details.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Deletion of identifying details. 5.16 Section 5.16 Education Office of the Secretary, Department of Education AVAILABILITY OF INFORMATION TO THE PUBLIC PURSUANT TO PUB. L. 90-23 (Eff. until 7-14-10) What Records Are Available § 5.16 Deletion of identifying...

  3. 76 FR 27999 - Procurement List; Addition and Deletion

    Science.gov (United States)

    2011-05-13

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Addition to and Deletion from the Procurement List. SUMMARY: This action adds a service to the Procurement... USA ROCK ISL Arsenal, Rock Island, IL. [[Page 28000

  4. 42 CFR 401.118 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Deletion of identifying details. 401.118 Section 401.118 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Deletion of identifying details. When CMS publishes or otherwise makes available an opinion or order...

  5. Solid-phase nested deletion: a new subcloning-less method for generating nested deletions.

    Science.gov (United States)

    Yohda, M; Kato, N; Endo, I

    1995-08-31

    We have developed a new subcloning-less method for generating nested deletions which we have termed Solid-Phase Nested Deletion. The basic procedure for this method is as follows. The target DNA fragment is cloned in the multiple cloning site of a cloning vector, pUC or its derivatives, and amplified by PCR using a set of primers, one of which is 5'-biotinylated. The amplified DNA is partially digested by a restriction enzyme with a 4-base recognition sequence. The digested DNA is ligated with a synthetic adapter DNA. Monodiverse beads coupled with streptavidin (Dynabeads M-280 streptavidin) are added to the mixture and the biotinylated DNA fragments are separated by applying magnetic field. The unidirectionally deleted DNA fragments are recovered by PCR from the magnetic beads, and size-fractionated by agarose gel electrophoresis. The DNA fragments are amplified by PCR and used for sequencing. We demonstrate the potential of this method using a 4878-bp EcoRI fragment of lambda phage DNA.

  6. Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity

    DEFF Research Database (Denmark)

    Abbott, Geoffrey W; Jepps, Thomas A

    2016-01-01

    ) subunits. We investigated the effects of targeted germline Kcne4 deletion on mesenteric artery reactivity in adult male and female mice. Kcne4 deletion increased mesenteric artery contractility in response to α-adrenoceptor agonist methoxamine, and decreased responses to Kv7.2-7.5 channel activator ML213......, in male but not female mice. In contrast, Kcne4 deletion markedly decreased vasorelaxation in response to isoprenaline in both male and female mice. Kcne4 expression was 2-fold lower in the female versus the male mouse mesenteric artery, and Kcne4 deletion elicited only moderate changes of other Kcne...... transcripts, with no striking sex-specific differences. However, Kv7.4 protein expression in females was twice that in males, and was reduced in both sexes by Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of Kv7 channel activity to modulate vascular tone, and provide the first...

  7. Attenuation of monkeypox virus by deletion of genomic regions

    Science.gov (United States)

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.

    2015-01-01

    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  8. Role of DNA deletion length in mutation and cell survival

    International Nuclear Information System (INIS)

    Braby, L.A.; Morgan, T.L.

    1992-01-01

    A model is presented which is based on the assumption that malignant transformation, mutation, chromosome aberration, and reproductive death of cells are all manifestations of radiation induced deletions in the DNA of the cell, and that the size of the deletion in relation to the spacing of essential genes determines the consequences of that deletion. It is assumed that two independent types of potentially lethal lesions can result in DNA deletions, and that the relative numbers of these types of damage is dependent on radiation quality. The repair of the damage reduces the length of a deletion, but does not always eliminate it. The predictions of this model are in good agreement with a wide variety of experimental evidence. (author)

  9. Ku80-deleted cells are defective at base excision repair

    International Nuclear Information System (INIS)

    Li, Han; Marple, Teresa; Hasty, Paul

    2013-01-01

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H 2 O 2 and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs

  10. Frequency of KLK3 gene deletions in the general population.

    Science.gov (United States)

    Rodriguez, Santiago; Al-Ghamdi, Osama A; Guthrie, Philip Ai; Shihab, Hashem A; McArdle, Wendy; Gaunt, Tom; Alharbi, Khalid K; Day, Ian Nm

    2017-07-01

    Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring.

  11. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  12. Advances in temporal logic

    CERN Document Server

    Fisher, Michael; Gabbay, Dov; Gough, Graham

    2000-01-01

    Time is a fascinating subject that has captured mankind's imagination from ancient times to the present. It has been, and continues to be studied across a wide range of disciplines, from the natural sciences to philosophy and logic. More than two decades ago, Pnueli in a seminal work showed the value of temporal logic in the specification and verification of computer programs. Today, a strong, vibrant international research community exists in the broad community of computer science and AI. This volume presents a number of articles from leading researchers containing state-of-the-art results in such areas as pure temporal/modal logic, specification and verification, temporal databases, temporal aspects in AI, tense and aspect in natural language, and temporal theorem proving. Earlier versions of some of the articles were given at the most recent International Conference on Temporal Logic, University of Manchester, UK. Readership: Any student of the area - postgraduate, postdoctoral or even research professor ...

  13. Tau deletion promotes brain insulin resistance.

    Science.gov (United States)

    Marciniak, Elodie; Leboucher, Antoine; Caron, Emilie; Ahmed, Tariq; Tailleux, Anne; Dumont, Julie; Issad, Tarik; Gerhardt, Ellen; Pagesy, Patrick; Vileno, Margaux; Bournonville, Clément; Hamdane, Malika; Bantubungi, Kadiombo; Lancel, Steve; Demeyer, Dominique; Eddarkaoui, Sabiha; Vallez, Emmanuelle; Vieau, Didier; Humez, Sandrine; Faivre, Emilie; Grenier-Boley, Benjamin; Outeiro, Tiago F; Staels, Bart; Amouyel, Philippe; Balschun, Detlef; Buee, Luc; Blum, David

    2017-08-07

    The molecular pathways underlying tau pathology-induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer's disease patients. © 2017 Marciniak et al.

  14. Dermatoglyphic Profile in 22q Deletion Syndrome

    Science.gov (United States)

    Martín, B.; Fañanás, L.; Gutiérrez, B.; Chow, E.W.C.; Bassett, A.S.

    2011-01-01

    A genetic subtype of schizophrenia has been described in 22q11 Deletion syndrome. Previous studies have described an excess of dermatoglyphic alterations in schizophrenia, such as low a–b ridge counts (ABRCs), a high frequency of ridge dissociations, and increased dermatoglyphic fluctuating asymmetry. Little is known however, about the dermatoglyphic profile of 22qDS subjects showing psychotic symptoms and its similarity to the previously reported anomalies in schizophrenia. We studied the palmar dermatoglyphics of 22 subjects with 22qDS of predominantly Caucasian origin, 15 of whom had psychotic illness, and in 84 healthy controls of similar ethnicity. We observed higher values for total ATD angle in cases than in controls (P = 0.04). In addition, there was an excess of radial figures in the hypothenar area in cases, especially in the left hand. Interestingly, greater fluctuating asymmetry, determined by the absolute difference between right and left ABRC, was observed in 22qDS subjects compared to controls (P = 0.05). However, no differences were found for ABRCs and frequency of dissociations. Despite the small sample size, the palmprints analyzed suggest the existence of an altered dermatoglyphic profile in 22qDS, involving: (i) ATD angle amplitude, (ii) presence of radial loops in the hypothenar area, and (iii) an increment of fluctuating asymmetry. The first two features are similar to those found in other genetic syndromes associated with low IQ, while high levels of fluctuating asymmetry have often been reported in schizophrenia. PMID:15211630

  15. Optimization of Internally Deleted Dystrophin Constructs.

    Science.gov (United States)

    Reza, Mojgan; Laval, Steve H; Roos, Andreas; Carr, Stephanie; Lochmüller, Hanns

    2016-10-01

    Duchenne muscular dystrophy (DMD) is a severe, genetic muscle disease caused by the absence of the sarcolemmal protein dystrophin. Gene replacement therapy is considered a potential strategy for the treatment of DMD, aiming to restore the missing protein. Although the elements of the dystrophin molecule have been identified and studies in transgenic mdx mice have explored the importance of a number of these structural domains, the resulting modified dystrophin protein products that have been developed so far are only partially characterized in relation to their structure and function in vivo. To optimize a dystrophin cDNA construct for therapeutic application we designed and produced four human minidystrophins within the packaging capacity of lentiviral vectors. Two novel minidystrophins retained the centrally located neuronal nitric oxide synthase (nNOS)-anchoring domain in order to achieve sarcolemmal nNOS restoration, which is lost in most internally deleted dystrophin constructs. Functionality of the resulting truncated dystrophin proteins was investigated in muscle of adult dystrophin-deficient mdx mice followed by a battery of detailed immunohistochemical and morphometric tests. This initial assessment aimed to determine the overall suitability of various constructs for cloning into lentiviral vectors for ex vivo gene delivery to stem cells for future preclinical studies.

  16. Gibson Deletion: a novel application of isothermal in vitro recombination.

    Science.gov (United States)

    Kalva, Swara; Boeke, Jef D; Mita, Paolo

    2018-01-01

    Recombinant DNA technology is today a fundamental tool for virtually all biological research fields. Among the many techniques available for the construction of a "custom DNA" molecule, the isothermal in vitro assembly, or Gibson assembly, allows for an efficient, one-step, scarless recombination-based assembly. Here, we apply and characterize the use of Gibson assembly for the deletion of DNA sequences around a DNA cut. This method, that we named "Gibson Deletion", can be used to easily substitute or delete one or more restriction sites within a DNA molecule. We show that Gibson Deletion is a viable method to delete up to 100 nucleotides from the DNA ends of a cleavage site. In addition, we found that Gibson Deletion can be performed using single strand DNA with the same efficiency as using double strand DNA molecules. Gibson Deletion is a novel, easy and convenient application of isothermal in vitro assembly, that performs with high efficiency and can be implemented for a broad range of applications.

  17. THE EFFECT OF TOPOLOGY ON TEMPORAL NETWORK DYNAMICS

    Directory of Open Access Journals (Sweden)

    Valentina Yu. Guleva

    2016-11-01

    Full Text Available The effect of initial network topology on a temporal network dynamics is studied. An example of interbank exposures network is considered. It is modeled with a graph, where banks are represented by nodes and interbank lending is represented by edges. The dynamical processes in аtemporal network are defined by state changes of nodes and lie in edges and nodes addition and deletion in a graph, and modification of node states contribute to network evolution. The algorithm of network modification over the whole evolution period is fixed. We present parameters of random, scale free and small world generative models corresponding to different simulation results with fixed modification algorithms. The influence of initial graph topologies on temporal network dynamics is demonstrated. The results obtained give the possibility to assess time interval before the attainment of unstable topology state, and to estimate an optimal topology for the transition to a steady state under fixed modification algorithms.

  18. Chondroblastoma of temporal bone

    Energy Technology Data Exchange (ETDEWEB)

    Tanohta, K.; Noda, M.; Katoh, H.; Okazaki, A.; Sugiyama, S.; Maehara, T.; Onishi, S.; Tanida, T.

    1986-07-01

    The case of a 55-year-old female with chondroblastoma arising from the left temporal bone is presented. Although 10 cases of temporal chondroblastoma have been reported, this is the first in which plain radiography, pluridirectional tomography, computed tomography (CT) and angiography were performed. We discuss the clinical and radiological aspects of this rare tumor.

  19. Dynamic Temporal Decoupling

    NARCIS (Netherlands)

    Mountakis, K.S.; Klos, T.; Witteveen, C.

    2017-01-01

    Temporal decoupling is a method to distribute a temporal constraint problem over a number of actors, such that each actor can solve its own part of the problem. It then ensures that the partial solutions provided can be always merged to obtain a complete solution. This paper discusses static and

  20. Performance of quantum cloning and deleting machines over coherence

    Science.gov (United States)

    Karmakar, Sumana; Sen, Ajoy; Sarkar, Debasis

    2017-10-01

    Coherence, being at the heart of interference phenomena, is found to be an useful resource in quantum information theory. Here we want to understand quantum coherence under the combination of two fundamentally dual processes, viz., cloning and deleting. We found the role of quantum cloning and deletion machines with the consumption and generation of quantum coherence. We establish cloning as a cohering process and deletion as a decohering process. Fidelity of the process will be shown to have connection with coherence generation and consumption of the processes.

  1. Precise mapping of 17 deletion breakpoints within the central hotspot deletion region (introns 50 and 51) of the DMD gene.

    Science.gov (United States)

    Esposito, Gabriella; Tremolaterra, Maria Roberta; Marsocci, Evelina; Tandurella, Igor Cm; Fioretti, Tiziana; Savarese, Maria; Carsana, Antonella

    2017-12-01

    Exon deletions in the human DMD gene, which encodes the dystrophin protein, are the molecular defect in 50-70% of cases of Duchenne/Becker muscular dystrophies. Deletions are preferentially clustered in the 5' (exons 2-20) and the central (exons 45-53) region of DMD, likely because local DNA structure predisposes to specific breakage or recombination events. Notably, innovative therapeutic strategies may rescue dystrophin function by homology-based specific targeting of sequences within the central DMD hot spot deletion region. To further study molecular mechanisms that generate such frequent genome variations and to identify residual intronic sequences, we sequenced 17 deletion breakpoints within introns 50 and 51 of DMD and analyzed the surrounding genomic architecture. There was no breakpoint clustering within the introns nor extensive homology between sequences adjacent to each junction. However, at or near the breakpoint, we found microhomology, short tandem repeats, interspersed repeat elements and short sequence stretches that predispose to DNA deletion or bending. Identification of such structural elements contributes to elucidate general mechanisms generating deletion within the DMD gene. Moreover, precise mapping of deletion breakpoints and localization of repeated elements are of interest, because residual intronic sequences may be targeted by therapeutic strategies based on genome editing correction.

  2. 22q11.2 deletion syndrome

    Science.gov (United States)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2016-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  3. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  4. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    International Nuclear Information System (INIS)

    Zhang, Y.; Woloschak, G.E.

    1996-01-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly γ-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF 1 male mice exposed to protracted neutron radiation

  5. Non-deletion mutations in Egyptian patients with Duchenne ...

    African Journals Online (AJOL)

    . Molecular analysis included Polymerase Chain Reaction (PCR) followed by multiplex ligation-dependent probe amplification (MLPA) to those patients with no deletion by PCR. Direct sequencing of the whole dystrophin gene was done to ...

  6. Additions and deletions to the known cerambycidae (Coleoptera) of Bolivia

    Science.gov (United States)

    An additional 137 species and two tribes are added to the known cerambycid fauna of Bolivia while 12 species are deleted. Comments and statistics regarding the growth of knowledge on the Bolivian Cerambycid fauna and species endemicity are included....

  7. Temporal form in interaction design

    DEFF Research Database (Denmark)

    Vallgårda, Anna; Winther, Morten Trøstrup; Mørch, Nina

    2015-01-01

    Interaction design is distinguished from most other design disciplines through its temporal form. Temporal form is the computational structure that enables and demands a temporal expression in the resulting design. Temporal form is what enables poetry. In music, temporal form is the composition o...

  8. Improved detection of small deletions in complex pools of DNA

    Science.gov (United States)

    Edgley, Mark; D’Souza, Anil; Moulder, Gary; McKay, Sheldon; Shen, Bin; Gilchrist, Erin; Moerman, Donald; Barstead, Robert

    2002-01-01

    About 40% of the genes in the nematode Caenorhabditis elegans have homologs in humans. Based on the history of this model system, it is clear that the application of genetic methods to the study of this set of genes would provide important clues to their function in humans. To facilitate such genetic studies, we are engaged in a project to derive deletion alleles in every gene in this set. Our standard methods make use of nested PCR to hunt for animals in mutagenized populations that carry deletions at a given locus. The deletion bearing animals exist initially in mixed populations where the majority of the animals are wild type at the target. Therefore, the production of the PCR fragment representing the deletion allele competes with the production of the wild type fragment. The size of the deletion fragment relative to wild type determines whether it can compete to a level where it can be detected above the background. Using our standard conditions, we have found that when the deletion is 600 bp, they do not work well to detect mutants with smaller deletions. Here we report a new strategy to detect small deletion alleles in complex DNA pools. Our new strategy is a modification of our standard PCR based screens. In the first round of the nested PCR, we include a third PCR primer between the two external primers. The presence of this third primer leads to the production of three fragments from wild type DNA. We configure the system so that two of these three fragments cannot serve as a template in the second round of the nested PCR. The addition of this third primer, therefore, handicaps the amplification from wild type template. On the other hand, the amplification of mutant fragments where the binding site for the third primer is deleted is unabated. Overall, we see at least a 500-fold increase in the sensitivity for small deletion fragments using our new method. Using this new method, we report the recovery of new deletion alleles within 12 C.elegans genes. PMID

  9. Optimizing Temporal Queries

    DEFF Research Database (Denmark)

    Toman, David; Bowman, Ivan Thomas

    2003-01-01

    , these query languages are implemented by translating temporal queries into standard relational queries. However, the compiled queries are often quite cumbersome and expensive to execute even using state-of-the-art relational products. This paper presents an optimization technique that produces more efficient...... translated SQL queries by taking into account the properties of the encoding used for temporal attributes. For concreteness, this translation technique is presented in the context of SQL/TP; however, these techniques are also applicable to other temporal query languages....

  10. The significance of chromosome deletions in atomic-bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Shigeta, Chiharu; Oguma, Nobuo; Kamada, Nanao; Deng, Z.; Niimi, Masanobu; Aisaka, Tadaichi.

    1986-01-01

    In 39 A-bomb survivors 40 years after exposure at ≤ 1,000 m from ground zero, the frequency and features of chromosome deletions in peripheral lymphocytes were examined using a differential staining technique. Simultaneously, in vitro irradiation experiment with Cf-252 was made to infer chromosome aberrations occuring immediately after exposure. Californium-252 with 100 rad induced dicentric and ring chromosomes in 40 % of the cells and acentric fragments in 44 %. Among the A-bomb survivors, chromosome aberrations were observed in 651 (21 %) of the total 3,136 cells. There were 146 cells with deletions (22 % of abnormal cells; 5 % of the total cells), and 10 cells with acentric fragment (0.3 % of the total cells). The figure for deletions was far higher than that reported in the literature. A large number of deletions were seen in chromosomes no.4, no.21, and no.22, and a few deletions in chromosomes no.7 and no.20. Significance of chromosome deletions is discussed. (Namekawa, K.)

  11. Temporal Lobe Seizure

    Science.gov (United States)

    ... pregnancy Temporal lobe seizure Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  12. Neocortical Temporal Lobe Epilepsy

    Science.gov (United States)

    Bercovici, Eduard; Kumar, Balagobal Santosh; Mirsattari, Seyed M.

    2012-01-01

    Complex partial seizures (CPSs) can present with various semiologies, while mesial temporal lobe epilepsy (mTLE) is a well-recognized cause of CPS, neocortical temporal lobe epilepsy (nTLE) albeit being less common is increasingly recognized as separate disease entity. Differentiating the two remains a challenge for epileptologists as many symptoms overlap due to reciprocal connections between the neocortical and the mesial temporal regions. Various studies have attempted to correctly localize the seizure focus in nTLE as patients with this disorder may benefit from surgery. While earlier work predicted poor outcomes in this population, recent work challenges those ideas yielding good outcomes in part due to better localization using improved anatomical and functional techniques. This paper provides a comprehensive review of the diagnostic workup, particularly the application of recent advances in electroencephalography and functional brain imaging, in neocortical temporal lobe epilepsy. PMID:22953057

  13. Temporal bone meningiomas.

    Science.gov (United States)

    Vrionis, F D; Robertson, J H; Gardner, G; Heilman, C B

    1999-01-01

    Meningiomas involving the temporal bone may originate from arachnoid cell nests present within the temporal bone (intratemporal), but more frequently originate from arachnoid cell nests of the posterior or middle cranial fossa with secondary invasion of the TB (extratemporal). In this study, we retrospectively reviewed the charts of 13 patients with meningiomas involving the temporal bone who underwent surgery. Tumors of the posterior fossa with only temporal bone hyperostosis, but without invasion, were excluded. Patients presented primarily with otologic symptoms and signs. The tumors originated in the temporal bone (5/13), jugular foramen (4/13), petroclival region (2/13), the asterion (1/13) or the internal auditory meatus (1/13). All of the intratemporal meningiomas had the radiological appearance of en-plaque menigiomas. The tumor extended into the middle ear (11/13), eustachian tube (5/13), and/or the labyrinth (3/13). A gross total resection was achieved in 11 patients and a subtotal resection in 2 patients. The lower cranial nerves were infiltrated by tumor in 4 patients, and were sacrificed. At a mean follow-up of approximately 6 years, 12 patients are currently alive and doing well and 1 died from tumor progression. Six patients showed tumor recurrence and were reoperated on (5/6) or followed conservatively (1/6). Surgical treatment of temporal bone meningiomas is associated with high recurrence rate due to indiscreet tumor margins. Combined surgical approaches (temporal craniotomy and mastoidectomy) by neurosurgical and otological teams are recommended for meningiomas originating in the temporal bone.

  14. 41 CFR 51-2.3 - Notice of proposed addition or deletion.

    Science.gov (United States)

    2010-07-01

    ... addition or deletion. 51-2.3 Section 51-2.3 Public Contracts and Property Management Other Provisions... or deletion. At least 30 days prior to the Committee's consideration of the addition or deletion of a... Register announcing the proposed addition or deletion and providing interested persons an opportunity to...

  15. 10 CFR 9.19 - Segregation of exempt information and deletion of identifying details.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Segregation of exempt information and deletion of... Information Act Regulations § 9.19 Segregation of exempt information and deletion of identifying details. (a... deletions are made from parts of the record by computer, the amount of information deleted will be indicated...

  16. Molecular studies of deletions at the human steroid sulfatase locus

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, L.J.; Yen, P.; Pomerantz, D.; Martin, E.; Rolewic, L.; Mohandas, T. (Univ. of California, Los Angeles (USA))

    1989-11-01

    The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment of DNA that is unique to the X chromosome. In contrast to most X chromosome-encoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS activity produced the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS{sup {minus}} individuals have large deletions at the STS locus. The authors and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome.

  17. Amino-acid composition after loop deletion drives domain swapping.

    Science.gov (United States)

    Nandwani, Neha; Surana, Parag; Udgaonkar, Jayant B; Das, Ranabir; Gosavi, Shachi

    2017-10-01

    Rational engineering of a protein to enable domain swapping requires an understanding of the sequence, structural and energetic factors that favor the domain-swapped oligomer over the monomer. While it is known that the deletion of loops between β-strands can promote domain swapping, the spliced sequence at the position of the loop deletion is thought to have a minimal role to play in such domain swapping. Here, two loop-deletion mutants of the non-domain-swapping protein monellin, frame-shifted by a single residue, were designed. Although the spliced sequence in the two mutants differed by only one residue at the site of the deletion, only one of them (YEIKG) promoted domain swapping. The mutant containing the spliced sequence YENKG was entirely monomeric. This new understanding that the domain swapping propensity after loop deletion may depend critically on the chemical composition of the shortened loop will facilitate the rational design of domain swapping. © 2017 The Protein Society.

  18. The Yeast Deletion Collection: A Decade of Functional Genomics

    Science.gov (United States)

    Giaever, Guri; Nislow, Corey

    2014-01-01

    The yeast deletion collections comprise >21,000 mutant strains that carry precise start-to-stop deletions of ∼6000 open reading frames. This collection includes heterozygous and homozygous diploids, and haploids of both MATa and MATα mating types. The yeast deletion collection, or yeast knockout (YKO) set, represents the first and only complete, systematically constructed deletion collection available for any organism. Conceived during the Saccharomyces cerevisiae sequencing project, work on the project began in 1998 and was completed in 2002. The YKO strains have been used in numerous laboratories in >1000 genome-wide screens. This landmark genome project has inspired development of numerous genome-wide technologies in organisms from yeast to man. Notable spinoff technologies include synthetic genetic array and HIPHOP chemogenomics. In this retrospective, we briefly describe the yeast deletion project and some of its most noteworthy biological contributions and the impact that these collections have had on the yeast research community and on genomics in general. PMID:24939991

  19. Molecular studies of deletions at the human steroid sulfatase locus

    International Nuclear Information System (INIS)

    Shapiro, L.J.; Yen, P.; Pomerantz, D.; Martin, E.; Rolewic, L.; Mohandas, T.

    1989-01-01

    The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment of DNA that is unique to the X chromosome. In contrast to most X chromosome-encoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS activity produced the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS - individuals have large deletions at the STS locus. The authors and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome

  20. Scalable Design of Paired CRISPR Guide RNAs for Genomic Deletion.

    Directory of Open Access Journals (Sweden)

    Carlos Pulido-Quetglas

    2017-03-01

    Full Text Available CRISPR-Cas9 technology can be used to engineer precise genomic deletions with pairs of single guide RNAs (sgRNAs. This approach has been widely adopted for diverse applications, from disease modelling of individual loci, to parallelized loss-of-function screens of thousands of regulatory elements. However, no solution has been presented for the unique bioinformatic design requirements of CRISPR deletion. We here present CRISPETa, a pipeline for flexible and scalable paired sgRNA design based on an empirical scoring model. Multiple sgRNA pairs are returned for each target, and any number of targets can be analyzed in parallel, making CRISPETa equally useful for focussed or high-throughput studies. Fast run-times are achieved using a pre-computed off-target database. sgRNA pair designs are output in a convenient format for visualisation and oligonucleotide ordering. We present pre-designed, high-coverage library designs for entire classes of protein-coding and non-coding elements in human, mouse, zebrafish, Drosophila melanogaster and Caenorhabditis elegans. In human cells, we reproducibly observe deletion efficiencies of ≥50% for CRISPETa designs targeting an enhancer and exonic fragment of the MALAT1 oncogene. In the latter case, deletion results in production of desired, truncated RNA. CRISPETa will be useful for researchers seeking to harness CRISPR for targeted genomic deletion, in a variety of model organisms, from single-target to high-throughput scales.

  1. Temporal network epidemiology

    CERN Document Server

    Holme, Petter

    2017-01-01

    This book covers recent developments in epidemic process models and related data on temporally varying networks. It is widely recognized that contact networks are indispensable for describing, understanding, and intervening to stop the spread of infectious diseases in human and animal populations; “network epidemiology” is an umbrella term to describe this research field. More recently, contact networks have been recognized as being highly dynamic. This observation, also supported by an increasing amount of new data, has led to research on temporal networks, a rapidly growing area. Changes in network structure are often informed by epidemic (or other) dynamics, in which case they are referred to as adaptive networks. This volume gathers contributions by prominent authors working in temporal and adaptive network epidemiology, a field essential to understanding infectious diseases in real society.

  2. Temporal Experience and Metaphysics

    Directory of Open Access Journals (Sweden)

    Graham Peebles

    Full Text Available ABSTRACT The well-known phenomenological argument draws metaphysical conclusions about time, specifically about change through time and the resulting passage or flow of time, from our temporal experience. The argument begins with the phenomenological premise that there is a class of properties which underlies our experience of time and change through time, and its conclusion is that these properties are not merely experienced but exemplified. I argue that the phenomenological argument is best served by the adoption of a representational theory of perception. I then present a representational theory of temporal experience.

  3. A Rare Syndrome of Deletion in 2 Siblings

    Directory of Open Access Journals (Sweden)

    Aravindhan Veerapandiyan MBBS

    2017-08-01

    Full Text Available The Glutamate receptor, ionotropic, delta 2 gene codes for an ionotropic glutamate delta-2 receptor, which is selectively expressed in cerebellar Purkinje cells, and facilitates cerebellar synapse organization and transmission. The phenotype associated with the deletion of Glutamate receptor, ionotropic, delta 2 gene in humans was initially defined in 2013. In this case report, the authors describe 2 brothers who presented with developmental delay, tonic upward gaze, nystagmus, oculomotor apraxia, hypotonia, hyperreflexia, and ataxia. They were found to have a homozygous intragenic deletion within the Glutamate receptor, ionotropic, delta 2 gene at exon 2. Our patients serve as an addition to the literature of previously reported children with this rare clinical syndrome associated with Glutamate receptor, ionotropic, delta 2 deletion.

  4. Physiological characterisation of acuB deletion in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; De Jongh, Willem Adriaan; Olsson, Lisbeth

    2009-01-01

    that a basal level of FacB activity exists under glucose-repressive conditions. In the present study, the effect of deletion of acuB on the physiology of A. niger was assessed. Differences in organic acid and acetate production, enzyme activities and extracellular amino and non-amino organic acid production...... pathways that are not directly involved in acetate metabolism are influenced by acuB deletion. Clear differences in organic acid consumption and production were detected between the a dagger acuB and reference strain. However, the hypothesis that AcuB is responsible for basal AcuA activity necessary...... for activation of acetate metabolic pathways, even during growth on glucose, could not be confirmed. The experiments demonstrated that also when acuB was deleted, no acetate was formed. Therefore, AcuB cannot be the only activator of AcuA, and another control mechanism has to be available for activating AcuA....

  5. The diagnosis and molecular analysis of a novel 21.9kb deletion (Qinzhou type deletion) causing α+ thalassemia.

    Science.gov (United States)

    Long, Ju; Yan, Shanhuo; Lao, Kegan; Pang, Wanrong; Ye, Xuehe; Sun, Lei

    2014-04-01

    α-Thalassemia is a common single-gene genetic disease that can cause Hb Bart's hydrops fetalis and Hb H disease in tropical and subtropical regions. When examining conventional thalassemia genes, an only detected --(SEA) genotype sample needs further analysis. In doing so, we found a novel 21.9kb deletion (Qinzhou type deletion). The deletion position of the novel 21.9kb deletion is from 14373bp to 36299bp of the α-globin gene cluster (NG_000006.1); thus, there exists a 21927bp sequence deletion, into which a 29bp sequence is added. After sequence analysis, a group of Gap-PCR primers were synthesized to diagnose this novel thalassemia genotype. Through pedigree analysis, we deduced that the propositus obtained the novel alleles from her mother. The genotype of this propositus is --(SEA)/-α(21.9) and its phenotype conforms to the characteristics of Hb H disease, establishing that the combination between -α(21.9) genotype and α(0) genotype can lead to Hb H disease. By molecular analysis, we established that this case fits the characteristic of an α(+) thalassemia genotype. © 2013.

  6. Dissecting the phenotypes of Dravet syndrome by gene deletion.

    Science.gov (United States)

    Rubinstein, Moran; Han, Sung; Tai, Chao; Westenbroek, Ruth E; Hunker, Avery; Scheuer, Todd; Catterall, William A

    2015-08-01

    Neurological and psychiatric syndromes often have multiple disease traits, yet it is unknown how such multi-faceted deficits arise from single mutations. Haploinsufficiency of the voltage-gated sodium channel Nav1.1 causes Dravet syndrome, an intractable childhood-onset epilepsy with hyperactivity, cognitive deficit, autistic-like behaviours, and premature death. Deletion of Nav1.1 channels selectively impairs excitability of GABAergic interneurons. We studied mice having selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons. In brain slices, these deletions cause increased threshold for action potential generation, impaired action potential firing in trains, and reduced amplification of postsynaptic potentials in those interneurons. Selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons increases susceptibility to thermally-induced seizures, which are strikingly prolonged when Nav1.1 is deleted in both interneuron types. Mice with global haploinsufficiency of Nav1.1 display autistic-like behaviours, hyperactivity and cognitive impairment. Haploinsufficiency of Nav1.1 in parvalbumin-expressing interneurons causes autistic-like behaviours, but not hyperactivity, whereas haploinsufficiency in somatostatin-expressing interneurons causes hyperactivity without autistic-like behaviours. Heterozygous deletion in both interneuron types is required to impair long-term spatial memory in context-dependent fear conditioning, without affecting short-term spatial learning or memory. Thus, the multi-faceted phenotypes of Dravet syndrome can be genetically dissected, revealing synergy in causing epilepsy, premature death and deficits in long-term spatial memory, but interneuron-specific effects on hyperactivity and autistic-like behaviours. These results show that multiple disease traits can arise from similar functional deficits in specific interneuron types. © The Author (2015). Published by Oxford University Press on

  7. Viable deletions of the M13 complementary strand origin

    OpenAIRE

    Kim, Myoung Hee; Hines, Jane C.; Ray, Dan S.

    1981-01-01

    The single-stranded DNA of bacteriophage M13 is converted to a duplex replicative form by a mechanism involving RNA-primed initiation at a single unique site on the viral DNA. The DNA sequence that specifies the RNA primer is contained largely within one of two adjacent hairpin structures protected from DNase degradation by RNA polymerase. We have used in vitro techniques to construct a series of M13 mutants having deletions in the region of the complementary strand origin. Deletions of the d...

  8. Embryonic mosaic deletion of APP results in displaced Reelin-expressing cells in the cerebral cortex.

    Science.gov (United States)

    Callahan, D G; Taylor, W M; Tilearcio, M; Cavanaugh, T; Selkoe, D J; Young-Pearse, T L

    2017-04-15

    It is widely accepted that amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease. In addition, APP has been proposed to have functions in numerous biological processes including neuronal proliferation, differentiation, migration, axon guidance, and neurite outgrowth, as well as in synapse formation and function. However, germline knockout of APP yields relatively subtle phenotypes, and brain development appears grossly normal. This is thought to be due in part to functional compensation by APP family members and other type I transmembrane proteins. Here, we have generated a conditional mouse knockout for APP that is controlled temporally using Cre ER and tamoxifen administration. We show that total cortical expression of APP is reduced following tamoxifen administration during embryonic time points critical for cortical lamination, and that this results in displacement of Reelin-positive cells below the cortical plate with a concurrent elevation in Reelin protein levels. These results support a role for APP in cortical lamination and demonstrate the utility of a conditional knockout approach in which APP can be deleted with temporal control in vivo. This new tool should be useful for many different applications in the study of APP function across the mammalian life span. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Increasing on-target cleavage efficiency for CRISPR/Cas9-induced large fragment deletion in Myxococcus xanthus.

    Science.gov (United States)

    Yang, Ying-Jie; Wang, Ye; Li, Zhi-Feng; Gong, Ya; Zhang, Peng; Hu, Wen-Chao; Sheng, Duo-Hong; Li, Yue-Zhong

    2017-08-16

    The CRISPR/Cas9 system is a powerful tool for genome editing, in which the sgRNA binds and guides the Cas9 protein for the sequence-specific cleavage. The protocol is employable in different organisms, but is often limited by cell damage due to the endonuclease activity of the introduced Cas9 and the potential off-target DNA cleavage from incorrect guide by the 20 nt spacer. In this study, after resolving some critical limits, we have established an efficient CRISPR/Cas9 system for the deletion of large genome fragments related to the biosynthesis of secondary metabolites in Myxococcus xanthus cells. We revealed that the high expression of a codon-optimized cas9 gene in M. xanthus was cytotoxic, and developed a temporally high expression strategy to reduce the cell damage from high expressions of Cas9. We optimized the deletion protocol by using the tRNA-sgRNA-tRNA chimeric structure to ensure correct sgRNA sequence. We found that, in addition to the position-dependent nucleotide preference, the free energy of a 20 nt spacer was a key factor for the deletion efficiency. By using the developed protocol, we achieved the CRISPR/Cas9-induced deletion of large biosynthetic gene clusters for secondary metabolites in M. xanthus DK1622 and its epothilone-producing mutant. The findings and the proposals described in this paper were suggested to be workable in other organisms, for example, other Gram negative bacteria with high GC content.

  10. Temporal logic motion planning

    CSIR Research Space (South Africa)

    Seotsanyana, M

    2010-01-01

    Full Text Available In this paper, a critical review on temporal logic motion planning is presented. The review paper aims to address the following problems: (a) In a realistic situation, the motion planning problem is carried out in real-time, in a dynamic, uncertain...

  11. Temporal compressive sensing systems

    Science.gov (United States)

    Reed, Bryan W.

    2017-12-12

    Methods and systems for temporal compressive sensing are disclosed, where within each of one or more sensor array data acquisition periods, one or more sensor array measurement datasets comprising distinct linear combinations of time slice data are acquired, and where mathematical reconstruction allows for calculation of accurate representations of the individual time slice datasets.

  12. Temporal Photon Differentials

    DEFF Research Database (Denmark)

    Schjøth, Lars; Frisvad, Jeppe Revall; Erleben, Kenny

    2010-01-01

    The finite frame rate also used in computer animated films is cause of adverse temporal aliasing effects. Most noticeable of these is a stroboscopic effect that is seen as intermittent movement of fast moving illumination. This effect can be mitigated using non-zero shutter times, effectively...

  13. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Valencia Posso, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...

  14. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Valencia, Frank Dan

    Concurrent constraint programming (ccp) is a formalism for concurrency in which agents interact with one another by telling (adding) and asking (reading) information in a shared medium. Temporal ccp extends ccp by allowing agents to be constrained by time conditions. This dissertation studies...

  15. Dynamic epistemic temporal logic

    NARCIS (Netherlands)

    Renne, B.; Sack, Joshua; Yap, Audrey; He, X.; Horty, J.; Pacuit, E.

    2009-01-01

    We introduce a new type of arrow in the update frames (or "action models") of Dynamic Epistemic Logic in a way that enables us to reason about epistemic temporal dynamics in multi-agent systems that need not be synchronous. Since van Benthem and Pacuit (later joined by Hoshi and Gerbrandy) showed

  16. Temporal bone imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemmerling, Marc [Algemeen Ziekenhuis Sint-Lucas, Gent (Belgium). Dept. of Radiology; Foer, Bert de (ed.) [Sint-Augustinus Ziekenhuis, Wilrijk (Belgium). Dept. of Radiology

    2015-04-01

    Complete overview of imaging of normal and diseased temporal bone. Straightforward structure to facilitate learning. Detailed consideration of newer imaging techniques, including the hot topic of diffusion-weighted imaging. Includes a chapter on anatomy that will be of great help to the novice interpreter of imaging findings. Excellent illustrations throughout. This book provides a complete overview of imaging of normal and diseased temporal bone. After description of indications for imaging and the cross-sectional imaging anatomy of the area, subsequent chapters address the various diseases and conditions that affect the temporal bone and are likely to be encountered regularly in clinical practice. The classic imaging methods are described and discussed in detail, and individual chapters are included on newer techniques such as functional imaging and diffusion-weighted imaging. There is also a strong focus on postoperative imaging. Throughout, imaging findings are documented with the aid of numerous informative, high-quality illustrations. Temporal Bone Imaging, with its straightforward structure based essentially on topography, will prove of immense value in daily practice.

  17. Information and Temporality

    Science.gov (United States)

    Flender, Christian

    2016-09-01

    Being able to give reasons for what the world is and how it works is one of the defining characteristics of modernity. Mathematical reason and empirical observation brought science and engineering to unprecedented success. However, modernity has reached a post-state where an instrumental view of technology needs revision with reasonable arguments and evidence, i.e. without falling back to superstition and mysticism. Instrumentally, technology bears the potential to ease and to harm. Easing and harming can't be controlled like the initial development of technology is a controlled exercise for a specific, mostly easing purpose. Therefore, a revised understanding of information technology is proposed based upon mathematical concepts and intuitions as developed in quantum mechanics. Quantum mechanics offers unequaled opportunities because it raises foundational questions in a precise form. Beyond instrumentalism it enables to raise the question of essences as that what remains through time what it is. The essence of information technology is acausality. The time of acausality is temporality. Temporality is not a concept or a category. It is not epistemological. As an existential and thus more comprehensive and fundamental than a concept or a category temporality is ontological; it does not simply have ontic properties. Rather it exhibits general essences. Datability, significance, spannedness and openness are general essences of equiprimordial time (temporality).

  18. Experimental temporal quantum steering

    Czech Academy of Sciences Publication Activity Database

    Bartkiewicz, K.; Černoch, Antonín; Lemr, K.; Miranowicz, A.; Nori, F.

    2016-01-01

    Roč. 6, Nov (2016), 1-8, č. článku 38076. ISSN 2045-2322 R&D Projects: GA ČR GAP205/12/0382 Institutional support: RVO:68378271 Keywords : temporal quantum steering * EPR steering Subject RIV: BH - Optics, Masers, Lasers Impact factor: 4.259, year: 2016

  19. Polymorphism of angiotensin converting enzyme (insertion/deletion ...

    Indian Academy of Sciences (India)

    and electrolyte balance, and blood pressure (Malik et al. 1997) contains a ... of diverse population groups with a variable prevalence of hypertension .... group were in HWE. The 287-bp insertion/deletion polymorphism located in intron 16 of ACE gene was detected by PCR analysis in the three ethnic groups. The insertion ...

  20. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  1. Commentary: The Thrill of Professionalization and the Agony of Deletes

    Science.gov (United States)

    Waite, Susan Field; Leavell, Judy A.

    2006-01-01

    Although some teacher educators hoped that the creation and use of standards would help to professionalize teaching, the discourse of standards and accountability is now being used to erode teacher education. Many teacher educators who anticipated the thrill of professionalization through standards are now experiencing the agony of deletes,…

  2. Case-Deletion Diagnostics for Nonlinear Structural Equation Models

    Science.gov (United States)

    Lee, Sik-Yum; Lu, Bin

    2003-01-01

    In this article, a case-deletion procedure is proposed to detect influential observations in a nonlinear structural equation model. The key idea is to develop the diagnostic measures based on the conditional expectation of the complete-data log-likelihood function in the EM algorithm. An one-step pseudo approximation is proposed to reduce the…

  3. Angiotensin-converting enzyme insertion/deletion gene ...

    Indian Academy of Sciences (India)

    Angiotensin-converting enzyme insertion/deletion gene polymorphism in cystic fibrosis patients. Sabrine Oueslati Sondess Hadj Fredj Hajer Siala Amina Bibi Hajer Aloulou Lamia Boughamoura Khadija Boussetta Sihem Barsaoui Taieb Messaoud. Research Note Volume 95 Issue 1 March 2016 pp 193-196 ...

  4. Induced pluripotent stem cells with a mitochondrial DNA deletion.

    Science.gov (United States)

    Cherry, Anne B C; Gagne, Katelyn E; McLoughlin, Erin M; Baccei, Anna; Gorman, Bryan; Hartung, Odelya; Miller, Justine D; Zhang, Jin; Zon, Rebecca L; Ince, Tan A; Neufeld, Ellis J; Lerou, Paul H; Fleming, Mark D; Daley, George Q; Agarwal, Suneet

    2013-07-01

    In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here, we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. Copyright © 2013 AlphaMed Press.

  5. Induced pluripotent stem cells with a pathological mitochondrial DNA deletion

    Science.gov (United States)

    Cherry, Anne B. C.; Gagne, Katelyn E.; McLoughlin, Erin M.; Baccei, Anna; Gorman, Bryan; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Ince, Tan A.; Neufeld, Ellis J.; Lerou, Paul H.; Fleming, Mark D.; Daley, George Q.; Agarwal, Suneet

    2013-01-01

    In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. PMID:23400930

  6. DSN1 deletion is deleterious to the Saccharomyces cerevisiae while ...

    African Journals Online (AJOL)

    insufficiency and segregational errors in yeast diploid single deletants. Expression of Dsn1p in CHO has been achieved using the pcDNA 3.1/HIS A expression vector. Analysis by DNA sequencing showed no changes in the DSN1 DNA sequence.

  7. The insertion/deletion polymorphism of angiotensin-converting ...

    African Journals Online (AJOL)

    The association between type 2 diabetes mellitus (T2DM) and essential hypertension (EH) is not well understood. Both conditions result from an interaction of multiple genetic (ethnic) and environmental (geographical) factors. One possible genetic determinant is the angiotensin-converting enzyme (ACE) insertion/deletion ...

  8. An angiotensin I-converting enzyme insertion/deletion ...

    Indian Academy of Sciences (India)

    Angiotensin I-converting enzyme (ACE) plays a majorrole in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the roleof ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects,including 333 asthma patients and ...

  9. QR in Child Grammar: Evidence from Antecedent-Contained Deletion

    Science.gov (United States)

    Syrett, Kristen; Lidz, Jeffrey

    2009-01-01

    We show that 4-year-olds assign the correct interpretation to antecedent-contained deletion (ACD) sentences because they have the correct representation of these structures. This representation involves Quantifier Raising (QR) of a Quantificational Noun Phrase (QNP) that must move out of the site of the verb phrase in which it is contained to…

  10. The detection of large deletions or duplications in genomic DNA.

    Science.gov (United States)

    Armour, J A L; Barton, D E; Cockburn, D J; Taylor, G R

    2002-11-01

    While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi-quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under-ascertained. Gene dosage methods provide the additional benefit of reporting allele drop-out in the PCR. This could impact on SNP surveys, where large-scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications. Copyright 2002 Wiley-Liss, Inc.

  11. Catalytic properties of ADAM12 and its domain deletion mutants

    DEFF Research Database (Denmark)

    Jacobsen, Jonas; Visse, Robert; Sørensen, Hans Peter

    2008-01-01

    of pro, catalytic, disintegrin, cysteine-rich, and EGF domains. Here we present a novel activity of recombinant ADAM12-S and its domain deletion mutants on S-carboxymethylated transferrin (Cm-Tf). Cleavage of Cm-Tf occurred at multiple sites, and N-terminal sequencing showed that the enzyme exhibits...

  12. Deletion Mutagenesis and Identification of Causative Mutations in Maize.

    Science.gov (United States)

    Jia, Shangang; Li, Aixia; Zhang, Chi; Holding, David

    2018-01-01

    We describe a method for gamma-irradiation of mature maize seeds to generate mutants with opaque endosperm and reduced kernel fill phenotypes. We also describe methods for mapping mutants and identifying causal gene mutations. Using this method, a population of 1788M2 families and 47 Mo17 × F2s showing stable, segregating, and viable kernel phenotypes was developed. For molecular characterization of the mutants, we utilized a novel functional genomics platform that combines separate Bulked Segregant RNA and exome sequencing data sets (BSREx-seq) to map causative mutations and identify candidate genes within mapping intervals. We also describe the use of exome capture sequencing of F2 mutant and normal pools to perform mapping and candidate gene identification without the need for separate RNA-seq (BSEx-seq). To exemplify the utility of the deletion mutants for functional genomics and provide proof-of-concept for the bioinformatics platform, we summarize the identification of the causative deletion in two mutants. Mutant 937, which was characterized by BSREx-seq, harbors a 6203-bp in-frame deletion covering six exons within the Opaque-1 gene on chromosome 4. Preliminary investigation of opaque mutant 1486 with BSEx-seq shows a tight mapping interval and associated deletion on chromosome 10.

  13. Association of insertion–deletion polymorphism of ACE gene and ...

    African Journals Online (AJOL)

    Introduction: Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Many studies proposed an association of the insertion (I)/deletion (D) polymorphism (indel) in intron 16 of the gene for angiotensin I-converting enzyme (ACE) on chromosome 17q23 with Alzheimer's disease. ACE indel and related ...

  14. 76 FR 16733 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2011-03-25

    ...-Wagner-O'Day Act (41 U.S.C. 46-48c) in connection with the product and services proposed for deletion... AVIATION, RICHMOND, VA. Services: Service Type/Locations: Janitorial/Custodial. U.S. Army Reserve Center... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed...

  15. [An updated review of 1p36 deletion (monosomy) syndrome].

    Science.gov (United States)

    Bello, Sabina; Rodríguez-Moreno, Antonio

    The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Approximately 100 cases have been documented since 1981. This rare disease is the most common subtelomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Variations in angiotensin-converting enzyme gene insertion/deletion ...

    Indian Academy of Sciences (India)

    deletion (I/D) polymorphism in the Indian population is poorly known. In order to determine the status of the polymorphism, young unrelated male army recruits were screened. The population had cultural and linguistic differences and lived in an ...

  17. Genetic Counseling for the 22q11.2 Deletion

    Science.gov (United States)

    McDonald-McGinn, Donna M.; Zackai, Elaine H.

    2008-01-01

    Because of advances in palliative medical care, children with the 22q11.2 deletion syndrome are surviving into adulthood. An increase in reproductive fitness will likely follow necessitating enhanced access to genetic counseling for these patients and their families. Primary care physicians/obstetric practitioners are in a unique position to…

  18. Lack of Association of Insertion/Deletion Polymorphism in ...

    African Journals Online (AJOL)

    DRNAQSHAB

    2012-01-19

    Jan 19, 2012 ... associated with nephropathy in type 2 diabetic patients of Punjabi population of Pakistan. Key words: Angiotensin converting enzymes, insertion/deletion polymorphism, albuminuria and type 2 diabetes mellitus. INTRODUCTION. Diabetic nephropathy is a leading cause of diabetic. *Corresponding author.

  19. 77 FR 31335 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2012-05-25

    .... Services Service Type/Location: Laundry and Dry Cleaning Service, Buckley Air Force Base Lodging & Medical... products and services to the Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have other severe disabilities, and deletes a service previously provided by such...

  20. Effect Alpha Globlin Gene Deletion And Gamma Globin Gene -158 ...

    African Journals Online (AJOL)

    ... have been unable to find a molecular basis for the benign clinical course in all our patients. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition. Keywords: β- thalassemia, Xmn1 polymorphism, α-globin gene deletion. Egyptian Journal of Biochemistry and Molecular Biology Vol.

  1. Rare copy number deletions predict individual variation in intelligence.

    Directory of Open Access Journals (Sweden)

    Ronald A Yeo

    2011-01-01

    Full Text Available Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in "mutation load" emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent copy number variations (CNVs, and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77 had been administered the Wechsler Abbreviated Scale of Intelligence (WASI. After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = -.30, p = .01. As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES, we also examined the impact of ethnicity (Anglo/White vs. Other, as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed.

  2. Deletion affecting band 7q36 not associated with holoprosencephaly

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahim, S.A.D.; Krivchenia, E.; Mohamed, A.N. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    Although the appearance of 7q36 aberrations have been postulated to be responsible for holoprosencephaly (HPE), the presence of a de novo 7q36 deletion in fetus without HPE has not been reported. We report the first case of a fetus with 7q36 deletion but lacking HPE. Ultrasound examination of a 25-year-old G3P1 Caucasian female showed small head circumference with microcephaly at 28 weeks. Decreased amniotic fluid volume, bilateral renal dilatation and abnormal facial features were also noted. Chromosome analysis after cordocentesis showed an abnormal female karyotype with a deletion involving the chromosome band 7q36, 46,XX,del(7)(q36). Chromosome studies on the biological parents were normal. In view of the chromosome finding and after extensive counseling, the couple elected to terminate the pregnancy. The chromosome findings were confirmed by fetal blood chromosome analysis at termination. Post-mortem examination confirmed dysmorphic features including a depressed nasal bridge and large flat ears with no lobules, but no cleft lip or palate was noted. Internal abnormalities included a bicuspid pulmonary valve and abnormally located lungs. The brain weighed 190g (249 {plus_minus} 64g expected) and had symmetric cerebral hemispheres without evidence of HPE or other gross or microscopic malformation, except focal cerebellar cortical dysplasia. In summary, our patient showed a deletion of the same chromosomal band implicated in HPE but lacked HPE. This finding indicates that 7q36 deletion may be seen in the absence of HPE and suggests that other genetic mechanisms may be responsible for HPE in this setting.

  3. Redefining phenotypes associated with mitochondrial DNA single deletion.

    Science.gov (United States)

    Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Carelli, Valerio; Comi, Giacomo Pietro; Donati, Maria Alice; Federico, Antonio; Minetti, Carlo; Moggio, Maurizio; Mongini, Tiziana; Santorelli, Filippo Maria; Servidei, Serenella; Tonin, Paola; Toscano, Antonio; Bruno, Claudio; Bello, Luca; Caldarazzo Ienco, Elena; Cardaioli, Elena; Catteruccia, Michela; Da Pozzo, Paola; Filosto, Massimiliano; Lamperti, Costanza; Moroni, Isabella; Musumeci, Olimpia; Pegoraro, Elena; Ronchi, Dario; Sauchelli, Donato; Scarpelli, Mauro; Sciacco, Monica; Valentino, Maria Lucia; Vercelli, Liliana; Zeviani, Massimo; Siciliano, Gabriele

    2015-05-01

    Progressive external ophthalmoplegia (PEO), Kearns-Sayre syndrome (KSS) and Pearson syndrome are the three sporadic clinical syndromes classically associated with single large-scale deletions of mitochondrial DNA (mtDNA). PEO plus is a term frequently utilized in the clinical setting to identify patients with PEO and some degree of multisystem involvement, but a precise definition is not available. The purpose of the present study is to better define the clinical phenotypes associated with a single mtDNA deletion, by a retrospective study on a large cohort of 228 patients from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". In our database, single deletions account for about a third of all patients with mtDNA-related disease, more than previously recognized. We elaborated new criteria for the definition of PEO and "KSS spectrum" (a category of which classic KSS represents the most severe extreme). The criteria for "KSS spectrum" include the resulting multisystem clinical features associated with the KSS features, and which therefore can predict their presence or subsequent development. With the new criteria, we were able to classify nearly all our single-deletion patients: 64.5% PEO, 31.6% KSS spectrum (including classic KSS 6.6%) and 2.6% Pearson syndrome. The deletion length was greater in KSS spectrum than in PEO, whereas heteroplasmy was inversely related with age at onset. We believe that the new phenotype definitions implemented here may contribute to a more homogeneous patient categorization, which will be useful in future cohort studies of natural history and clinical trials.

  4. Temporal lobe epilepsy semiology.

    Science.gov (United States)

    Blair, Robert D G

    2012-01-01

    Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone.

  5. Qualitative and temporal aggregation

    OpenAIRE

    Kakarot-Handtke, Egmont

    2011-01-01

    Behavioral assumptions, rational or otherwise, are not solid enough to be eligible as first principles of theoretical economics. Hence all endeavors to lay the formal foundation on a new site and at a deeper level actually need no further vindication. The present paper suggests three non-behavioral axioms as groundwork and applies them to the analysis of qualitative and temporal aggregation in the pure consumption economy. It turns out that the structural axiom set is self-similar with regard...

  6. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Palamidessi, Catuscia; Valencia, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...... reflect the reactive interactions between concurrent constraint processes and their environment, as well as internal interactions between individual processes. Relationships between the suggested notions are studied, and they are all proved to be decidable for a substantial fragment of the calculus...

  7. Velo-cardio-facial syndrome: Frequency and textent of 22q11 deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Goldberg, R.; Jurecic, V. [and others

    1995-07-03

    Velo-cardio-facial (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phenotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH). In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions. 22 refs., 2 figs., 1 tab.

  8. Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family

    Energy Technology Data Exchange (ETDEWEB)

    Hoop, R.C.; Schwartz, L.S.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Russo, L.S. [Univ. of Florida, Jacksonville, FL (United States); Riconda, D.L. [Orlando Regional Medical Center, Orlando, FL (United States)

    1994-02-01

    Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions-one in the 5{prime}, proximal deletional hotspot region, and the other in the 3{prime}, more distal deletional hotspot region. The second propositus showed only the 5{prime} deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, the authors show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier`s dystrophin genes, giving rise to a son with a partially {open_quotes}repaired{close_quotes} gene retaining only the 5{prime} deletion. 20 refs., 4 figs.

  9. p27KIP1 Deletions in Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hiroaki Komuro

    1999-08-01

    Full Text Available The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations in childhood acute lymphoblastic leukemia (ALL. As described here, fluorescence in situ hybridization (FISH analysis of 35 primary ALL samples with cytogenetic evidence of 12p abnormalities revealed hemizygous deletions of p27KIP1 in 29 cases. Further analysis of 19 of these cases with two additional gene-specific probes from the 12p region (hematopoietic cell phosphatase, HCP and cyclin D2, CCND2 showed that p27KIP1 is located more proximally on the short arm of chromosome 12 and is deleted more frequently than either HCP or CCND2. Of 16 of these cases with hemizygous deletion of p27KIP1, only eight showed loss of HCP or CCND2, whereas loss of either of the latter two loci was uniformly associated with loss of p27KIP1. Missense mutations or mutations leading to premature termination codons were not detected in the coding sequences of the retained p27KIP1 alleles in any of the 16 ALL cases examined, indicating a lack of homozygous inactivation. By Southern blot analysis, one case of primary T-cell ALL had hemizygous loss of a single p27KIP1 allele and a 34.5-kb deletion, including the second coding exon of the other allele. Despite homozygous inactivation of p27KIP1 in this case, our data suggest that haploinsufficiency for p27KIP1 is the primary consequence of 12p chromosomal deletions in childhood ALL. The oncogenic role of reduced, but not absent, levels of p27KIP1 is supported by recent studies in murine models and evidence that this protein not only inhibits the activity of complexes containing CDK2 and cyclin E, but also promotes the assembly and catalytic activity of CDK4 or CDK6 in complexes with cyclin D.

  10. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Directory of Open Access Journals (Sweden)

    Bekim Sadikovic

    2010-12-01

    Full Text Available Mitochondrial DNA (mtDNA deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM, progressive external ophthalmoplegia (PEO, and Kearns-Sayre syndrome (KSS, to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41. Only 15% (3/20 of the young patients (<6 years old carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17 exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier

  11. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Science.gov (United States)

    Sadikovic, Bekim; Wang, Jing; El-Hattab, Ayman W; Landsverk, Megan; Douglas, Ganka; Brundage, Ellen K; Craigen, William J; Schmitt, Eric S; Wong, Lee-Jun C

    2010-12-20

    Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement.

  12. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  13. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions : a European collaborative study

    NARCIS (Netherlands)

    Ryan, AK; Goodship, JA; Wilson, DI; Philip, N; Levy, A; Seidel, H; Schuffenhauer, S; Oechsler, H; Belohradsky, B; Prieur, M; Aurias, A; Raymond, FL; ClaytonSmith, J; Hatchwell, E; McKeown, C; Beemer, FA; Dallapiccola, B; Novelli, G; Hurst, JA; Ignatius, J; Green, AJ; Brueton, L; BrondumNielsen, K; Stewart, F; VanEssen, T; Patton, M; Paterson, J; Scambler, PJ

    1997-01-01

    We present clinical data on 558 patients with deletions within the DiGeorge syndrome critical region of chromosome 22q11. Twenty-eight percent of the cases where parents had been tested had inherited deletions, with a marked excess of maternally inherited deletions (maternal 61, paternal 18). Eight

  14. Differentiated psychopharmacological treatment in three genetic subtypes of 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Egger, J.I.M.; Leeuw, N. de

    2017-01-01

    Introduction: The 22q11.2 deletion syndrome (22q11DS), mostly caused by the common deletion including the TBX- and COMT-genes (LCR22A-D), is highly associated with somatic anomalies. The distal deletion (distal of LCR22D) comprises the MAPK1-gene and is associated with specific heart defects. The

  15. 41 CFR 51-6.8 - Deletion of items from the Procurement List.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Deletion of items from...-PROCUREMENT PROCEDURES § 51-6.8 Deletion of items from the Procurement List. (a) When a central nonprofit... shall notify the Committee staff immediately. Before reaching a decision to request a deletion of an...

  16. 36 CFR 902.14 - Deletion of nondiscloseable information from requested records.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Deletion of nondiscloseable... AVENUE DEVELOPMENT CORPORATION FREEDOM OF INFORMATION ACT General Administration § 902.14 Deletion of... segregable after deletion of the nondiscloseable portions, will be released. If the information in the...

  17. 46 CFR 67.513 - Application for evidence of deletion from documentation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Application for evidence of deletion from documentation... AND MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS Fees § 67.513 Application for evidence of deletion from documentation. An application fee is charged for evidence of deletion from documentation in...

  18. 14 CFR 1206.202 - Deletion of segregable portions of a record.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Deletion of segregable portions of a record... AVAILABILITY OF AGENCY RECORDS TO MEMBERS OF THE PUBLIC Records Available § 1206.202 Deletion of segregable... that indication would harm an interest protected by the exemption in Subpart 3 under which the deletion...

  19. 32 CFR 310.34 - Amendment and deletion of system notices.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Amendment and deletion of system notices. 310.34... (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Publication Requirements § 310.34 Amendment and deletion of... system. (see § 310.32(q)). (c) Deletion of system notices. (1) Whenever a system is discontinued...

  20. 19 CFR 176.22 - Deletion of protest or entry number.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Deletion of protest or entry number. 176.22... Facts § 176.22 Deletion of protest or entry number. If any protest number or entry number is to be... authorized official making and approving the deletion. [T.D. 70-181, 35 FR 13433, Aug. 22, 1970] ...

  1. 47 CFR 76.1601 - Deletion or repositioning of broadcast signals.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Deletion or repositioning of broadcast signals... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1601 Deletion or... to § 76.1601: No deletion or repositioning of a local commercial television station shall occur...

  2. Detection of mitochondrial DNA deletions in human cells induced by ionizing radiation

    International Nuclear Information System (INIS)

    Liu, Qing-Jie; Feng, Jiang-Bin; Lu, Xue; Li, Yu-Wen; Chen, De-Qing

    2008-01-01

    Full text: Purpose: To screen the novel mitochondrial DNA (mt DNA) deletions induced by ionizing radiation, and analyze the several kinds of mt DNA deletions, known as 3895 bp, 889 bp, 7436 bp or 4934 bp deletions. Methods: Long-range PCR with two pairs of primers, which could amplify the whole human mitochondrial genome, was used to analyze the lymphoblastoid cell line before and after exposed to 10 Gy 60 Co γ-rays. The limited condition PCR was used to certify the possible mt DNA deletion showed by long-range PCR. The PCR products were purified, cloned, sequenced and the sequence result were BLASTed. Regular PCR or nest-PCR were used to analyze the 3895 bp, 889 bp, 7436 bp or 4934 bp deletions before and after radiation exposure. The final PCR products were purified, sequenced and BALSTed on standard human mitochondrial genome sequence database. Results: (1) The predicted bands of mt DNA were observed on the control cell lines, and the possible mt DNA deletions were also detected on the irradiated cell lines. The deletions were certified by the limited condition PCR. The sequence BLAST results of the cloned PCR products showed that two kinds of deletions, 7455 bp deletion (nt 475-7929 in heavy strand) and 9225 bp deletion (nt 7714-369 in heavy strand), which were between two 8 bp direct repeats. Further bioinformatics analysis showed that the two deletions were novel deletions. (2) The 889 bp and 3895 bp deletion were not detected for the cell line samples not exposed to 60 Co γ-rays. The 889 bp and 3895 bp deletions were detected on samples exposed to 10 Gy 60 Co γ-rays. The BALST results showed that the 889 bp and 3895 deletions flanked nt 11688 bp-12576, nt 548 bp-4443, respectively. The 7436 bp deletion levels were not changed much before and after irradiation. (3) The 4934 bp deletions had the same pattern as 7436 bp deletion, but it could induced by radiation. Conclusions: Ionizing radiation could induce the human lymphoblastoid two novel mt DNA

  3. Spatio-Temporal Rule Mining

    DEFF Research Database (Denmark)

    Gidofalvi, Gyozo; Pedersen, Torben Bach

    2005-01-01

    Recent advances in communication and information technology, such as the increasing accuracy of GPS technology and the miniaturization of wireless communication devices pave the road for Location-Based Services (LBS). To achieve high quality for such services, spatio-temporal data mining techniques...... are needed. In this paper, we describe experiences with spatio-temporal rule mining in a Danish data mining company. First, a number of real world spatio-temporal data sets are described, leading to a taxonomy of spatio-temporal data. Second, the paper describes a general methodology that transforms...... the spatio-temporal rule mining task to the traditional market basket analysis task and applies it to the described data sets, enabling traditional association rule mining methods to discover spatio-temporal rules for LBS. Finally, unique issues in spatio-temporal rule mining are identified and discussed....

  4. Targeted deletions of cyclooxygenase-2 and atherogenesis in mice

    DEFF Research Database (Denmark)

    Hui, Yiqun; Ricciotti, Emanuela; Crichton, Irene

    2010-01-01

    BACKGROUND: Although the dominant product of vascular Cyclooxygenase-2 (COX-2), prostacyclin (PGI(2)), restrains atherogenesis, inhibition and deletion of COX-2 have yielded conflicting results in mouse models of atherosclerosis. Floxed mice were used to parse distinct cellular contributions of COX......-2 in macrophages and T cells (TCs) to atherogenesis. METHODS AND RESULTS: Deletion of macrophage-COX-2 (Mac-COX-2KOs) was attained with LysMCre mice and completely suppressed lipopolysaccharide-stimulated macrophage prostaglandin (PG) formation and lipopolysaccharide-evoked systemic PG biosynthesis...... by approximately 30%. Lipopolysaccharide-stimulated COX-2 expression was suppressed in polymorphonuclear leukocytes isolated from MacKOs, but PG formation was not even detected in polymorphonuclear leukocyte supernatants from control mice. Atherogenesis was attenuated when MacKOs were crossed into hyperlipidemic...

  5. Combinations of probabilistic and approximate quantum cloning and deleting

    International Nuclear Information System (INIS)

    Qiu Daowen

    2002-01-01

    We first construct a probabilistic and approximate quantum cloning machine (PACM) and then clarify the relation between the PACM and other cloning machines. After that, we estimate the global fidelity of the approximate cloning that improves the previous estimation for the deterministic cloning machine; and also derive a bound on the success probability of producing perfect multiple clones. Afterwards, we further establish a more generalized probabilistic and approximate cloning and deleting machine (PACDM) and discuss the connections of the PACDM to some of the existing quantum cloning and deleting machines. Finally the global fidelity and a bound on the success probability of the PACDM are obtained. Summarily, the quantum devices established in this paper improve and also greatly generalize some of the existing machines

  6. Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Raquel Gomes; Ferreira-Machado, Samara C.; Almeida, Carlos E.V. de, E-mail: raquelgsiqueira@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Ciencias Radiologicas; Silva, Dayse A. da; Carvalho, Elizeu F. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Diagnosticos por DNA; Melo, Luiz D.B. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho. Lab. de Parasitologia Molecular

    2014-05-15

    The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels. (author)

  7. Mitochondrial DNA exhibits resistance to induced point and deletion mutations

    Science.gov (United States)

    Valente, William J.; Ericson, Nolan G.; Long, Alexandra S.; White, Paul A.; Marchetti, Francesco; Bielas, Jason H.

    2016-01-01

    The accumulation of somatic mitochondrial DNA (mtDNA) mutations contributes to the pathogenesis of human disease. Currently, mitochondrial mutations are largely considered results of inaccurate processing of its heavily damaged genome. However, mainly from a lack of methods to monitor mtDNA mutations with sufficient sensitivity and accuracy, a link between mtDNA damage and mutation has not been established. To test the hypothesis that mtDNA-damaging agents induce mtDNA mutations, we exposed MutaTMMouse mice to benzo[a]pyrene (B[a]P) or N-ethyl-N-nitrosourea (ENU), daily for 28 consecutive days, and quantified mtDNA point and deletion mutations in bone marrow and liver using our newly developed Digital Random Mutation Capture (dRMC) and Digital Deletion Detection (3D) assays. Surprisingly, our results demonstrate mutagen treatment did not increase mitochondrial point or deletion mutation frequencies, despite evidence both compounds increase nuclear DNA mutations and demonstrated B[a]P adduct formation in mtDNA. These findings contradict models of mtDNA mutagenesis that assert the elevated rate of mtDNA mutation stems from damage sensitivity and abridged repair capacity. Rather, our results demonstrate induced mtDNA damage does not readily convert into mutation. These findings suggest robust mitochondrial damage responses repress induced mutations after mutagen exposure. PMID:27550180

  8. Distinct phenotype of PHF6 deletions in females.

    Science.gov (United States)

    Di Donato, N; Isidor, B; Lopez Cazaux, S; Le Caignec, C; Klink, B; Kraus, C; Schrock, E; Hackmann, K

    2014-02-01

    We report on two female patients carrying small overlapping Xq26.2 deletions of 100 kb and 270 kb involving the PHF6 gene. Mutations in PHF6 have been reported in individuals with Borjeson-Forssman-Lehmann syndrome, a condition present almost exclusively in males. Two very recent papers revealed de novo PHF6 defects in seven female patients with intellectual disability and a phenotype resembling Coffin-Siris syndrome (sparse hair, bitemporal narrowing, arched eyebrows, synophrys, high nasal root, bulbous nasal tip, marked clinodactyly with the hypoplastic terminal phalanges of the fifth fingers and cutaneous syndactyly of the toes, Blaschkoid linear skin hyperpigmentation, dental anomalies and occasional major malformations). The clinical presentation of these patients overlaps completely with our first patient, who carries a germline deletion involving PHF6. The second patient has a mosaic deletion and presented with a very mild phenotype of PHF6 loss in females. Our report confirms that PHF6 loss in females results in a recognizable phenotype overlapping with Coffin-Siris syndrome and distinct from Borjeson-Forssman-Lehmann syndrome. We expand the clinical spectrum and provide the first summary of the recommended medical evaluation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. SHANK1 Deletions in Males with Autism Spectrum Disorder.

    Science.gov (United States)

    Sato, Daisuke; Lionel, Anath C; Leblond, Claire S; Prasad, Aparna; Pinto, Dalila; Walker, Susan; O'Connor, Irene; Russell, Carolyn; Drmic, Irene E; Hamdan, Fadi F; Michaud, Jacques L; Endris, Volker; Roeth, Ralph; Delorme, Richard; Huguet, Guillaume; Leboyer, Marion; Rastam, Maria; Gillberg, Christopher; Lathrop, Mark; Stavropoulos, Dimitri J; Anagnostou, Evdokia; Weksberg, Rosanna; Fombonne, Eric; Zwaigenbaum, Lonnie; Fernandez, Bridget A; Roberts, Wendy; Rappold, Gudrun A; Marshall, Christian R; Bourgeron, Thomas; Szatmari, Peter; Scherer, Stephen W

    2012-05-04

    Recent studies have highlighted the involvement of rare (number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ASD and intellectual disability, the involvement of SHANK1 is unknown. Here, we assess microarray data from 1,158 Canadian and 456 European individuals with ASD to discover microdeletions at the SHANK1 locus on chromosome 19. We identify a hemizygous SHANK1 deletion that segregates in a four-generation family in which male carriers--but not female carriers--have ASD with higher functioning. A de novo SHANK1 deletion was also detected in an unrelated male individual with ASD with higher functioning, and no equivalent SHANK1 mutations were found in >15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Deletion of PREPl causes growth impairment and hypotonia in mice.

    Directory of Open Access Journals (Sweden)

    Anna Mari Lone

    Full Text Available Genetic studies of rare diseases can identify genes of unknown function that strongly impact human physiology. Prolyl endopeptidase-like (PREPL is an uncharacterized member of the prolyl peptidase family that was discovered because of its deletion in humans with hypotonia-cystinuria syndrome (HCS. HCS is characterized by a number of physiological changes including diminished growth and neonatal hypotonia or low muscle tone. HCS patients have deletions in other genes as well, making it difficult to tease apart the specific role of PREPL. Here, we develop a PREPL null (PREPL(-/- mouse model to address the physiological role of this enzyme. Deletion of exon 11 from the Prepl gene, which encodes key catalytic amino acids, leads to a loss of PREPL protein as well as lower Prepl mRNA levels. PREPL(-/- mice have a pronounced growth phenotype, being significantly shorter and lighter than their wild type (PREPL(+/+ counterparts. A righting assay revealed that PREPL(-/- pups took significantly longer than PREPL(+/+ pups to right themselves when placed on their backs. This deficit indicates that PREPL(-/- mice suffer from neonatal hypotonia. According to these results, PREPL regulates growth and neonatal hypotonia in mice, which supports the idea that PREPL causes diminished growth and neonatal hypotonia in humans with HCS. These animals provide a valuable asset in deciphering the underlying biochemical, cellular and physiological pathways that link PREPL to HCS, and this may eventually lead to new insights in the treatment of this disease.

  11. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  12. Familial 22q11.2 deletion syndrome with autosomal dominant inheritance

    Directory of Open Access Journals (Sweden)

    Bahar Gokturk

    2016-06-01

    Full Text Available 22q11.2 deletion syndrome is the most frequent microdeletion syndrome in humans and caused by hemizygote deletion on only one chromosome. Most of probands have a de novo deletion of 22q11.2, but 8-20% have inherited the 22q11.2 deletion from a parent (autosomal dominant mutation. Genotype-phenotype correlation is weak in this patient group. We aimed to present three members in the same family due to an autosomal dominant inheritance with 22q11.2 deletion and different clinical findings. [Cukurova Med J 2016; 41(2.000: 379-385

  13. Molecular and cytogenetic investigation of Y chromosome deletions over three generations facilitated by intracytoplasmic sperm injection.

    Science.gov (United States)

    Minor, Agata; Wong, Edgar Chan; Harmer, Karynn; Ma, Sai

    2007-08-01

    The azoospermic factor (AZF) region is critical for normal spermatogenesis since microdeletions and partial deletions have been associated with infertility. We investigate the diagnostic ability of karyotyping in detecting clinically relevant Y chromosome deletions. The clinical significance of heterochromatin deletions, microdeletions and partial AZFc deletions is also evaluated. A patient with a Yq deletion, affected by severe oligoasthenoteratozoospermia, underwent intracytoplasmic sperm injection (ICSI) which resulted in the birth of a healthy baby boy. The patient, his father and his son underwent Y chromosome microdeletion and partial AZFc deletion screening. We also studied the aneuploidy rate in the sperm of the patient by fluorescent in situ hybridization. AZF microdeletions were absent in the family. However, microdeletion analysis confirmed that the Yq deletion was limited to the heterochromatin. We found a partial AZFc gr/gr deletion in all three family members. We observed an increased rate of sex chromosome aneuploidy in the infertile patient. Cytogenetic analysis was misleading in identifying the Yq breakpoint. Infertility observed in the patient was associated with the gr/gr partial deletion. However, because of the incomplete penetrance of gr/gr deletions, the consequence of the vertical transmission of the deletion through ICSI remains unknown. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. Exonic deletions of FXN and early-onset Friedreich ataxia.

    Science.gov (United States)

    Anheim, Mathieu; Mariani, Louise-Laure; Calvas, Patrick; Cheuret, Emmanuel; Zagnoli, Fabien; Odent, Sylvie; Seguela, Claire; Marelli, Cecilia; Fritsch, Marlène; Delaunoy, Jean-Pierre; Brice, Alexis; Dürr, Alexandra; Koenig, Michel

    2012-07-01

    Friedreich ataxia (FA) is the most frequent type of autosomal recessive cerebellar ataxia, occurring at a mean age of 16 years. Nearly 98% of patients with FA present with homozygous GAA expansions in the FXN gene. The remaining patients are compound heterozygous for an expansion and a point mutation. Patients who are compound heterozygous for an exonic deletion and an expansion are exquisitely rare. To describe 6 patients affected with FA due to an exonic deletion mutation (FAexdel) and to compare these 6 patients with FAexdel with 46 patients consecutively diagnosed with typical FA due to homozygous GAA expansion and whose small expansions were within the same range as that of the expansions of the patients with FAexdel. Description of a series. Academic research. Six patients with FAexdel and 46 patients with typical FA. FXN gene analysis, including assessments of GAA expansion and exon sequencing and determination of exonic copy numbers using multiplex ligation-dependent probe amplification. We identified 6 patients with FA who presented with the combination of 1 GAA expansion and 1 FXN exonic deletion. The mean (SD) age at onset of the disease was earlier for patients with FAexdel (7 [4] years [range, 3-12 years]) than for patients with typical FA (15 [5] years [range, 6-30 years]) (P = .001), and the median time to confinement to wheelchair was shorter for patients with FAexdel (20 years) than for patients with typical FA (28 years) (P = .002). There was no difference between the mean (SD) size of the expansion for the patients with FAexdel (780 [256] GAA triplet repeat sequences [range, 340-1070 GAA triplet repeat sequences]) and the mean (SD) size of the short expansion for the patients with typical FA (634 [163] GAA triplet repeat sequences [range, 367-1000 GAA triplet repeat sequences]) (P = .10). The mean disease duration before becoming wheelchair bound was shorter for patients with FAexdel (9 years) than for patients with typical FA (13 years), and the

  15. Generating Bona Fide Mammalian Prions with Internal Deletions.

    Science.gov (United States)

    Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel

    2016-08-01

    Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative

  16. Interstitial deletion 5p accompanied by dicentric ring formation of the deleted segment resulting in trisomy 5p13-cen

    Energy Technology Data Exchange (ETDEWEB)

    Schuffenhauer, S.; Daumer-Haas, C.; Murken, J. [Ludwig-Maximilians-Universitaet Muenchen (Germany)] [and others

    1996-10-02

    Karyotypes with an interstitial deletion and a marker chromosome formed from the deleted segment are rare. We identified such a rearrangement in a newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet. The karyotype 46,XY,del(5)(pter{r_arrow}p13::cen{r_arrow}qter)/47,XY,+dicr(5)(:p13{r_arrow}cen::p13{r_arrow}cen),del(5)(pter{r_arrow}p13::cen{r_arrow}qter) was identified by banding studies and FISH analysis in the peripheral lymphocytes. One breakpoint on the del(5) maps distal to GDNF, and FISH analysis using an {alpha}-satellite probe suggests that the proximal breakpoint maps within the centromere. The dicentric r(5) consists of two copies of the segment deleted in the del(5), resulting in trisomy of proximal 5p (5p13-cen). The phenotype of the propositus is compared with other trisomy 5p cases and possible mechanisms for the generation of this unique chromosomal rearrangement are discussed. 27 refs., 3 figs.

  17. Characterization of genetic deletions in Becker muscular dystrophy using monoclonal antibodies against a deletion-prone region of dystrophin

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, L.T.; Man, Nguyen Thi; Morris, G.E. [Wales Institute, Clwyd (United Kingdom)] [and others

    1995-08-28

    We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion-prone region of the Duchenne muscular dystrophy gene (exons 45-50). We show that immunohistochemistry or Western blotting with these {open_quotes}exon-specific{close_quotes} mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying {open_quotes}revertant{close_quotes} fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. 27 refs., 7 figs., 3 tabs.

  18. DNA-based detection of chromosome deletion and amplification: diagnostic and mechanistic significance

    International Nuclear Information System (INIS)

    Latt, S.A.; Lalande, M.; Donlon, T.

    1986-01-01

    This paper describes a few of the many possible examples in which application of a molecular cytogenetic approach can ultimately lead to a new, important understanding about the statics and dynamics of human chromosome structure. In the case of retinoblastoma, cytological observations of deletions and linkage analysis have positioned the retinoblastoma locus to bank 13q14. This locus is grossly deleted in some spontaneous tumors. It is still necessary to locate more precisely and characterize the nature of the retinoblastoma locus, as well as the basis for the heterogeneity in deletions removing one copy of this locus. One is left with the possibility that those deletions that may be observed cytologically reflect but the tip of the iceberg of deletions; detection of others may require molecular probes. A related question is the nature of the DNA sequences at the deletion boundaries and the role they play in promoting these deletions

  19. Single gene deletions of orexin, leptin, neuropeptide Y, and ghrelin do not appreciably alter food anticipatory activity in mice.

    Directory of Open Access Journals (Sweden)

    Keith M Gunapala

    Full Text Available Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA involves temporally restricting unlimited food access (RF to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR, giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.

  20. Model Based Temporal Reasoning

    Science.gov (United States)

    Rabin, Marla J.; Spinrad, Paul R.; Fall, Thomas C.

    1988-03-01

    Systems that assess the real world must cope with evidence that is uncertain, ambiguous, and spread over time. Typically, the most important function of an assessment system is to identify when activities are occurring that are unusual or unanticipated. Model based temporal reasoning addresses both of these requirements. The differences among temporal reasoning schemes lies in the methods used to avoid computational intractability. If we had n pieces of data and we wanted to examine how they were related, the worst case would be where we had to examine every subset of these points to see if that subset satisfied the relations. This would be 2n, which is intractable. Models compress this; if several data points are all compatible with a model, then that model represents all those data points. Data points are then considered related if they lie within the same model or if they lie in models that are related. Models thus address the intractability problem. They also address the problem of determining unusual activities if the data do not agree with models that are indicated by earlier data then something out of the norm is taking place. The models can summarize what we know up to that time, so when they are not predicting correctly, either something unusual is happening or we need to revise our models. The model based reasoner developed at Advanced Decision Systems is thus both intuitive and powerful. It is currently being used on one operational system and several prototype systems. It has enough power to be used in domains spanning the spectrum from manufacturing engineering and project management to low-intensity conflict and strategic assessment.

  1. Multiple Temporalities, Layered Histories

    Directory of Open Access Journals (Sweden)

    Steven Pearson

    2017-11-01

    Full Text Available In Quotational Practices: Repeating the Future in Contemporary Art, Patrick Greaney asserts, “the past matters not only because of what actually happened but also because of the possibilities that were not realized and that still could be. Quotation evokes those possibilities. By repeating the past, artists and writers may be attempting to repeat that past’s unrealized futures.”[1]  In the information age, the Internet, for instance, provides us an expanded collection of visual information—quite literally available at our fingertips—summoning together aspects of the past and possibilities of the future into a boundless present. Sketchbook Revisions (2014–2015, a series of mixed-media paintings, represents my attempt to communicate the ways in which I experience my contemporary moment constructed from multiple temporalities excavated from my past. This body of work combines fragments of representational paintings created between 1995 and 2003 and nonrepresentational renderings produced between 2003 and 2014. Using traditional tracing paper and graphic color, I randomly select moments of my previous work to transfer and layer over selected areas of already-filled pages of a sketchbook I used from 2003 to 2004. These sketches depict objects I encountered in studio art classrooms and iconic architecture on the campus of McDaniel College, and often incorporate teaching notes. The final renditions of fragmented and layered histories enact the ways that we collectively experience multiple temporalities in the present. Quoting my various bodies of work, Sketchbook Revisions challenges both material and conceptual boundaries that determine fixed notions of artistic identity.

  2. Molecular cytogenetic detection of chromosome 15 deletions in patients with Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, D.E.; Weksberg, R.; Shuman, C. [Hospital for Sick Children, Toronto (Canada)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct genetic disorders involving alterations of chromosome 15q11-q13. Approximately 75% of individuals with PWS and AS have deletions within 15q11-q13 by molecular analysis. We have evaluated fluorescence in situ hybridization (FISH) for the clinical laboratory detection of del(15)(q11q13) using the cosmid probes D15S11 and GABRB3 (ONCOR, Gaithersburg, NY). 4/4 PWS and 1/1 AS patients previously identified as having cytogenetic deletions were deleted for both probes. In a prospectively ascertained series of 54 patient samples referred to rule out either PWS or AS, 8 were deleted for D15S11 and GABRB3. In addition, an atypical deletion patient with PWS was also identified who was found to be deleted for GABRB3 but not D15S11. The SNRPN locus was also deleted in this patient. Only 4 of the 9 patient samples having molecular cytogenetic deletions were clearly deleted by high resolution banding (HRB) analysis. The microscopic and submicroscopic deletions have been confirmed by dinucleotide (CA) repeat analysis. Microsatellite polymorphism analysis was also used to demonstrate that five non-deletion patients in this series had biparental inheritance of chromosome 15, including region q11-q13. Deletions were not detected by either HRB, FISH or microsatellite polymorphism analysis in samples obtained from parents of the deletion patients. Methylation studies of chromosome 15q11-q13 are in progress for this series of PWS and AS families. FISH analysis of chromosome 15q11-q13 in patients with PWS and AS is a rapid, sensitive and reliable method for deletion detection.

  3. [Temporal meaning of suffering].

    Science.gov (United States)

    Porée, J

    2015-09-01

    If we had to find a few simple words to express what a suffering human being experiences, no matter what ills are causing the suffering and no matter what circumstances underlie the ills themselves, we could unmistakably say that it is the experience of not being able to go on like this. Suffering can be described, in this same sense, as an alteration in temporality. However, describing suffering as such only makes sense if we already have a conception of normal temporality. Yet for this, philosophical tradition offers not one but four competing conceptions. In the present article, we begin by briefly presenting these different conceptions. We then show how each one sheds light, by way of contrast, on a phenomenon whose meaning thus appears to be essentially negative. But does this phenomenon have a negative meaning only? Doesn't it correspond as much to a transformation as an alteration of temporality? This is what we will strive to establish in the third part of the article by relating suffering to hope, in a paradoxical sense of the term. Of the four conceptions of time likely to shed a contrasting light on the upheavals that suffering introduces into our life experience, the one described by Aristotle in Physics is historically the first. In particular, the notion of succession originates therein. But this conception does not account for what makes time the unit of a past, a present, and a future. In Book XI of Confessions, St. Augustine situated this unit not in nature but in the human mind. Hence, his definition of time as a distension of the soul and the necessary division into physical time and psychic time it entails. Husserl's Lessons on the phenomenology of the consciousness of internal time lend credit to this division, but they illuminate only the internal constitution of the "present", which is at the heart of the psychological conception of time. In Being and Time, Heidegger breaks away from this long-standing tradition; in his view, physical time

  4. Temporal Representation in Semantic Graphs

    Energy Technology Data Exchange (ETDEWEB)

    Levandoski, J J; Abdulla, G M

    2007-08-07

    A wide range of knowledge discovery and analysis applications, ranging from business to biological, make use of semantic graphs when modeling relationships and concepts. Most of the semantic graphs used in these applications are assumed to be static pieces of information, meaning temporal evolution of concepts and relationships are not taken into account. Guided by the need for more advanced semantic graph queries involving temporal concepts, this paper surveys the existing work involving temporal representations in semantic graphs.

  5. Malformations of the middle and inner ear on CT imaging in 22q11 deletion syndrome.

    Science.gov (United States)

    Loos, Elke; Verhaert, Nicolas; Willaert, Annelore; Devriendt, Koenraad; Swillen, Ann; Hermans, Robert; Op de Beeck, Katya; Hens, Greet

    2016-11-01

    The 22q11 deletion syndrome (22q11DS), the most frequent microdeletion syndrome in humans, presents with a large variety of abnormalities. A common abnormality is hearing impairment. The exact pathophysiological explanation of the observed hearing loss remains largely unknown. The aim of this study was to analyze the middle and inner ear malformations as seen on computer tomographic imaging in patients with 22q11DS. We retrospectively reviewed the charts of 11 22q11DS patients who had undergone a CT of the temporal bone in the past. Of the 22 examined ears, two showed an abnormal malleus and incus, 10 presented with a dense stapes superstructure, and three ears had an abnormal orientation of the stapes. With regard to the inner ear, 12 ears showed an incomplete partition type II with a normal vestibular aqueduct. In four ears the vestibule and lateral semicircular canal were composed of a single cavity, in 14 ears the vestibule was too wide, and three ears had a broadened lateral semicircular canal. These findings suggest that malformations of the stapes, cochlea, vestibule, and lateral semicircular canal are frequent in 22q11DS. To our knowledge, the current study involves the largest case series describing middle and inner ear malformations in 22q11DS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures.

    Science.gov (United States)

    Lionel, Anath C; Vaags, Andrea K; Sato, Daisuke; Gazzellone, Matthew J; Mitchell, Elyse B; Chen, Hong Yang; Costain, Gregory; Walker, Susan; Egger, Gerald; Thiruvahindrapuram, Bhooma; Merico, Daniele; Prasad, Aparna; Anagnostou, Evdokia; Fombonne, Eric; Zwaigenbaum, Lonnie; Roberts, Wendy; Szatmari, Peter; Fernandez, Bridget A; Georgieva, Lyudmila; Brzustowicz, Linda M; Roetzer, Katharina; Kaschnitz, Wolfgang; Vincent, John B; Windpassinger, Christian; Marshall, Christian R; Trifiletti, Rosario R; Kirmani, Salman; Kirov, George; Petek, Erwin; Hodge, Jennelle C; Bassett, Anne S; Scherer, Stephen W

    2013-05-15

    The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.

  7. Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Hung, Pi-Lien; Huang, Li-Tung; Kwan, Shang-Yeong; Chang, Kai-Ping; Chen, Hsin-Hung; Lee, Yi-Yen; Fan, Hueng-Chuen; Chen, Chien

    2017-03-01

    We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic-clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video-EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack. The ictal vomiting ceased following management with oxcarbazepine, high-dose phenobarbital, and a ketogenic diet. The unique seizure type and rare ictal EEG findings are the first reported in a child with chromosome 22q11.2 deletion syndrome. This case highlights that ictus emeticus without detectable epileptic discharge on EEG is one potential epileptic presentation in this genetic syndrome. [Published with video sequence on www.epilepticdisorders.com].

  8. Join Operations in Temporal Databases

    DEFF Research Database (Denmark)

    Gao, D.; Jensen, Christian Søndergaard; Snodgrass, R.T.

    2005-01-01

    with equality predicates rather than the inequality predicates prevalent in valid-time queries. Second, the presence of temporally varying data dramatically increases the size of a database. These factors indicate that specialized techniques are needed to efficiently evaluate temporal joins. We address......, if any, comparison of the various operators. We then address evaluation algorithms, comparing the applicability of various algorithms to the temporal join operators and describing a performance study involving algorithms for one important operator, the temporal equijoin. Our focus, with respect...... to implementation, is on non-index-based join algorithms. Such algorithms do not rely on auxiliary access paths but may exploit sort orderings to achieve efficiency....

  9. Deletion involving D15S113 in a mother and son without Angelman syndrome: Refinement of the Angelman syndrome critical deletion region

    Energy Technology Data Exchange (ETDEWEB)

    Michaelis, R.C.; Skinner, S.A.; Lethco, B.A. [Greenwood Genetic Center, SC (United States)] [and others

    1995-01-02

    Deletions of 15q11-q13 typically result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The critical deletion region for Angelman syndrome has recently been restricted by a report of an Angelman syndrome patient with a deletion spanning less than 200 kb around the D15S113 locus. We report here on a mother and son with a deletion of chromosome 15 that includes the D15S113 locus. The son has mild to moderate mental retardation and minor anomalies, while the mother has a borderline intellectual deficit and slightly downslanting palpebral fissures. Neither patient has the seizures, excessive laughter and hand clapping, ataxia or the facial anomalies which are characteristic of Angelman syndrome. The proximal boundary of the deletion in our patients lies between the D15S10 and The D15S113 loci. Our patients do not have Angelman syndrome, despite the deletion of the D15S113 marker. This suggests that the Angelman syndrome critical deletion region is now defined as the overlap between the deletion found in the previously reported Angelman syndrome patient and the region that is intact in our patients. 28 refs., 6 figs.

  10. The Temporality of Power and the Power of Temporality

    DEFF Research Database (Denmark)

    Costas, Jana; Grey, Christopher

    2014-01-01

    This paper extends existing understandings of power, resistance and subjectivity in professional service organizations by developing an analysis of how these relate to temporality. Drawing in particular on Hoy’s reading of the Foucauldian account of temporality, we conceive of disciplinary power...... light on the interplay of power, resistance and subjectivity....

  11. A Tunisian patient with Pearson syndrome harboring the 4.977kb common deletion associated to two novel large-scale mitochondrial deletions.

    Science.gov (United States)

    Ayed, Imen Ben; Chamkha, Imen; Mkaouar-Rebai, Emna; Kammoun, Thouraya; Mezghani, Najla; Chabchoub, Imen; Aloulou, Hajer; Hachicha, Mongia; Fakhfakh, Faiza

    2011-07-29

    Pearson syndrome (PS) is a multisystem disease including refractory anemia, vacuolization of marrow precursors and pancreatic fibrosis. The disease starts during infancy and affects various tissues and organs, and most affected children die before the age of 3years. Pearson syndrome is caused by de novo large-scale deletions or, more rarely, duplications in the mitochondrial genome. In the present report, we described a Pearson syndrome patient harboring multiple mitochondrial deletions which is, in our knowledge, the first case described and studied in Tunisia. In fact, we reported the common 4.977kb deletion and two novel heteroplasmic deletions (5.030 and 5.234kb) of the mtDNA. These deletions affect several protein-coding and tRNAs genes and could strongly lead to defects in mitochondrial polypeptides synthesis, and impair oxidative phosphorylation and energy metabolism in the respiratory chain in the studied patient. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Mouse Rad1 deletion enhances susceptibility for skin tumor development

    Directory of Open Access Journals (Sweden)

    Wang Xiangyuan

    2010-03-01

    Full Text Available Abstract Background Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. Results To address this question, we constructed mice with a deletion of Mrad1. Matings between heterozygous Mrad1 mutant mice produced Mrad1+/+ and Mrad1+/- but no Mrad1-/- progeny, suggesting the Mrad1 null is embryonic lethal. Mrad1+/- mice demonstrated no overt abnormalities up to one and half years of age. DMBA-TPA combinational treatment was used to induce tumors on mouse skin. Tumors were larger, more numerous, and appeared earlier on the skin of Mrad1+/- mice compared to Mrad1+/+ animals. Keratinocytes isolated from Mrad1+/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1+/+ control cells. Conclusion These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study, suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells.

  13. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    International Nuclear Information System (INIS)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela; Martinelli, Diego; Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella; Dionisi-Vici, Carlo; Nobili, Valerio; Francalanci, Paola; Boldrini, Renata; Callea, Francesco; Santorelli, Filippo Maria; Bertini, Enrico

    2011-01-01

    Highlights: ► Expanded array of mtDNA deletions. ► Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. ► Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. ► Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  14. Prevalence of large-scale mitochondrial DNA deletions in an adult Finnish population.

    Science.gov (United States)

    Remes, A M; Majamaa-Voltti, K; Kärppä, M; Moilanen, J S; Uimonen, S; Helander, H; Rusanen, H; Salmela, P I; Sorri, M; Hassinen, I E; Majamaa, K

    2005-03-22

    Large-scale mitochondrial DNA (mtDNA) deletions are associated with clinical conditions such as Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia in adults and Pearson syndrome in children. Reported case series have suggested that deletions are not uncommon in the population, but their prevalence has not been documented. The authors ascertained patients with clinical features associated with mtDNA deletions in a defined adult population in northern Finland. Buccal epithelial samples were requested from each patient fulfilling the selection criteria, and full-length mtDNA was amplified using the long PCR method. Deletion breakpoints were identified using sequencing. Patients with deletions were examined clinically. The authors identified four patients with single large-scale mtDNA deletions. The prevalence of deletions was calculated to be 1.6/100,000 in the adult population in the province of Northern Ostrobothnia (0.0 to 3.2; 95% CI). Analysis of incident cases from a neighboring province revealed two patients with deletions and yielded a similar population frequency. The frequency of large-scale mitochondrial DNA deletions is similar among populations, suggesting that there is a constant rate of new deletions.

  15. Deletion mapping of 22q11 in CATCH22 syndrome: Identification of a second critical region

    Energy Technology Data Exchange (ETDEWEB)

    Kurahashi, Hiroki; Nakayama, Takahiro; Nishisho, Isamu [Osaka Univ. Medical School, Yokohama (Japan)] [and others

    1996-06-01

    The deletion at 22q11.2 implicates a variety of congenital anomaly syndromes, for which the acronym CATCH22 has been proposed . Most patients with these syndromes share the common large deletion spanning 1-2 Mb, while the phenotypic variability of the patients does not seem to correlate with the extent of the deletions. On the basis of the deletions of rare cases with unbalanced translocation, the shortest region of overlap (SRO) had been identified in the most-centromeric region of the common large deletion. One patient (ADU) has been reported to carry a balanced translocation with the breakpoint located in the SRO. Recently, three transcripts were identified at or very close to the ADU breakpoint (ADUBP), making them strong candidates for CATCH22 syndrome. Here, we describe one patient with a unique deletion at 22q11.2 revealed by quantitative hybridization and/or FISH with six DNA markers in the common large deletion. The patient was dizygous at loci within the SRO and hemizygous only at the most-telomeric locus in the common large deletion. This finding suggests that there must be another critical region in the common large deletion besides the breakpoint of the ADU and that haploinsufficiency of genes in this deletion may also play a major role in CATCH22 pathogenesis. 15 refs., 3 figs.

  16. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  17. The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome.

    Science.gov (United States)

    Cook, R Kimberley; Christensen, Stacey J; Deal, Jennifer A; Coburn, Rachel A; Deal, Megan E; Gresens, Jill M; Kaufman, Thomas C; Cook, Kevin R

    2012-01-01

    Chromosomal deletions are used extensively in Drosophila melanogaster genetics research. Deletion mapping is the primary method used for fine-scale gene localization. Effective and efficient deletion mapping requires both extensive genomic coverage and a high density of molecularly defined breakpoints across the genome. A large-scale resource development project at the Bloomington Drosophila Stock Center has improved the choice of deletions beyond that provided by previous projects. FLP-mediated recombination between FRT-bearing transposon insertions was used to generate deletions, because it is efficient and provides single-nucleotide resolution in planning deletion screens. The 793 deletions generated pushed coverage of the euchromatic genome to 98.4%. Gaps in coverage contain haplolethal and haplosterile genes, but the sizes of these gaps were minimized by flanking these genes as closely as possible with deletions. In improving coverage, a complete inventory of haplolethal and haplosterile genes was generated and extensive information on other haploinsufficient genes was compiled. To aid mapping experiments, a subset of deletions was organized into a Deficiency Kit to provide maximal coverage efficiently. To improve the resolution of deletion mapping, screens were planned to distribute deletion breakpoints evenly across the genome. The median chromosomal interval between breakpoints now contains only nine genes and 377 intervals contain only single genes. Drosophila melanogaster now has the most extensive genomic deletion coverage and breakpoint subdivision as well as the most comprehensive inventory of haploinsufficient genes of any multicellular organism. The improved selection of chromosomal deletion strains will be useful to nearly all Drosophila researchers.

  18. Angelman syndrome: Validation of molecular cytogenetic analysis of chromosome 15q11-q13 for deletion detection

    Energy Technology Data Exchange (ETDEWEB)

    White, L.; Knoll, J.H.M. [Harvard Medical School, Boston, MA (United States)

    1995-03-13

    In a series of 18 individuals comprising parents of Angelman syndrome (AS) patients and AS patients with large deletions, microdeletions, and no deletions, we utilized fluorescence in situ hybridization (FISH) with genomic phage clones for loci D15S63 and GABRB3 for deletion detection of chromosome 15q11-q13. Utilization of probes at these loci allows detection of common large deletions and permits discrimination of less common small deletions. In all individuals the molecular cytogenetic data were concordant with the DNA deletion analyses. FISH provides an accurate method of deletion detection for chromosome 15q11-q13. 23 refs., 2 figs., 1 tab.

  19. Massive Temporal Lobe Cholesteatoma

    Directory of Open Access Journals (Sweden)

    Pasan Waidyasekara

    2015-01-01

    Full Text Available Introduction. Intracranial extension of cholesteatoma is rare. This may occur de novo or recur some time later either contiguous with or separate to the site of the original cholesteatoma. Presentation of Case. A 63-year-old female presented to a tertiary referral hospital with a fluctuating level of consciousness, fever, headache, and right-sided otorrhoea, progressing over several days. Her past medical history included surgery for right ear cholesteatoma and drainage of intracranial abscess 23 years priorly. There had been no relevant symptoms in the interim until 6 weeks prior to this presentation. Imaging demonstrated a large right temporal lobe mass contiguous with the middle ear and mastoid cavity with features consistent with cholesteatoma. The patient underwent a combined transmastoid/middle fossa approach for removal of the cholesteatoma and repair of the tegmen dehiscence. The patient made an uneventful recovery and remains well over 12 months later. Conclusion. This case presentation details a large intracranial cholesteatoma which had extended through a tegmen tympani dehiscence from recurrent right ear cholesteatoma treated by modified radical mastoidectomy over two decades priorly. There was a completely asymptomatic progression of disease until several weeks prior to this presentation.

  20. Temporal Cyber Attack Detection.

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, Joey Burton [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Draelos, Timothy J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Galiardi, Meghan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Doak, Justin E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-11-01

    Rigorous characterization of the performance and generalization ability of cyber defense systems is extremely difficult, making it hard to gauge uncertainty, and thus, confidence. This difficulty largely stems from a lack of labeled attack data that fully explores the potential adversarial space. Currently, performance of cyber defense systems is typically evaluated in a qualitative manner by manually inspecting the results of the system on live data and adjusting as needed. Additionally, machine learning has shown promise in deriving models that automatically learn indicators of compromise that are more robust than analyst-derived detectors. However, to generate these models, most algorithms require large amounts of labeled data (i.e., examples of attacks). Algorithms that do not require annotated data to derive models are similarly at a disadvantage, because labeled data is still necessary when evaluating performance. In this work, we explore the use of temporal generative models to learn cyber attack graph representations and automatically generate data for experimentation and evaluation. Training and evaluating cyber systems and machine learning models requires significant, annotated data, which is typically collected and labeled by hand for one-off experiments. Automatically generating such data helps derive/evaluate detection models and ensures reproducibility of results. Experimentally, we demonstrate the efficacy of generative sequence analysis techniques on learning the structure of attack graphs, based on a realistic example. These derived models can then be used to generate more data. Additionally, we provide a roadmap for future research efforts in this area.

  1. Spatial Grouping Determines Temporal Integration

    Science.gov (United States)

    Hermens, Frouke; Scharnowski, Frank; Herzog, Michael H.

    2009-01-01

    To make sense out of a continuously changing visual world, people need to integrate features across space and time. Despite more than a century of research, the mechanisms of features integration are still a matter of debate. To examine how temporal and spatial integration interact, the authors measured the amount of temporal fusion (a measure of…

  2. Model Checking Discounted Temporal Properties

    NARCIS (Netherlands)

    de Alfaro, Luca; Faella, Marco; Henzinger, Thomas A.; Majumdar, Rupak; Stoelinga, Mariëlle Ida Antoinette; Jensen, K; Podelski, A.

    2004-01-01

    Temporal logic is two-valued: a property is either true or false. When applied to the analysis of stochastic systems, or systems with imprecise formal models, temporal logic is therefore fragile: even small changes in the model can lead to opposite truth values for a specification. We present a

  3. Model Checking Discounted Temporal Properties

    NARCIS (Netherlands)

    de Alfaro, Luca; Faella, Marco; Henzinger, Thomas A.; Majumdar, Rupak; Stoelinga, Mariëlle Ida Antoinette

    2005-01-01

    Temporal logic is two-valued: a property is either true or false. When applied to the analysis of stochastic systems, or systems with imprecise formal models, temporal logic is therefore fragile: even small changes in the model can lead to opposite truth values for a specification. We present a

  4. Deletion Mutations in an Australian Series of HNPCC Patients

    Directory of Open Access Journals (Sweden)

    McPhillips Mary

    2005-11-01

    Full Text Available Abstract Hereditary non polyposis colorectal cancer (HNPCC is characterized by the presence of early onset colorectal cancer and other epithelial malignancies. The genetic basis of HNPCC is a deficiency in DNA mismatch repair, which manifests itself as DNA microsatellite instability in tumours. There are four genes involved in DNA mismatch repair that have been linked to HNPCC; these include hMSH2, hMLH1, hMSH6 and hPMS2. Of these four genes hMLH1 and hMSH2 account for the majority of families diagnosed with the disease. Notwithstanding, up to 40 percent of families do not appear to harbour a change in either hMSH2 or hMLH1 that can be detected using standard screening procedures such as direct DNA sequencing or a variety of methods all based on a heteroduplex analysis. In this report we have screened a series of 118 probands that all have the clinical diagnosis of HNPCC for medium to large deletions by the Multiplex Ligation-Dependent Probe Amplification assay (MLPA to determine the frequency of this type of mutation. The results indicate that a significant proportion of Australian HNPCC patients harbour deletion or duplication mutations primarily in hMSH2 but also in hMLH1.

  5. Production planning and coronal stop deletion in spontaneous speech

    Directory of Open Access Journals (Sweden)

    James Tanner

    2017-06-01

    Full Text Available Many phonological processes can be affected by segmental context spanning word boundaries, which often lead to variable outcomes. This paper tests the idea that some of this variability can be explained by reference to production planning. We examine coronal stop deletion (CSD, a variable process conditioned by preceding and upcoming phonological context, in a corpus of spontaneous British English speech, as a means of investigating a number of variables associated with planning: Prosodic boundary strength, word frequency, conditional probability of the following word, and speech rate. From the perspective of production planning, (1 prosodic boundaries should affect deletion rate independently of following context; (2 given the locality of production planning, the effect of the following context should decrease at stronger prosodic boundaries; and (3 other factors affecting planning scope should modulate the effect of upcoming phonological material above and beyond the modulating effect of prosodic boundaries. We build a statistical model of CSD realization, using pause length as a quantitative proxy for boundary strength, and find support for these predictions. These findings are compatible with the hypothesis that the locality of production planning constrains variability in speech production, and have practical implications for work on CSD and other variable processes.

  6. Neuroradiographic findings in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Bohm, Lauren A; Zhou, Tom C; Mingo, Tyler J; Dugan, Sarah L; Patterson, Richard J; Sidman, James D; Roby, Brianne B

    2017-08-01

    22q11.2 deletion syndrome (22q11.2DS) is a common genetic disorder with enormous phenotypic heterogeneity. Despite the established prevalence of developmental and neuropsychiatric issues in this syndrome, its neuroanatomical correlates are not as well understood. A retrospective chart review was performed on 111 patients diagnosed with 22q11.2DS. Of the 111 patients, 24 with genetically confirmed 22q11.2 deletion and brain MRI or MRA were included in this study. The most common indications for imaging were unexplained developmental delay (6/24), seizures of unknown etiology (5/24), and unilateral weakness (3/24). More than half (13/24) of the patients had significant radiographic findings, including persistent cavum septi pellucidi and/or cavum vergae (8/24), aberrant cortical veins (6/24), polymicrogyria or cortical dysplasia (4/24), inner ear deformities (3/24), hypoplastic internal carotid artery (2/24), and hypoplastic cerebellum (1/24). These findings reveal the types and frequencies of brain malformations in this case series, and suggest that the prevalence of neuroanatomical abnormalities in 22q11.2DS may be underestimated. Understanding indications for imaging and frequently encountered brain malformations will result in early diagnosis and intervention in an effort to optimize patient outcomes. © 2017 Wiley Periodicals, Inc.

  7. Hematological abnormalities and 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano Machado Rosa

    2011-01-01

    Full Text Available The 22q11.2 deletion syndrome (22q11DS is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.

  8. Files synchronization from a large number of insertions and deletions

    Science.gov (United States)

    Ellappan, Vijayan; Kumari, Savera

    2017-11-01

    Synchronization between different versions of files is becoming a major issue that most of the applications are facing. To make the applications more efficient a economical algorithm is developed from the previously used algorithm of “File Loading Algorithm”. I am extending this algorithm in three ways: First, dealing with non-binary files, Second backup is generated for uploaded files and lastly each files are synchronized with insertions and deletions. User can reconstruct file from the former file with minimizing the error and also provides interactive communication by eliminating the frequency without any disturbance. The drawback of previous system is overcome by using synchronization, in which multiple copies of each file/record is created and stored in backup database and is efficiently restored in case of any unwanted deletion or loss of data. That is, to introduce a protocol that user B may use to reconstruct file X from file Y with suitably low probability of error. Synchronization algorithms find numerous areas of use, including data storage, file sharing, source code control systems, and cloud applications. For example, cloud storage services such as Drop box synchronize between local copies and cloud backups each time users make changes to local versions. Similarly, synchronization tools are necessary in mobile devices. Specialized synchronization algorithms are used for video and sound editing. Synchronization tools are also capable of performing data duplication.

  9. Enhanced N2-fixing ability of a deletion mutant of arctic rhizobia with sainfoin (Onobrychis viciifolia).

    Science.gov (United States)

    Jain, D K; Bordeleau, L M

    1990-12-01

    Mutagenesis provoked by exposure at elevated temperature of the cold-adapted, arctic Rhizobium strain N31 resulted in the generation of five deletion mutants, which exhibited loss of their smaller plasmid (200 kb), whereas the larger plasmid (> 500 kb) was still present in all mutants. Deletion mutants did not show differences from the wild type in the antibiotic resistance pattern, the carbohydrates and organic acids utilization, and the growth rate at low temperature. However, deletion mutants differed from the wild type and among themselves in the ex planta nitrogenase activity, the nodulation index, and the symbiotic effectiveness. The deletion mutant N31.6rif (r) showed higher nodulation index and exhibited higher nitrogenase activity and symbiotic efficiency than the other deletion mutants and the wild type. The process of deletion mutation resulted in the improvement of an arctic Rhizobium strain having an earlier and higher symbiotic nitrogen fixation efficiency than the wild type.

  10. Branchio-oto-renal syndrome caused by partial EYA1 deletion due to LINE-1 insertion

    DEFF Research Database (Denmark)

    Morisada, Naoya; Rendtorff, Nanna Dahl; Nozu, Kandai

    2010-01-01

    multiplex ligation-dependent probe amplification (MLPA) analysis, a heterozygous EYA1 gene deletion comprising at least exons 5 to 7. In her parents, we did not detect any deletion in EYA1 by MLPA, so the deletion was a de novo mutation. PCR analysis and sequencing of patient DNA revealed a heterozygous...... approximately 17 kb EYA1 deletion starting from the eight last bases of exon 4 and proceeding to base 1,217 of intron 7. Furthermore, in place of this deleted region was inserted a 3756-bp-long interspersed nuclear elements-1 (LINE-1, L1). Accordingly, RT-PCR showed that exons 4-7 were not present in EYA1 m......RNA expressed from the mutated allele. Although there are reports of L1 element insertion occurring in various human diseases, this is the first report of a large EYA1 deletion in combination with L1 element insertion....

  11. Toughness Condition for a Graph to Be a Fractional (g,f,n-Critical Deleted Graph

    Directory of Open Access Journals (Sweden)

    Wei Gao

    2014-01-01

    Full Text Available A graph G is called a fractional (g,f-deleted graph if G-{e} admits a fractional (g,f-factor for any e∈E(G. A graph G is called a fractional (g,f,n-critical deleted graph if, after deleting any n vertices from G, the resulting graph is still a fractional (g,f-deleted graph. The toughness, as the parameter for measuring the vulnerability of communication networks, has received significant attention in computer science. In this paper, we present the relationship between toughness and fractional (g,f,n-critical deleted graphs. It is determined that G is fractional (g,f,n-critical deleted if t(G≥((b2-1+bn/a.

  12. Anatomic Malformations of the Middle and Inner Ear in 22q11.2 Deletion Syndrome: Case Series and Literature Review.

    Science.gov (United States)

    Verheij, E; Elden, L; Crowley, T B; Pameijer, F A; Zackai, E H; McDonald-McGinn, D M; Thomeer, H G X M

    2018-03-15

    The 22q11.2 deletion syndrome is characterized by a heterogenic phenotype, including hearing loss. The underlying cause of hearing loss, especially sensorineural hearing loss, is not yet clear. Therefore, our objective was to describe anatomic malformations in the middle and inner ear in patients with 22q11.2 deletion syndrome. A retrospective case series was conducted in 2 tertiary referral centers. All patients with 22q11.2 deletion syndrome who had undergone CT or MR imaging of the temporal bones were included. Radiologic images were evaluated on predetermined parameters, including abnormalities of the ossicular chain, cochlea, semicircular canals, and vestibule. There were 26 patients (52 ears) with a CT or MR imaging scan available. A dense stapes superstructure was found in 18 ears (36%), an incomplete partition type II was suspected in 12 cochleas (23%), the lateral semicircular canal was malformed with a small bony island in 17 ears (33%), and the lateral semicircular canal and vestibule were fused to a single cavity in 15 ears (29%). Middle and inner ear abnormalities were frequently encountered in our cohort, including malformations of the lateral semicircular canal. © 2018 by American Journal of Neuroradiology.

  13. The rates and patterns of deletions in the human factor IX gene

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1994-02-01

    Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

  14. Improved pestalotiollide B production by deleting competing polyketide synthase genes in Pestalotiopsis microspora.

    Science.gov (United States)

    Chen, Longfei; Li, Yingying; Zhang, Qian; Wang, Dan; Akhberdi, Oren; Wei, Dongsheng; Pan, Jiao; Zhu, Xudong

    2017-02-01

    Pestalotiollide B, an analog of dibenzodioxocinones which are inhibitors of cholesterol ester transfer proteins, is produced by Pestalotiopsis microspora NK17. To increase the production of pestalotiollide B, we attempted to eliminate competing polyketide products by deleting the genes responsible for their biosynthesis. We successfully deleted 41 out of 48 putative polyketide synthases (PKSs) in the genome of NK17. Nine of the 41 PKS deleted strains had significant increased production of pestalotiollide B (P polyketides.

  15. Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of cell bodies, dendrites, and axons.

    Science.gov (United States)

    Gallent, Erin A; Steward, Oswald

    2018-05-01

    Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood (Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5 of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's identified by tdT expression and retrograde labeling with fluorogold (FG) were significantly enlarged four months following PTEN deletion, and continued to increase in size through the latest time intervals examined (12-15 months post-deletion). Sholl analyses of tdT-positive pyramidal neurons revealed increases in dendritic branches at 6 months following adult PTEN deletion, and greater increases at 12 months. 12 months after adult PTEN deletion, axons in the medullary pyramids were significantly larger and G-ratios were higher. Mice with PTEN deletion exhibited no overt neurological symptoms and no seizures. Assessment of motor function on the rotarod and cylinder test revealed slight impairment of coordination with unilateral deletion; however, mice with bilateral PTEN deletion in the motor cortex performed better than controls on the rotarod at 8 and 10 months post-deletion. Our findings demonstrate that robust neuronal growth can be induced in fully mature cortical neurons long after the developmental period has ended and that this continuous growth occurs without obvious functional impairments. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation

    OpenAIRE

    ISOBE, KAZUTOSHI; KAKIMOTO, ATSUSHI; MIKAMI, TETSUO; KABURAKI, KYOHEI; KOBAYASHI, HIROSHI; YOSHIZAWA, TAKAHIRO; MAKINO, TAKASHI; OTSUKA, HAJIME; SANO, GO; SUGINO, KEISHI; SAKAMOTO, SUSUMU; TAKAI, YUJIRO; TOCHIGI, NAOBUMI; IYODA, AKIRA; HOMMA, SAKAE

    2016-01-01

    Aim: This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). Patients and Methods: The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). Results: BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM ...

  17. Semantics of Temporal Models with Multiple Temporal Dimensions

    DEFF Research Database (Denmark)

    Kraft, Peter; Sørensen, Jens Otto

    ending up with lexical data models. In particular we look upon the representations by sets of normalised tables, by sets of 1NF tables and by sets of N1NF/nested tables. At each translation step we focus on how the temporal semantic is consistently maintained. In this way we recognise the requirements...... for representation of temporal properties in different models and the correspondence between the models. The results rely on the assumptions that the temporal dimensions are interdependent and ordered. Thus for example the valid periods of existences of a property in a mini world are dependent on the transaction...... periods in which the corresponding recordings are valid. This is not the normal way of looking at temporal dimensions and we give arguments supporting our assumption....

  18. Analysis of spontaneous deletions and gene amplification in the lac region of Escherichia coli

    International Nuclear Information System (INIS)

    Albertini, A.M.; Hofer, M.; Calos, M.P.; Tlsty, T.D.; Miller, J.H.

    1983-01-01

    Spontaneous rearrangements, such as large deletions and duplications, have important implications for the structure of the genome. It is therefore of great interest to analyze these events at the molecular level. We have constructed derivatives of a lacI-Z fusion strain, which allow us to study deletions in a more systematic manner than was previously possible. These derivatives have been used to investigate how frequently larger deletions (> 700 bp) occur between short homologies on both recA and recA - strains and to determine the effect of the lengths of the short homologies and of the distance between homologies on the frequency of deletion formation. 38 references, 11 figures

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

    Science.gov (United States)

    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.

  20. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  1. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-06-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with {sup 137}Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H{sub 2}O{sub 2}-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H{sub 2}O{sub 2}-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

  2. Mosaic deletion of 20pter due to rescue by somatic recombination.

    Science.gov (United States)

    Martin, Megan M; Vanzo, Rena J; Sdano, Mallory R; Baxter, Adrianne L; South, Sarah T

    2016-01-01

    We report on a unique case of a mosaic 20pter-p13 deletion due to a somatic repair event identified by allele differentiating single nucleotide polymorphism (SNP) probes on chromosomal microarray. Small terminal deletions of 20p have been reported in a few individuals and appear to result in a variable phenotype. This patient was a 24-month-old female who presented with failure to thrive and speech delay. Chromosomal microarray analysis (CMA) performed on peripheral blood showed a 1.6 Mb deletion involving the terminus of 20p (20pter-20p13). This deletion appeared mosaic by CMA and this suspicion was confirmed by fluorescence in situ hybridization (FISH) analysis. Additionally, the deletion interval at 20p was directly adjacent to 15 Mb of mosaic copy-neutral loss of heterozygosity (LOH). The pattern of SNP probes was highly suggestive of a somatic repair event that resulted in rescue of the deleted region using the non-deleted homologue as a template. Structural mosaicism is rare and most often believed to be due to a postzygotic mechanism. This case demonstrates the additional utility of allele patterns to help distinguish mechanisms and in this case identified the possibility of either a post-zygotic repair of a germline deletion or a post-zygotic deletion with somatic recombination repair in a single step. © 2015 Wiley Periodicals, Inc.

  3. Concurrent deletion of 16q23 and PTEN is an independent prognostic feature in prostate cancer.

    Science.gov (United States)

    Kluth, Martina; Runte, Frederic; Barow, Philipp; Omari, Jazan; Abdelaziz, Zaid M; Paustian, Lisa; Steurer, Stefan; Christina Tsourlakis, Maria; Fisch, Margit; Graefen, Markus; Tennstedt, Pierre; Huland, Hartwig; Michl, Uwe; Minner, Sarah; Sauter, Guido; Simon, Ronald; Adam, Meike; Schlomm, Thorsten

    2015-11-15

    The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p deletions including phosphatase and tensin homolog (PTEN) (p deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low- and intermediated grade prostate cancers. © 2015 UICC.

  4. Join Operations in Temporal Databases

    DEFF Research Database (Denmark)

    Gao, D.; Jensen, Christian Søndergaard; Snodgrass, R.T.

    2005-01-01

    Joins are arguably the most important relational operators. Poor implementations are tantamount to computing the Cartesian product of the input relations. In a temporal database, the problem is more acute for two reasons. First, conventional techniques are designed for the evaluation of joins wit...... to implementation, is on non-index-based join algorithms. Such algorithms do not rely on auxiliary access paths but may exploit sort orderings to achieve efficiency......., if any, comparison of the various operators. We then address evaluation algorithms, comparing the applicability of various algorithms to the temporal join operators and describing a performance study involving algorithms for one important operator, the temporal equijoin. Our focus, with respect...

  5. Treatment of Temporal Bone Fractures

    Science.gov (United States)

    Diaz, Rodney C.; Cervenka, Brian; Brodie, Hilary A.

    2016-01-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted. PMID:27648399

  6. Temporal bone trauma and imaging

    International Nuclear Information System (INIS)

    Turetschek, K.; Czerny, C.; Wunderbaldinger, P.; Steiner, E.

    1997-01-01

    Fractures of the temporal bone result from direct trauma to the temporal bone or occur as one component of a severe craniocerebral injury. Complications of temporal trauma are hemotympanon, facial nerve paralysis, conductive or sensorineur hearing loss, and leakage of cerebrospinal fluid. Erly recognition and an appropiate therapy may improve or prevent permanent deficits related to such complications. Only 20-30% of temporal bone fractures can be visualized by plain films. CT has displaced plain radiography in the investigation of the otological trauma because subtle bony details are best evaluated by CT which even can be reformatted in multiple projections, regardless of the original plane of scanning. Associated epidural, subdural, and intracerebral hemorrhagic lesions are better defined by MRI. (orig.) [de

  7. Syndrome of proximal interstitial deletion 4p15

    Energy Technology Data Exchange (ETDEWEB)

    Fryns, J.P. [Univ. of Leuven (Belgium)

    1995-09-11

    In this journal, Chitayat et al. reported on 2 boys and a girl with interstitial deletion in the short arm of chromosome 4, including p15.2p15.33. All 3 patients had a characteristic face distinct from that of Wolf-Hirschhorn syndrome and multiple minor congenital anomalies. One patient had a congenitally enlarged penis. The authors noted that all had normal growth, and all had moderate psychomotor retardation (patient 1, developmental age of 4-6 years at age 9 years; patient 2, mental age 6 years at age 25 years; and patient 3, global delay with hypotonia, difficulties in both gross and fine motor development, and persistent delay in language skills). 5 refs., 1 fig.

  8. Stella-Cre mice are highly efficient Cre deleters.

    Science.gov (United States)

    Liu, Hui; Wang, Wei; Chew, Su-Kit; Lee, Song-Choon; Li, Juan; Vassiliou, George S; Green, Tony; Futreal, P Andrew; Bradley, Allan; Zhang, Shujun; Liu, Pentao

    2011-08-01

    Cre-loxP recombination is widely used for genetic manipulation of the mouse genome. Here, we report generation and characterization of a new Cre line, Stella-Cre, where Cre expression cassette was targeted to the 3' UTR of the Stella locus. Stella is specifically expressed in preimplantation embryos and in the germline. Cre-loxP recombination efficiency in Stella-Cre mice was investigated at several genomic loci including Rosa26, Jak2, and Npm1. At all the loci examined, we observed 100% Cre-loxP recombination efficiency in the embryos and in the germline. Thus, Stella-Cre mice serve as a very efficient deleter line. Copyright © 2011 Wiley-Liss, Inc.

  9. A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat

    Directory of Open Access Journals (Sweden)

    Li Zhongyi

    2010-11-01

    Full Text Available Abstract Background Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (Triticum aestivum L. is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation that frequently generate whole-gene deletions. Results To facilitate the screening for specific homoeologous gene deletions in hexaploid wheat, we have developed a TaqMan qPCR-based method that allows high-throughput detection of deletions in homoeologous copies of any gene of interest, provided that sufficient polymorphism (as little as a single nucleotide difference amongst homoeologues exists for specific probe design. We used this method to identify deletions of individual TaPFT1 homoeologues, a wheat orthologue of the disease susceptibility and flowering regulatory gene PFT1 in Arabidopsis. This method was applied to wheat nullisomic-tetrasomic lines as well as other chromosomal deletion lines to locate the TaPFT1 gene to the long arm of chromosome 5. By screening of individual DNA samples from

  10. Deletion of 7q33-q35 in a Patient with Intellectual Disability and Dysmorphic Features: Further Characterization of 7q Interstitial Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Kristen Dilzell

    2015-01-01

    Full Text Available This case report concerns a 16-year-old girl with a 9.92 Mb, heterozygous interstitial chromosome deletion at 7q33-q35, identified using array comparative genomic hybridization. The patient has dysmorphic facial features, intellectual disability, recurrent infections, self-injurious behavior, obesity, and recent onset of hemihypertrophy. This patient has overlapping features with previously reported individuals who have similar deletions spanning the 7q32-q36 region. It has been difficult to describe an interstitial 7q deletion syndrome due to variations in the sizes and regions in the few patients reported in the literature. This case contributes to the further characterization of an interstitial distal 7q deletion syndrome.

  11. Genotype-phenotype correlation in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Michaelovsky Elena

    2012-12-01

    Full Text Available Abstract Background The 22q11.2 deletion syndrome (22q11.2DS is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion. Methods Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation. Results Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2% carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted. Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes. Conclusions MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms. Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.

  12. Sex-specific aspects of endogenous retroviral insertion and deletion.

    Science.gov (United States)

    Gemmell, Patrick; Hein, Jotun; Katzourakis, Aris

    2013-11-07

    We wish to understand how sex and recombination affect endogenous retroviral insertion and deletion. While theory suggests that the risk of ectopic recombination will limit the accumulation of repetitive DNA in areas of high meiotic recombination, the experimental evidence so far has been inconsistent. Under the assumption of neutrality, we examine the genomes of eighteen species of animal in order to compute the ratio of solo-LTRs that derive from insertions occurring down the male germ line as opposed to the female one (male bias). We also extend the simple idea of comparing autosome to allosome in order to predict the ratio of full-length proviruses we would expect to see under conditions of recombination linked deletion or otherwise. Using our model, we predict the ratio of allosomal to autosomal full-length proviruses to lie between32 and 23 under increasing male bias in mammals and between 1 and 2 under increasing male bias in birds. In contrast to our expectations, we find that a pattern of male bias is not universal across species and that there is a frequent overabundance of full-length proviruses on the allosome beyond the ratios predicted by our model. We use our data as a whole to argue that full-length proviruses should be treated as deleterious mutations or as effectively neutral mutations whose persistence in a full-length state is linked to the rate of meiotic recombination and whose origin is not universally male biased. These conclusions suggest that retroviral insertions on the allosome may be more prolific and that it might be possible to identify mechanisms of replication that are enhanced in the female sex.

  13. Bad Clade Deletion Supertrees: A Fast and Accurate Supertree Algorithm.

    Science.gov (United States)

    Fleischauer, Markus; Böcker, Sebastian

    2017-09-01

    Supertree methods merge a set of overlapping phylogenetic trees into a supertree containing all taxa of the input trees. The challenge in supertree reconstruction is the way of dealing with conflicting information in the input trees. Many different algorithms for different objective functions have been suggested to resolve these conflicts. In particular, there exist methods based on encoding the source trees in a matrix, where the supertree is constructed applying a local search heuristic to optimize the respective objective function. We present a novel heuristic supertree algorithm called Bad Clade Deletion (BCD) supertrees. It uses minimum cuts to delete a locally minimal number of columns from such a matrix representation so that it is compatible. This is the complement problem to Matrix Representation with Compatibility (Maximum Split Fit). Our algorithm has guaranteed polynomial worst-case running time and performs swiftly in practice. Different from local search heuristics, it guarantees to return the directed perfect phylogeny for the input matrix, corresponding to the parent tree of the input trees, if one exists. Comparing supertrees to model trees for simulated data, BCD shows a better accuracy (F1 score) than the state-of-the-art algorithms SuperFine (up to 3%) and Matrix Representation with Parsimony (up to 7%); at the same time, BCD is up to 7 times faster than SuperFine, and up to 600 times faster than Matrix Representation with Parsimony. Finally, using the BCD supertree as a starting tree for a combined Maximum Likelihood analysis using RAxML, we reach significantly improved accuracy (1% higher F1 score) and running time (1.7-fold speedup). © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Potential complications when developing gene deletion clones in Xylella fastidiosa.

    Science.gov (United States)

    Johnson, Kameka L; Cursino, Luciana; Athinuwat, Dusit; Burr, Thomas J; Mowery, Patricia

    2015-04-16

    The Gram-negative xylem-limited bacterium, Xylella fastidiosa, is an important plant pathogen that infects a number of high value crops. The Temecula 1 strain infects grapevines and induces Pierce's disease, which causes symptoms such as scorching on leaves, cluster collapse, and eventual plant death. In order to understand the pathogenesis of X. fastidiosa, researchers routinely perform gene deletion studies and select mutants via antibiotic markers. Site-directed pilJ mutant of X. fastidiosa were generated and selected on antibiotic media. Mutant cultures were assessed by PCR to determine if they were composed of purely transformant cells or included mixtures of non-transformants cells. Then pure pilJ mutant and wildtype cells were mixed in PD2 medium and following incubation and exposure to kanamycin were assessed by PCR for presence of mutant and wildtype populations. We have discovered that when creating clones of targeted mutants of X. fastidiosa Temecula 1 with selection on antibiotic plates, X. fastidiosa lacking the gene deletion often persist in association with targeted mutant cells. We believe this phenomenon is due to spontaneous antibiotic resistance and/or X. fastidiosa characteristically forming aggregates that can be comprised of transformed and non-transformed cells. A combined population was confirmed by PCR, which showed that targeted mutant clones were mixed with non-transformed cells. After repeated transfer and storage the non-transformed cells became the dominant clone present. We have discovered that special precautions are warranted when developing a targeted gene mutation in X. fastidiosa because colonies that arise following transformation and selection are often comprised of transformed and non-transformed cells. Following transfer and storage the cells can consist primarily of the non-transformed strain. As a result, careful monitoring of targeted mutant strains must be performed to avoid mixed populations and confounding results.

  15. The grounding of temporal metaphors.

    Science.gov (United States)

    Lai, Vicky T; Desai, Rutvik H

    2016-03-01

    Grounded cognition suggests that the processing of conceptual knowledge cued by language relies on the sensory-motor regions. Does temporal language similarly engage brain areas involved in time perception? Participants read sentences that describe the temporal extent of events with motion verbs (The hours crawled until the release of the news) and their static controls. Comparison conditions were fictive motion (The trail crawled until the end of the hills) and literal motion (The caterpillar crawled towards the top of the tree), along with their static controls. Several time sensitive locations, identified using a meta-analysis, showed activation specific to temporal metaphors, including in the left insula, right claustrum, and bilateral posterior superior temporal sulci. Fictive and literal motion contrasts did not show this difference. Fictive motion contrast showed activation in a conceptual motion sensitive area of the left posterior inferior temporal sulcus (ITS). These data suggest that language of time is at least partially grounded in experiential time. In addition, motion semantics has different consequences for events and objects: temporal events become animate, while static entities become motional. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Deletional rearrangement in the human T-cell receptor α-chain locus

    International Nuclear Information System (INIS)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-01-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4 - , CD8 - ) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

  17. [Chromosomal large fragment deletion induced by CRISPR/Cas9 gene editing system].

    Science.gov (United States)

    Cheng, L H; Liu, Y; Niu, T

    2017-05-14

    Objective: Using CRISPR-Cas9 gene editing technology to achieve a number of genes co-deletion on the same chromosome. Methods: CRISPR-Cas9 lentiviral plasmid that could induce deletion of Aloxe3-Alox12b-Alox8 cluster genes located on mouse 11B3 chromosome was constructed via molecular clone. HEK293T cells were transfected to package lentivirus of CRISPR or Cas9 cDNA, then mouse NIH3T3 cells were infected by lentivirus and genomic DNA of these cells was extracted. The deleted fragment was amplified by PCR, TA clone, Sanger sequencing and other techniques were used to confirm the deletion of Aloxe3-Alox12b-Alox8 cluster genes. Results: The CRISPR-Cas9 lentiviral plasmid, which could induce deletion of Aloxe3-Alox12b-Alox8 cluster genes, was successfully constructed. Deletion of target chromosome fragment (Aloxe3-Alox12b-Alox8 cluster genes) was verified by PCR. The deletion of Aloxe3-Alox12b-Alox8 cluster genes was affirmed by TA clone, Sanger sequencing, and the breakpoint junctions of the CRISPR-Cas9 system mediate cutting events were accurately recombined, insertion mutation did not occur between two cleavage sites at all. Conclusion: Large fragment deletion of Aloxe3-Alox12b-Alox8 cluster genes located on mouse chromosome 11B3 was successfully induced by CRISPR-Cas9 gene editing system.

  18. Deletion of amino acid residues 33-46 in growth hormone alters the ...

    African Journals Online (AJOL)

    To investigate the effect of deletion on the chemistry of the molecule, computational biology tools were employed. The mutant with the deletion of amino acid residues 33-46, was designed and the model was visualized on computer. The structure of 20k bGH was compared with bGH and dissected for hydrogen bonds and ...

  19. 31 CFR 363.144 - May I delete a pending transaction involving a certificate of indebtedness?

    Science.gov (United States)

    2010-07-01

    ... involving a certificate of indebtedness? 363.144 Section 363.144 Money and Finance: Treasury Regulations... DEBT REGULATIONS GOVERNING SECURITIES HELD IN TREASURYDIRECT Certificate of Indebtedness § 363.144 May I delete a pending transaction involving a certificate of indebtedness? (a) You may delete a pending...

  20. AZFc deletions do not affect the function of human spermatogonia in vitro

    NARCIS (Netherlands)

    Nickkholgh, B.; Korver, C. M.; van Daalen, S. K. M.; van Pelt, A. M. M.; Repping, S.

    2015-01-01

    Azoospermic factor c (AZFc) deletions are the underlying cause in 10% of azoo- or severe oligozoospermia. Through extensive molecular analysis the precise genetic content of the AZFc region and the origin of its deletion have been determined. However, little is known about the effect of AZFc

  1. Deletion of SNURF/SNRPN U1B and U1B* upstream exons in a ...

    Indian Academy of Sciences (India)

    Array-CGH analysis of the proband indicated a 15q11.2 deletion. The presence and the breakpoints of the deletion are underlined in red which correspond to approximately 13 kb (pos. 25,068,955–25,082,444) residing in the SNRNP gene as indicated by green line. MEO28-B2 (MRC, Holland) which is specific for Prader–.

  2. Rapid deletion plasmid construction methods for protoplast and Agrobacterium based fungal transformation systems

    Science.gov (United States)

    Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Gene deletion is a critical tool for functional analysis. The targeted deletion of genes requires both a suitable method for the trans...

  3. De novo Xp terminal deletion in a triple X female with recurrent ...

    Indian Academy of Sciences (India)

    (MLS), a rare congenital, X-linked dominant syndrome is also most commonly caused by terminal deletions of Xp. (Vergult et al. 2013). In contrast with these reports, the patient in discussion was a true 47,XXX female without any mosaic cell line, but had an Xp terminal deletion in the extra copy of the X chromosome that had ...

  4. Pearson syndrome and the role of deletion dimers and duplications in the mtDNA

    NARCIS (Netherlands)

    Jacobs, L. J. A. M.; Jongbloed, R. J. E.; Wijburg, F. A.; de Klerk, J. B. C.; Geraedts, J. P. M.; Nijland, J. G.; Scholte, H. R.; de Coo, I. F. M.; Smeets, H. J. M.

    2004-01-01

    Pearson syndrome is an often fatal multisystem disease associated with mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with deletion dimers. The mutation percentage in different tissues (blood,

  5. Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication

    DEFF Research Database (Denmark)

    Hoeffding, Louise K; Trabjerg, Betina B; Olsen, Line

    2017-01-01

    .64-14.69) and childhood autism (IRR, 8.94; 95%CI, 3.21-19.23). Conclusions and relevance: Individuals with the 22q11.2 deletion or duplication have a significantly increased risk of developing psychiatric disorders. Survival analysis of persons carrying either the 22q11.2 deletion or duplication provides estimates...

  6. Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

    DEFF Research Database (Denmark)

    Wolfe, Kate; McQuillin, Andrew; Alesi, Viola

    2018-01-01

    ) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence...

  7. Neuroimaging Correlates of 22q11.2 Deletion Syndrome: Implications for Schizophrenia Research

    NARCIS (Netherlands)

    Boot, E.; van Amelsvoort, T. A. M. J.

    2012-01-01

    22q11.2 Deletion syndrome (22q11DS) is the most common known recurrent copy-number variant disorder. It is also the most common known genetic risk factor for schizophrenia. The greater homogeneity of subjects with schizophrenia in 22q11DS compared with schizophrenia in the wider non-deleted

  8. Characteristics of dystonia in the 18p deletion syndrome, including a new case

    NARCIS (Netherlands)

    Postma, Anna G.; Verschuuren - Bemelmans, Corien C.; Kok, Klaas; van Laar, Teus

    2009-01-01

    Objective of the present study was to evaluate the possible pathophysiology and clinical characteristics of dystonia in patients with the 18p deletion syndrome by describing a new case and reviewing the literature. Dystonia in patients with the 18p deletion syndrome seems to present heterogeneously

  9. Computational prediction of the tolerance to amino-acid deletion in green-fluorescent protein.

    Science.gov (United States)

    Jackson, Eleisha L; Spielman, Stephanie J; Wilke, Claus O

    2017-01-01

    Proteins evolve through two primary mechanisms: substitution, where mutations alter a protein's amino-acid sequence, and insertions and deletions (indels), where amino acids are either added to or removed from the sequence. Protein structure has been shown to influence the rate at which substitutions accumulate across sites in proteins, but whether structure similarly constrains the occurrence of indels has not been rigorously studied. Here, we investigate the extent to which structural properties known to covary with protein evolutionary rates might also predict protein tolerance to indels. Specifically, we analyze a publicly available dataset of single-amino-acid deletion mutations in enhanced green fluorescent protein (eGFP) to assess how well the functional effect of deletions can be predicted from protein structure. We find that weighted contact number (WCN), which measures how densely packed a residue is within the protein's three-dimensional structure, provides the best single predictor for whether eGFP will tolerate a given deletion. We additionally find that using protein design to explicitly model deletions results in improved predictions of functional status when combined with other structural predictors. Our work suggests that structure plays fundamental role in constraining deletions at sites in proteins, and further that similar biophysical constraints influence both substitutions and deletions. This study therefore provides a solid foundation for future work to examine how protein structure influences tolerance of more complex indel events, such as insertions or large deletions.

  10. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion

    DEFF Research Database (Denmark)

    Styrkársdóttir, U; Egel, R; Nielsen, O

    1993-01-01

    Mating-type switching in the fission yeast, S. pombe, is initiated by a DNA double-strand break (DSB) between the mat1 cassette and the H1 homology box. The mat1-cis-acting mutant, smt-0, abolishes mating-type switching and is shown here to be a 263-bp deletion. This deletion starts in the middle...

  11. Deletion of /T, D/ and the Acquisition of Linguistic Variation by Second Language Learners of English

    Science.gov (United States)

    Edwards, Jette G. Hansen

    2011-01-01

    This study investigated second language (L2) learners' acquisition of English /t, d/ deletion patterns in word-final consonant clusters, (a) focusing on how constraints such as grammatical conditioning and phonological environment affect deletion of /t, d/ in L2 acquisition and (b) determining the extent to which these L2 learners had acquired…

  12. Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients

    International Nuclear Information System (INIS)

    Ismail, H.M.S.; Zakhary, N.I.; Medhat, A.M.; Karim, A.M.

    2011-01-01

    Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients clinico pathological parameters including patients age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P<0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P<0.0001), Exon 8 (P<0.027), and exon 9 (P=0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P<0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

  13. 40 CFR 63.60 - Deletion of caprolactam from the list of hazardous air pollutants.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Deletion of caprolactam from the list of hazardous air pollutants. 63.60 Section 63.60 Protection of Environment ENVIRONMENTAL PROTECTION..., Source Category List § 63.60 Deletion of caprolactam from the list of hazardous air pollutants. The...

  14. Autism, ADHD, Mental Retardation and Behavior Problems in 100 Individuals with 22q11 Deletion Syndrome

    Science.gov (United States)

    Niklasson, Lena; Rasmussen, Peder; Oskarsdottir, Solveig; Gillberg, Christopher

    2009-01-01

    This study assessed the prevalence and type of associated neuropsychiatric problems in children and adults with 22q11 deletion syndrome. One-hundred consecutively referred individuals with 22q11 deletion syndrome were given in-depth neuropsychiatric assessments and questionnaires screens. Autism spectrum disorders (ASDs) and/or attention…

  15. Cardiac Defects and Results of Cardiac Surgery in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Carotti, Adriano; Digilio, Maria Cristina; Piacentini, Gerardo; Saffirio, Claudia; Di Donato, Roberto M.; Marino, Bruno

    2008-01-01

    Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic…

  16. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.

    2010-01-01

    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene

  17. Maladaptive Behavior Differences in Prader-Willi Syndrome Due to Paternal Deletion versus Maternal Uniparental Disomy.

    Science.gov (United States)

    Dykens, Elisabeth M.; King, Bryan H.; Cassidy, Suzanne B.

    1999-01-01

    This study compared maladaptive behavior in 23 people with Prader-Willi syndrome due to paternal deletion and in 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for IQs, the deletion cases showed significantly higher maladaptive ratings, more symptom-related distress, and more behavior problems. Findings suggest a…

  18. Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report

    Directory of Open Access Journals (Sweden)

    Bao Bihui

    2012-08-01

    Full Text Available Abstract Background With an increasing incidence of congenital heart defects (CHDs in recent years, genotype-phenotype correlation and array-based methods have contributed to the genome-wide analysis and understanding of genetic variations in the CHD population. Here, we report a copy number deletion of chromosomal 14q23.1 in a female fetus with complex congenital heart defects. This is the first description of DAAM1 gene deletion associated with congenital heart anomalies. Case Presentation Compared with the control population, one CHD fetus showed a unique copy number deletion of 14q23.1, a region that harbored DAAM1 and KIAA0666 genes. Conclusions Results suggest that the copy number deletion on chromosome 14q23.1 may be critical for cardiogenesis. However, the exact relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the onset of CHD is yet to be determined.

  19. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation

    DEFF Research Database (Denmark)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria

    2010-01-01

    12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating...... that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P......-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation....

  20. FAMILIAL CASE OF CHROMOSOME 22q11.2 DELETION SYNDROME

    Directory of Open Access Journals (Sweden)

    I. A. Tuzankina

    2017-01-01

    Full Text Available The work represents a family which includes two siblings with chromosome 22q11.2 deletion syndrome. Their mother carries the same chromosome anomaly, but with apparently normal phenotype. Hence, this interesting case of 22q11.2 deletion syndrome exists in 2 generations of the same family. The aim of this study was analysis of phenotypic manifestations in the family members with 22q11.2 deletion syndrome. Clinical examination of the patients, their life story and pedigree and, along with routine clinical and biochemical analysis, and immune state testing, along with ultrasound imaging of thymus and thyroid glands, heart and abdominal cavity. We made conclusions that the phenotypic features associated with chromosome 22q11.2 deletion may be different for distinct family members. Further studies are required to determine length of deleted segment and the genes affected, as well as to establish the genotype-phenotype interactions and disease prognosis.

  1. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  2. Temporal anteroinferior encephalocele: An underrecognized etiology of temporal lobe epilepsy?

    Science.gov (United States)

    Saavalainen, Taavi; Jutila, Leena; Mervaala, Esa; Kälviäinen, Reetta; Vanninen, Ritva; Immonen, Arto

    2015-10-27

    To report the increasing frequency with which temporal anteroinferior encephalocele is a cause of adult temporal lobe epilepsy, to illustrate the clinical and imaging characteristics of this condition, and to report its surgical treatment in a series of 23 adult patients. Epilepsy patients diagnosed with temporal anteroinferior encephalocele from January 2006 to December 2013 in a national epilepsy reference center were included in this noninterventional study. Twenty-three epilepsy patients (14 female, mean age 43.8 years) were diagnosed with temporal anteroinferior encephalocele in our institute. Thirteen patients had ≥2 encephaloceles; 7 cases presented bilaterally. The estimated frequency of this condition was 0.3% among MRI examinations performed due to newly diagnosed epilepsy (n = 6) and 1.9% among drug-resistant patients referred to our center (n = 17). Nine patients with local encephalocele disconnection (n = 4) or anterior temporal lobectomy and amygdalohippocampectomy (n = 5) have become seizure-free (Engel 1) for a mean 2.8 years (range 3 months-6.2 years) of follow-up. Three patients with local encephalocele disconnection were almost seizure-free or exhibited worthwhile improvement. Histologically, all 12 surgical patients had gliosis at the base of the encephalocele; some had cortical laminar disorganization (n = 5) or mild hippocampal degeneration (n = 1). The possibility of a temporal encephalocele should be considered when interpreting MRI examinations of patients with medically intractable focal epilepsy. These patients can significantly benefit from unitemporal epilepsy surgery, even in cases with bilateral encephaloceles. © 2015 American Academy of Neurology.

  3. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102

    International Nuclear Information System (INIS)

    Levin, D.E.; Marnett, L.J.; Ames, B.N.

    1984-01-01

    Salmonella tester strain TA102 carries the hisG428 ochre mutation on the multicopy plasmid pAQ1. DNA sequence analysis of 45 spontaneous revertants of hisG428 on the chromosome in the presence of pKM101 (strain TA103) indicates that hisG428 revertants fall into three major categories: (i) small, in-frame deletions (3 or 6 base pairs) that remove part or all of the ochre triplet; (ii) base substitution mutations at the ochre site; (iii) extragenic ochre suppressors. Deletion revertants are identified in a simple phenotypic screen by their resistance to the inhibitory histidine analog thiazolealanine, which feedback inhibits the wild-type hisG enzyme but not the enzyme resulting from the deletions. The effect of various genetic backgrounds on the generation of spontaneous deletion revertants was examined. The presence of a uvrB mutation or a recA mutation suppressed the generation of spontaneous deletion revertants to approximately 1/2.5. When hisG428 was in multiple copies on pAQ1, the frequency of spontaneous deletion revertants increased by 40-fold, which is the approximate copy number of pAQ1. Mutagenic agents that induce single-strand breaks in DNA (e.g., x-rays, bleomycin, and nalidixic acid) induced deletion revertants in TA102. These agents induced deletion revertants only in hisG428 on pAQ1 and only in the presence of pKM101. Deletion revertants were not induced by frameshift mutagens (i.e., ICR-191 and 9aminoacridine). These results indicate that different pathways exist for the generation of spontaneous and mutagen-induced deletion revertants of hisG428. 41 references, 2 figures, 3 tables

  4. APOBEC3 deletion polymorphism is associated with breast cancer risk among women of European ancestry.

    Science.gov (United States)

    Xuan, Dennis; Li, Guoliang; Cai, Qiuyin; Deming-Halverson, Sandra; Shrubsole, Martha J; Shu, Xiao-Ou; Kelley, Mark C; Zheng, Wei; Long, Jirong

    2013-10-01

    Copy number variations occur frequently in the genome and are a significant source of human genetic variation accounting for disease. Recently, we discovered a common deletion located in the APOBEC3A and APOBEC3B genes significantly associated with breast cancer in Chinese women. Investigating this locus in other populations would be an expedient way to evaluate the generalizability of the novel finding. We analyzed the APOBEC3 deletion in a large study of 3273 European-ancestry women (including 1671 breast cancer cases and 1602 controls) from the population-based Nashville Breast Health Study. All participants were genotyped using real-time qualitative PCR. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the deletion polymorphism and breast cancer risk. The APOBEC3 deletion was observed in 12.4% of cases and 10.4% of controls. The deletion was significantly associated with breast cancer risk, with ORs and 95% CIs of 1.21 (1.02-1.43) associated with one-copy deletion and 2.29 (1.04-5.06) associated with two-copy deletion compared with women with no deletion (P for trend = 0.005). The positive association of the APOBEC3 deletion with breast cancer risk was similar for estrogen receptor-positive and estrogen receptor-negative breast cancer and was not modified by known breast cancer risk factors. Results from this study confirmed the association of the APOBEC3 deletion with breast cancer risk among women of European ancestry.

  5. Analysis of human HPRT- deletion mutants by the microarray-CGH (comparative genomic hybridization)

    International Nuclear Information System (INIS)

    Kodaira, M.; Sasaki, K.; Tagawa, H.; Omine, H.; Kushiro, J.; Takahashi, N.; Katayama, H.

    2003-01-01

    We are trying to evaluate genetic effects of radiation on human using mutation frequency as an indicator. For the efficient detection of mutations, it is important to understand the mechanism and the characteristics of radiation-induced mutations. We have started the analysis of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutants induced by X-ray in order to clarify the deletion size and the mutation-distribution. We analyzed 39 human X-ray induced HPRT-deletion mutants by using the microarray-CGH. The array for this analysis contains 57 BAC clones covering as much as possible of the 4Mb of the 5' side and 10Mb of the 3' side of the HPRT gene based on the NCBI genome database. DNA from parent strain and each HPRT-mutant strain are labeled with Cy5 and Cy3 respectively, and were mixed and hybridized on the array. Fluorescent intensity ratio of the obtained spots was analyzed using software we developed to identify clones corresponding to the deletion region. The deletion in these strains ranged up to 3.5 Mb on the 5' side and 6 Mb on the 3' side of the HPRT gene. Deletions in 13 strains ended around BAC clones located at about 3 Mb on the 5' side. On the 3' side, deletions extended up to the specific clones located at 1.5 Mb in 11 strains. The mutations seem to be complex on the 3' end of deletion; some accompanied duplications with deletions and others could not be explained by one mutation event. We need to confirm these results, taking into account the experimental reproducibility and the accuracy of the published genetic map. The results of the research using the microarray-CGH help us to search the regions where deletions are easily induced and to identify the factors affecting the range of deletions

  6. Incidence of the 22q11.2 deletion in a large cohort of miscarriage samples.

    Science.gov (United States)

    Maisenbacher, Melissa K; Merrion, Katrina; Pettersen, Barbara; Young, Michael; Paik, Kiyoung; Iyengar, Sushma; Kareht, Stephanie; Sigurjonsson, Styrmir; Demko, Zachary P; Martin, Kimberly A

    2017-01-01

    The 22q11.2 deletion syndrome is the most common microdeletion syndrome in livebirths, but data regarding its incidence in other populations is limited and also include ascertainment bias. This study was designed to determine the incidence of the 22q11.2 deletion in miscarriage samples sent for clinical molecular cytogenetic testing. Twenty-six thousand one hundred one fresh product of conception (POC) samples were sent to a CLIA- certified, CAP-accredited laboratory from April 2010--May 2016 for molecular cytogenetic miscarriage testing using a single-nucleotide polymorphism (SNP)-based microarray platform. A retrospective review determined the incidence of the 22q11.2 deletion in this sample set. Fetal results were obtained in 22,451 (86%) cases, of which, 15 (0.07%) had a microdeletion in the 22q11.2 region (incidence, 1/1497). Of those, 12 (80%) cases were found in samples that were normal at the resolution of traditional karyotyping (i.e., had no chromosome abnormalities above 10 Mb in size) and three (20%) cases had additional findings (Trisomy 15, Trisomy 16, XXY). Ten (67%) cases with a 22q11.2 deletion had the common ~3 Mb deletion; the remaining 5 cases had deletions ranging in size from 0.65 to 1.5 Mb. A majority (12/15) of cases had a deletion on the maternally inherited chromosome. No significant relationship between maternal age and presence of a fetal 22q11.2 deletion was observed. The observed incidence of 1/1497 for the 22q11.2 deletion in miscarriage samples is higher than the reported general population prevalence (1/4000-1/6000). Further research is needed to determine whether the 22q11.2 deletion is a causal factor for miscarriage.

  7. Envelhecimento do processamento temporal auditivo

    Directory of Open Access Journals (Sweden)

    Vera Tôrres das Neves

    Full Text Available O presente artigo faz uma revisão breve da literatura sobre envelhecimento auditivo, abordando os estudos sobre o envelhecimento do processamento temporal auditivo, especificamente, estudos sobre detecção de interrupções em sons, por sujeitos adultos de mais idade. São apresentadas definições e descrições da presbiacusia, suas conseqüências, e sua prevalência. São descritos os procedimentos experimentais para estudo de processamento temporal envolvendo a detecção de interrupções em ruídos com faixas amplas de freqüência, a discriminação de sons com reversão temporal, a detecção de mudanças na amplitude de sons, a detecção de interrupções em sons com faixas estreitas de freqüências, a detecção de diferenças de duração entre dois estímulos, bem como a discriminação da ordem temporal de diferentes canais de freqüência componentes de tons complexos. São revisados, adicionalmente, estudos que descrevem as características psicofísicas do processamento auditivo temporal em idosos. Finalmente, são apresentadas sugestões sobre direções futuras para pesquisa.

  8. Envelhecimento do processamento temporal auditivo

    Directory of Open Access Journals (Sweden)

    Neves Vera Tôrres das

    2002-01-01

    Full Text Available O presente artigo faz uma revisão breve da literatura sobre envelhecimento auditivo, abordando os estudos sobre o envelhecimento do processamento temporal auditivo, especificamente, estudos sobre detecção de interrupções em sons, por sujeitos adultos de mais idade. São apresentadas definições e descrições da presbiacusia, suas conseqüências, e sua prevalência. São descritos os procedimentos experimentais para estudo de processamento temporal envolvendo a detecção de interrupções em ruídos com faixas amplas de freqüência, a discriminação de sons com reversão temporal, a detecção de mudanças na amplitude de sons, a detecção de interrupções em sons com faixas estreitas de freqüências, a detecção de diferenças de duração entre dois estímulos, bem como a discriminação da ordem temporal de diferentes canais de freqüência componentes de tons complexos. São revisados, adicionalmente, estudos que descrevem as características psicofísicas do processamento auditivo temporal em idosos. Finalmente, são apresentadas sugestões sobre direções futuras para pesquisa.

  9. Temporal coordination between performing musicians.

    Science.gov (United States)

    Loehr, Janeen D; Palmer, Caroline

    2011-11-01

    Many common behaviours require people to coordinate the timing of their actions with the timing of others' actions. We examined whether representations of musicians' actions are activated in coperformers with whom they must coordinate their actions in time and whether coperformers simulate each other's actions using their own motor systems during temporal coordination. Pianists performed right-hand melodies along with simple or complex left-hand accompaniments produced by themselves or by another pianist. Individual performers' preferred performance rates were measured in solo performance of the right-hand melody. The complexity of the left-hand accompaniment influenced the temporal grouping structure of the right-hand melody in the same way when it was performed by the self or by the duet partner, providing some support for the action corepresentation hypothesis. In contrast, accompaniment complexity had little influence on temporal coordination measures (asynchronies and cross-correlations between parts). Temporal coordination measures were influenced by a priori similarities between partners' preferred rates; partners who had similar preferred rates in solo performance were better synchronized and showed mutual adaptation to each other's timing during duet performances. These findings extend previous findings of action corepresentation and action simulation to a task that requires precise temporal coordination of independent yet simultaneous actions.

  10. Processing Temporal Constraints: An ERP Study

    Science.gov (United States)

    Baggio, Giosue

    2008-01-01

    This article investigates how linguistic expressions of time--in particular, temporal adverbs and verb tense morphemes--are used to establish temporal reference at the level of brain physiology. First, a formal semantic analysis of tense and temporal adverbs is outlined. It is argued that computing temporal reference amounts to solving a…

  11. Temporal interpolation in Meteosat images

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Hansen, Johan Dore; Ersbøll, Bjarne Kjær

    in such animated films are perceived as being jerky due to t he low temporal sampling rate in general and missing images in particular. In order to perform a satisfactory temporal interpolation we estimate and use the optical flow corresponding to every image in the sequenc e. The estimation of the optical flow...... a threshold between clouds and land/water. The temperature maps are estimated using observations from the image sequence itself at cloud free pixels and ground temperature measurements from a series of meteor ological observation stations in Europe. The temporal interpolation of the images is bas ed on a path...... of each pixel determined by the estimated optical flow. The performance of the algorithm is illustrated by the interpolation of a sequence of Meteosat infrared images....

  12. Temporal Lobe Epilepsy in Children

    Science.gov (United States)

    Nickels, Katherine C.; Wong-Kisiel, Lily C.; Moseley, Brian D.; Wirrell, Elaine C.

    2012-01-01

    The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in infants and children differs from the relatively homogeneous syndrome seen in adults in several important clinical and pathological ways. Seizure semiology varies by age, and the ictal EEG pattern may be less clear cut than what is seen in adults. Additionally, the occurrence of intractable seizures in the developing brain may impact neurocognitive function remote from the temporal area. While many children will respond favorably to medical therapy, those with focal imaging abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade tumors are likely to be intractable. Expedient workup and surgical intervention in these medically intractable cases are needed to maximize long-term developmental outcome. PMID:22957247

  13. Emotions are temporal interpersonal systems.

    Science.gov (United States)

    Butler, Emily A

    2017-10-01

    Several characteristics of emotions are that they: first, evolve dynamically over time, second, extend beyond the individual to incorporate multiple people, and third, function as a system. In other words, emotions can be seen as temporal interpersonal systems. This review summarizes current models for temporal interpersonal emotion systems (TIES), evidence they matter beyond levels of emotional responding, their connections with relationship quality and interpersonal regulation, and some of the challenges for studying them. Important directions for future research include distinguishing between different patterns of interpersonal emotional dynamics and extending theory and experimental work to uncover mechanisms for altering harmful TIES and promoting beneficial ones. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Ethnographies of Youth and Temporality

    DEFF Research Database (Denmark)

    Dalsgård, Anne Line; Frederiksen, Martin Demant; Højlund, Susanne

    As we experience and manipulate time—be it as boredom or impatience—it becomes an object: something materialized and social, something that affects perception, or something that may motivate reconsideration and change. The editors and contributors to this important new book, Ethnographies of Youth...... and Temporality, have provided a diverse collection of ethnographic studies and theoretical explorations of youth experiencing time in a variety of contemporary socio-cultural settings. The essays in this volume focus on time as an external and often troubling factor in young people’s lives, and show how...... of Youth and Temporality use youth as a prism to understand time and its subjective experience....

  15. TEMPORAL QUERY PROCESSIG USING SQL SERVER

    OpenAIRE

    Vali Shaik, Mastan; Sujatha, P

    2017-01-01

    Most data sources in real-life are not static but change their information in time. This evolution of data in time can give valuable insights to business analysts. Temporal data refers to data, where changes over time or temporal aspects play a central role. Temporal data denotes the evaluation of object characteristics over time. One of the main unresolved problems that arise during the data mining process is treating data that contains temporal information. Temporal queries on time evolving...

  16. Remote Wiping and Secure Deletion on Mobile Devices: A Review.

    Science.gov (United States)

    Leom, Ming Di; Choo, Kim-Kwang Raymond; Hunt, Ray

    2016-11-01

    Mobile devices have become ubiquitous in almost every sector of both private and commercial endeavors. As a result of such widespread use in everyday life, many users knowingly and unknowingly save significant amounts of personal and/or commercial data on these mobile devices. Thus, loss of mobile devices through accident or theft can expose users-and their businesses-to significant personal and corporate cost. To mitigate this data leakage issue, remote wiping features have been introduced to modern mobile devices. Given the destructive nature of such a feature, however, it may be subject to criminal exploitation (e.g., a criminal exploiting one or more vulnerabilities to issue a remote wiping command to the victim's device). To obtain a better understanding of remote wiping, we survey the literature, focusing on existing approaches to secure flash storage deletion and provide a critical analysis and comparison of a variety of published research in this area. In support of our analysis, we further provide prototype experimental results for three Android devices, thus providing both a theoretical and applied focus to this article as well as providing directions for further research. © 2016 American Academy of Forensic Sciences.

  17. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2016-11-01

    Full Text Available Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A, a regulatory subunit of protein phosphatase 2A (PP2A, is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR, plays an important role in the excitation-contraction (EC coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated proteins (Cas system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening. Hematoxylin and eosin (H&E staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT. Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function.

  18. Upper limb malformations in chromosome 22q11 deletions

    Energy Technology Data Exchange (ETDEWEB)

    Shalev, S.A.; Dar, H.; Barel, H.; Borochowitz, Z. [Bnai Zion Medical Center, Haifa (Israel)

    1996-03-29

    We read with interest the report of Cormier-Daire et al. in a recent issue of the journal, describing upper limb malformations in DiGeorge syndrome. We observed a family with this group of rare clinical expression of chromosome 22q11 deletions. The proposita was examined in our clinic when she was 4 years old. She was mildly mentally retarded. Clinical evaluation showed normal growth, long thin nose with squared tip, nasal speech, and abundant scalp hair and no cardiac anomalies. The girl was accompanied by her mother. Facial similarities were noted between the two. The mother reported to be treated with oral calcium due to hypoparathyroidism, diagnosed several years ago. Clinical evaluation showed wide flat face, short stature, mild mental retardation, slight hypertelorism, peculiar nose similar to her daughter`s, and nasal speech. No cardiac anomalies were found. Recently, a brother was born. Clinical examination documented large ventriculo-septal defect, retrognathia, narrow palpebral fissures, and long thin nose with squared tip. 1 ref.

  19. Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

    Directory of Open Access Journals (Sweden)

    I.J.P. Arnhold

    1998-04-01

    Full Text Available Genomic DNA from 23 patients with isolated growth hormone (GH deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13% Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67% with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions

  20. FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, I.; Chadwick, D.; Chitayat, D. [Hospital for Sick Children and Univ. of Toronto, Ontario (Canada)

    1996-03-29

    We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or AS, 29 had deletions by FISH analysis. These included two brothers with a paternally transmitted deletion detectable with the probe for SNRPN only. G-banding analysis was less sensitive for deletion detection but useful in demonstrating other cytogenetic alterations in four cases. Methylation and CA-repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical findings of patients with deletions were variable, ranging from newborns with hypotonia as the only presenting feature to children who were classically affected. We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered. 41 refs., 4 figs., 2 tabs.

  1. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.

    Science.gov (United States)

    Isobe, Kazutoshi; Kakimoto, Atsushi; Mikami, Tetsuo; Kaburaki, Kyohei; Kobayashi, Hiroshi; Yoshizawa, Takahiro; Makino, Takashi; Otsuka, Hajime; Sano, G O; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Tochigi, Naobumi; Iyoda, Akira; Homma, Sakae

    This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  2. Microarray-based ultra-high resolution discovery of genomic deletion mutations

    Science.gov (United States)

    2014-01-01

    Background Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low. Results Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size. Conclusions Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence. PMID:24655320

  3. Exploration of methods to localize DNA sequences missing from c-locus deletions

    International Nuclear Information System (INIS)

    Albritton, L.M.; Russell, L.B.; Montgomery, C.S.

    1987-01-01

    The authors have earlier characterized a large number of radiation-induced mutations at the c locus (on Chromosome 7) through genetic analysis, including extensive complementation tests. Based on this work, they have postulated that many of these mutations are deletions of various lengths, overlapping at c (the marker used in the mutation-rate experiments that generated the mutants). It was possible to apportion these deletions among 13 complementation groups and to fit them to a linear map of 8 functional units. Collectively, the deletions extend from a point between tp and c to one between sh-1 and Hbb, i.e., a genetic distance of from 6 to 10 cM, corresponding to at least 10 4 Kb of DNA. This year, the authors completed a pilot study designed to explore methods for finding DNA sequences that map to the region covered by the various c-deletions. The general plan was to probe DNA with clones derived from Chromosome-7-enriched libraries or with sequences known (or suspected) to reside in Chromosome 7. Three methods were explored for deriving the c-region-deficient DNA: (a) from mouse-hamster somatic-cell hydrids retaining a deleted mouse Chromosome 7, but no homologue; (b) from F 1 hybrids of M. musculus domesticus (carrying a c-locus deletion) by M. spretus; and (c) from F 1 hybrids of M. domesticus stocks carrying complementing deletions

  4. Growth hormone (GH-1) gene deletions in children with isolated growth hormone deficiency (IGHD).

    Science.gov (United States)

    Desai, Meena P; Mithbawkar, Shilpa M; Upadhye, Pradnya S; Shalia, Kavita K

    2012-07-01

    To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile. Thirty (M16,F14) prepubertal IGHD patients aged 0.25 to 14 y, from 25 families were screened. Duration of growth failure, relevant history, clinical phenotype, and height SDS were recorded. Peak GH response to Clonidine (0.15 mg/m(2)), IGF-1, IGFBP-3 and pituitary/target gland hormones were studied. Genomic DNA of patients and family was analysed by PCR and DNA fragments were visualized on agarose gel electrophoresis. This series was divided into deletion +ve, Group I (n=12,40%) inclusive of six familial/six nonfamilial patients, and deletion -ve Group II (n=18,60%), 5 familial/13 nonfamilial cases; in total 11/30 were familial. Onset of growth failure was earlier in Group I (pGH hormones were normal and MRI showed hypoplastic adenohypophysis. 40% had GH-1 gene deletion (6.7 kb deletion in 83%, 7.6 kb and a compound heterozygote in 8% each). In this series of 30 IGHD patients, frequency of GH-1 gene deletions (12/30) was 40%, and 54% among familial patients, and 31% with height SDS>-4. 83% had 6.7 kb deletion. Height SDS>-4, clinical phenotype, peak GH<1 ng/ml and hypoglycemia characterised IGHD Type IA.

  5. Sequence characterisation of deletion breakpoints in the dystrophin gene by PCR

    Energy Technology Data Exchange (ETDEWEB)

    Abbs, S.; Sandhu, S.; Bobrow, M. [Guy`s Hospital, London (United Kingdom)

    1994-09-01

    Partial deletions of the dystrophin gene account for 65% of cases of Duchenne muscular dystrophy. A high proportion of these structural changes are generated by new mutational events, and lie predominantly within two `hotspot` regions, yet the underlying reasons for this are not known. We are characterizing and sequencing the regions surrounding deletion breakpoints in order to: (i) investigate the mechanisms of deletion mutation, and (ii) enable the design of PCR assays to specifically amplify mutant and normal sequences, allowing us to search for the presence of somatic mosaicism in appropriate family members. Using this approach we have been able to demonstrate the presence of somatic mosaicism in a maternal grandfather of a DMD-affected male, deleted for exons 49-50. Three deletions, namely of exons 48-49, 49-50, and 50, have been characterized using a PCR approach that avoids any cloning procedures. Breakpoints were initially localized to within regions of a few kilobases using Southern blot restriction analyses with exon-specific probes and PCR amplification of exonic and intronic loci. Sequencing was performed directly on PCR products: (i) mutant sequences were obtained from long-range or inverse-PCR across the deletion junction fragments, and (ii) normal sequences were obtained from the products of standard PCR, vectorette PCR, or inverse-PCR performed on YACs. Further characterization of intronic sequences will allow us to amplify and sequence across other deletion breakpoints and increase our knowledge of the mechanisms of mutation in the dystophin gene.

  6. Dual entanglement measures based on no local cloning and no local deleting

    International Nuclear Information System (INIS)

    Horodecki, Michal; Sen, Aditi; Sen, Ujjwal

    2004-01-01

    The impossibility of cloning and deleting of unknown states constitute important restrictions on processing of information in the quantum world. On the other hand, a known quantum state can always be cloned or deleted. However, if we restrict the class of allowed operations, there will arise restrictions on the ability of cloning and deleting machines. We have shown that cloning and deleting of known states is in general not possible by local operations. This impossibility hints at quantum correlation in the state. We propose dual measures of quantum correlation based on the dual restrictions of no local cloning and no local deleting. The measures are relative entropy distances of the desired states in a (generally impossible) perfect local cloning or local deleting process from the best approximate state that is actually obtained by imperfect local cloning or deleting machines. Just like the dual measures of entanglement cost and distillable entanglement, the proposed measures are based on important processes in quantum information. We discuss their properties. For the case of pure states, estimations of these two measures are also provided. Interestingly, the entanglement of cloning for a maximally entangled state of two two-level systems is not unity

  7. The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats.

    Science.gov (United States)

    Yin, Shankai; Yu, Zhiping; Sockalingam, Ravi; Bance, Manohar; Sun, Genlou; Wang, Jian

    2007-09-01

    Age-related hearing loss, or presbycusis, has been associated with large-scale mitochondrial DNA (mtDNA) deletion in previous studies. However, the role of this mtDNA damage in presbycusis is still not clear because the deletion in inner ears has not been measured quantitatively and analyzed in parallel with the time course of presbycusis. In the present study, the deletion was quantified using quantitative real-time PCR (qRT-PCR) in male Fischer 344 rats of different ages. It was found that the deletion increased quickly during young adulthood and reached over 60% at 6 months of age. However, a significant hearing loss was not seen until after 12 months of age. The results suggest that the existence of the deletion per se does not necessarily imply cochlear damage, but rather a critical level of the accumulated deletion seems to precede the hearing loss. The long delay may indicate the involvement of mechanisms other than mtDNA deletion in the development of presbycusis.

  8. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Larsen Michael

    2011-04-01

    Full Text Available Abstract Background Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500 is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients. Methods Forty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA. When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible. Results Ten families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease. Conclusion Deletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis.

  9. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.

    Science.gov (United States)

    Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo

    2016-03-01

    Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. © 2015 Wiley Periodicals, Inc.

  10. Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome.

    Science.gov (United States)

    Vieira, Gustavo H; Rodriguez, Jayson D; Carmona-Mora, Paulina; Cao, Lei; Gamba, Bruno F; Carvalho, Daniel R; de Rezende Duarte, Andréa; Santos, Suely R; de Souza, Deise H; DuPont, Barbara R; Walz, Katherina; Moretti-Ferreira, Danilo; Srivastava, Anand K

    2012-02-01

    Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ~139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS.

  11. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Directory of Open Access Journals (Sweden)

    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  12. Selection of Mycoplasma hominis PG21 deletion mutants by cultivation in the presence of monoclonal antibody 552

    DEFF Research Database (Denmark)

    Jensen, L T; Ladefoged, S; Birkelund, S

    1995-01-01

    characterized. The mutants showed deletions of a various number of repeats. The deletions were accompanied by a decrease in size of the proteins. With increasing size of deletions, agglutination and growth inhibition by MAb 552 became less pronounced. Spontaneous aggregation of the mutant M. hominis cells...

  13. Construction and characterization of a glycoprotein E deletion mutant of bovine herpesvirus type 1.2 strain isolated in Brazil

    NARCIS (Netherlands)

    Franco, A.C.; Rijsewijk, F.A.M.; Flores, E.F.; Weiblen, R.; Roehe, P.M.

    2002-01-01

    This paper describes the construction and characterization of a Brazilian strain of bovine herpesvirus type 1.2a (BoHV-1.2a) with a deletion of the glycoprotein E (gE) gene. The deletion was introduced by co-transfection of a deletion fragment containing the 5´and 3´gE flanking regions and genomic

  14. Correlation between chromosome 9p21 locus deletion and prognosis in clinically localized prostate cancer.

    Science.gov (United States)

    Barros, Érika Aparecida Felix de; Pontes-Junior, José; Reis, Sabrina Thalita; Lima, Amanda Eunice Ramos; Souza, Isida C; Salgueiro, Jose Lucas; Fontes, Douglas; Dellê, Humberto; Coelho, Rafael Ferreira; Viana, Nayara Izabel; Leite, Kátia Ramos Moreira; Nahas, William C; Srougi, Miguel

    2017-05-04

    Some studies have reported that deletions at chromosome arm 9p occur frequently and represent a critical step in carcinogenesis of some neoplasms. Our aim was to evaluate the deletion of locus 9p21 and chromosomes 3, 7 and 17 in localized prostate cancer (PC) and correlate these alterations with prognostic factors and biochemical recurrence after surgery. We retrospectively evaluated surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Biochemical recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and the mean postoperative follow-up was 123 months. The deletions were evaluated using fluorescence in situ hybridization with centromeric and locus-specific probes in a tissue microarray containing 2 samples from each patient. We correlated the occurrence of any deletion with pathological stage, Gleason score, ISUP grade group, PSA and biochemical recurrence. We observed a loss of any probe in only 8 patients (7.2%). The most common deletion was the loss of locus 9p21, which occurred in 6.4% of cases. Deletions of chromosomes 3, 7 and 17 were observed in 2.3%, 1.2% and 1.8% patients, respectively. There was no correlation between chromosome loss and Gleason score, ISUP, PSA or stage. Biochemical recurrence occurred in 83% cases involving 9p21 deletions. Loss of 9p21 locus was significantly associated with time to recurrence (p = 0.038). We found low rates of deletion in chromosomes 3, 7 and 17 and 9p21 locus. We observed that 9p21 locus deletion was associated with worse prognosis in localized PC treated by radical prostatectomy.

  15. Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome

    Science.gov (United States)

    Lee, Mi-Young; Baek, Ju Won; Cho, Jae-Hyun; Shim, Jae-Yoon; Lee, Pil-Ryang; Kim, Ahm

    2014-01-01

    Objective To analyze the spectrum of prenatally diagnosed congenital heart disease in a Korean population with 22q11.2 deletion syndrome, and to provide guidelines for screening 22q11.2 deletion prenatally. Methods This retrospective study evaluated 1,137 consecutive fetuses that had prenatal genetic testing for 22q11.2 deletion because of suspected congenital heart disease between September 2002 and December 2012, at Asan Medical Center, Seoul, Korea. Results Main cardiovascular diseases in the 53 fetuses with confirmed 22q11.2 deletions were tetralogy of Fallot (n = 24, 45%), interrupted aortic arch (n = 10, 19%), ventricular septal defect (n = 5, 9%), double outlet right ventricle (n = 4, 8%), and coarctation of the aorta (n = 4, 8%). Other cardiac defects were rarely associated with 22q11.2 deletion. One fetus had persistent truncus arteriosus, one had aortic stenosis, and one had hypoplastic right heart syndrome. Two fetuses had normal intracardiac anatomy with an isolated right aortic arch, and one had an isolated bilateral superior vena cava. Conclusion A variety of congenital heart diseases were seen during the prenatal period. Conotruncal cardiac defects except transposition of great arteries were strongly associated with 22q11.2 deletion. When such anomalies are diagnosed by fetal echocardiography, genetic testing for 22q11.2 deletion should be offered. Even if less frequent deletion-related cardiac defects are detected, other related anomalies, such as thymic hypoplasia or aplasia, should be evaluated to rule out a 22q11.2 deletion. PMID:24596813

  16. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: Evaluation of 235 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lowery, M.C.; Brothman, L.J.; Leonard, C.O. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States)] [and others

    1995-07-01

    Williams syndrome (WS) is generally characterized by mental deficiency, gregarious personality, dysmorphic facies, supravalvular aortic stenosis, and idiopathic infantile hypercalcemia. Patients with WS show allelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascular abnormalities in WS patients. A series of 235 patients was studied, and molecular cytogenetic deletions were seen in 96% of patients with classic WS. Patients included 195 solicited through the Williams Syndrome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WSA subjects were reviewed, and patients were identified as {open_quotes}classic{open_quotes} (n = 114) or{open_quotes}uncertain{close_quotes} (n = 39). An additional 42 WSA patients were evaluated without clinical information. FISH was performed with biotinylated ELN cosmids on metaphase cells from immortalized lymphoblastoid lines from WSA patients and after high-resolution banding analysis on clinical referral patients. An alpha-satellite probe for chromosome 7 was included in hybridizations, as an internal control. Ninety-six percent of the patients with classic WS showed a deletion in one ELN allele; four of these did not show a deletion. Of the uncertain WS patients, only 3 of 39 showed a deletion. Of the 42 who were not classified phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cytogenetics cases showed an ELN deletion and no cytogenetic deletion by banded analysis. These results support the usefulness of FISH for the detection of elastin deletions as an initial diagnostic assay for WS. 14 refs., 2 figs., 4 tabs.

  17. Temporal context for authorship attribution

    DEFF Research Database (Denmark)

    Hansen, Niels Dalum; Lioma, Christina; Larsen, Birger

    2014-01-01

    A study of temporal aspects of authorship attribution - a task which aims to distinguish automatically between texts written by different authors by measuring textual features. This task is important in a number of areas, including plagiarism detection in secondary education, which we study...

  18. Temporal scaling in information propagation

    Science.gov (United States)

    Huang, Junming; Li, Chao; Wang, Wen-Qiang; Shen, Hua-Wei; Li, Guojie; Cheng, Xue-Qi

    2014-06-01

    For the study of information propagation, one fundamental problem is uncovering universal laws governing the dynamics of information propagation. This problem, from the microscopic perspective, is formulated as estimating the propagation probability that a piece of information propagates from one individual to another. Such a propagation probability generally depends on two major classes of factors: the intrinsic attractiveness of information and the interactions between individuals. Despite the fact that the temporal effect of attractiveness is widely studied, temporal laws underlying individual interactions remain unclear, causing inaccurate prediction of information propagation on evolving social networks. In this report, we empirically study the dynamics of information propagation, using the dataset from a population-scale social media website. We discover a temporal scaling in information propagation: the probability a message propagates between two individuals decays with the length of time latency since their latest interaction, obeying a power-law rule. Leveraging the scaling law, we further propose a temporal model to estimate future propagation probabilities between individuals, reducing the error rate of information propagation prediction from 6.7% to 2.6% and improving viral marketing with 9.7% incremental customers.

  19. Osteoradionecrosis of the temporal bone

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, Masato; Koyama, Yukiko; Enomoto, Fuyuki; Ichikawa, Ginichiro [Juntendo Univ., Tokyo (Japan). School of Medicine

    2002-08-01

    We report a case of temporal bone necrosis that emerged after radiotherapy for epipharyngeal carcinoma performed 13 years ago. The patient was a 51-year-old male. His major complaint was left facial swelling. The patient underwent chemotherapy and radiotherapy (Co 60, 6120 rad), as the treatment of that period, for epipharyngeal carcinoma from September 30, 1986 to January 31, 1987. He also underwent lobectomy of the left temporal lobe in brain surgery for left temporal lobe necrosis in August, 1989. After that operation, we saw constriction in his left external acoustic meatus and continued the follow-up. On October 22, 1999 he felt a left facial swelling. We found skin defects and ulcer formation in the front part of his left ear. Although we administered an antiseptic and antibiotic to the diseased area, his condition did not improve. He was hospitalized for the purpose of undergoing medical treatment on January 6, 2000. We found extensive skin necrosis and defects in his left auricular area. The corrupted temporal bone reached the zygomatic, the bone department external acoustic meatus and the mastoid process was exposing. We performed debridement of the diseased area on January 19, 2000. On February 23, we performed reconstruction by left trapezius muscle flap after debridement once again. One year after the operation, the flap was completely incorporated. (author)

  20. Temporal structures in shell models

    DEFF Research Database (Denmark)

    Okkels, F.

    2001-01-01

    The intermittent dynamics of the turbulent Gledzer, Ohkitani, and Yamada shell-model is completely characterized by a single type of burstlike structure, which moves through the shells like a front. This temporal structure is described by the dynamics of the instantaneous configuration of the shell...

  1. Algorithms for Simple Temporal Reasoning

    NARCIS (Netherlands)

    Planken, L.R.

    2013-01-01

    This dissertation describes research into new methods for automated temporal reasoning. For this purpose, several frameworks are available in literature. Chapter 1 presents a concise literature survey that provides a new overview of their interrelation. In the remainder of the dissertation, the

  2. Temporal Coding of Volumetric Imagery

    Science.gov (United States)

    Llull, Patrick Ryan

    'Image volumes' refer to realizations of images in other dimensions such as time, spectrum, and focus. Recent advances in scientific, medical, and consumer applications demand improvements in image volume capture. Though image volume acquisition continues to advance, it maintains the same sampling mechanisms that have been used for decades; every voxel must be scanned and is presumed independent of its neighbors. Under these conditions, improving performance comes at the cost of increased system complexity, data rates, and power consumption. This dissertation explores systems and methods capable of efficiently improving sensitivity and performance for image volume cameras, and specifically proposes several sampling strategies that utilize temporal coding to improve imaging system performance and enhance our awareness for a variety of dynamic applications. Video cameras and camcorders sample the video volume (x,y,t) at fixed intervals to gain understanding of the volume's temporal evolution. Conventionally, one must reduce the spatial resolution to increase the framerate of such cameras. Using temporal coding via physical translation of an optical element known as a coded aperture, the compressive temporal imaging (CACTI) camera emonstrates a method which which to embed the temporal dimension of the video volume into spatial (x,y) measurements, thereby greatly improving temporal resolution with minimal loss of spatial resolution. This technique, which is among a family of compressive sampling strategies developed at Duke University, temporally codes the exposure readout functions at the pixel level. Since video cameras nominally integrate the remaining image volume dimensions (e.g. spectrum and focus) at capture time, spectral (x,y,t,lambda) and focal (x,y,t,z) image volumes are traditionally captured via sequential changes to the spectral and focal state of the system, respectively. The CACTI camera's ability to embed video volumes into images leads to exploration

  3. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mt

  4. 20q13.2-q13.33 deletion syndrome: A case report.

    Science.gov (United States)

    Butler, Merlin G; Usrey, Kelly M; Roberts, Jennifer L; Manzardo, Ann M; Schroeder, Stephen R

    2013-01-01

    We report a 32-month-old female of Peruvian ethnicity identified with a rare 20q13.2-q13.33 deletion using microarray analysis. She presented with intellectual disability, absent speech, hypotonia, pre- and post-natal growth retardation and an abnormal face with a unilateral cleft lip. Clinical features and genetic findings with the loss of 30 genes, including GNAS, MC3R, CDH4 and TFAP2C , are described in relationship to the very few cases of 20q13 deletion reported in the literature. Deletion of this region may play an important role in neurodevelopment and function and in causing specific craniofacial features.

  5. ErasuCrypto: A Light-weight Secure Data Deletion Scheme for Solid State Drives

    Directory of Open Access Journals (Sweden)

    Liu Chen

    2017-01-01

    Full Text Available Securely deleting invalid data from secondary storage is critical to protect users’ data privacy against unauthorized accesses. However, secure deletion is very costly for solid state drives (SSDs, which unlike hard disks do not support in-place update. When applied to SSDs, both erasure-based and cryptography-based secure deletion methods inevitably incur large amount of valid data migrations and/or block erasures, which not only introduce extra latency and energy consumption, but also harm SSD lifetime.

  6. A novel large deletion of the ICR1 region including H19 and putative enhancer elements.

    Science.gov (United States)

    Fryssira, Helen; Amenta, Stella; Kanber, Deniz; Sofocleous, Christalena; Lykopoulou, Evangelia; Kanaka-Gantenbein, Christina; Cerrato, Flavia; Lüdecke, Hermann-Josef; Bens, Susanne; Riccio, Andrea; Buiting, Karin

    2015-05-06

    Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth disorder with a variable clinical phenotype caused by deregulation affecting imprinted genes in the chromosomal region 11p15. Alterations of the imprinting control region 1 (ICR1) at the IGF2/H19 locus resulting in biallelic expression of IGF2 and biallelic silencing of H19 account for approximately 10% of patients with BWS. The majority of these patients have epimutations of the ICR1 without detectable DNA sequence changes. Only a few patients were found to have deletions. Most of these deletions are small affecting different parts of the ICR1 differentially methylated region (ICR1-DMR) removing target sequences for CTCF. Only a very few deletions reported so far include the H19 gene in addition to the CTCF binding sites. None of these deletions include IGF2. A male patient was born with hypotonia, facial dysmorphisms and hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation-specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have identified a maternally inherited large deletion of the ICR1 region in a patient and his mother. The deletion results in a variable clinical expression with a classical BWS in the mother and a more severe presentation of BWS in her son. By genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA including the ICR1DMR, H19, two adjacent non-imprinted genes and two of three predicted enhancer elements downstream to H19. Methylation analysis by deep bisulfite next generation sequencing revealed hypermethylation of the maternal allele at the IGF2 locus in both, mother and child, although IGF2 is not affected by the deletion. We here report on a novel large familial deletion of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF binding cannot take place and the residual enhancer elements have access to the IGF2 promoters. The aberrant methylation (hypermethylation) of the maternal IGF2

  7. 22q11.2 deletion (DiGeorge syndrome: a mother’s open letter

    Directory of Open Access Journals (Sweden)

    Antonio Baldini

    2011-07-01

    Full Text Available Dear E.G., this is an open letter on 22q11.2 deletion syndrome (DiGeorge syndrome. You are the mother of a beautiful 3 year old child. And you are one of the most active members of Aidel22, the Italian Association of 22q deletion syndrome patients and families. We would like to hear your story and learn from you. But before that, we asked some scholars in the field to help us understand what 22q11.2 deletion syndrome is.

  8. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah L. Pachtman

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia.

  9. Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome

    OpenAIRE

    Bassett, Anne S.; Marshall, Christian R.; Lionel, Anath C.; Chow, Eva W.C.; Scherer, Stephen W.

    2008-01-01

    22q11.2 Deletion Syndrome (22q11.2DS) is a common microdeletion syndrome with congenital and late-onset features. Testing for the genomic content of copy number variations (CNVs) may help elucidate the 22q11.2 deletion mechanism and the variable clinical expression of the syndrome including the high (25%) risk for schizophrenia. We used genome-wide microarrays to assess CNV content and the parental origin of 22q11.2 deletions in a cohort of 100 adults with 22q11.2DS (44 with schizophrenia) an...

  10. [Diagnosis of 22q11.2 deletion syndrome in the context of newly developed psychosis].

    Science.gov (United States)

    Kaltenboeck, Alexander; Friedrich, Fabian; Hinterbuchinger, Barbara; Litvan, Zsuzsa; Mossaheb, Nilufar

    2016-12-01

    22q11.2 deletion syndrome (clinically also known as velocardiofacial or DiGeorge syndrome) is the most common human microdeletion syndrome and can be associated with a multitude of clinical features. In this article we report the case of a 22-year-old patient from Austria who was diagnosed with previously unknown 22q11.2 deletion syndrome in the context of newly developed psychosis. Using this case as an example, we then discuss the implications of 22q11.2 deletion syndrome for clinical psychiatric practice.

  11. Axenfeld-Rieger ocular anomaly and retinoblastoma caused by constitutional chromosome 13q deletion.

    Science.gov (United States)

    Roche, Ana; Mora, Jaume; Perez, Maria Del Mar; Gean, Esther; Perez, Belen; O'Callaghan, Mar; Catala, Jaume; De Torres, Carmen; Cruz, Ofelia; Prat, Joan; Parareda, Andreu

    2010-03-01

    Axenfeld-Rieger (AR) ocular anomaly might be due to deletions of different chromosomes. No association between AR, mental retardation, and retinoblastoma has been described. We report a 2-month-old female with general development delay and dysmorphic features. AR anomaly was detected, and a retinoblastoma (RB) was diagnosed in a very early stage. De novo 13q deletion was identified. Systemic chemotherapy, focal cryotherapy, transpupillary thermotherapy, brachytherapy, and intra-arterial chemotherapy were needed to control the RB. This is the first report of an association of AR, 13q deletion, and retinoblastoma, to be disclosed in patients born with such ocular and dysmorphic features. Copyright 2009 Wiley-Liss, Inc.

  12. Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Mostacciuolo, M.L.; Miorin, M.; Vitiello, L.; Rampazzo, A.; Fanin, M.; Angelini, C.; Danieli, G.A. [Univ. of Padua (Italy)

    1994-03-01

    The occurrence of 2 different intragenic deletions (exons 10-44 and exon 45, respectively) is reported in 2 male relatives affected with Duchenne muscular dystrophy, both showing the same haplotype for DNA markers not included in the deleted segment. The 2 different deletions seem to have occurred independently in the same X chromosome. This finding, together with other reports, suggests possibly an increased predisposition to mutations within the DMD locus in some families. Therefore, when dealing with prenatal diagnosis, the investigation on fetal DNA cannot be restricted only to the region in which a mutation was previously identified in the family. 14 refs., 1 fig.

  13. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period.

  14. Mapping the end points of large deletions affecting the hprt locus in human peripheral blood cells and cell lines

    International Nuclear Information System (INIS)

    Nelson, S.L.; Grosovsky, A.J.; Jones, I.M.; Burkhart-Schultz, K.; Fuscoe, J.C.

    1995-01-01

    We have examined the extent of of HPRT - total gene deletions in three mutant collections: spontaneous and X-ray-induced deletions in TK6 human B lymphoblasts, and HPRT - deletions arising in vivo in T cells. A set of 13 Xq26 STS markers surrounding hprt and spanning approximately 3.3 Mb was used. Each marker used was observed to be missing in at least one of the hprt deletion mutants analyzed. The largest deletion observed encompassed at least 3 Mb. Nine deletions extended outside of the mapped region in the centromeric direction (>1.7 Mb). In contrast, only two telomeric deletions extended to marker 342R (1.26 Mb), and both exhibited slowed or limited cell growth. These data suggest the existence of a gene, within the vicinity of 342R, which establishes the telomeric limit of recoverable deletions. Most (25/41) X-ray-induced total gene deletion mutants exhibited marker loss, but only 1/8 of the spontaneous deletions encompassed any Xq26 markers (P = 0.0187). Furthermore, nearly half (3/8) of the spontaneous 3' total deletion breakpoints were within 14 kb of the hprt coding sequence. In contrast, 40/41 X-ray-induced HPRT - total deletions extended beyond this point (P = 0.011). Although the overall representation of total gene deletions in the in vivo spectrum is low, 4/5 encompass Xq26 markers flanking hprt. This pattern differs significantly from spontaneous HPRT - large deletions occurring in vitro (P = 0.032) but resembles the spectrum of X-ray-induced deletions. 24 refs., 6 figs., 1 tab

  15. The prevalence of chromosomal deletions relating to developmental delay and/or intellectual disability in human euploid blastocysts.

    Science.gov (United States)

    He, Wenyin; Sun, Xiaofang; Liu, Lian; Li, Man; Jin, Hua; Wang, Wei-Hua

    2014-01-01

    Chromosomal anomalies in human embryos produced by in vitro fertilization are very common, which include numerical (aneuploidy) and structural (deletion, duplication or others) anomalies. Our previous study indicated that chromosomal deletion(s) is the most common structural anomaly accounting for approximately 8% of euploid blastocysts. It is still unknown if these deletions in human euploid blastocysts have clinical significance. In this study, we analyzed 15 previously diagnosed euploid blastocysts that had chromosomal deletion(s) using Agilent oligonucleotide DNA microarray platform and localized the gene location in each deletion. Then, we used OMIM gene map and phenotype database to investigate if these deletions are related with some important genes that cause genetic diseases, especially developmental delay or intellectual disability. As results, we found that the detectable chromosomal deletion size with Agilent microarray is above 2.38 Mb, while the deletions observed in human blastocysts are between 11.6 to 103 Mb. With OMIM gene map and phenotype database information, we found that deletions can result in loss of 81-464 genes. Out of these genes, 34-149 genes are related with known genetic problems. Furthermore, we found that 5 out of 15 samples lost genes in the deleted region, which were related to developmental delay and/or intellectual disability. In conclusion, our data indicates that all human euploid blastocysts with chromosomal deletion(s) are abnormal and transfer of these embryos may cause birth defects and/or developmental and intellectual disabilities. Therefore, the embryos with chromosomal deletion revealed by DNA microarray should not be transferred to the patients, or further gene map and/or phenotype seeking is necessary before making a final decision.

  16. Discrimination of Deletion and Duplication Subtypes of the Deleted in Azoospermia Gene Family in the Context of Frequent Interloci Gene Conversion

    Science.gov (United States)

    Vaszkó, Tibor; Papp, János; Krausz, Csilla; Casamonti, Elena; Géczi, Lajos; Olah, Edith

    2016-01-01

    Due to its palindromic setup, AZFc (Azoospermia Factor c) region of chromosome Y is one of the most unstable regions of the human genome. It contains eight gene families expressed mainly in the testes. Several types of rearrangement resulting in changes in the cumulative copy number of the gene families were reported to be associated with diseases such as male infertility and testicular germ cell tumors. The best studied AZFc rearrangement is gr/gr deletion. Its carriers show widespread phenotypic variation from azoospermia to normospermia. This phenomenon was initially attributed to different gr/gr subtypes that would eliminate distinct members of the affected gene families. However, studies conducted to confirm this hypothesis have brought controversial results, perhaps, in part, due to the shortcomings of the utilized subtyping methodology. This proof-of-concept paper is meant to introduce here a novel method aimed at subtyping AZFc rearrangements. It is able to differentiate the partial deletion and partial duplication subtypes of the Deleted in Azoospermia (DAZ) gene family. The keystone of the method is the determination of the copy number of the gene family member-specific variant(s) in a series of sequence family variant (SFV) positions. Most importantly, we present a novel approach for the correct interpretation of the variant copy number data to determine the copy number of the individual DAZ family members in the context of frequent interloci gene conversion.Besides DAZ1/DAZ2 and DAZ3/DAZ4 deletions, not yet described rearrangements such as DAZ2/DAZ4 deletion and three duplication subtypes were also found by the utilization of the novel approach. A striking feature is the extremely high concordance among the individual data pointing to a certain type of rearrangement. In addition to being able to identify DAZ deletion subtypes more reliably than the methods used previously, this approach is the first that can discriminate DAZ duplication subtypes as well

  17. Developmental trajectories in 22q11.2 deletion.

    Science.gov (United States)

    Swillen, Ann; McDonald-McGinn, Donna

    2015-06-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000-4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70-84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions. © 2015 Wiley Periodicals, Inc.

  18. Growth hormone deficiency in 18q deletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Ghidoni, P.D.; Cody, J.; Danney, J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1994-09-01

    The 18q- syndrome is one of the most common chromosomal deletion syndromes. Clinical characteristics are variable but may include: hypotonia, cleft palate, mental retardation and hearing impairment. Growth failure (GF) (<3% weight/height) is present in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 15 patients with 18q- syndrome. Of these 15 patients, 10 have growth failure (<3% weight/height); of the remaining 5, 3 had normal growth parameters and 2 had growth along the 5%. Twelve patients failed to produce adequate GH following standard stimulation testing. Of these 12 patients with inadequate GH production, 2 had normal growth (above 3%). Of the 15, only 1 has normal GH production and normal growth parameters. Bone age was obtained on 1 patient with both GH deficiency and GF, and revealed significant delays. GH levels in response to GH releasing factor were normal in 3 out of 4 patients. MRI studies of GH-deficient patients indicated normal midline structures. Myelination in the few studied GH-deficient patients appeared delayed. The gene for myelin basic protein (MBP) is known to be located on the terminal portion of the long arm of chromosome 18. Neither the gene for GH, GH releasing factor nor GH releasing factor receptor is on chromosome 18. These genes are located on chromosomes 17, chromosome 20 and chromosome 7, respectively. Findings to date suggest that GH deficiency is common in individuals with 18q- syndrome. The etiology of this finding is unknown. We postulate that a gene(s) on chromosome 18q is involved in GH expression.

  19. Clonal Expansion of Mitochondrial DNA Deletions in Multiple Sclerosis

    Science.gov (United States)

    Campbell, Graham R; Kraytsberg, Yevgenya; Krishnan, Kim J; Ohno, Nobuhiko; Ziabreva, Iryna; Reeve, Amy; Newcombe, Jia; Reynolds, Richard; Lassmann, Hans; Khrapko, Konstantin; Turnbull, Doug M; Mahad, Don J

    2013-01-01

    Objective Mitochondrial DNA deletions (Δ-mtDNA) are implicated in the pathogenesis of multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD) and ageing. Given the diffuse nature of inflammation in MS, aim of this study was to determine whether Δ-mtDNA caused respiratory deficient cells in excess of age within choroid plexus (CP) and ongoing mutagenesis or clonal expansion accounted for the respiratory deficiency in MS. Methods Respiratory chain complex IV and complex II activity was determined sequentially using histochemistry. Δ-mtDNA were characterized using real time PCR, long range PCR, sequencing and single molecule PCR. Sources of reactive oxygen and nitrogen species (RONS) were explored using immunohistochemistry. Results Respiratory deficient cells (lacking complex IV and with intact complex II activity) within CP epithelium were in excess of age in MS, PD and AD. Subunit-I of complex IV was lacking to a greater extent in MS than controls. Percentage of respiratory deficient cells harboring >50% heteroplasmy level of Δ-mtDNA was significantly greater in MS than PD, AD and controls. Long range PCR and sequencing confirmed Δ-mtDNA. Single molecule PCR identified clonally expanded Δ-mtDNA in MS, despite an increase in sources of RONS. Interpretation Our findings establish clonal expansion of Δ-mtDNA causing respiratory deficiency in MS and the extraparenchymal intracranial location indicated the potential to involve multiple cell types. Understanding factors that influence clonal expansion of Δ-mtDNA, a molecular link between inflammation and delayed cellular energy failure, may identify potential therapeutic targets for progressive forms of MS as well as other neurodegenerative disorders. PMID:22688405

  20. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mullighan, Charles G.; Su, Xiaoping; Zhang, Jinghui; Radtke, Ina; Phillips, Letha A.A.; Miller, Christopher B.; Ma, Jing; Liu, Wei; Cheng, Cheng; Schulman, Brenda A.; Harvey, Richard C.; Chen, I-Ming; Clifford, Robert J.; Carroll, William L.; Reaman, Gregory; Bowman, W. Paul; Devidas, Meenakshi; Gerhard, Daniela S.; Yang, Wenjian; Relling, Mary V.; Shurtleff, Sheila A.; Campana, Dario; Borowitz, Michael J.; Pui, Ching-Hon; Smith, Malcolm; Hunger, Stephen P.; Willman, Cheryl L.; Downing, James R.

    2009-01-01

    Background Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. Methods We studied a cohort of 221 children with high-risk B-cell–progenitor ALL with the use of single-nucleotide–polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1–positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell–progenitor ALL. Results More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients in the original cohort); PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Using copy-number abnormalities, we identified a predictor of poor outcome that was validated in the independent validation cohort. This predictor was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS. The gene-expression signature of the group of patients with a poor outcome revealed increased expression of hematopoietic stem-cell genes and reduced expression of B-cell–lineage genes, and it was similar to the signature of BCR-ABL1–positive ALL, another high-risk subtype of ALL with a high frequency of IKZF1 deletion. Conclusions Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell–progenitor ALL. PMID:19129520

  1. 22q11.2 deletion syndrome in diverse populations.

    Science.gov (United States)

    Kruszka, Paul; Addissie, Yonit A; McGinn, Daniel E; Porras, Antonio R; Biggs, Elijah; Share, Matthew; Crowley, T Blaine; Chung, Brian H Y; Mok, Gary T K; Mak, Christopher C Y; Muthukumarasamy, Premala; Thong, Meow-Keong; Sirisena, Nirmala D; Dissanayake, Vajira H W; Paththinige, C Sampath; Prabodha, L B Lahiru; Mishra, Rupesh; Shotelersuk, Vorasuk; Ekure, Ekanem Nsikak; Sokunbi, Ogochukwu Jidechukwu; Kalu, Nnenna; Ferreira, Carlos R; Duncan, Jordann-Mishael; Patil, Siddaramappa Jagdish; Jones, Kelly L; Kaplan, Julie D; Abdul-Rahman, Omar A; Uwineza, Annette; Mutesa, Leon; Moresco, Angélica; Obregon, María Gabriela; Richieri-Costa, Antonio; Gil-da-Silva-Lopes, Vera L; Adeyemo, Adebowale A; Summar, Marshall; Zackai, Elaine H; McDonald-McGinn, Donna M; Linguraru, Marius George; Muenke, Maximilian

    2017-04-01

    22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world. © 2017 Wiley Periodicals, Inc.

  2. Developmental Trajectories in 22q11.2 Deletion

    Science.gov (United States)

    Swillen, Ann; McDonald-McGinn, Donna M.

    2016-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000–4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70–84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions. PMID:25989227

  3. Quantification of the mitochondrial DNA common deletion in presbycusis.

    Science.gov (United States)

    Markaryan, Adam; Nelson, Erik G; Hinojosa, Raul

    2009-06-01

    This study was conducted to evaluate the association between the mitochondrial DNA (mtDNA) common deletion (CD) level in cochlear tissue and the severity of hearing loss in individuals with presbycusis. Nineteen individuals with presbycusis, ranging from 60 to 87 years of age, who met strict audiometric criteria were compared with four age frequency-matched normal hearing controls ranging from 51 to 76 years of age. Five additional normal hearing individuals, ranging from 9 to 50 years of age, were also studied. A duplex real time polymerase chain reaction assay was used to quantify the mtDNA in archival cochlear tissue samples. Linear regression models were used for comparison of the CD level between groups. The presbycusis group had a mean CD level of 32% with a standard deviation of 14%, and the normal hearing age matched control group had a mean CD level of 12% with a standard deviation of 2%. This difference in CD levels reached statistical significance (P = .011) and remained significant after adjusting for any differences in age between the two groups (age-adjusted P = .007). Furthermore, there was evidence for a significant association between the CD level and the severity of hearing loss based on audiometric thresholds at 8 kHz (r = 0.44, P = .034; age-adjusted partial correlation = 0.55, P = .007). For the first time, to our knowledge, these results demonstrate a relationship between quantitatively measured levels of the CD in human cochlear tissue and the severity of hearing loss in individuals with presbycusis. Laryngoscope, 2009.

  4. The complex spatio-temporal regulation of the Drosophila myoblast attractant gene duf/kirre.

    Directory of Open Access Journals (Sweden)

    K G Guruharsha

    2009-09-01

    Full Text Available A key early player in the regulation of myoblast fusion is the gene dumbfounded (duf, also known as kirre. Duf must be expressed, and function, in founder cells (FCs. A fixed number of FCs are chosen from a pool of equivalent myoblasts and serve to attract fusion-competent myoblasts (FCMs to fuse with them to form a multinucleate muscle-fibre. The spatial and temporal regulation of duf expression and function are important and play a deciding role in choice of fibre number, location and perhaps size. We have used a combination of bioinformatics and functional enhancer deletion approaches to understand the regulation of duf. By transgenic enhancer-reporter deletion analysis of the duf regulatory region, we found that several distinct enhancer modules regulate duf expression in specific muscle founders of the embryo and the adult. In addition to existing bioinformatics tools, we used a new program for analysis of regulatory sequence, PhyloGibbs-MP, whose development was largely motivated by the requirements of this work. The results complement our deletion analysis by identifying transcription factors whose predicted binding regions match with our deletion constructs. Experimental evidence for the relevance of some of these TF binding sites comes from available ChIP-on-chip from the literature, and from our analysis of localization of myogenic transcription factors with duf enhancer reporter gene expression. Our results demonstrate the complex regulation in each founder cell of a gene that is expressed in all founder cells. They provide evidence for transcriptional control--both activation and repression--as an important player in the regulation of myoblast fusion. The set of enhancer constructs generated will be valuable in identifying novel trans-acting factor-binding sites and chromatin regulation during myoblast fusion in Drosophila. Our results and the bioinformatics tools developed provide a basis for the study of the transcriptional

  5. How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

    OpenAIRE

    Ohi, Kazutaka; Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Nakatani, Noriko; Kamino, Kouzin; Takeda, Masatoshi

    2013-01-01

    The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%?2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. T...

  6. A catalog of hemizygous variation in 127 22q11 deletion patients.

    Science.gov (United States)

    Hestand, Matthew S; Nowakowska, Beata A; Vergaelen, Elfi; Van Houdt, Jeroen; Dehaspe, Luc; Suhl, Joshua A; Del-Favero, Jurgen; Mortier, Geert; Zackai, Elaine; Swillen, Ann; Devriendt, Koenraad; Gur, Raquel E; McDonald-McGinn, Donna M; Warren, Stephen T; Emanuel, Beverly S; Vermeesch, Joris R

    2016-01-01

    The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype.

  7. Novel Vascular Malformation in an Affected Newborn with Deletion Del(4(q31.3

    Directory of Open Access Journals (Sweden)

    Norma Elena de León Ojeda

    2012-01-01

    Full Text Available We report on a newborn male patient with a terminal deletion in the long arm of the chromosome 4 with a congenital heart defect unreported before in association with this syndrome. The patient had multiple congenital anomalies including a pointed duplicated fingernail, low set posteriorly rotated ears, large anterior fontanel, micrognathia, glabellar capillary vascular malformation, and Interrupted Aortic Arch type C. The patient died due to multiple congenital malformations; a peripheral chromosome analysis showed 46, XY, del(4(q31.3 de novo. The only reported case with the same deletion was a male newborn that exhibited the pattern of minor anomalies of deletion 4q31 syndrome. The parents were cytogenetically normal. We compare clinical signs to other cases with a deletion in long arm of chromosome 4.

  8. Neonatal hyperinsulinemic hypoglycemia in a patient with 9p deletion syndrome

    DEFF Research Database (Denmark)

    Bayat, Allan; Kirchhoff, Maria; Madsen, Camilla Gøbel

    2018-01-01

    We report the clinical and neuroradiological findings in a young boy harboring the 9p deletion syndrome including the novel findings of thalamic infarction and germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the hypoglycemic events and the ventriculomegaly found...

  9. Retention or deletion of personality disorder diagnoses for DSM-5: an expert consensus approach.

    Science.gov (United States)

    Mullins-Sweatt, Stephanie N; Bernstein, David P; Widiger, Thomas A

    2012-10-01

    One of the official proposals for the fifth edition of the American Psychiatric Association's (APA) diagnostic manual (DSM-5) is to delete half of the existing personality disorders (i.e., dependent, histrionic, narcissistic, paranoid, and schizoid). Within the APA guidelines for DSM-5 decisions, it is stated that there should be expert consensus agreement for the deletion of a diagnostic category. Additionally, categories to be deleted should have low clinical utility and/or minimal evidence for validity. The current study surveyed members of two personality disorder associations (n = 146) with respect to the utility, validity, and status of each DSM-IV-TR personality disorder diagnosis. Findings indicated that the proposal to delete five of the personality disorders lacks consensus support within the personality disorder community.

  10. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  11. Myopathology and a mitochondrial DNA deletion in the Pearson marrow and pancreas syndrome.

    Science.gov (United States)

    de Vries, D D; Buzing, C J; Ruitenbeek, W; van der Wouw, M P; Sperl, W; Sengers, R C; Trijbels, J M; van Oost, B A

    1992-01-01

    A patient with the Pearson marrow and pancreas syndrome is presented. She showed an anaemia with neutropenia and thrombopenia, failure to thrive, diarrhoea, disturbed glucose homeostasis and lactic acidosis. An exocrine pancreatic insufficiency was lacking. The disease followed a fatal course. Biochemical investigations of skeletal muscle revealed a disturbed mitochondrial energy metabolism, while many ultrastructural abnormal features were observed in the muscle tissue. Molecular genetic studies showed a de novo deletion in the mitochondrial DNA (mtDNA), different in size from the already published deletions and flanked by two 4 bp direct repeats, interspaced by 4-5 non-repeated nucleotides. mtDNA from 12 other tissues showed the same deletion in different percentages. No obvious relation between these percentages and tissue dysfunction was found. In spite of an open reading frame of 74 codons, only little transcription product of the genomic region resulting from the deletion was found.

  12. 77 FR 26279 - Scheduled Change and Deletion of Agenda Item From April 27, 2012, Open Meeting

    Science.gov (United States)

    2012-05-03

    ... From the Federal Register Online via the Government Publishing Office FEDERAL COMMUNICATIONS COMMISSION Scheduled Change and Deletion of Agenda Item From April 27, 2012, Open Meeting Date: April 25... of Managing Director. BILLING CODE 6712-01-P ...

  13. A method for the analysis of 32 X chromosome insertion deletion polymorphisms in a single PCR

    DEFF Research Database (Denmark)

    Pereira, Rui; Pereira, Vania; Gomes, Iva

    2012-01-01

    Studies of human genetic variation predominantly use short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) but Insertion deletion polymorphisms (Indels) are being increasingly explored. They combine desirable characteristics of other genetic markers, especially the possibility...

  14. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...

  15. Identifying and calling insertions, deletions, and single-base mutations efficiently from sequence data

    Science.gov (United States)

    Whole genome sequencing studies can directly identify causative mutations for subsequent use in genomic evaluations, but sequence variant identification is a lengthy and sometimes inaccurate process. The speed and accuracy of identifying small insertions and deletions of sequence, collectively terme...

  16. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation

    DEFF Research Database (Denmark)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria

    2010-01-01

    ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected...... 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating...... that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P...

  17. Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels.

    Science.gov (United States)

    Boettger, Linda M; Salem, Rany M; Handsaker, Robert E; Peloso, Gina M; Kathiresan, Sekar; Hirschhorn, Joel N; McCarroll, Steven A

    2016-04-01

    One of the first protein polymorphisms identified in humans involves the abundant blood protein haptoglobin. Two exons of the HP gene (encoding haptoglobin) exhibit copy number variation that affects HP protein structure and multimerization. The evolutionary origins and medical relevance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from many recurring deletions, more specifically, reversions of an ancient hominin-specific duplication of these exons. Although this polymorphism has been largely invisible to genome-wide genetic studies thus far, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We further show that these deletions, and a SNP that affects HP expression, appear to drive the strong association of cholesterol levels with SNPs near HP. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood.

  18. Absence of the 9-bp deletion of mitochondrial DNA in pre-Hispanic inhabitants of Argentina.

    Science.gov (United States)

    Demarchi, D A; Panzetta-Dutari, G M; Colantonio, S E; Marcellino, A J

    2001-08-01

    We investigated the incidence of the Region V mitochondrial DNA 9-base-pair (bp) deletion from human remains recovered from several archaeological sites and contexts throughout Argentina. Of the 34 samples analyzed, 24 yielded DNA extractions that gave clear amplification results. All of the individuals carried two repeats of the 9 bp, one of which has been shown to be deleted in some individuals of Asian origin and defines mitochondrial lineage B. Although most of the modern Amerindian groups in the region exhibit the deletion in high frequencies, the absence of the 9-bp deletion among ancient populations of South America seems to be the rule rather than the exception, as was reported by several studies involving extinct populations. The evidence gathered until now suggests that the earliest settlers of this region of South America did not carry mitochondrial lineage B.

  19. Deletion analysis of susy-sl promoter for the identification of optimal promoter sequence

    International Nuclear Information System (INIS)

    Bacha, S.; Khatoon, A.; Asif, M.; Bshir, A.

    2015-01-01

    The promoter region of sucrose synthase (susy-Sl) was identified and isolated from tomato. The 5? deletion analysis was carried out for the identification of minimum optimal promoter. Transgenic lines of Arabidopsis thaliana were developed by floral dip method incorporating various promoter deletion cassettes controlling GUS reporter gene. GUS assay of transgenic tissues indicated that full length susy-Sl promoter and its deletion mutants were constitutively expressed in vegetative and floral tissues of A. thaliana. The expression was observed in roots, shoots and flowers of A. thaliana. Analysis of 5? deletion series of susy-Sl promoter showed that a minimum of 679 bp fragment of the promoter was sufficient to drive expression of GUS reporter gene in the major tissues of transgenic A. thaliana. (author)

  20. Characterization of a novel mitochondrial DNA deletion in a patient with a variant of the Pearson marrow-pancreas syndrome.

    Science.gov (United States)

    van den Ouweland, J M; de Klerk, J B; van de Corput, M P; Dirks, R W; Raap, A K; Scholte, H R; Huijmans, J G; Hart, L M; Bruining, G J; Maassen, J A

    2000-03-01

    We have recently diagnosed a patient with anaemia, severe tubulopathy, and diabetes mellitus. As the clinical characteristics resembled Pearson marrow-pancreas syndrome, despite the absence of malfunctioning of the exocrine pancreas in this patient, we have performed DNA analysis to seek for deletions in mtDNA. DNA analysis showed a novel heteroplasmic deletion in mtDNA of 8034bp in length, with high proportions of deleted mtDNA in leukocytes, liver, kidney, and muscle. No deletion could be detected in mtDNA of leukocytes from her mother and young brother, indicating the sporadic occurrence of this deletion. During culture, skin fibroblasts exhibited a rapid decrease of heteroplasmy indicating a selection against the deletion in proliferating cells. We estimate that per cell division heteroplasmy levels decrease by 0.8%. By techniques of fluorescent in situ hybridisation (FISH) and mitochondria-mediated transformation of rho(o) cells we could show inter- as well as intracellular variation in the distribution of deleted mtDNA in a cell population of cultured skin fibroblasts. Furthermore, we studied the mitochondrial translation capacity in cybrid cells containing various proportions of deleted mtDNA. This result revealed a sharp threshold, around 80%, in the proportion of deleted mtDNA, above which there was strong depression of overall mitochondrial translation, and below which there was complementation of the deleted mtDNA by the wild-type DNA. Moreover, catastrophic loss of mtDNA occurred in cybrid cells containing 80% deleted mtDNA.

  1. Enhancement of astaxanthin production in Xanthophyllomyces dendrorhous by efficient method for the complete deletion of genes.

    Science.gov (United States)

    Yamamoto, Keisuke; Hara, Kiyotaka Y; Morita, Toshihiko; Nishimura, Akira; Sasaki, Daisuke; Ishii, Jun; Ogino, Chiaki; Kizaki, Noriyuki; Kondo, Akihiko

    2016-09-13

    Red yeast, Xanthophyllomyces dendrorhous is the only yeast known to produce astaxanthin, an anti-oxidant isoprenoid (carotenoid) widely used in the aquaculture, food, pharmaceutical and cosmetic industries. The potential of this microorganism as a platform cell factory for isoprenoid production has been recognized because of high flux through its native terpene pathway. Recently, we developed a multiple gene expression system in X. dendrorhous and enhanced the mevalonate synthetic pathway to increase astaxanthin production. In contrast, the mevalonate synthetic pathway is suppressed by ergosterol through feedback inhibition. Therefore, releasing the mevalonate synthetic pathway from this inhibition through the deletion of genes involved in ergosterol synthesis is a promising strategy to improve isoprenoid production. An efficient method for deleting diploid genes in X. dendrorhous, however, has not yet been developed. Xanthophyllomyces dendrorhous was cultivated under gradually increasing concentrations of antibiotics following the introduction of antibiotic resistant genes to be replaced with target genes. Using this method, double CYP61 genes encoding C-22 sterol desaturases relating to ergosterol biosynthesis were deleted sequentially. This double CYP61 deleted strain showed decreased ergosterol biosynthesis compared with the parental strain and single CYP61 disrupted strain. Additionally, this double deletion of CYP61 genes showed increased astaxanthin production compared with the parental strain and the single CYP61 knockout strain. Finally, astaxanthin production was enhanced by 1.4-fold compared with the parental strain, although astaxanthin production was not affected in the single CYP61 knockout strain. In this study, we developed a system to completely delete target diploid genes in X. dendrorhous. Using this method, we deleted diploid CYP61 genes involved in the synthesis of ergosterol that inhibits the pathway for mevalonate, which is a common

  2. Deleting Items and Disturbing Mesh Theorems for Riemann Definite Integral and Their Applications

    OpenAIRE

    Liu, Jingwei; Liu, Yi

    2017-01-01

    Based on the definition of Riemann definite integral,deleting items and disturbing mesh theorems on Riemann sums are given. After deleting some items or disturbing the mesh of partition, the limit of Riemann sums still converges to Riemann definite integral under specific conditions. These theorems can deal with a class of complicate limitation of sum and product of series of a function, and demonstrate that the geometric intuition of Riemann definite integral is more profound than ordinary t...

  3. Prevalence and Nature of Hearing Loss in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Van Eynde, Charlotte; Swillen, Ann; Lambeens, Elien; Verhaert, Nicolas; Desloovere, Christian; Luts, Heleen; Vander Poorten, Vincent; Devriendt, Koenraad; Hens, Greet

    2016-01-01

    Purpose: The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome. Method: Extensive audiological measurements were conducted in 40 persons with proven 22q11.2 deletion (aged 6-36 years). Besides air and bone conduction thresholds in the frequency range between 0.125…

  4. Nasal dimple as part of the 22q11.2 deletion syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gripp, K.W.; Reed, L.A. [Children`s Hospital of Philadelphia, PA (United States); Emanuel, B.S. [Children`s Hospital of Philadelphia, PA (United States)]|[Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1997-03-31

    The phenotype of the 22q11.2 microdeletion syndrome is quite variable. We describe 2 patients with a 22q11.2 deletion and a dimpled nasal tip, which, we suggest can be the extreme of the broad or bulbous nose commonly found in the 22q11.2 deletion syndrome, and should not be confused with the more severe nasal abnormalities seen in frontonasal dysplasia. 11 refs., 2 figs.

  5. Candidate Genes and the Behavioral Phenotype in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Prasad, Sarah E.; Howley, Sarah; Murphy, Kieran C.

    2008-01-01

    There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk…

  6. Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22q11.

    OpenAIRE

    Burn, J; Takao, A; Wilson, D; Cross, I; Momma, K; Wadey, R; Scambler, P; Goodship, J

    1993-01-01

    The conotruncal anomaly face syndrome was described in a Japanese publication in 1976 and comprises dysmorphic facial appearance and outflow tract defects of the heart. The authors subsequently noted similarities to Shprintzen syndrome and DiGeorge syndrome. Chromosome analysis in five cases did not show a deletion at high resolution, but fluorescent in situ hybridisation using probe DO832 showed a deletion within chromosome 22q11 in all cases.

  7. Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy

    DEFF Research Database (Denmark)

    Møller, Rikke S; Weber, Yvonne G; Klitten, Laura L

    2013-01-01

    Neurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been ...... associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs)....

  8. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Juyal, R.C.; Figuera, L.E.; Hauge, X. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-05-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (1) FISH analysis, (2) PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (3) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS. 49 refs.

  9. Spatio-Temporal Data Construction

    Directory of Open Access Journals (Sweden)

    Hai Ha Le

    2013-08-01

    Full Text Available On the route to a spatio-temporal geoscience information system, an appropriate data model for geo-objects in space and time has been developed. In this model, geo-objects are represented as sequences of geometries and properties with continuous evolution in each time interval. Because geomodeling software systems usually model objects at specific time instances, we want to interpolate the geometry and properties from two models of an object with only geometrical constraints (no physical or mechanical constraints. This process is called spatio-temporal data construction or morphological interpolation of intermediate geometries. This paper is strictly related to shape morphing, shape deformation, cross-parameterization and compatible remeshing and is only concerned with geological surfaces. In this study, two main sub-solutions construct compatible meshes and find trajectories in which vertices of the mesh evolve. This research aims to find an algorithm to construct spatio-temporal data with some constraints from the geosciences, such as cutting surfaces by faulting or fracturing phenomena and evolving boundaries attached to other surfaces. Another goal of this research is the implementation of the algorithm in a software product, namely a gOcad plug-in. The four main procedures of the algorithm are cutting the surfaces, setting up constraints, partitioning and calculating the parameterizations and trajectories. The software has been tested to construct data for a salt dome and other surfaces in regard to the geological processes of faulting, deposition and erosion. The result of this research is an algorithm and software for the construction of spatio-temporal data.

  10. The Machinic Temporality of Metadata

    Directory of Open Access Journals (Sweden)

    Claudio Celis

    2015-03-01

    Full Text Available In 1990 Deleuze introduced the hypothesis that disciplinary societies are gradually being replaced by a new logic of power: control. Accordingly, Matteo Pasquinelli has recently argued that we are moving towards societies of metadata, which correspond to a new stage of what Deleuze called control societies. Societies of metadata are characterised for the central role that meta-information acquires both as a source of surplus value and as an apparatus of social control. The aim of this article is to develop Pasquinelli’s thesis by examining the temporal scope of these emerging societies of metadata. In particular, this article employs Guattari’s distinction between human and machinic times. Through these two concepts, this article attempts to show how societies of metadata combine the two poles of capitalist power formations as identified by Deleuze and Guattari, i.e. social subjection and machinic enslavement. It begins by presenting the notion of metadata in order to identify some of the defining traits of contemporary capitalism. It then examines Berardi’s account of the temporality of the attention economy from the perspective of the asymmetric relation between cyber-time and human time. The third section challenges Berardi’s definition of the temporality of the attention economy by using Guattari’s notions of human and machinic times. Parts four and five fall back upon Deleuze and Guattari’s notions of machinic surplus labour and machinic enslavement, respectively. The concluding section tries to show that machinic and human times constitute two poles of contemporary power formations that articulate the temporal dimension of societies of metadata.

  11. Temporal nonlocality in bistable perception

    Science.gov (United States)

    Atmanspacher, Harald; Filk, Thomas

    2012-12-01

    A novel conceptual framework for theoretical psychology is presented and illustrated for the example of bistable perception. A basic formal feature of this framework is the non-commutativity of operations acting on mental states. A corresponding model for the bistable perception of ambiguous stimuli, the Necker-Zeno model, is sketched and some empirical evidence for it so far is described. It is discussed how a temporal nonlocality of mental states, predicted by the model, can be understood and tested.

  12. Xp22. 3 deletions in isolated familial Kallmann's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hardelin, J.P.; Levilliers, J.; Legouis, R.; Petit, C. (Institut Pasteur, Paris (France)); Young, J.; Pholsena, M.; Schaison, G. (Centre Hospitalier de Bicetre, Le Kremlin-Bicetre (France)); Kirk, J.; Bouloux, P. (Royal Free Hospital, London (United Kingdom))

    1993-04-01

    Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X-chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. The authors report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss. 47 refs., 2 figs., 1 tab.

  13. Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Lin Lung-Huang

    2009-02-01

    Full Text Available Abstract Background Chromosome 22q11 deletion syndrome (22q11DS causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH, quantitative real-time polymerase chain reaction (qPCR and multiplex ligation-dependent probe amplification (MLPA. Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

  14. Haploid deletion strains of Saccharomyces cerevisiae that determine survival during space flight

    Science.gov (United States)

    Johanson, Kelly; Allen, Patricia L.; Gonzalez-Villalobos, Romer A.; Nesbit, Jacqueline; Nickerson, Cheryl A.; Höner zu Bentrup, Kerstin; Wilson, James W.; Ramamurthy, Rajee; D'Elia, Riccardo; Muse, Kenneth E.; Hammond, Jeffrey; Freeman, Jake; Stodieck, Louis S.; Hammond, Timothy G.

    2007-02-01

    This study identifies genes that determine survival during a space flight, using the model eukaryotic organism, Saccharomyces cerevisiae. Select strains of a haploid yeast deletion series grew during storage in distilled water in space, but not in ground based static or clinorotation controls. The survival advantages in space in distilled water include a 133-fold advantage for the deletion of PEX19, a chaperone and import receptor for newly- synthesized class I peroxisomal membrane proteins, to 77-40 fold for deletion strains lacking elements of aerobic respiration, isocitrate metabolism, and mitochondrial electron transport. Following automated addition of rich growth media, the space flight was associated with a marked survival advantage of strains with deletions in catalytically active genes including hydrolases, oxidoreductases and transferases. When compared to static controls, space flight was associated with a marked survival disadvantage of deletion strains lacking transporter, antioxidant and catalytic activity. This study identifies yeast deletion strains with a survival advantage during storage in distilled water and space flight, and amplifies our understanding of the genes critical for survival in space.

  15. Skin fibroblasts from a D-deletion type retinoblastoma patient are abnormally X-ray sensitive

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1977-01-01

    Retinoblastoma is a rare malignant eye tumour that appears either spontaneously or in genetically predisposed persons. The latter group is composed of persons who inherit the tumour with a dominant mode of transmission (the familial type) and those who have a deletion in the long arm of chromosome 13 referred to as the D-deletion type. When this deletion is present it is observed in many somatic cells and is often associated with structural defects. Survivors of the genetic forms of retinoblastoma have an increased risk of the development of cancers at other sites. A single genetic locus is unlikely to predispose many somatic cells to tumour formation unless a fundamental molecular defect, possibly related to DNA repair, is present. In order to investigate this hypothesis a study was made of the in vitro X-ray sensitivity of skin fibroblasts derived from three retinoblastoma patients, comprising a pair of twins with the familial type accompanied by no gross chromosome abnormalities, and a patient with the D-deletion type. It was found that fibroblasts derived from the D-deletion patient were significantly more radiosensitive than those from the other two patients. X-ray survival curves are shown. It is concluded that skin fibroblasts derived from a patient with the D-deletion variant of retinoblastoma are abnormally radiosensitive. Future investigations may indicate a specific defect in molecular repair of DNA that will explain the predisposition of these patients to the development of other tumours. (U.K.)

  16. Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress.

    Science.gov (United States)

    Nie, Hezhongrong; Chen, Guorong; He, Jing; Zhang, Fengjiao; Li, Ming; Wang, Qiufeng; Zhou, Huaibin; Lyu, Jianxin; Bai, Yidong

    2016-01-01

    The 4977 bp common deletion is one of the most frequently observed mitochondrial DNA (mtDNA) mutations in human tissues and has been implicated in various human cancer types. It is generally believed that continuous generation of intracellular reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS) is a major underlying mechanism for generation of such mtDNA deletions while antioxidant systems, including Manganese superoxide dismutase (MnSOD), mitigating the deleterious effects of ROS. However, the clinical significance of this common deletion remains to be explored. A comprehensive investigation on occurrence and accumulation of the common deletion and mtDNA copy number was carried out in breast carcinoma (BC) patients, benign breast disease (BBD) patients and age-matched healthy donors in our study. Meanwhile, the representative oxidative (ROS production, mtDNA and lipid oxidative damage) and anti-oxidative features (MnSOD expression level and variation) in blood samples from these groups were also analyzed. We found that the mtDNA common deletion is much more likely to be detected in BC patients at relatively high levels while the mtDNA content is lower. This alteration has been associated with a higher MnSOD level and higher oxidative damages in both BC and BBD patients. Our results indicate that the mtDNA common deletion in blood may serve a biomarker for the breast cancer. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  17. Molecular evidence for the induction of large interstitial deletions on mouse chromosome 8 by ionizing radiation

    International Nuclear Information System (INIS)

    Turker, Mitchell S.; Pieretti, Maura; Kumar, Sudha

    1997-01-01

    The P19H22 mouse embryonal carcinoma cell line is characterized by a hemizygous deficiency for the chromosome 8 encoded aprt (adenine phosphoribosyltransferase) gene and heterozygosity for many chromosome 8 loci. We have previously demonstrated that this cell line is suitable for mutational studies because it is permissive of events ranging in size from base-pair substitutions at the aprt locus to apparent loss of chromosome 8. Large mutational events, defined by loss of the remaining aprt allele, were found to predominate in spontaneous mutants and those induced by ionizing radiation. In this study we have used a PCR based assay to screen for loss of heterozygosity at microsatellite loci both proximal and distal to aprt in 137 Cs-induced and spontaneous aprt mutants. This approach allowed us to distinguish apparent interstitial deletional events from apparent recombinational events. Significantly, 32.5% (26 of 80) of the mutational events induced by 137 Cs appeared to be interstitial deletions as compared with 7.7% (6 of 78) in the spontaneous group. This difference was statistically significant (p 137 Cs caused a significant number of deletion mutations. Most 137 Cs-induced interstitial deletions were larger than 6 cM, whereas none of the spontaneous deletions were larger than 6 cM. These results provide further support for the notion that ionizing radiation induces deletion mutations and validate the use of the P19H22 cell line for the study of events induced by ionizing radiation

  18. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  19. DiGeorge anomaly in the absence of chromosome 22q11.2 deletion.

    Science.gov (United States)

    Rope, Alan F; Cragun, Deborah L; Saal, Howard M; Hopkin, Robert J

    2009-10-01

    To test the hypothesis that the prevalence of deletion 22q11.2 among individuals who meet criteria for DiGeorge anomaly (DGA) is lower than the 90% commonly cited. Participants were identified through retrospective chart reviews on all patients who underwent testing for deletion 22q11.2 and all patients with a diagnosis of "DiGeorge" or any of the major criteria associated with DGA at a large pediatric hospital over a period of 6 years. DGA was confirmed in 64 individuals, based on the presence of at least 2 of the following features: (1) cellular immune deficiency and/or absence of part or all of the thymus; (2) hypocalcemia and/or parathyroid deficiency; (3) congenital heart disease. Of the 64 individuals with DGA, 29 (45%) did not have a chromosome 22q11.2 deletion. Among this deletion-negative subset, diabetic embryopathy and other chromosome abnormalities were the most commonly recognized underlying etiologies. These findings challenge a widely held belief that nearly 90% of DGA is due to chromosome 22q11.2 deletion. This study also calls attention to the heterogeneity of DGA, highlights similarities and differences between those with and without a chromosome 22q11.2 deletion, and attempts to resolve some confusing features of conditions associated with DGA.

  20. Clinical Implications of the BIM Deletion Polymorphism in Advanced Lung Adenocarcinoma Treated With Gefitinib.

    Science.gov (United States)

    Yuan, Jupeng; Li, Bo; Zhang, Nasha; Zhu, Hui; Zhou, Liqing; Zhang, Li; Yang, Ming

    2018-02-19

    Proapoptotic protein Bcl-2-like 11 (BIM) is a crucial tumor suppressor gene in lung cancer development. A 2903-bp genomic deletion polymorphism is present in BIM intron 2, which alters RNA splicing and impairs the generation of the death-inducing isoform of BIM and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present study, we investigated the clinical implications of this genetic polymorphism in patients with advanced lung adenocarcinoma treated with gefitinib. After genotyping the BIM deletion polymorphism in 111 patients with stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival and overall survival were estimated using Cox proportional hazards models. Possession of ≥ 1 deletion allele of the BIM polymorphism was observed in 18.02% of the patients. The BIM deletion polymorphism was an independent indicator of a shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005) and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P = .003). Additionally, patients carrying the BIM deletion allele were more likely to experience acquired gefitinib-resistant disease. Our results indicate that the BIM deletion polymorphism might be a promising germline biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. [Mitochondrial DNA4568 deletions in guinea-pig associated with presbycusis].

    Science.gov (United States)

    Wei, Xue-mei; Yang, Yuan; Liang, Chuang-yu; Zheng, Zhong

    2006-12-01

    To determine weather or not the mtDNA(4568) deletions in guinea-pig contribute to the development of presbycusis. Forty-four guinea-pigs were divided into 2 groups: group A (young control group, normal hearing, 22 guineas) and group B (aged group). The group B was subdivided into group B(1) (old normal hearing, 6 guineas) and group B(2) (old hearing loss, 16 guineas). First the guineas were tested by auditory brainstem response (ABR), and then the Cortis's tissues, auditory nerve tissues, brain and blood were harvested and the total DNA was extracted. The mtDNA(4568) deletion was analyzed by PCR. Hearing loss was occurred with age. The mtDNA(4568) deletion incidence of aged group in all tissues was significant higher than that of young control group (Ppresbycusis (B(2) group) were significant higher than that of aged normal hearing group (B(1) group) (Ppresbycusis and aged normal hearing group (P> 0.05). mtDNA(4568) deletion of guinea-pig possibly contributes to aging and mtDNA(4568) deletion in Cortis's and auditory nerve tissues of guinea-pig may be associated with presbycusis. There is no enough evidence to prove that the mtDNA(4568) deletions in brain and blood are related with presbycusis.

  2. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-05-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma}-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  3. Temporal compressive imaging for video

    Science.gov (United States)

    Zhou, Qun; Zhang, Linxia; Ke, Jun

    2018-01-01

    In many situations, imagers are required to have higher imaging speed, such as gunpowder blasting analysis and observing high-speed biology phenomena. However, measuring high-speed video is a challenge to camera design, especially, in infrared spectrum. In this paper, we reconstruct a high-frame-rate video from compressive video measurements using temporal compressive imaging (TCI) with a temporal compression ratio T=8. This means that, 8 unique high-speed temporal frames will be obtained from a single compressive frame using a reconstruction algorithm. Equivalently, the video frame rates is increased by 8 times. Two methods, two-step iterative shrinkage/threshold (TwIST) algorithm and the Gaussian mixture model (GMM) method, are used for reconstruction. To reduce reconstruction time and memory usage, each frame of size 256×256 is divided into patches of size 8×8. The influence of different coded mask to reconstruction is discussed. The reconstruction qualities using TwIST and GMM are also compared.

  4. Temporal ecology in the Anthropocene.

    Science.gov (United States)

    Wolkovich, E M; Cook, B I; McLauchlan, K K; Davies, T J

    2014-11-01

    Two fundamental axes - space and time - shape ecological systems. Over the last 30 years spatial ecology has developed as an integrative, multidisciplinary science that has improved our understanding of the ecological consequences of habitat fragmentation and loss. We argue that accelerating climate change - the effective manipulation of time by humans - has generated a current need to build an equivalent framework for temporal ecology. Climate change has at once pressed ecologists to understand and predict ecological dynamics in non-stationary environments, while also challenged fundamental assumptions of many concepts, models and approaches. However, similarities between space and time, especially related issues of scaling, provide an outline for improving ecological models and forecasting of temporal dynamics, while the unique attributes of time, particularly its emphasis on events and its singular direction, highlight where new approaches are needed. We emphasise how a renewed, interdisciplinary focus on time would coalesce related concepts, help develop new theories and methods and guide further data collection. The next challenge will be to unite predictive frameworks from spatial and temporal ecology to build robust forecasts of when and where environmental change will pose the largest threats to species and ecosystems, as well as identifying the best opportunities for conservation. © 2014 John Wiley & Sons Ltd/CNRS.

  5. Rare Deletions at 16p13.11 Predispose to a Diverse Spectrum of Sporadic Epilepsy Syndromes

    Science.gov (United States)

    Heinzen, Erin L.; Radtke, Rodney A.; Urban, Thomas J.; Cavalleri, Gianpiero L.; Depondt, Chantal; Need, Anna C.; Walley, Nicole M.; Nicoletti, Paola; Ge, Dongliang; Catarino, Claudia B.; Duncan, John S.; Kasperavičiūtė, Dalia; Tate, Sarah K.; Caboclo, Luis O.; Sander, Josemir W.; Clayton, Lisa; Linney, Kristen N.; Shianna, Kevin V.; Gumbs, Curtis E.; Smith, Jason; Cronin, Kenneth D.; Maia, Jessica M.; Doherty, Colin P.; Pandolfo, Massimo; Leppert, David; Middleton, Lefkos T.; Gibson, Rachel A.; Johnson, Michael R.; Matthews, Paul M.; Hosford, David; Kälviäinen, Reetta; Eriksson, Kai; Kantanen, Anne-Mari; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Wieser, Heinz-Gregor; Zumsteg, Dominik; Ortega, Marcos; Wood, Nicholas W.; Huxley-Jones, Julie; Mikati, Mohamad; Gallentine, William B.; Husain, Aatif M.; Buckley, Patrick G.; Stallings, Ray L.; Podgoreanu, Mihai V.; Delanty, Norman; Sisodiya, Sanjay M.; Goldstein, David B.

    2010-01-01

    Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions. PMID:20398883

  6. Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes.

    Science.gov (United States)

    Heinzen, Erin L; Radtke, Rodney A; Urban, Thomas J; Cavalleri, Gianpiero L; Depondt, Chantal; Need, Anna C; Walley, Nicole M; Nicoletti, Paola; Ge, Dongliang; Catarino, Claudia B; Duncan, John S; Kasperaviciūte, Dalia; Tate, Sarah K; Caboclo, Luis O; Sander, Josemir W; Clayton, Lisa; Linney, Kristen N; Shianna, Kevin V; Gumbs, Curtis E; Smith, Jason; Cronin, Kenneth D; Maia, Jessica M; Doherty, Colin P; Pandolfo, Massimo; Leppert, David; Middleton, Lefkos T; Gibson, Rachel A; Johnson, Michael R; Matthews, Paul M; Hosford, David; Kälviäinen, Reetta; Eriksson, Kai; Kantanen, Anne-Mari; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J; Wieser, Heinz-Gregor; Zumsteg, Dominik; Ortega, Marcos; Wood, Nicholas W; Huxley-Jones, Julie; Mikati, Mohamad; Gallentine, William B; Husain, Aatif M; Buckley, Patrick G; Stallings, Ray L; Podgoreanu, Mihai V; Delanty, Norman; Sisodiya, Sanjay M; Goldstein, David B

    2010-05-14

    Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Osteocyte-specific deletion of Fgfr1 suppresses FGF23.

    Directory of Open Access Journals (Sweden)

    Zhousheng Xiao

    Full Text Available Increases in fibroblastic growth factor 23 (FGF23 or Fgf23 production by osteocytes result in hypophosphatemia and rickets in the Hyp mouse homologue of X-linked hypophosphatemia (XLH. Fibroblastic growth factor (FGF signaling has been implicated in the pathogenesis of Hyp. Here, we conditionally deleted FGF receptor 1 (FGFR1 or Fgfr1 in osteocytes of Hyp mice to investigate the role of autocrine/paracrine FGFR signaling in regulating FGF23 production by osteocytes. Crossing dentin matrix protein 1 (Dmp1-Cre;Fgfr1null/+ mice with female Hyp;Fgfr1flox/flox mice created Hyp and Fgfr1 (Fgfr1Dmp1-cKO-null mice (Hyp;Fgfr1Dmp1-cKO with a 70% decrease in bone Fgfr1 transcripts. Fgfr1Dmp1-cKO-null mice exhibited a 50% reduction in FGF23 expression in bone and 3-fold reduction in serum FGF23 concentrations, as well as reductions in sclerostin (Sost, phosphate regulating endopeptidase on X chromosome (PHEX or Phex, matrix extracellular phosphoglycoprotein (Mepe, and Dmp1 transcripts, but had no demonstrable alterations in phosphate or vitamin D homeostasis or skeletal morphology. Hyp mice had hypophosphatemia, reductions in 1,25(OH2D levels, rickets/osteomalacia and elevated FGF2 expression in bone. Compared to Hyp mice, compound Hyp;Fgfr1Dmp1-cKO-null mice had significant improvement in rickets and osteomalacia in association with a decrease in serum FGF23 (3607 to 1099 pg/ml, an increase in serum phosphate (6.0 mg/dl to 9.3 mg/dl and 1,25(OH2D (121±23 to 192±34 pg/ml levels, but only a 30% reduction in bone FGF23 mRNA expression. FGF23 promoter activity in osteoblasts was stimulated by FGFR1 activation and inhibited by overexpression of a dominant negative FGFR1(TK-, PLCγ and MAPK inhibitors. FGF2 also stimulated the translation of an FGF23 cDNA transfected into osteoblasts via a FGFR1 and PI3K/Akt-dependent mechanism. Thus, activation of autocrine/paracrine FGF pathways is involved in the pathogenesis of Hyp through FGFR1-dependent regulation of FGF

  8. Grin1 receptor deletion within CRF neurons enhances fear memory.

    Directory of Open Access Journals (Sweden)

    Georgette Gafford

    Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

  9. Brain SPECT imaging in temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Krausz, Y.; Yaffe, S.; Atlan, H.; Cohen, D.; Konstantini, S.; Meiner, Z.

    1991-01-01

    Temporal lobe epilepsy is diagnosed by clinical symptoms and signs and by localization of an epileptogenic focus. A brain SPECT study of two patients with temporal lobe epilepsy, using 99m Tc-HMPAO, was used to demonstrate a perfusion abnormality in the temporal lobe, while brain CT and MRI were non-contributory. The electroencephalogram, though abnormal, did not localize the diseased area. The potential role of the SPECT study in diagnosis and localization of temporal lobe epilepsy is discussed. (orig.)

  10. Constructing catalogue of temporal situations

    Directory of Open Access Journals (Sweden)

    Violetta Koseska-Toszewa

    2015-11-01

    Full Text Available Constructing catalogue of temporal situations The paper is aiming to create a common basis for description, comparing, and analysis natural languages. As a subject of comparison we have chosen temporal structures of some languages. For such a choice there exists a perfect tool, describing basic temporal phenomena, namely an ordering of states and events in time, certainty and uncertainty, independency of histories of separate objects, necessity and possibility. This tool is supported by the Petri nets formalism, which seems to be well suited for expressing the above mentioned phenomena. Petri nets are built form three primitive notions: of states, of events that begin or end the states, and so-called flow relation indicating succession of states and events. This simple constituents give rise to many possibilities of representing temporal phenomena; it turns out that such representations are sufficient for many (clearly, not necessarily all temporal situations appearing in natural languages. In description formalisms used till now there is no possibility of expressing such reality phenomena as temporal dependencies in compound statement, or combination of temporality and modality. Moreover, using these formalisms one cannot distinguish between two different sources of uncertainty of the speaker while describing the reality: one, due to the lack of knowledge of the speaker what is going on in outside world, the second, due to objective impossibility of foreseen ways in which some conflict situations will be (or already have been resolved. Petri net formalism seems to be perfectly suited for such differentiations. There are two main description principles that encompassed this paper. First, that assigns meaning to names of grammatical structures in different languages may lead to misunderstanding. Two grammatical structures with apparently close names may describe different reality. Additionally, some grammatical terms used in one language may be

  11. Epilepsia temporal: relato de caso = Temporal epilepsy: case report

    Directory of Open Access Journals (Sweden)

    Souza, Taís Amara da Costa de

    2006-01-01

    Full Text Available Este trabalho tem o objetivo de divulgar um recurso terapêutico da epilepsia do lobo temporal por esclerose hipocampal: a cirurgia. Aproximadamente vinte e cinco mil pacientes com esta patologia são refratários aos tratamentos medicamentosos no sul do país e muitos chegam ao neurocirurgião com 30-40 anos de evolução, muitas vezes já mutilados em conseqüência das crises. Convulsões parciais originadas no lobo temporal são comuns, e grande parte originam-se em estruturas mesiais (esclerose mesial temporal – EMT. Como aí se encontram a sede de funções nobres do sistema nervoso – memória, aprendizagem, comportamento, entre outras –, os sintomas podem apresentar-se como alterações em qualquer uma delas. Ressaltamos a necessidade do correto diagnóstico e dos métodos para fazê-lo: através da anamnese, da ressonância magnética, do eletroencefalograma (EEG, do vídeo-EEG e por vezes através de sensores intracranianos (strips. Apesar de existirem métodos confiáveis para realizar o diagnóstico e tratamento cirúrgico com grande índice de sucesso, a desinformação dos profissionais que atendem pacientes com EMT acerca do assunto leva ao prolongamento de tratamentos clínico ineficiente e conseqüente seqüelas físicas, psicológicas e sociais

  12. Lateralized Temporal Order Judgement in Dyslexia

    Science.gov (United States)

    Liddle, Elizabeth B.; Jackson, Georgina M.; Rorden, Chris; Jackson, Stephen R.

    2009-01-01

    Temporal and spatial attentional deficits in dyslexia were investigated using a lateralized visual temporal order judgment (TOJ) paradigm that allowed both sensitivity to temporal order and spatial attentional bias to be measured. Findings indicate that adult participants with a positive screen for dyslexia were significantly less sensitive to the…

  13. Gene expression patterns of chicken neuregulin 3 in association with copy number variation and frameshift deletion.

    Science.gov (United States)

    Abe, Hideaki; Aoya, Daiki; Takeuchi, Hiro-Aki; Inoue-Murayama, Miho

    2017-07-21

    Neuregulin 3 (NRG3) plays a key role in central nervous system development and is a strong candidate for human mental disorders. Thus, genetic variation in NRG3 may have some impact on a variety of phenotypes in non-mammalian vertebrates. Recently, genome-wide screening for short insertions and deletions in chicken (Gallus gallus) genomes has provided useful information about structural variation in functionally important genes. NRG3 is one such gene that has a putative frameshift deletion in exon 2, resulting in premature termination of translation. Our aims were to characterize the structure of chicken NRG3 and to compare expression patterns between NRG3 isoforms. Depending on the presence or absence of the 2-bp deletion in chicken NRG3, 3 breeds (red junglefowl [RJF], Boris Brown [BB], and Hinai-jidori [HJ]) were genotyped using flanking primers. In the commercial breeds (BB and HJ), approximately 45% of individuals had at least one exon 2 allele with the 2-bp deletion, whereas there was no deletion allele in RJF. The lack of a homozygous mutant indicated the existence of duplicated NRG3 segments in the chicken genome. Indeed, highly conserved elements consisting of exon 1, intron 1, exon 2, and part of intron 2 were found in the reference RJF genome, and quantitative PCR detected copy number variation (CNV) between breeds as well as between individuals. The copy number of conserved elements was significantly higher in chicks harboring the 2-bp deletion in exon 2. We identified 7 novel transcript variants using total mRNA isolated from the amygdala. Novel isoforms were found to lack the exon 2 cassette, which probably harbored the premature termination codon. The relative transcription levels of the newly identified isoforms were almost the same between chick groups with and without the 2-bp deletion, while chicks with the deletion showed significant suppression of the expression of previously reported isoforms. A putative frameshift deletion and CNV in chicken

  14. Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Yao, Qiu-Mei; Liu, Kai-Yan; Gale, Robert Peter; Jiang, Bin; Liu, Yan-Rong; Jiang, Qian; Jiang, Hao; Zhang, Xiao-Hui; Zhang, Mei-Jie; Chen, Shan-Shan; Huang, Xiao-Jun; Xu, Lan-Ping; Ruan, Guo-Rui

    2016-04-11

    Interrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia. One hundred sixty-five consecutive adults with common B-cell ALL were tested for IKZF1 deletion and for BCR/ABL. Deletions in IKZF1 were detected using multiplex RQ-PCR, multiplex fluorescent PCR, sequence analysis and multiplex ligation-dependent probe amplification (MLPA). BCR/ABL was detected using RQ-PCR. All subjects received chemotherapy and some also received an allotransplant and tyrosine kinase-inhibitors. Multivariate analyses were done to identify associations between IKZF1 deletion and other variables on non-relapse mortality (NRM), cumulative incidence of relapse (CIR), leukemia-free survival (LFS) and survival. Amongst subjects achieving complete remission those with IKZF1 deletion had similar 5-year non-relapse mortality (NRM) (11% [2-20%] vs. 16% [4-28%]; P = 0.736), a higher 5-year cumulative incidence of relapse (CIR) (55% [35-76%] vs. 25% [12-38%]; P = 0.004), and worse 5-year leukemia-free survival (LFS) (33% [16-52%] vs. 59% [42-73%]; P = 0.012) and survival (48% [33-62%] vs. 75% [57-86%]; P = 0.002). In multivariate analyses IKZF1 deletion was associated with an increased relapse (relative risk [RR] =2.7, [1.4-5.2]; P = 0.002), a higher risk of treatment-failure (inverse of LFS; RR = 2.1, [1.2-3.6]; P = 0.007) and a higher risk of death (RR = 2.8, [1.5-5.5]; P = 0.002). The adverse impact of IKZF1 deletion on outcomes was stronger in subjects without vs. with BCR-ABL1 and in subjects receiving chemotherapy-only vs. an allotransplant. IKZF1 deletion was independently-associated with a higher relapse risk and worse LFS and survival in adults with common B-cell ALL after adjusting for other prognostic variables and differences in therapies. These data suggest IKZF1 deletion may be a useful prognostic variable in adults with common B-cell ALL, especially in persons without BCR-ABL1 and those receiving chemotherapy

  15. Interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q

    International Nuclear Information System (INIS)

    Le Beau, M.M.; Epstein, N.D.; O'Brien, S.J.; Nienhuis, A.W.; Yang, Y.C.; Clark, S.C.; Rowley, J.D.

    1987-01-01

    The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, the authors localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33[del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent from the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF, CSF-1, and FMS. The findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q- chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q)

  16. Structural plasticity of green fluorescent protein to amino acid deletions and fluorescence rescue by folding-enhancing mutations.

    Science.gov (United States)

    Liu, Shu-su; Wei, Xuan; Dong, Xue; Xu, Liang; Liu, Jia; Jiang, Biao

    2015-07-25

    Green fluorescent protein (GFP) and its derivative fluorescent proteins (FPs) are among the most commonly used reporter systems for studying gene expression and protein interaction in biomedical research. Most commercially available FPs have been optimized for their oligomerization state to prevent potential structural constraints that may interfere with the native function of fused proteins. Other approach to reducing structural constraints may include minimizing the structure of GFPs. Previous studies in an enhanced GFP variant (EGFP) identified a series of deletions that can retain GFP fluorescence. In this study, we interrogated the structural plasticity of a UV-optimized GFP variant (GFP(UV)) to amino acid deletions, characterized the effects of deletions and explored the feasibility of rescuing the fluorescence of deletion mutants using folding-enhancing mutations. Transposon mutagenesis was used to screen amino acid deletions in GFP that led to fluorescent and nonfluorescent phenotypes. The fluorescent GFP mutants were characterized for their whole-cell fluorescence and fraction soluble. Fluorescent GFP mutants with internal deletions were purified and characterized for their spectral and folding properties. Folding-ehancing mutations were introduced to deletion mutants to rescue their compromised fluorescence. We identified twelve amino acid deletions that can retain the fluorescence of GFP(UV). Seven of these deletions are either at the N- or C- terminus, while the other five are located at internal helices or strands. Further analysis suggested that the five internal deletions diminished the efficiency of protein folding and chromophore maturation. Protein expression under hypothermic condition or incorporation of folding-enhancing mutations could rescue the compromised fluorescence of deletion mutants. In addition, we generated dual deletion mutants that can retain GFP fluorescence. Our results suggested that a "size-minimized" GFP may be developed by

  17. Annotating temporal information in clinical narratives.

    Science.gov (United States)

    Sun, Weiyi; Rumshisky, Anna; Uzuner, Ozlem

    2013-12-01

    Temporal information in clinical narratives plays an important role in patients' diagnosis, treatment and prognosis. In order to represent narrative information accurately, medical natural language processing (MLP) systems need to correctly identify and interpret temporal information. To promote research in this area, the Informatics for Integrating Biology and the Bedside (i2b2) project developed a temporally annotated corpus of clinical narratives. This corpus contains 310 de-identified discharge summaries, with annotations of clinical events, temporal expressions and temporal relations. This paper describes the process followed for the development of this corpus and discusses annotation guideline development, annotation methodology, and corpus quality. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

    Directory of Open Access Journals (Sweden)

    Devilee Peter

    2009-04-01

    Full Text Available Abstract Background Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH, the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. Methods We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. Results A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. Conclusion The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.

  19. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    Energy Technology Data Exchange (ETDEWEB)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  20. Multi-exon deletions of the FBN1 gene in Marfan syndrome

    Directory of Open Access Journals (Sweden)

    Schrijver Iris

    2001-10-01

    Full Text Available Abstract Background Mutations in the fibrillin -1 gene (FBN1 cause Marfan syndrome (MFS, an autosomal dominant multi-system connective tissue disorder. The 200 different mutations reported in the 235 kb, 65 exon-containing gene include only one family with a genomic multi-exon deletion. Methods We used long-range RT-PCR for mutation detection and long-range genomic PCR and DNA sequencing for identification of deletion breakpoints, allele-specific transcript analyses to determine stability of the mutant RNA, and pulse-chase studies to quantitate fibrillin synthesis and extracellular matrix deposition in cultured fibroblasts. Southern blots of genomic DNA were probed with three overlapping fragments covering the FBN1 coding exons Results Two novel multi-exon FBN1 deletions were discovered. Identical nucleotide pentamers were found at or near the intronic breakpoints. In a Case with classic MFS, an in-frame deletion of exons 42 and 43 removed the C-terminal 24 amino acids of the 5th LTBP (8-cysteine domain and the adjacent 25th calcium-binding EGF-like (6-cysteine domain. The mutant mRNA was stable, but fibrillin synthesis and matrix deposition were significantly reduced. A Case with severe childhood-onset MFS has a de novo deletion of exons 44–46 that removed three EGF-like domains. Fibrillin protein synthesis was normal, but matrix deposition was strikingly reduced. No genomic rearrangements were detected by Southern analysis of 18 unrelated MFS samples negative for FBN1 mutation screening. Conclusions Two novel deletion cases expand knowledge of mutational mechanisms and genotype/phenotype correlations of fibrillinopathies. Deletions or mutations affecting an LTBP domain may result in unstable mutant protein cleavage products that interfere with microfibril assembly.

  1. Mitochondrial DNA Depletion and Deletions in Paediatric Patients with Neuromuscular Diseases: Novel Phenotypes.

    Science.gov (United States)

    Komulainen, Tuomas; Hautakangas, Milla-Riikka; Hinttala, Reetta; Pakanen, Salla; Vähäsarja, Vesa; Lehenkari, Petri; Olsen, Päivi; Vieira, Päivi; Saarenpää-Heikkilä, Outi; Palmio, Johanna; Tuominen, Hannu; Kinnunen, Pietari; Majamaa, Kari; Rantala, Heikki; Uusimaa, Johanna

    2015-01-01

    To study the clinical manifestations and occurrence of mtDNA depletion and deletions in paediatric patients with neuromuscular diseases and to identify novel clinical phenotypes associated with mtDNA depletion or deletions. Muscle DNA samples from patients presenting with undefined encephalomyopathies or myopathies were analysed for mtDNA content by quantitative real-time PCR and for deletions by long-range PCR. Direct sequencing of mtDNA maintenance genes and whole-exome sequencing were used to study the genetic aetiologies of the diseases. Clinical and laboratory findings were collected. Muscle samples were obtained from 104 paediatric patients with neuromuscular diseases. mtDNA depletion was found in three patients with severe early-onset encephalomyopathy or myopathy. Two of these patients presented with novel types of mitochondrial DNA depletion syndromes associated with increased serum creatine kinase (CK) and multiorgan disease without mutations in any of the known mtDNA maintenance genes; one patient had pathologic endoplasmic reticulum (ER) membranes in muscle. The third patient with mtDNA depletion was diagnosed with merosine-deficient muscular dystrophy caused by a homozygous mutation in the LAMA2 gene. Two patients with an early-onset Kearns-Sayre/Pearson-like phenotype harboured a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content. Novel encephalomyopathic mtDNA depletion syndrome with structural alterations in muscle ER was identified. mtDNA depletion may also refer to secondary mitochondrial changes related to muscular dystrophy. We suggest that a large-scale mtDNA deletion, minor multiple deletions and high mtDNA content associated with Kearns-Sayre/Pearson syndromes may be secondary changes caused by mutations in an unknown nuclear gene.

  2. Detection of the deletion on Yp11.2 in a Chinese population.

    Science.gov (United States)

    Chen, Wenjing; Wu, Weiwei; Cheng, Jianding; Zhang, Yinming; Chen, Yong; Sun, Hongyu

    2014-01-01

    Sex determination tests based on Amelogenin gene as part of commercial PCR multiplex reaction kits have been widely applied in forensic DNA analysis. Mutations that cause dropout of Y chromosomal Amelogenin gene (AMELY) could lead to errors in gender determination and mixture interpretation. To infer the mechanism and estimate the dropout frequency of AMELY and adjacent Y-STRs, we studied 3 samples with AMELY dropout combined with DYS458 and/or DYS456 and 37 samples with DYS456 dropout. DYS456, DYS458 and AMELY are located in the Yp11.2 region. The singleplex amplification system showed the null alleles could be caused by fragment deletion in Yp11.2 rather than a point mutation in the primer binding region. After detection of the 17 Y-STR and 77 STS markers, the deletion map showed different patterns. The DYS456-AMELY-DYS458 deletion pattern was the largest, breaking from 3.60 Mb to 8.29 Mb in the Y chromosome, and the overall frequency was 0.0077%. The AMELY-DYS458 deletion pattern was broke from 6.74 Mb to 9.17 Mb, with a 0.0155% frequency. The DYS456 negative pattern was concentrated in two main deletion regions, with a 0.8220% frequency. The frequency of all negative pattern was 0.0155%. All the AMELY-DYS458 and DYS456-AMELY-DYS458, and 92% of the DYS456 deletion patterns belonged to Hg O3, the rest belonged to Hg Q. The DYS456 deletion pattern was first reported in Chinese population. The current and previous findings suggest additional gender test for ambiguous sex determination may be required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Utilization of deletion bins to anchor and order sequences along the wheat 7B chromosome.

    Science.gov (United States)

    Belova, Tatiana; Grønvold, Lars; Kumar, Ajay; Kianian, Shahryar; He, Xinyao; Lillemo, Morten; Springer, Nathan M; Lien, Sigbjørn; Olsen, Odd-Arne; Sandve, Simen R

    2014-09-01

    A total of 3,671 sequence contigs and scaffolds were mapped to deletion bins on wheat chromosome 7B providing a foundation for developing high-resolution integrated physical map for this chromosome. Bread wheat (Triticum aestivum L.) has a large, complex and highly repetitive genome which is challenging to assemble into high quality pseudo-chromosomes. As part of the international effort to sequence the hexaploid bread wheat genome by the international wheat genome sequencing consortium (IWGSC) we are focused on assembling a reference sequence for chromosome 7B. The successful completion of the reference chromosome sequence is highly dependent on the integration of genetic and physical maps. To aid the integration of these two types of maps, we have constructed a high-density deletion bin map of chromosome 7B. Using the 270 K Nimblegen comparative genomic hybridization (CGH) array on a set of cv. Chinese spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8 % of chromosome 7B physical length) were mapped into nine deletion bins. Our method of genotyping deletions on chromosome 7B relied on a model-based clustering algorithm (Mclust) to accurately predict the presence or absence of a given genomic sequence in a deletion line. The bin mapping results were validated using three different approaches, viz. (a) PCR-based amplification of randomly selected bin mapped sequences (b) comparison with previously mapped ESTs and (c) comparison with a 7B genetic map developed in the present study. Validation of the bin mapping results suggested a high accuracy of the assignment of 7B sequence contigs and scaffolds to the 7B deletion bins.

  4. Deletion at the GCNT2 Locus Causes Autosomal Recessive Congenital Cataracts.

    Science.gov (United States)

    Irum, Bushra; Khan, Shahid Y; Ali, Muhammad; Daud, Muhammad; Kabir, Firoz; Rauf, Bushra; Fatima, Fareeha; Iqbal, Hira; Khan, Arif O; Al Obaisi, Saif; Naeem, Muhammad Asif; Nasir, Idrees A; Khan, Shaheen N; Husnain, Tayyab; Riazuddin, Sheikh; Akram, Javed; Eghrari, Allen O; Riazuddin, S Amer

    2016-01-01

    The aim of this study is to identify the molecular basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous pedigree. All participating individuals underwent a detailed ophthalmic examination. Each patient's medical history, particularly of cataracts and other ocular abnormalities, was compiled from available medical records and interviews with family elders. Blood samples were donated by all participating family members and used to extract genomic DNA. Genetic analysis was performed to rule out linkage to known arCC loci and genes. Whole-exome sequencing libraries were prepared and paired-end sequenced. A large deletion was found that segregated with arCC in the family, and chromosome walking was conducted to estimate the proximal and distal boundaries of the deletion mutation. Exclusion and linkage analysis suggested linkage to a region of chromosome 6p24 harboring GCNT2 (glucosaminyl (N-acetyl) transferase 2) with a two-point logarithm of odds score of 5.78. PCR amplifications of the coding exons of GCNT2 failed in individuals with arCC, and whole-exome data analysis revealed a large deletion on chromosome 6p in the region harboring GCNT2. Chromosomal walking using multiple primer pairs delineated the extent of the deletion to approximately 190 kb. Interestingly, a failure to amplify a junctional fragment of the deletion break strongly suggests an insertion in addition to the large deletion. Here, we report a novel insertion/deletion mutation at the GCNT2 locus that is responsible for congenital cataracts in a large consanguineous family.

  5. DELISHUS: an efficient and exact algorithm for genome-wide detection of deletion polymorphism in autism

    Science.gov (United States)

    Aguiar, Derek; Halldórsson, Bjarni V.; Morrow, Eric M.; Istrail, Sorin

    2012-01-01

    Motivation: The understanding of the genetic determinants of complex disease is undergoing a paradigm shift. Genetic heterogeneity of rare mutations with deleterious effects is more commonly being viewed as a major component of disease. Autism is an excellent example where research is active in identifying matches between the phenotypic and genomic heterogeneities. A considerable portion of autism appears to be correlated with copy number variation, which is not directly probed by single nucleotide polymorphism (SNP) array or sequencing technologies. Identifying the genetic heterogeneity of small deletions remains a major unresolved computational problem partly due to the inability of algorithms to detect them. Results: In this article, we present an algorithmic framework, which we term DELISHUS, that implements three exact algorithms for inferring regions of hemizygosity containing genomic deletions of all sizes and frequencies in SNP genotype data. We implement an efficient backtracking algorithm—that processes a 1 billion entry genome-wide association study SNP matrix in a few minutes—to compute all inherited deletions in a dataset. We further extend our model to give an efficient algorithm for detecting de novo deletions. Finally, given a set of called deletions, we also give a polynomial time algorithm for computing the critical regions of recurrent deletions. DELISHUS achieves significantly lower false-positive rates and higher power than previously published algorithms partly because it considers all individuals in the sample simultaneously. DELISHUS may be applied to SNP array or sequencing data to identify the deletion spectrum for family-based association studies. Availability: DELISHUS is available at http://www.brown.edu/Research/Istrail_Lab/. Contact: Eric_Morrow@brown.edu and Sorin_Istrail@brown.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22689755

  6. Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome.

    Science.gov (United States)

    Koczkowska, Magdalena; Wierzba, Jolanta; Śmigiel, Robert; Sąsiadek, Maria; Cabała, Magdalena; Ślężak, Ryszard; Iliszko, Mariola; Kardaś, Iwona; Limon, Janusz; Lipska-Ziętkiewicz, Beata S

    2017-02-01

    Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.5 to 3 Mb hemizygous deletion at chromosome 22q11.2, resulting in pathognomic TBX1, CRKL and/or MAPK1 haploinsufficiency. However, there are some individuals with clinical features resembling the syndrome who are eventually diagnosed with genomic disorders affecting other chromosomal regions. The objective of this study was to evaluate the additive value of high-resolution array-CGH testing in the cohort of 41 patients with clinical features of 22q11.2 deletion syndrome and negative results of standard cytogenetic diagnostic testing (karyotype and FISH for 22q11.2 locus). Array-CGH analysis revealed no aberrations at chromosomes 22 or 10 allegedly related to the syndrome. Five (12.2 %) patients were found to have other genomic imbalances, namely 17q21.31 microdeletion syndrome (MIM#610443), 1p36 deletion syndrome (MIM#607872), NF1 microduplication syndrome (MIM#613675), chromosome 6pter-p24 deletion syndrome (MIM#612582) and a novel interstitial deletion at 3q26.31 of 0.65 Mb encompassing a dosage-dependent gene NAALADL2. Our study demonstrates that the implementation of array-CGH into the panel of classic diagnostic procedures adds significantly to their efficacy. It allows for detection of constitutional genomic imbalances in 12 % of subjects with negative result of karyotype and FISH targeted for 22q11.2 region. Moreover, if used as first-tier genetic test, the method would provide immediate diagnosis in ∼40 % phenotypic 22q11.2 deletion subjects.

  7. Total alpha-globin gene cluster deletion has high frequency in Filipinos

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, J.A.; Haruyama, A.Z.; Chu, B.M. [Kapiolani Medical Center, Honolulu, HI (United States)] [and others

    1994-09-01

    Most {alpha}-thalassemias [Thal] are due to large deletions. In Southeast Asians, the (--{sup SEA}) double {alpha}-globin gene deletion is common, 3 (--{sup Tot}) total {alpha}-globin cluster deletions are known: Filipino (--{sup Fil}), Thai (--{sup Thai}), and Chinese (--{sup Chin}). In a Hawaii Thal project, provisional diagnosis of {alpha}-Thal-1 heterozygotes was based on microcytosis, normal isoelectric focusing, and no iron deficiency. One in 10 unselected Filipinos was an {alpha}-Thal-1 heterozygote, 2/3 of these had a (--{sup Tot}) deletion: a {var_sigma}-cDNA probe consistently showed fainter intensity of the constant 5.5 kb {var_sigma}{sub 2} BamHI band, with no heterzygosity for {var_sigma}-globin region polymorphisms; {alpha}-cDNA or {var_sigma}-cDNA probes showed no BamHI or BglII bands diagnostic of the (--{sup SEA}) deletion; bands for the (-{alpha}) {alpha}-Thal-2 single {alpha}-globin deletions were only seen in Hb H cases. A reliable monoclonal anti-{var_sigma}-peptide antibody test for the (--{sup SEA}) deletion was always negative in (--{sup Tot}) samples. Southern digests with the Lo probe, a gift from D. Higgs of Oxford Univ., confirmed that 49 of 50 (--{sup Tot}) chromosomes in Filipinos were (--{sup Fil}). Of 20 {alpha}-Thal-1 hydrops born to Filipinos, 11 were (--{sup Fil}/--{sup SEA}) compound heterozygotes; 9 were (--{sup SEA}/--{sup SEA}) homozygotes, but none was a (--{sup Fil}/--{sup Fil}).

  8. Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients.

    Science.gov (United States)

    Broadbent, Hannah; Farran, Emily K; Chin, Esther; Metcalfe, Kay; Tassabehji, May; Turnpenny, Peter; Sansbury, Francis; Meaburn, Emma; Karmiloff-Smith, Annette

    2014-01-01

    Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. WE REPORT ON VISUOSPATIAL COGNITION IN TWO INDIVIDUALS WITH CONTRASTING PARTIAL DELETIONS IN THE WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB's atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed.

  9. Chondroblastoma of the temporal bone

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yuko; Murakami, Ryusuke; Toba, Masahiro; Ichikawa, Taro [Dept. of Radiology, Nippon Medical School, Tokyo (Japan); Kanazawa, Ryuzaburo; Sanno, Naoko; Shimura, Toshiro [Dept. of Neurosurgery, Nippon Medical School, Tokyo (Japan); Sawada, Namie; Hosone, Masaru [Dept. of Pathology, Nippon Medical School, Tokyo (Japan); Kumazaki, Tatsuo [Dept. of Radiology, Nippon Medical School, Tokyo (Japan)

    2001-12-01

    A rare case of chondroblastoma arising from the temporal bone that occurred in a 60-year-old woman is reported. The tumor appeared well demarcated and osteolytic on the radiographs. CT scan clearly depicted marginal and central calcification in the tumor. MR imaging demonstrated two components in the tumor: a solid component with predominantly low signal intensities on both T1- and T2-weighted sequences, and a multilocular cystic component with T1- and T2-elongation and fluid-fluid levels on the T2-weighted images. Postcontrast MR imaging revealed marked enhancement in the solid component and the septa of the cystic component. (orig.)

  10. Measuring temporal trends in biodiversity

    OpenAIRE

    Buckland, S. T.; Yuan, Y.; Marcon, Eric

    2017-01-01

    Yuan was part-funded by EPSRC/NERC Grant EP/1000917/1 and Marcon by ANR-10-LABX-25-01. In 2002, nearly 200 nations signed up to the 2010 target of the Convention for Biological Diversity, ‘to significantly reduce the rate of biodiversity loss by 2010’. In order to assess whether the target was met, it became necessary to quantify temporal trends in measures of diversity. This resulted in a marked shift in focus for biodiversity measurement. We explore the developments in measuring biodiver...

  11. SILAC-Based Temporal Phosphoproteomics

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Hekmat, Omid; Blagoev, Blagoy

    2014-01-01

    In recent years, thanks to advances in Mass Spectrometry (MS)-based quantitative proteomics, studies on signaling pathways have moved from a detailed description of individual components to system-wide analysis of entire signaling cascades, also providing spatio-temporal views of intracellular...... pathways. Quantitative proteomics that combines stable isotope labeling by amino acid in cell culture (SILAC) with enrichment strategies for post-translational modification-bearing peptides and high-performance tandem mass spectrometry represents a powerful and unbiased approach to monitor dynamic...

  12. Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer

    DEFF Research Database (Denmark)

    Kluth, Martina; Jung, Simon; Habib, Omar

    2017-01-01

    317 patients for 6q and 16q deletion length heterogeneity and found that the deletion expanded within 50-60% of 6q and 16q deleted cancers. Taken together, these data suggest continuous "deletion lengthening" as a key mechanism for prostate cancer progression leading to parallel down regulation......Prostate cancer is characterized by recurrent deletions that can considerably vary in size. We hypothesized that large deletions develop from small deletions and that this "deletion lengthening" might have a "per se" carcinogenic role through a combinatorial effect of multiple down regulated genes.......In vitroknockdown of 37 genes located inside the 6q12-q22 deletion region identified 4 genes with additive tumor suppressive effects, further supporting a role of the deletion size for cancer aggressiveness. Employing fluorescencein-situhybridization analysis on prostate cancer tissue microarrays, we determined...

  13. Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express the same deviant patterns of resting state EEG microstates: A candidate endophenotype of schizophrenia

    Directory of Open Access Journals (Sweden)

    Miralena I. Tomescu

    2015-09-01

    Full Text Available Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80 ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia.

  14. Isolation and Genetic Analysis of Extragenic Suppressors of the Hyper-Deletion Phenotype of the Saccharomyces Cerevisiae Hpr1δ Mutation

    OpenAIRE

    Santos-Rosa, H.; Aguilera, A.

    1995-01-01

    The HPR1 gene of Saccharomyces cerevisae is involved in maintaining low levels of deletions between DNA repeats. To understand how deletions initiate in the absence of the Hpr1 protein and the mechanisms of recombination leading to deletions in S. cerevisiae, we have isolated mutations as suppressors of the hyper-deletion phenotype of the hpr1δ mutation. The mutations defined five different genes called HRS for hyper-recombination suppression. They suppress the hyper-deletion phenotype of hpr...

  15. A macaque's-eye view of human insertions and deletions: differences in mechanisms.

    Directory of Open Access Journals (Sweden)

    Erika M Kvikstad

    2007-09-01

    Full Text Available Insertions and deletions (indels cause numerous genetic diseases and lead to pronounced evolutionary differences among genomes. The macaque sequences provide an opportunity to gain insights into the mechanisms generating these mutations on a genome-wide scale by establishing the polarity of indels occurring in the human lineage since its divergence from the chimpanzee. Here we apply novel regression techniques and multiscale analyses to demonstrate an extensive regional indel rate variation stemming from local fluctuations in divergence, GC content, male and female recombination rates, proximity to telomeres, and other genomic factors. We find that both replication and, surprisingly, recombination are significantly associated with the occurrence of small indels. Intriguingly, the relative inputs of replication versus recombination differ between insertions and deletions, thus the two types of mutations are likely guided in part by distinct mechanisms. Namely, insertions are more strongly associated with factors linked to recombination, while deletions are mostly associated with replication-related features. Indel as a term misleadingly groups the two types of mutations together by their effect on a sequence alignment. However, here we establish that the correct identification of a small gap as an insertion or a deletion (by use of an outgroup is crucial to determining its mechanism of origin. In addition to providing novel insights into insertion and deletion mutagenesis, these results will assist in gap penalty modeling and eventually lead to more reliable genomic alignments.

  16. Clinical and molecular consequences of exon 78 deletion in DMD gene.

    Science.gov (United States)

    Traverso, Monica; Assereto, Stefania; Baratto, Serena; Iacomino, Michele; Pedemonte, Marina; Diana, Maria Cristina; Ferretti, Marta; Broda, Paolo; Minetti, Carlo; Gazzerro, Elisabetta; Madia, Francesca; Bruno, Claudio; Zara, Federico; Fiorillo, Chiara

    2018-03-19

    We present a 13-year-old patient with persistent increase of serum Creatine Kinase (CK) and myalgia after exertion. Skeletal muscle biopsy showed marked reduction of dystrophin expression leading to genetic analysis of DMD gene by MLPA, which detected a single deletion of exon 78. To the best of our knowledge, DMD exon 78 deletion has never been described in literature and, according to prediction, it should lead to loss of reading frame in the dystrophin gene. To further assess the actual effect of exon 78 deletion, we analysed cDNA from muscle mRNA. This analysis confirmed the absence of 32 bp of exon 78. Exclusion of exon 78 changes the open reading frame of exon 79 and generate a downstream stop codon, producing a dystrophin protein of 3703 amino acids instead of 3685 amino acids. Albeit loss of reading frame usually leads to protein degradation and severe phenotype, in this case, we demonstrated that deletion of DMD exon 78 can be associated with a functional protein able to bind DGC complex and a very mild phenotype. This study adds a novel deletion in DMD gene in human and helps to define the compliance between maintaining/disrupting the reading frame and clinical form of the disease.

  17. Large deletions play a minor but essential role in congenital coagulation factor VII and X deficiencies.

    Science.gov (United States)

    Rath, M; Najm, J; Sirb, H; Kentouche, K; Dufke, A; Pauli, S; Hackmann, K; Liehr, T; Hübner, C A; Felbor, U

    2015-01-01

    Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11 recurrent in the F10 gene including one homozygous 4.35 kb deletion within F7 (c.64+430_131-6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation. Large deletions play a minor but essential role in the mutational spectrum of the F7 and F10 genes. Copy number analyses (e. g. MLPA) should be considered if sequencing cannot clarify the underlying reason of an observed coagulopathy. Of note, in cases of combined FVII/FX deficiency, a deletion of the two contiguous genes might be part of a larger chromosomal rearrangement.

  18. Boyer-Moore Algorithm in Retrieving Deleted Short Message Service in Android Platform

    Science.gov (United States)

    Rahmat, R. F.; Prayoga, D. F.; Gunawan, D.; Sitompul, O. S.

    2018-02-01

    Short message service (SMS) can be used as digital evidence of disclosure of crime because it can strengthen the charges against the offenders. Criminals use various ways to destroy the evidence, including by deleting SMS. On the Android OS, SMS is stored in a SQLite database file. Deletion of SMS data is not followed by bit deletion in memory so that it is possible to rediscover the deleted SMS. Based on this case, the mobile forensic needs to be done to rediscover the short message service. The proposed method in this study is Boyer-Moore algorithm for searching string matching. An auto finds feature is designed to rediscover the short message service by searching using a particular pattern to rematch a text with the result of the hex value conversion in the database file. The system will redisplay the message for each of a match. From all the testing results, the proposed method has quite a high accuracy in rediscovering the short message service using the used dataset. The search results to rediscover the deleted SMS depend on the possibility of overwriting process and the vacuum procedure on the database file.

  19. Differential effects of N- and C-terminal deletions on the two activities of rubisco activase.

    Science.gov (United States)

    Esau, B D; Snyder, G W; Portis, A R

    1996-02-01

    Spinach (Spinacea oleracea) leaf ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) activase was subjected to limited proteolysis with trypsin and directed deletions were made by modifying the spinach rubisco activase cDNA and expressing the 41-kDa isoform in Escherichia coli. Protein exposed to trypsin displayed a more rapid loss of the ability to promote the activation of decarbamylated rubisco than ATP hydrolysis (e.g., 10 and 50% activity remaining, respectively, after 1 h). A series of N-terminal deletions exhibited near abolition of rubisco activation after the 12th residue, a conserved tryptophan, was deleted. Conversely, a deletion of 19 residues at the C-terminus increased rubisco activation with little effect on ATP hydrolysis, resulting in an increased efficiency of activation. The C-terminal deletion mutant was further modified by a site-directed mutation in the ATP binding region (Q109E) which was previously observed to increase the efficiency of activation (J. B. Shen and W. L. Ogren, 1991, Plant Physiol. 99, 1201-1207). The efficiency of activation with this double mutant was greater than that for either of the original mutants. The results indicate that a conserved tryptophan in the N-terminal portion of rubisco activase is critical for promotion of the activation of rubisco, consistent with a possible role in interaction with rubisco. The C-terminus appears to have a regulatory effect on both rubisco activation and ATP hydrolysis.

  20. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Woloschak, G.E. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  1. Multiplex PCR screening detects small p53 deletions and insertions in human ovarian cancer cell lines.

    Science.gov (United States)

    Runnebaum, I B; Tong, X W; Moebus, V; Heilmann, V; Kieback, D G; Kreienberg, R

    1994-06-01

    Mutations at the p53 tumor suppressor gene locus are a frequent genetic alteration associated with human ovarian carcinoma. Little information exists regarding whether mutational events occur other than point mutations and large deletions, causing loss of heterozygosity. Small intragenic deletions and insertions in the p53 gene have been observed in various human neoplasias. We developed a multiplex polymerase chain reaction (MPCR) screening assay to amplify the complete p53 coding region from genomic DNA in a single step. Deletions and/or insertions were found in six out of 11 newly established ovarian carcinoma cell lines. MPCR detected deletions as small as 2 bp, as confirmed by nucleotide sequence analysis. Most of the observed alterations (6/7) were homozygous or hemizygous. Structural aberrations of the p53 gene possibly leading to loss of p53 cell cycle control may be a consequence of a slipped-mispairing mechanism in rapid DNA replication during repetitious ovulation and wound repair of ovarian epithelial cells. MPCR may be a valuable tool for screening for possible p53 deletion and insertion mutations not only in ovarian cancer but also in other malignancies.

  2. RBPJ is disrupted in a case of proximal 4p deletion syndrome with epilepsy.

    Science.gov (United States)

    Nakayama, Tojo; Saitsu, Hirotomo; Endo, Wakaba; Kikuchi, Atsuo; Uematsu, Mitsugu; Haginoya, Kazuhiro; Hino-fukuyo, Naomi; Kobayashi, Tomoko; Iwasaki, Masaki; Tominaga, Teiji; Kure, Shigeo; Matsumoto, Naomichi

    2014-06-01

    Proximal 4p deletion syndrome is characterized clinically by mental retardation, minor dysmorphic facial features, and is occasionally complicated with epilepsy. More than 20 cases of proximal 4p deletion syndrome have been reported, but the causative gene(s) remain elusive. We describe here a 2-year-old female patient with a common manifestation of proximal 4p deletion syndrome and infantile epileptic encephalopathy possessing a de novo balanced translocation t(4;13)(p15.2;q12.13). The patient was diagnosed as infantile spasms at 9 months of age. She presented with dysmorphic facial features and global developmental delay, compatible with proximal 4p deletion syndrome. Using fluorescence in situ hybridization, we determined the translocation breakpoint at 4p15.2 to be within RBPJ. RBPJ is a transcription factor in the Notch/RBPJ signaling pathway, playing a crucial role in the developing human brain, and particularly telencephalon development. Our findings, combined with those of previous studies, strongly suggest that RBPJ is causative for proximal 4p deletion syndrome and epilepsy in this case. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. [Changes of biological behavioral of E. coli K1 after ppk1 gene deletion].

    Science.gov (United States)

    Peng, Liang; Pan, Jiayun; Luo, Su; Yang, Zhenghui; Huang, Mufang; Cao, Hong

    2014-06-01

    To study the changes in biological behaviors of meningitis E. coli K1 strain E44 after deletion of polyphosphate kinase 1 (ppk1) gene and explore the role of ppk1 in the pathogenesis of E. coli K1-induced meningitis. The wild-type strain E. coli K1 and ppk1 deletion mutant were exposed to heat at 56 degrees celsius; for 6 min, and their survival rates were determined. The adhesion and invasion of the bacteria to human brain microvascular endothelial cells (HBMECs) were observed using electron microscopy and quantitative tests. HBMECs were co-incubated with wild-type strain or ppk1 deletion mutant, and the cytoskeleton rearrangement was observed under laser scanning confocal microscope. The survival rate of the ppk1 deletion mutant was significantly lower than that of the wild-type strain after heat exposure. The ppk1 deletion mutant also showed lowered cell adhesion and invasion abilities and weakened ability to induce cytoskeleton rearrangement in HBMECs. ppk1 gene is important for E.coli K1 for heat resistance, cell adhesion and invasion, and for inducing cytoskeletal rearrangement in HBMECs.

  4. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Directory of Open Access Journals (Sweden)

    Erin A Gutilla

    2016-01-01

    Full Text Available The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  5. Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis.

    Science.gov (United States)

    Rachinger, Michael; Bauch, Melanie; Strittmatter, Axel; Bongaerts, Johannes; Evers, Stefan; Maurer, Karl-Heinz; Daniel, Rolf; Liebl, Wolfgang; Liesegang, Heiko; Ehrenreich, Armin

    2013-09-20

    Conjugative shuttle vectors of the pKVM series, based on an IncP transfer origin and the pMAD vector with a temperature sensitive replication were constructed to establish a markerless gene deletion protocol for Bacilli without natural competence such as the exoenzyme producer Bacillus licheniformis. The pKVM plasmids can be conjugated to strains of B. licheniformis and B. subtilis. For chromosomal gene deletion, regions flanking the target gene are fused and cloned in a pKVM vector prior to conjugative transfer from Escherichia coli to B. licheniformis. Appropriate markers on the vector backbone allow for the identification of the integration at the target locus and thereafter the vector excision, both events taking place via homologous recombination. The functionality of the deletion system was demonstrated with B. licheniformis by a markerless 939 bp in-frame deletion of the yqfD gene and the deletion of a 31 kbp genomic segment carrying a PBSX-like prophage. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome.

    Science.gov (United States)

    Beygo, J; Buiting, K; Seland, S; Lüdecke, H-J; Hehr, U; Lich, C; Prager, B; Lohmann, D R; Wieczorek, D

    2012-01-01

    Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the TCOF1 gene and follows autosomal dominant inheritance. Recently, mutations in the POLR1D and POLR1C genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout TCOF1. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within TCOF1 lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in TCOF1, POLR1D and POLR1C. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within TCOF1. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by TCOF1.

  7. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain.

    Directory of Open Access Journals (Sweden)

    Guocai Li

    Full Text Available Neisseria gonorrhoeae (N. gonorrhoeae outer membrane protein reduction modifiable protein (Rmp has strong immunogenicity. However, anti-Rmp antibodies block rather than preserve the antibacterial effects of protective antibodies, which hampers the development of vaccines for gonococcal infections. We herein constructed an Rmp deletion mutant strain of N. gonorrhoeae by gene homologous recombination. The 261-460 nucleotide residues of Rmp gene amplified from N. gonorrhoeae WHO-A strain were replaced with a kanamycin-resistant Kan gene amplified from pET-28a. The resultant hybridized DNA was transformed into N. gonorrhoeae WHO-A strain. PCR was used to screen the colonies in which wild-type Rmp gene was replaced with a mutant gene fragment. Western blotting revealed that the Rmp deletion mutant strain did not express Rmp protein. Rmp deletion did not alter the morphological and Gram staining properties of the mutant strain that grew slightly more slowly than the wild-type one. Rmp gene mutated stably throughout 25 generations of passage. Antibody-mediated complement-dependent cytotoxicity assay indicated that the antibodies induced by the mutant strain had evidently higher bactericidal activities than those induced by the wild-type strain. Further modification of the Rmp deletion mutant strain is still required in the development of novel live attenuated vaccines for gonorrhea by Opa genes deletion or screening of phenotypic variant strains that do not express Opa proteins.

  8. Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

    Science.gov (United States)

    Demopoulos, Carly; Kothare, Hardik; Mizuiri, Danielle; Henderson-Sabes, Jennifer; Fregeau, Brieana; Tjernagel, Jennifer; Houde, John F; Sherr, Elliott H; Nagarajan, Srikantan S

    2018-01-19

    Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals.

  9. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    Energy Technology Data Exchange (ETDEWEB)

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Chen, Han [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Zhou, You [Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States); Nebraska Center for Virology, Lincoln, NE (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Nebraska Center for Virology, Lincoln, NE (United States)

    2014-11-15

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release.

  10. Polymerase chain reaction detection of retinoblastoma gene deletions in paraffin-embedded mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1991-01-01

    A Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene using microtomed sections from paraffin-embedded radiation-induced and spontaneous tumors as the DNA source. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons) were analyzed. Tumors in six neutron-irradiated mice also had no mRb deletions. However, one of six tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  11. Deletions induced by gamma rays in the genome of Escherichia coli

    International Nuclear Information System (INIS)

    Raha, Manidipa; Hutchinson, Franklin

    1991-01-01

    An Escherichia coli lysogen was constructed with a lambda phage bearing a lacZ gene surrounded by about 100 x 10 3 base-pairs of dispensable DNA. The lacZ mutants induced by gamma rays in this lysogen were more than 10% large deletions, ranging in size from 0.6 x 10 -3 to 70 x 10 3 base-pairs. These deletions were centered, not on lacZ, but on a ColE1 origin of DNA replication located 1.2 x 10 3 bases downstream from lacZ, suggesting that this origin of replication was involved in the process by which deletions were formed. In agreement with this hypothesis, a lysogen of the same phage without the ColE1 origin showed a very much lower percentage of radiation-induced deletions, as did a second lysogen of a lambda phage without any known plasmid origin of replication. Indirect evidence is presented for radiation-induced deletions centered on the lambda origin of DNA replication in a lysogen. (author)

  12. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    International Nuclear Information System (INIS)

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J.; Chen, Han; Zhou, You; Belshan, Michael

    2014-01-01

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release

  13. [Unexpected discovery of a fetus with DMD gene deletion using single nucleotide polymorphism array].

    Science.gov (United States)

    Lin, Shaobin; Zhou, Yu; Zhou, Bingyi; Gu, Heng

    2017-08-10

    To investigate the value of single nucleotide polymorphism array (SNP array) for the identification of de novo mutations in the DMD gene among fetuses. G-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy (DMD/BMD). Multiplex ligation-dependent probe amplification (MLPA) was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations. Karyotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion (chrX: 32 455 741-32 571 504) at Xp21.1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother. The de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.

  14. Primary lymphedema and other lymphatic anomalies are associated with 22q11.2 deletion syndrome.

    Science.gov (United States)

    Unolt, Marta; Barry, Jessica; Digilio, Maria Cristina; Marino, Bruno; Bassett, Anne; Oechslin, Erwin; Low, David W; Belasco, Jean B; Kallish, Staci; Sullivan, Kathleen; Zackai, Elaine H; McDonald-McGinn, Donna M

    2018-02-12

    Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome. We identified 4 patients with 22q11.2 deletion syndrome and primary lymphedema via our International 22q11.2 Deletion Syndrome Consortium. All patients underwent comprehensive clinical, laboratory and imaging assessments to rule out other causes of lymphedema. All patients had de novo typical deletions and family histories were negative for lymphedema. We report the novel association of primary lymphedema with 22q11.2 deletion syndrome. Importantly, animal models demonstrated Tbx1 playing a critical role in lymphangiogenesis by reducing Vegfr3 expression in lymphatic endothelial cells. Moreover, the VEGFR3 pathway is essential for lymphangiogenesis with mutations identified in hereditary primary lymphedema. Accordingly, our findings provide a new insight into understanding cellular mechanisms of lymphangiogenesis disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. Opitz GBBB syndrome and the 22q11.2 deletion

    Energy Technology Data Exchange (ETDEWEB)

    Lacassie, Y.; Arriaza, M.I. [Louisiani State Univ. Medical Center and Children`s Hospital, New Orleans, LA (United States)

    1996-03-29

    Recently, McDonald-McGinn et al. reported the presence of a deletion 22q11.2 in a family with autosomal dominant inheritance and in a sporadic case with the Opitz GBBB syndrome. The presence of a vascular ring in these patients prompted them to look for this deletion, since this anomaly may be associated with the 22q11.2 deletion. They reviewed the Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome, finding considerable overlap of manifestations. They proposed that, in some patients, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. We recently examined a newborn boy referred because of MCA. The cardinal findings in this patient (hypertelorism, hypospadias with descended testicles, characteristic nose and truncus arteriosus type I) were suggestive of the Opitz GBBB syndrome and of the velocardiofacial syndrome. The chromosomes were apparently normal (46,XY), but the FISH study showed a 22q11.2 deletion. The patient developed hypocalcemia with very low level of PTH and heart failure requiring surgery. His immunological status was normal except that CD4 cells were mildly low and natural killer cells were increased in number. The family history was noncontributory, but the full evaluation of the family is pending. The mother at first glance presents apparent hypertelorism. 3 refs.

  16. Congenital respiratory tract disorders in 22q11.2 deletion syndrome.

    Science.gov (United States)

    Verheij, Emmy; Speleman, Lucienne; Mink van der Molen, Aebele B; Thomeer, Henricus G X M

    2018-01-01

    Respiratory tract disorders have been reported in patients with 22q11.2 deletion syndrome, however infrequently. This study describes the respiratory tract disorders encountered in a cohort of 278 patients with 22q11.2 deletion syndrome. We conducted a retrospective, cross-sectional, study at a single tertiary referral center. We identified the patients with 22q11.2 deletion syndrome and with an upper and/or lower respiratory tract disorder at our otorhinolaryngologic department. The different disorders were described. Out of 278 patients referred to the otorhinolaryngologic department, we identified 14 patients with a laryngeal and/or tracheal disorder. Nine patients had more than one congenital disorder in this anatomical area. Disorders included a choanal stenosis (n = 1), laryngeal web (n = 5), laryngeal cleft (n = 2), subglottic stenosis (n = 3), pharyngo-, laryngo-, tracheo- and/or bronchomalacia (n = 11) and tracheal stenosis (n = 1). Different types of respiratory tract disorders can be present in patients with 22q11.2 deletion syndrome. Clinicians should be aware of this clinical association for timely and accurate diagnosis and treatment. In addition, the diagnosis 22q11.2 deletion syndrome should be considered in patients presenting with a congenital respiratory tract disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Neuropsychiatric aspects of 22q11.2 deletion syndrome: considerations in the prenatal setting

    Science.gov (United States)

    Bassett, Anne S.; Costain, Gregory; Marshall, Christian R.

    2016-01-01

    Most major neuropsychiatric outcomes of concern to families are not detectable by prenatal ultrasound. The introduction of genome-wide chromosomal microarray analysis to prenatal clinical diagnostic testing has increased the detection of pathogenic 22q11.2 deletions, which cause the most common genomic disorder. The recent addition of this and other microdeletions to non-invasive prenatal screening methods using cell-free fetal DNA has further propelled interest in outcomes. Conditions associated with 22q11.2 deletions include intellect ranging from intellectual disability to average, schizophrenia and other treatable psychiatric conditions, epilepsy, and early-onset Parkinson’s disease. However, there is currently no way to predict how severe the lifetime expression will be. Available evidence suggests no major role in these neuropsychiatric outcomes for the congenital cardiac or most other structural anomalies that may be detectable on ultrasound. This article provides an outline of the lifetime neuropsychiatric phenotype of 22q11.2 deletion syndrome that will be useful to clinicians involved in prenatal diagnosis and related genetic counselling. The focus is on information that will be most relevant to two common situations: detection of a 22q11.2 deletion in a fetus or newborn, and new diagnosis of 22q11.2 deletion syndrome in a parent without a previous molecular diagnosis. PMID:27718271

  18. Terminal 14q32.33 deletion as a novel cause of agammaglobulinemia.

    Science.gov (United States)

    Geier, Christoph B; Piller, Alexander; Eibl, Martha M; Ciznar, Peter; Ilencikova, Denisa; Wolf, Hermann M

    2017-10-01

    Over the past decades, a pleiotropic spectrum of B-cell intrinsic defects leading to early onset agammaglobulinemia and absent B cells has been described. Herein we report terminal 14q32.33 deletion as a novel cause of agammaglobulinemia. We describe a 20-year old man with a 1MB terminal 14q32.33 deletion resulting in a loss of the entire Immunoglobulin heavy chain gene region of chromosome 14. The patient presented with absent serum immunoglobulin levels and absent circulating B cells since age 2. The clinical picture was dominated by severe episodes of recurrent upper respiratory tract infections. In the literature, the most prevalent features of terminal 14q32.33 deletions include mental disability, facial malformation, hypotonia, seizures, and visual problems with retinal abnormalities. Neither increased susceptibility to infections nor agammaglobulinemia have been described as a manifestation of terminal 14q32.33 deletion. Thus, our findings expand the known clinical spectrum of terminal 14q32.33 deletion to include susceptibility to infections. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Abnormal auditory and language pathways in children with 16p11.2 deletion

    Directory of Open Access Journals (Sweden)

    Jeffrey I. Berman

    2015-01-01

    Full Text Available Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD. This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4–BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.

  20. Duchenne muscular dystrophy in a female with compound heterozygous contiguous exon deletions.

    Science.gov (United States)

    Takeshita, Eri; Minami, Narihiro; Minami, Kumiko; Suzuki, Mikiya; Awashima, Takeya; Ishiyama, Akihiko; Komaki, Hirofumi; Nishino, Ichizo; Sasaki, Masayuki

    2017-06-01

    Females with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) mutations rarely exhibit clinical symptoms from childhood, although potential mechanisms for symptoms associated with DMD and BMD in females have been reported. We report the case of a female DMD patient with a clinical course indistinguishable from that of a male DMD patient, and who possessed compound heterozygous contiguous exon deletions in the dystrophin gene. She exhibited Gowers' sign, calf muscle hypertrophy, and a high serum creatine kinase level at 2 years. Her muscle pathology showed most of the fibers were negative for dystrophin immunohistochemical staining. She lost ambulation at 11 years. Multiplex ligation-dependent probe amplification analysis of this gene detected one copy of exons 48-53; she was found to be a BMD carrier with an in-frame deletion. Messenger RNA from her muscle demonstrated out-of-frame deletions of exons 48-50 and 51-53 occurring on separate alleles. Genomic DNA from her lymphocytes demonstrated the accurate deletion region on each allele. To our knowledge, this is the first report on a female patient possessing compound heterozygous contiguous exon deletions in the dystrophin gene, leading to DMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma.

    Science.gov (United States)

    Korpi-Hyövälti, Eeva; Cranston, Treena; Ryhänen, Eeva; Arola, Johanna; Aittomäki, Kristiina; Sane, Timo; Thakker, Rajesh V; Schalin-Jäntti, Camilla

    2014-09-01

    CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations. To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations. Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA. A previously unreported deletion of CDC73 involving exons 1-10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts. A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder.

  2. 22q11.2 Deletion Syndrome Is Associated With Impaired Auditory Steady-State Gamma Response

    DEFF Research Database (Denmark)

    Larsen, Kit Melissa; Pellegrino, Giovanni; Birknow, Michelle Rosgaard

    2017-01-01

    The 22q11.2 deletion syndrome confers a markedly increased risk for schizophrenia. 22q11.2 deletion carriers without manifest psychotic disorder offer the possibility to identify functional abnormalities that precede clinical onset. Since schizophrenia is associated with a reduced cortical gamma...... response to auditory stimulation at 40 Hz, we hypothesized that the 40 Hz auditory steady-state response (ASSR) may be attenuated in nonpsychotic individuals with a 22q11.2 deletion. Eighteen young nonpsychotic 22q11.2 deletion carriers and a control group of 27 noncarriers with comparable age range (12...... Hz click stimulation. Both gamma power and inter-trial phase coherence of the ASSR were markedly reduced in the 22q11.2 deletion group. The ability to phase lock cortical gamma activity to regular auditory 40 Hz stimulation correlated with the individual expression of negative symptoms in deletion...

  3. Prediction of radiosensitivity of human tumor cell lines in vitro by determining 4977bp deletion in mitochondrial DNA

    International Nuclear Information System (INIS)

    Rong Qinglin; Cao Yongzhen; Zhang Yaowen; Zhao Xinran; Wang Qin; Li Jin; Liu Qiang

    2008-01-01

    Objective: To evaluate the possibility of predicting the radiosensitivity of tumor cell lines using the assay of the mtDNA4977bp deletion. Methods: The mtDNA4977bp deletion of HepG 2 cells and PC-3 cells were detected by nested PCR after irradiated by various doses of x-ray. Results: The radiation-induced mtDNA4977bp deletion of the tumor cell lines of HepG 2 and PC-3 were detected after irradiated. There was a dose dependent in the mtDNA4977bp deletion of two tumor cell lines. The deletion rate of HepG 2 was higher significantly than that of PC-3 at each point of radiation dose (P 2 was higher than that of PC-3. Conclusion: The assay of the mtDNA4977bp deletion may be an approach to predict the radiosensitivity of tumor cells. (authors)

  4. Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications.

    Directory of Open Access Journals (Sweden)

    Antonio Marchetti

    Full Text Available Microdeletions at exon 19 are the most frequent genetic alterations affecting the Epidermal Growth Factor Receptor (EGFR gene in non-small cell lung cancer (NSCLC and they are strongly associated with response to treatment with tyrosine kinase inhibitors. A series of 116 NSCLC DNA samples investigated by Sanger Sequencing (SS, including 106 samples carrying exon 19 EGFR deletions and 10 without deletions (control samples, were subjected to deep next generation sequencing (NGS. All samples with deletions at SS showed deletions with NGS. No deletions were seen in control cases. In 93 (88% cases, deletions detected by NGS were exactly corresponding to those identified by SS. In 13 cases (12% NGS resolved deletions not accurately characterized by SS. In 21 (20% cases the NGS showed presence of complex (double/multiple frameshift deletions producing a net in-frame change. In 5 of these cases the SS could not define the exact sequence of mutant alleles, in the other 16 cases the results obtained by SS were conventionally considered as deletions plus insertions. Different interpretative hypotheses for complex mutations are discussed. In 46 (43% tumors deep NGS showed, for the first time to our knowledge, subpopulations of DNA molecules carrying EGFR deletions different from the main one. Each of these subpopulations accounted for 0.1% to 17% of the genomic DNA in the different tumors investigated. Our findings suggest that a region in exon 19 is highly unstable in a large proportion of patients carrying EGFR deletions. As a corollary to this study, NGS data were compared with those obtained by immunohistochemistry using the 6B6 anti-mutant EGFR antibody. The immunoreaction was E746-A750del specific. In conclusion, NGS analysis of EGFR exon 19 in NSCLCs allowed us to formulate a new interpretative hypothesis for complex mutations and revealed the presence of subpopulations of deletions with potential pathogenetic and clinical impact.

  5. Three types of preS1 start codon deletion variants in the natural course of chronic hepatitis B infection.

    Science.gov (United States)

    Choe, Won Hyeok; Kim, Hong; Lee, So-Young; Choi, Yu-Min; Kwon, So Young; Moon, Hee Won; Hur, Mina; Kim, Bum-Joon

    2017-12-12

    Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P start codon deletion variants changes according to the immune phases of CHB infection, and each variant type is associated with different clinical parameters. PreS1 start codon deletion variants might interact with the host immune response differently according to their variant types. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  6. How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

    Science.gov (United States)

    2013-01-01

    The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%–2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. Therefore, it may be difficult to diagnose 22q11.2 deletion in patients with schizophrenia on the basis of clinical symptoms. To date, only two Japanese patients with the deletion have been identified through microdeletion studies of patients with schizophrenia in the Japanese population. Herein, we report the case study of a 48-year-old Japanese woman with 22q11.2 deletion who had a 30-year history of schizophrenia. Based on craniofacial anomalies, unpredictable agitation, hypocalcemia, and brain imaging finding, we suspected the 22q11.2 deletion in clinical populations and diagnosed the deletion using fluorescence in situ hybridization analysis. To find common phenotypes in Japanese patients with the deletion who have schizophrenia-like symptoms, we compared phenotypes among three Japanese cases. The common phenotypes were an absence of congenital cardiovascular anomalies and the presence of current findings of low intellectual ability, agitation, and hypocalcemia. We propose that hypocalcemia and agitation in patients with schizophrenia may derive from the 22q11.2 deletion, particularly when these phenotypes are coupled with schizophrenia-like symptoms. PMID:24063534

  7. Interstitial deletion of 5q33.3q35.1 in a boy with severe mental retardation

    OpenAIRE

    Lee, Jin Hwan; Kim, Hyo Jeong; Yoon, Jung Min; Cheon, Eun Jung; Lim, Jae Woo; Ko, Kyong Og; Lee, Gyung Min

    2016-01-01

    Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cas...

  8. Lateral temporal encephaloceles: case-based review.

    Science.gov (United States)

    Nagata, Yuichi; Takeuchi, Kazuhito; Kato, Mihoko; Chu, Jonsu; Wakabayashi, Toshihiko

    2016-06-01

    Lateral temporal encephalocele is an extremely rare clinical condition, with only 18 cases presented in the literature to date. No review articles have examined lateral temporal encephalocele in depth. We therefore reviewed past cases of lateral encephalocele to clarify the clinical characteristics of this extremely rare deformity. We also present a case of lateral encephalocele with arachnoid cyst which has never been reported in past reports. We identified 8 reports describing 18 cases of lateral temporal encephalocele. We therefore reviewed 19 cases of lateral temporal encephalocele, including our own experience, and discussed the clinical characteristics of this pathology. All the cases with lateral temporal encephalocele were detected at birth except for an occult case. The majority occurred at the pterion, and occurrence at the asterion appears much rarer. Due to the preference for the pterion, the ipsilateral orbital wall was also distorted in some cases. Lateral temporal encephalocele seems to have fewer associated malformations: only 3 cases of lateral temporal encephalocele had associated malformations, including our case which was associated with intracranial arachnoid cyst. The only case of lateral temporal encephalocele to have shown hydrocephalus was our own case. Patients with this deformity have relatively good prognoses: only 3 of the 19 cases showed delayed psychomotor development during follow-up. Provision of adequate treatment is likely to achieve a good prognosis in patients with lateral temporal encephalocele, so we should keep in mind this deformity when encountering pediatric patients with mass lesions on the temporal cranium.

  9. Auditory evoked fields elicited by spectral, temporal, and spectral-temporal changes in human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Hidehiko eOkamoto

    2012-05-01

    Full Text Available Natural sounds contain complex spectral components, which are temporally modulated as time-varying signals. Recent studies have suggested that the auditory system encodes spectral and temporal sound information differently. However, it remains unresolved how the human brain processes sounds containing both spectral and temporal changes. In the present study, we investigated human auditory evoked responses elicited by spectral, temporal, and spectral-temporal sound changes by means of magnetoencephalography (MEG. The auditory evoked responses elicited by the spectral-temporal change were very similar to those elicited by the spectral change, but those elicited by the temporal change were delayed by 30 – 50 ms and differed from the others in morphology. The results suggest that human brain responses corresponding to spectral sound changes precede those corresponding to temporal sound changes, even when the spectral and temporal changes occur simultaneously.

  10. Temporal sensitivity. [time dependent human perception of visual stimuli

    Science.gov (United States)

    Watson, Andrew B.

    1986-01-01

    Human visual temporal sensitivity is examined. The stimuli used to measure temporal sensitivity are described and the linear systems theory is reviewed in terms of temporal sensitivity. A working model which represents temporal sensitivity is proposed. The visibility of a number of temporal wave forms, sinusoids, rectangular pulses, and pulse pairs, is analyzed. The relation between spatial and temporal effects is studied. Temporal variations induced by image motion and the effects of light adaptation on temporal sensitivity are considered.

  11. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein.

    Science.gov (United States)

    Arpino, James A J; Rizkallah, Pierre J; Jones, D Dafydd

    2014-08-01

    Single-amino-acid deletions are a common part of the natural evolutionary landscape but are rarely sampled during protein engineering owing to limited and prejudiced molecular understanding of mutations that shorten the protein backbone. Single-amino-acid deletion variants of enhanced green fluorescent protein (EGFP) have been identified by directed evolution with the beneficial effect of imparting increased cellular fluorescence. Biophysical characterization revealed that increased functional protein production and not changes to the fluorescence parameters was the mechanism that was likely to be responsible. The structure EGFP(D190Δ) containing a deletion within a loop revealed propagated changes only after the deleted residue. The structure of EGFP(A227Δ) revealed that a `flipping' mechanism was used to adjust for residue deletion at the end of a β-strand, with amino acids C-terminal to the deletion site repositioning to take the place of the deleted amino acid. In both variants new networks of short-range and long-range interactions are generated while maintaining the integrity of the hydrophobic core. Both deletion variants also displayed significant local and long-range changes in dynamics, as evident by changes in B factors compared with EGFP. Rather than being detrimental, deletion mutations can introduce beneficial structural effects through altering core protein properties, folding and dynamics, as well as function.

  12. Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome

    DEFF Research Database (Denmark)

    Starnawska, A; Hansen, C S; Sparsø, T

    2017-01-01

    Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous...... deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate...

  13. Novel 31.2 kb α0 Deletion in a Palestinian Family with α-Thalassemia

    DEFF Research Database (Denmark)

    Brieghel, Christian; Birgens, Henrik; Frederiksen, Henrik

    2015-01-01

    A previously unknown α(0) deletion, designated - -(DANE), was found in three generations of a Danish family of Palestinian origin. Six patients were heterozygous and three patients had deletional Hb H (β4) disease with a compound heterozygosity for the common -α(3.7) (rightward) deletion. Multiplex...... ligation-dependent probe amplification (MLPA) supplemented by repeated polymerase chain reaction (PCR) amplification identified the 5' and 3' breakpoints in the α-globin gene cluster. This novel 31.2 kb deletion (NG_000006.1: g.8800_40007del31208) leads to the removal of the HBZ, HBA2 and HBA1 genes....

  14. A New Intergenic α-Globin Deletion (α-αΔ125) Found in a Kabyle Population.

    Science.gov (United States)

    Singh, Amrathlal Rabbind; Lacan, Philippe; Cadet, Estelle; Bignet, Patricia; Dumesnil, Cécile; Vannier, Jean-Pierre; Joly, Philippe; Rochette, Jacques

    2016-01-01

    We have identified a deletion of 125 bp (α-α(Δ125)) (NG_000006.1: g.37040_37164del) in the α-globin gene cluster in a Kabyle population. A combination of singlex and multiplex polymerase chain reaction (PCR)-based assays have been used to identify the molecular defect. Sequencing of the abnormal PCR amplification product revealed a novel α1-globin promoter deletion. The endpoints of the deletion were characterized by sequencing the deletion junctions of the mutated allele. The observed deletion was located 378 bp upstream of the α1-globin gene transcription initiation site and leaves the α2 gene intact. In some patients, the α-α(Δ125) deletion was shown to segregate with Hb S (HBB: c.20A>T) and/or Hb C (HBB: c.19G>A) or a β-thalassemic allele. The α-α(Δ125) deletion has no discernible effect on red cell indices when inherited with no other abnormal globin genes. The family study demonstrated that the deletion is heritable. This is the only example of an intergenic α2-α1 non coding DNA deletion, leaving the α2-globin gene and the α1 coding part intact.

  15. The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

    Science.gov (United States)

    2011-01-01

    Background Qualitative and quantitative changes in human mitochondrial DNA (mtDNA) have been implicated in various cancer types. A 4,977 bp deletion in the major arch of the mitochondrial genome is one of the most common mutations associated with a variety of human diseases and aging. Methods We conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients. Results We found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells. PMID:21232124

  16. The benefits and limitations of cell-free DNA screening for 22q11.2 deletion syndrome.

    Science.gov (United States)

    Dugoff, Lorraine; Mennuti, Michael T; McDonald-McGinn, Donna M

    2017-01-01

    Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  17. Prenatal diagnosis of interstitial deletion of 17(p11.2p11.2) (Smith-Magenis Syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-01-15

    Interstitial deletion of 17p11.2 is associated with Smith-Magenis syndrome. This is a recognizable chromosomal deletion syndrome, characterized by brachycephaly, midface hypoplasia, growth and mental retardation, behavioral problems, and ocular abnormalities. Molecular analysis indicates it is a contiguous gene syndrome. Over 50 patients have been reported since the deletion was first described by Smith et al. [1982]. Cases include one with mosaicism and a familial example. None were prenatally diagnosed. The authors report on the prenatal detection of interstitial deletion of 17p11.2. 11 refs., 1 fig.

  18. An extensive deletion causing overproduction of yeast iso-2-cytochrome c

    International Nuclear Information System (INIS)

    McKnight, G.L.; Cardillo, T.S.; Sherman, F.

    1981-01-01

    CYC7-H3 is a cis-dominant regulatory mutation that causes a 20-fold overproduction of yeast iso-2-cytochrome c. The CYC7-H3 mutation is an approximately 5 kb deletion with one breakpoint located in the 5' noncoding region of the CYC7 gene, approximately 200 base from the ATG initiation codon. The deletion apparently fuses a new regulatory region to the structural portion of the CYC7 locus. The CYC7-H3 deletion encompasses the RAD23 locus, which controls UV sensitivity and the ANP1 locus, which controls osmotic sensitivity. The gene cluster CYC7-RAD23-ANP1 displays striking similarity to the gene cluster CYC1-OSM1-RAD7, which controls, respectively, iso-1-cytochrome c, osmotic sensitivity and UV sensitivity. We suggest that these gene clusters are related by an ancient transpositional event

  19. Karect: accurate correction of substitution, insertion and deletion errors for next-generation sequencing data

    KAUST Repository

    Allam, Amin

    2015-07-14

    Motivation: Next-generation sequencing generates large amounts of data affected by errors in the form of substitutions, insertions or deletions of bases. Error correction based on the high-coverage information, typically improves de novo assembly. Most existing tools can correct substitution errors only; some support insertions and deletions, but accuracy in many cases is low. Results: We present Karect, a novel error correction technique based on multiple alignment. Our approach supports substitution, insertion and deletion errors. It can handle non-uniform coverage as well as moderately covered areas of the sequenced genome. Experiments with data from Illumina, 454 FLX and Ion Torrent sequencing machines demonstrate that Karect is more accurate than previous methods, both in terms of correcting individual-bases errors (up to 10% increase in accuracy gain) and post de novo assembly quality (up to 10% increase in NGA50). We also introduce an improved framework for evaluating the quality of error correction.

  20. Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

    Science.gov (United States)

    Gawlik-Kuklinska, Katarzyna; Wierzba, Jolanta; Wozniak, Agnieszka; Iliszko, Mariola; Debiec-Rychter, Maria; Dubaniewicz-Wybieralska, Miroslawa; Limon, Janusz

    2008-01-01

    We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

  1. Pearson syndrome and the role of deletion dimers and duplications in the mtDNA.

    Science.gov (United States)

    Jacobs, L J A M; Jongbloed, R J E; Wijburg, F A; de Klerk, J B C; Geraedts, J P M; Nijland, J G; Scholte, H R; de Coo, I F M; Smeets, H J M

    2004-01-01

    Pearson syndrome is an often fatal multisystem disease associated with mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with deletion dimers. The mutation percentage in different tissues (blood, muscle and liver) varied between 64% and 95%. After a remission period of about a year, the patient suddenly died at the age of 3 years owing to a severe lactic acidosis. A second patient with a previously reported deletion of 8 kb and a milder phenotype was found to have mitochondrial duplications and died at the age of 10 years. From these data and data from previous reports, we hypothesize that duplications might be beneficial in the clinical course of the disease and in life expectancy.

  2. A novel mtDNA deletion in an infant with Pearson syndrome.

    Science.gov (United States)

    Kapsa, R; Thompson, G N; Thorburn, D R; Dahl, H H; Marzuki, S; Byrne, E; Blok, R B

    1994-01-01

    Pearson syndrome is a multisystem mitochondrial disorder of infancy that is associated with deletions in the mitochondrial DNA (mtDNA) genome. We report a study on a male infant with Pearson syndrome. Assessment of oxidative phosphorylation activity indicated combined respiratory-chain defects in muscle, liver and fibroblasts; in particular, activity of complex I was reduced. Analysis of the patient's mtDNA identified a novel heteroplasmic 2.461 kb deletion, present at levels greater than 50% of the total mtDNA in the tissues examined. The deletion spanned nucleotides 10368 to 12828 and was flanked by a 3 bp GCC direct repeat sequence. Gene sequences affected are subunits 3, 4, 4L and 5 of complex I, and tRNAs for arginine, histidine, serine and leucine. Our findings correlate with the multiorgan involvement observed in Pearson syndrome.

  3. The association between haematological manifestation and mtDNA deletions in Pearson syndrome.

    Science.gov (United States)

    Muraki, K; Nishimura, S; Goto, Y; Nonaka, I; Sakura, N; Ueda, K

    1997-09-01

    We studied the proportion of deleted mitochondrial DNA in blood cells from patients with Pearson syndrome. Patient 1 is a 17-year-old female with Kearns-Sayre syndrome who survived Pearson syndrome. Patient 2 is a 5-year-old boy with Pearson syndrome who recovered from refractory anaemia but continues to have thrombocytopenia and neutropenia. Patient 3 is a female neonate who died with severe acidosis and pancytopenia at 14 days of age. Southern blot analysis was performed with total DNA from three patients' blood cells and two samples of bone marrow cells from one patient. In peripheral blood, patients with a higher proportion of deleted mitochondrial DNA had lower blood cell counts. In patient 2, the percentage of mutant mitochondrial DNA in bone marrow cells decreased as anaemia improved. This indicates that the proportion of deleted mitochondrial DNA in peripheral blood and in bone marrow has a tendency to correlate to the severity of haematological manifestation.

  4. Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial DNA deletion.

    Science.gov (United States)

    McDonald, D G M; McMenamin, J B; Farrell, M A; Droogan, O; Green, A J

    2002-08-01

    The common 4977 base pair mitochondrial deletion has been identified in association with a number of distinct clinical phenotypes. These include the Kearns-Sayre syndrome, the Pearson marrow-pancreas syndrome, and chronic progressive external ophthalmoplegia. We report the clinical and pathological findings in two siblings in whom the 4977 base pair mitochondrial DNA deletion was identified in muscle-derived mitochondrial DNA. One sibling manifested early onset liver and renal failure, and both developed prominent peripheral sensorimotor neuropathy. These clinical findings have not been previously described in association with the 4977bp mtDNA deletion and thus represent a further expansion of the spectrum of mitochondrial disease. Copyright 2002 Wiley-Liss, Inc.

  5. Allelic deletions of cell growth regulators during progression of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, H; von der Maase, H; Christensen, M

    2000-01-01

    Cell growth regulators include proteins of the p53 pathway encoded by the genes CDKN2A (p16, p14arf), MDM2, TP53, and CDKN1A (p21) as well as proteins encoded by genes like RB1, E2F, and MYCL. In the present study we investigated allelic deletions of all these genes in each recurrent bladder tumor...... difference in the numbers of gene loci hit by deletions muscle-invasive versus noninvasive tumors (P = 0.0000002), with the genes most often hit by deletions in muscle-invasive tumors being TP53, RB1, and MYCL. A number of novel findings were made. Losses of MYCL and RB1 alleles were more pronounced...... that a characteristic difference between recurrent noninvasive and recurrent progressing bladder tumors is loss of cell cycle-regulatory genes in the latter group....

  6. Effect of 5'-flanking sequence deletions on expression of the human insulin gene in transgenic mice

    DEFF Research Database (Denmark)

    Fromont-Racine, M; Bucchini, D; Madsen, O

    1990-01-01

    Expression of the human insulin gene was examined in transgenic mouse lines carrying the gene with various lengths of DNA sequences 5' to the transcription start site (+1). Expression of the transgene was demonstrated by 1) the presence of human C-peptide in urine, 2) the presence of specific......, and -168 allowed correct initiation of the transcripts and cell specificity of expression, while quantitative expression gradually decreased. Deletion to -58 completely abolished the expression of the gene. The amount of human product that in mice harboring the longest fragment contributes up to 50......% of the total insulin does not alter the normal proportion of mice insulins I and II. These results suggest that expression of the human insulin gene in vivo results from the cooperation of several cis-regulatory elements present in the various deleted fragments. With none of the deletions used, expression...

  7. Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Stefánsson, Hreinn; Riff Jensen, Lars

    2016-01-01

    -affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations. METHODS: We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes. The most promising....... Subsequently, expression of the candidate gene in the central nervous system was investigated using human and mouse brain tissues. RESULTS: In the Danish cohort, we identified eight patients with overlapping deletions of AADAC. Investigation of the additional five countries showed a significant association...... between the AADAC deletion and GTS, and a final meta-analysis confirmed the significant association (p = 4.4 × 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33-2.71). Furthermore, RNA in situ hybridization and reverse transcription-polymerase chain reaction studies revealed that AADAC is expressed...

  8. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy

    DEFF Research Database (Denmark)

    Vissing, John; Barresi, Rita; Witting, Nanna

    2016-01-01

    screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal...... creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did...... not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation...

  9. Routine diagnostic testing of Y chromosome deletions in male infertile and subfertile.

    Science.gov (United States)

    Ghorbian, Saeid

    2012-07-15

    Male factor infertility elucidated about half the couple of infertility and in around 50% of cases, its etiology remains unknown. The aim of this study was to investigate a predisposing genetic background for Yq deletions and male infertility and effectiveness of molecular genetic approaches have uncovered several etiopathogenetic factors, such as microdeletions of Yq chromosome. The Y chromosome microdeletions removing the azoospermia factor (AZF) regions, which are most common molecular genetic causes of oligospermia or azoospermia. However, with the analysis of Yq deletions, we are able to obtain a better understanding of the clinical significance of genetic anomaly and to the identifying of fertility candidate genes in the AZF regions. Molecular genetic approaches, becomes a routine diagnostic test, that provides an etiology for spermatogenic disturbances, and prognosis for testicular sperm retrieval according to the type of deletion. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Molecular analysis of the Duchenne muscular dystrophy gene in Spanish individuals: Deletion detection and familial diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Patino, A.; Garcia-Delgado, M.; Narbona, J. [Univ. of Navarra, Pamplona (Spain)

    1995-11-06

    Deletion studies were performed in 26 Duchenne muscular dystrophy (DMD) patients through amplification of nine different exons by multiplex polymerase chain reaction (PCR). DNA from paraffin-embedded muscle biopsies was analyzed in 12 of the 26 patients studied. Optimization of this technique is of great utility because it enables analysis of material stored in pathology archives. PCR deletion detection, useful in DMD-affected boys, is problematic in determining the carrier state in female relatives. For this reason, to perform familial linkage diagnosis, we made use of a dinucleotide repeat polymorphism (STRP, or short tandem repeat polymorphism) located in intron 49 of the gene. We designed a new pair of primers that enabled the detection of 22 different alleles in relatives in the 14 DMD families studied. The use of this marker allowed familial diagnosis in 11 of the 14 DMD families and detection of de novo deletions in 3 of the probands. 8 refs., 5 figs., 2 tabs.

  11. Recurring exon deletions in the haptoglobin (HP) gene associate with lower blood cholesterol levels

    Science.gov (United States)

    Boettger, Linda M.; Salem, Rany M.; Handsaker, Robert E.; Peloso, Gina; Kathiresan, Sekar; Hirschhorn, Joel; McCarroll, Steven A.

    2016-01-01

    Two exons of the human haptoglobin (HP) gene exhibit copy number variation that affects HP multimerization and underlies one of the first protein polymorphisms identified in humans. The evolutionary origins and medical significance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from the recurring reversion of an ancient hominin-specific duplication of these exons. Though this polymorphism has been largely invisible to genome-wide genetic studies to date, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We show that these deletions, and a SNP that affects HP expression, are the likely drivers of the strong but complex association of cholesterol levels to SNPs near HP. Recurring exonic deletions in the haptoglobin gene likely enhance human health by lowering cholesterol levels in the blood. PMID:26901066

  12. Deletion of JJJ1 improves acetic acid tolerance and bioethanol fermentation performance of Saccharomyces cerevisiae strains.

    Science.gov (United States)

    Wu, Xuechang; Zhang, Lijie; Jin, Xinna; Fang, Yahong; Zhang, Ke; Qi, Lei; Zheng, Daoqiong

    2016-07-01

    To improve tolerance to acetic acid that is present in lignocellulosic hydrolysates and affects bioethanol production by Saccharomyces cerevisiae. Saccharomyces cerevisiae strains with improved tolerance to acetic acid were obtained through deletion of the JJJ1 gene. The lag phase of the JJJ1 deletion mutant BYΔJJJ1 was ~16 h shorter than that of the parent strain, BY4741, when the fermentation medium contained 4.5 g acetic acid/l. Additionally, the specific ethanol production rate of BYΔJJJ1 was increased (0.057 g/g h) compared to that of the parent strain (0.051 g/g h). Comparative transcription and physiological analyses revealed higher long chain fatty acid, trehalose, and catalase contents might be critical factors responsible for the acetic acid resistance of JJJ1 knockout strains. JJJ1 deletion improves acetic acid tolerance and ethanol fermentation performance of S. cerevisiae.

  13. Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies

    Directory of Open Access Journals (Sweden)

    Sun-Mi Cho

    2014-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22 gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

  14. Uterine deletion of Trp53 compromises antioxidant responses in mouse decidua

    Energy Technology Data Exchange (ETDEWEB)

    Burnum, Kristin E.; Hirota, Yasushi; Baker, Erin Shammel; Yoshie, Mikihiro; Ibrahim, Yehia M.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Daikoku, Takiko; Dey, Sudhansu K.

    2012-09-01

    Preterm birth is a global health issue impacting both mothers and children. However, the etiology of preterm birth is not clearly understood. From our recent finding that premature decidual senescence with terminal differentiation is a cause of preterm birth in mice with uterine Trp53 deletion, encoding p53 protein, led us to explore other potential factors that are related to preterm birth. Utilizing proteomics approaches, here we show that 183 candidate proteins cause significant changes in decidua with Trp53 deletion as compared to normal decidua. Functional categorization of these proteins unveiled new pathways that are influenced by p53. In particular, downregulation of a cluster of antioxidant proteins in p53 deficient decidua suggests that increased oxidative stress could be one cause of preterm birth in mice with uterine deletion of Trp53.

  15. Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth

    2009-01-01

    With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell...... factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which...... the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger....

  16. Unmarked gene deletion and host-vector system for the hyperthermophilic crenarchaeon Sulfolobus islandicus

    DEFF Research Database (Denmark)

    Deng, Ling; Zhu, Haojun; Chen, Zhengjun

    2009-01-01

    , and unmarked lacS mutants were obtained by each method. A new alternative recombination mechanism, i.e., marker circularization and integration, was shown to operate in the latter method, which did not yield the designed deletion mutation. Subsequently, Sulfolobus-E. coli plasmid shuttle vectors were...... mutant was obtained containing only 233 bp of the original pyrE sequence in the mutant allele and it was used as a host to delete the beta-glycosidase (lacS) gene. Two unmarked gene deletion methods were employed, namely plasmid integration and segregation, and marker replacement and looping out...... constructed, which genetically complemented DeltapyrEFDeltalacS mutation after transformation. Thus, a complete set of genetic tools was established for S. islandicus with pyrEF and lacS as genetic markers....

  17. The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty

    Directory of Open Access Journals (Sweden)

    Fang Carrie

    2001-04-01

    Full Text Available Abstract Background Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. Methods The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. Results The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26. Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32. Conclusions Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis.

  18. 22q11.2 Deletion syndrome is associated with perioperative outcome in tetralogy of Fallot.

    Science.gov (United States)

    Mercer-Rosa, Laura; Pinto, Nelangi; Yang, Wei; Tanel, Ronn; Goldmuntz, Elizabeth

    2013-10-01

    We sought to investigate the impact of 22q11.2 deletion on perioperative outcome in tetralogy of Fallot. We conducted a retrospective review of patients with tetralogy of Fallot who underwent complete surgical reconstruction at The Children's Hospital of Philadelphia between 1995 and 2006. Inclusion criteria included diagnosis of tetralogy of Fallot and known genotype. Fisher exact and Mann-Whitney tests were used for categoric and continuous variables, respectively. Regression analysis was used to determine whether deletion status predicts outcome. We studied 208 subjects with tetralogy of Fallot, 164 (79%) without and 44 (20%) with 22q11.2 deletion syndrome. There were no differences in sex, race, gestational age, age at diagnosis, admission weight, and duration of mechanical ventilation. Presenting anatomy, survival, complications and reoperations were also comparable between patients with and without 22q11.2 deletion syndrome. Those with 22q11.2 deletion syndrome had more aortopulmonary shunts preceding complete surgical repair (21% vs 7%, P = .02). This association was present after adjustment for presenting anatomy (stenosis, atresia, or absence of pulmonary valve and common atrioventricular canal) and surgical era. In addition, those with 22q11.2 deletion syndrome had longer cardiopulmonary bypass time (84 vs 72 minutes, P = .02) and duration of intensive care (6 vs 4 days, P = .007). Genotype affects early operative outcomes in tetralogy of Fallot resulting, in particular, in longer duration of intensive care. Future studies are required to determine factors contributing to such differences in this susceptible population. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  19. 1p/14q co-deletion: A determinant of recurrence in histologically benign meningiomas

    Directory of Open Access Journals (Sweden)

    Aanchal Kakkar

    2015-01-01

    Full Text Available Background: Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors. Materials and Methods: We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR, p53, and MIB-1. Results: 18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III with their parent tumors (14 grade I, 2 grade II and 2 grade III were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co-deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI, PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence. Conclusion: Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion.

  20. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jeremy M Van Raamsdonk

    2009-02-01

    Full Text Available The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS generated during normal metabolism. Superoxide dismutases (SODs counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants-including slow development, low brood size, and slow defecation-this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm