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Sample records for chromosome inactivation pattern

  1. The pituitary-thyroid axis set point in women is uninfluenced by X chromosome inactivation pattern? A twin study

    DEFF Research Database (Denmark)

    Brix, Thomas H; Hansen, Pia S; Kyvik, Kirsten O; Hegedüs, Laszlo

    2010-01-01

    The pituitary-thyroid axis (PTA) set point is determined by a combination of genetic and environmental factors. However, despite considerable efforts to characterize the background, the causative genes as well as environmental factors are not well established. Theoretically, as shown for autoimmune...... thyroid disease, the pattern of X chromosome inactivation (XCI) could offer a novel explanation for the observed variability of the PTA set point in women....

  2. X-chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate

    DEFF Research Database (Denmark)

    Kimani, Jane W; Shi, Min; Daack-Hirsch, Sandra;

    2007-01-01

    Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X...... XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft......, particularly cleft lip and palate....

  3. Clonality - X Chromosome Inactivation Assay

    OpenAIRE

    sprotocols

    2014-01-01

    Author: Molecular Profiling Initiative, NCI This method was successful in our lab using prostate tissue and for our specific objectives. Investigators must be aware that they will need to tailor the following protocol for their own research objectives and tissue under study. Investigators can utilize X chromosome inactivation (methylation) to determine the clonality status of a tumor or premalignant lesion in females. The technique is based on a methylation-sensitive restriction enzym...

  4. Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice.

    Science.gov (United States)

    Patrat, Catherine; Okamoto, Ikuhiro; Diabangouaya, Patricia; Vialon, Vivian; Le Baccon, Patricia; Chow, Jennifer; Heard, Edith

    2009-03-31

    In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene silencing have been the subject of debate. We performed a systematic, single-cell transcriptional analysis to examine the activity of the Xp chromosome for a panel of X-linked genes throughout early preimplantation development in the mouse. Rather than being preinactivated, we found the Xp to be fully active at the time of zygotic gene activation, with silencing beginning from the 4-cell stage onward. X-inactivation patterns were, however, surprisingly diverse between genes. Some loci showed early onset (4-8-cell stage) of X inactivation, and some showed extremely late onset (postblastocyst stage), whereas others were never fully inactivated. Thus, we show that silencing of some X-chromosomal regions occurs outside of the usual time window and that escape from X inactivation can be highly lineage specific. These results reveal that imprinted X inactivation in mice is far less concerted than previously thought and highlight the epigenetic diversity underlying the dosage compensation process during early mammalian development. PMID:19273861

  5. Origin and evolution of X chromosome inactivation.

    Science.gov (United States)

    Gribnau, Joost; Grootegoed, J Anton

    2012-06-01

    Evolution of the mammalian sex chromosomes heavily impacts on the expression of X-encoded genes, both in marsupials and placental mammals. The loss of genes from the Y chromosome forced a two-fold upregulation of dose sensitive X-linked homologues. As a corollary, female cells would experience a lethal dose of X-linked genes, if this upregulation was not counteracted by evolution of X chromosome inactivation (XCI) that allows for only one active X chromosome per diploid genome. Marsupials rely on imprinted XCI, which inactivates always the paternally inherited X chromosome. In placental mammals, random XCI (rXCI) is the predominant form, inactivating either the maternal or paternal X. In this review, we discuss recent new insights in the regulation of XCI. Based on these findings, we propose an X inactivation center (Xic), composed of a cis-Xic and trans-Xic that encompass all elements and factors acting to control rXCI either in cis or in trans. We also highlight that XCI may have evolved from a very small nucleation site on the X chromosome in the vicinity of the Sox3 gene. Finally, we discuss the possible evolutionary road maps that resulted in imprinted XCI and rXCI as observed in present day mammals. PMID:22425180

  6. Female meiotic sex chromosome inactivation in chicken.

    Directory of Open Access Journals (Sweden)

    Sam Schoenmakers

    2009-05-01

    Full Text Available During meiotic prophase in male mammals, the heterologous X and Y chromosomes remain largely unsynapsed, and meiotic sex chromosome inactivation (MSCI leads to formation of the transcriptionally silenced XY body. In birds, the heterogametic sex is female, carrying Z and W chromosomes (ZW, whereas males have the homogametic ZZ constitution. During chicken oogenesis, the heterologous ZW pair reaches a state of complete heterologous synapsis, and this might enable maintenance of transcription of Z- and W chromosomal genes during meiotic prophase. Herein, we show that the ZW pair is transiently silenced, from early pachytene to early diplotene using immunocytochemistry and gene expression analyses. We propose that ZW inactivation is most likely achieved via spreading of heterochromatin from the W on the Z chromosome. Also, persistent meiotic DNA double-strand breaks (DSBs may contribute to silencing of Z. Surprisingly, gammaH2AX, a marker of DSBs, and also the earliest histone modification that is associated with XY body formation in mammalian and marsupial spermatocytes, does not cover the ZW during the synapsed stage. However, when the ZW pair starts to desynapse, a second wave of gammaH2AX accumulates on the unsynapsed regions of Z, which also show a reappearance of the DSB repair protein RAD51. This indicates that repair of meiotic DSBs on the heterologous part of Z is postponed until late pachytene/diplotene, possibly to avoid recombination with regions on the heterologously synapsed W chromosome. Two days after entering diplotene, the Z looses gammaH2AX and shows reactivation. This is the first report of meiotic sex chromosome inactivation in a species with female heterogamety, providing evidence that this mechanism is not specific to spermatogenesis. It also indicates the presence of an evolutionary force that drives meiotic sex chromosome inactivation independent of the final achievement of synapsis.

  7. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    Czech Academy of Sciences Publication Activity Database

    Homolka, David; Ivánek, Robert; Čapková, Jana; Jansa, Petr; Forejt, Jiří

    2007-01-01

    Roč. 17, č. 10 (2007), s. 1431-1437. ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA301/06/1334; GA ČR GA301/07/1383 Grant ostatní: Howard Hughes Medical Institute(US) HHMI 55000306 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromosomal translocations * meiotic X chromosome inactivation * spermatogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

  8. The Evolutionary Pathway of X Chromosome Inactivation in Mammals

    OpenAIRE

    Shevchenko, A.; Zakharova, I.; Zakian, S.

    2013-01-01

    X chromosome inactivation is a complex process that occurs in marsupial and eutherian mammals. The process is thought to have arisen during the differentiation of mammalian sex chromosomes to achieve an equal dosage of X chromosome genes in males and females. The differences in the X chromosome inactivation processes in marsupial and eutherian mammals are considered, and the hypotheses on its origin and evolution are discussed in this review.

  9. Detailed analysis of X chromosome inactivation in a 49,XXXXX pentasomy

    Science.gov (United States)

    Moraes, Lucia M; Cardoso, Leila CA; Moura, Vera LS; Moreira, Miguel AM; Menezes, Albert N; Llerena, Juan C; Seuánez, Héctor N

    2009-01-01

    Background Pentasomy X (49,XXXXX) has been associated with a severe clinical condition, presumably resulting from failure or disruption of X chromosome inactivation. Here we report that some human X chromosomes from a patient with 49,XXXXX pentasomy were functionally active following isolation in inter-specific (human-rodent) cell hybrids. A comparison with cytogenetic and molecular findings provided evidence that more than one active X chromosome was likely to be present in the cells of this patient, accounting for her abnormal phenotype. Results 5-bromodeoxyuridine (BrdU)-pulsed cultures showed different patterns among late replicating X chromosomes suggesting that their replication was asynchronic and likely to result in irregular inactivation. Genotyping of the proband and her mother identified four maternal and one paternal X chromosomes in the proband. It also identified the paternal X chromosome haplotype (P), indicating that origin of this X pentasomy resulted from two maternal, meiotic non-disjunctions. Analysis of the HUMANDREC region of the androgen receptor (AR) gene in the patient's mother showed a skewed inactivation pattern, while a similar analysis in the proband showed an active paternal X chromosome and preferentially inactivated X chromosomes carrying the 173 AR allele. Analyses of 33 cell hybrid cell lines selected in medium containing hypoxanthine, aminopterin and thymidine (HAT) allowed for the identification of three maternal X haplotypes (M1, M2 and MR) and showed that X chromosomes with the M1, M2 and P haplotypes were functionally active. In 27 cell hybrids in which more than one X haplotype were detected, analysis of X inactivation patterns provided evidence of preferential inactivation. Conclusion Our findings indicated that 12% of X chromosomes with the M1 haplotype, 43.5% of X chromosomes with the M2 haplotype, and 100% of the paternal X chromosome (with the P haplotype) were likely to be functionally active in the proband's cells, a

  10. X-Chromosome Inactivation Counting and Choice: Change or Design

    NARCIS (Netherlands)

    K. Monkhorst (Kim)

    2008-01-01

    textabstractPlacental mammalian female cells have two X chromosomes. One of these chromosomes is randomly inactivated in each nucleus so that females are functionally mosaic for genes expressed from their X chromosomes. The evolutionary basis for this phenomenon is based on the fact that females wou

  11. Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice

    OpenAIRE

    Patrat, Catherine; Okamoto, Ikuhiro; Diabangouaya, Patricia; Vialon, Vivian; Le Baccon, Patricia; Chow, Jennifer; Heard, Edith

    2009-01-01

    In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene si...

  12. Unique sex chromosome systems in Ellobius: How do male XX chromosomes recombine and undergo pachytene chromatin inactivation?

    Science.gov (United States)

    Matveevsky, Sergey; Bakloushinskaya, Irina; Kolomiets, Oxana

    2016-01-01

    Most mammalian species have heteromorphic sex chromosomes in males, except for a few enigmatic groups such as the mole voles Ellobius, which do not have the Y chromosome and Sry gene. The Ellobius (XX ♀♂) system of sex chromosomes has no analogues among other animals. The structure and meiotic behaviour of the two X chromosomes were investigated for males of the sibling species Ellobius talpinus and Ellobius tancrei. Their sex chromosomes, despite their identical G-structure, demonstrate short synaptic fragments and crossover-associated MLH1 foci in both telomeric regions only. The chromatin undergoes modifications in the meiotic sex chromosomes. SUMO-1 marks a small nucleolus-like body of the meiotic XX. ATR and ubiH2A are localized in the asynaptic area and the histone γH2AFX covers the entire XX bivalent. The distribution of some markers of chromatin inactivation differentiates sex chromosomes of mole voles from those of other mammals. Sex chromosomes of both studied species have identical recombination and meiotic inactivation patterns. In Ellobius, similar chromosome morphology masks the functional heteromorphism of the male sex chromosomes, which can be seen at meiosis. PMID:27425629

  13. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

    Directory of Open Access Journals (Sweden)

    Colin D Meiklejohn

    2011-08-01

    Full Text Available The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

  14. X-chromosome inactivation in female patients with Fabry disease.

    Science.gov (United States)

    Echevarria, L; Benistan, K; Toussaint, A; Dubourg, O; Hagege, A A; Eladari, D; Jabbour, F; Beldjord, C; De Mazancourt, P; Germain, D P

    2016-01-01

    Fabry disease (FD) is an X-linked genetic disorder caused by the deficient activity of lysosomal α-galactosidase (α-Gal). While males are usually severely affected, clinical presentation in female patients may be more variable ranging from asymptomatic to, occasionally, as severely affected as male patients. The aim of this study was to evaluate the existence of skewed X-chromosome inactivation (XCI) in females with FD, its concordance between tissues, and its contribution to the phenotype. Fifty-six females with FD were enrolled. Clinical and biological work-up included two global scores [Mainz Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging, measured glomerular filtration rate, and measurement of α-Gal activity. XCI was analyzed in four tissues using DNA methylation studies. Skewed XCI was found in 29% of the study population. A correlation was found in XCI patterns between blood and the other analyzed tissues although some punctual variability was detected. Significant differences in residual α-Gal levels, severity scores, progression of cardiomyopathy and deterioration of kidney function, depending on the direction and degree of skewing of XCI were evidenced. XCI significantly impacts the phenotype and natural history of FD in females. PMID:25974833

  15. Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis

    DEFF Research Database (Denmark)

    Canevari, Renata A; Pontes, Anaglória; Rosa, Fabíola E;

    2005-01-01

    OBJECTIVE: In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis....... STUDY DESIGN: We have used a set of 15 microsatellite polymorphism markers mapped on 3q, 7p, 11, and 15q by automated analysis. The X chromosome inactivation was evaluated by the methylation status of the X-linked androgen receptor gene. RESULTS: Loss of heterozygosity analysis showed a different...... pattern in 7 of the 8 cases with allelic loss for at least 1 of 15 microsatellite markers that were analyzed. A similar loss of heterozygosity findings at 7p22-15 was detected in 3 samples from the same patient. X chromosome inactivation analysis demonstrated the same inactivated allele in all tumors...

  16. A Chromosomal Memory Triggered by Xist Regulates Histone Methylation in X Inactivation

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    Kohlmaier Alexander

    2004-01-01

    Full Text Available We have elucidated the kinetics of histone methylation during X inactivation using an inducible Xist expression system in mouse embryonic stem (ES cells. Previous reports showed that the ability of Xist to trigger silencing is restricted to an early window in ES cell differentiation. Here we show that this window is also important for establishing methylation patterns on the potential inactive X chromosome. By immunofluorescence and chromatin immunoprecipitation experiments we show that histone H3 lysine 27 trimethylation (H3K27m3 and H4 lysine 20 monomethylation (H4K20m1 are associated with Xist expression in undifferentiated ES cells and mark the initiation of X inactivation. Both marks depend on Xist RNA localisation but are independent of silencing. Induction of Xist expression after the initiation window leads to a markedly reduced ability to induce H3K27m3, whereas expression before the restrictive time point allows efficient H3K27m3 establishment. Our data show that Xist expression early in ES cell differentiation establishes a chromosomal memory, which is maintained in the absence of silencing. One consequence of this memory is the ability to introduce H3K27m3 efficiently after the restrictive time point on the chromosome that has expressed Xist early. Our results suggest that this silencing-independent chromosomal memory has important implications for the maintenance of X inactivation, where previously self-perpetuating heterochromatin structures were viewed as the principal form of memory.

  17. Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

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    Norwood Thomas H

    2006-07-01

    Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

  18. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Watson, J.M.; Spencer, J.A.; Graves, J.A.M. (La Trobe Univ., Bundoora, Victoria (Australia)); Riggs, A.D. (Beckman Inst., Duarte, CA (USA))

    1990-09-01

    Eight genes, located on the long arm of the human X chromosome and present on the marsupial X chromosome, were mapped by in situ hybridization to the chromosomes of the platypus Ornithorhynchus anatinus, one of the three species of monotreme mammals. All were located on the X chromosome. The authors conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a mammalian ancestor at least 150 million years ago. Since three of these genes are located on the long arm of the platypus X chromosome, which is G-band homologous to the Y chromosome and apparently exempt from X chromosome inactivation, the conservation of this region has evidently not depended on isolation by X-Y chromosome differentiation and X chromosome inactivation.

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

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    Juan-Mateu Jonàs

    2012-10-01

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

  20. X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria.

    Science.gov (United States)

    Brancaleoni, V; Balwani, M; Granata, F; Graziadei, G; Missineo, P; Fiorentino, V; Fustinoni, S; Cappellini, M D; Naik, H; Desnick, R J; Di Pierro, E

    2016-01-01

    X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromosomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

  1. Enlightening the contribution of the dark matter to the X chromosome inactivation process in mammals.

    Science.gov (United States)

    Casanova, Miguel; Liyakat Ali, Tharvesh Moideen; Rougeulle, Claire

    2016-08-01

    X-chromosome inactivation (XCI) in mammals represents an exceptional example of transcriptional co-regulation occurring at the level of an entire chromosome. XCI is considered as a means to compensate for gene dosage imbalance between sexes, yet the largest part of the chromosome is composed of repeated elements of different nature and origins. Here we consider XCI from a repeat point of view, interrogating the mechanisms for inactivating X chromosome-derived repeated sequences and discussing the contribution of repetitive elements to the silencing process itself and to its evolution. PMID:27174438

  2. Mutual inactivation of Notch receptors and ligands facilitates developmental patterning.

    Directory of Open Access Journals (Sweden)

    David Sprinzak

    2011-06-01

    Full Text Available Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells. Recent work has shown that Notch and Delta, the canonical metazoan juxtacrine signaling receptor and ligand, mutually inactivate each other in the same cell. This cis-interaction generates mutually exclusive sending and receiving states in individual cells. It generally remains unclear, however, how this mutual inactivation and the resulting switching behavior can impact developmental patterning circuits. Here we address this question using mathematical modeling in the context of two canonical pattern formation processes: boundary formation and lateral inhibition. For boundary formation, in a model motivated by Drosophila wing vein patterning, we find that mutual inactivation allows sharp boundary formation across a broader range of parameters than models lacking mutual inactivation. This model with mutual inactivation also exhibits robustness to correlated gene expression perturbations. For lateral inhibition, we find that mutual inactivation speeds up patterning dynamics, relieves the need for cooperative regulatory interactions, and expands the range of parameter values that permit pattern formation, compared to canonical models. Furthermore, mutual inactivation enables a simple lateral inhibition circuit architecture which requires only a single downstream regulatory step. Both model systems show how mutual inactivation can facilitate robust fine-grained patterning processes that would be difficult to implement without it, by encoding a difference-promoting feedback within the signaling system itself. Together, these results provide a framework for analysis of more complex Notch-dependent developmental systems.

  3. Imprinted X chromosome inactivation: evolution of mechanisms in distantly related mammals

    OpenAIRE

    Waters, Shafagh A.; Waters, Paul D.

    2015-01-01

    In females, X chromosome inactivation (XCI) ensures transcriptional silencing of one of the two Xs (either in a random or imprinted fashion) in somatic cells. Comparing this silencing between species has offered insight into different mechanisms of X inactivation, providing clues into the evolution of this epigenetic process in mammals. Long-noncoding RNAs have emerged as a common theme in XCI of therian mammals (eutherian and marsupial). Eutherian X inactivation is regulated by the noncoding...

  4. A Tth111I RFLP in intron 1 of the mouse Pgk-1 gene allows tracing of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Shanmugan, V.; Saha, B.K. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1994-09-01

    The X-linked immunodeficiency (xid) in CBA/N mice serves as a model for the X-linked agammaglobulinemia (XLA) syndrome in humans. Like the XLA carriers, the female mice heterozygous for xid (X{sup xid}/X{sup W}) are asymptomatic. The pattern of X chromosome inactivation in the F1 heterozygotes [CBA/N (X{sup xid}/X{sup xid}) X CAST/Ei (X{sup W}/Y)] was investigated by monitoring the methylation status of the two Pgk-1 alleles. Methylation of a CpG dinucleotide in the 5{prime} region of the Pgk-1 gene was previously shown to absolutely correlate with the inactivation of the corresponding X chromosome. In order to distinguish the two alleles, the proximal end of intron 1 of the Pgk-1 gene from CBA/N and CAST/Ei was sequenced. Several nucleotide polymorphisms, including a Tth111I RFLP, were detected in close proximity of the critical CpG dinucleotide. This allowed us to devise an assay based on PCR-amplification of a target DNA encompassing the CpG site as well as the Tth111I site. Results indicate that in circulating B lymphocytes of the female heterozygote only the X-chromosome carrying the normal allele is active (non-random inactivation of the X chromosome) whereas in non-B cells both the X chromosomes are active (random inactivation of the X chromosome). These results were further confirmed by direct measurement of transcription of the two alleles (X{sup xid} and X{sup W}).

  5. Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Oestavik, R.E.; Eiklid, K.; Oerstavik, K.H. [Ulleval Univ. Hospital, Oslo (Norway)] [and others

    1995-03-27

    Wiedemann-Beckwith syndrome (WBS) is a syndrome including exomphalos, macroglossia, and generalized overgrowth. The locus has been assigned to 11p15, and genomic imprinting may play a part in the expression of one or more genes involved. Most cases are sporadic. An excess of female monozygotic twins discordant for WBS have been reported, and it has been proposed that this excess could be related to the process of X chromosome inactivation. We have therefore studied X chromosome inactivation in 13-year-old monozygotic twin girls who were discordant for WBS. In addition, both twins had Tourette syndrome. The twins were monochorionic and therefore the result of a late twinning process. This has also been the case in previously reported discordant twin pairs with information on placentation. X chromosome inactivation was determined in DNA from peripheral blood cells by PCR analysis at the androgen receptor locus. The affected twin had a completely skewed X inactivation, where the paternal allele was on the active X chromosome in all cells. The unaffected twin had a moderately skewed X inactivation in the same direction, whereas the mother had a random pattern. Further studies are necessary to establish a possible association between the expression of WBS and X chromosome inactivation. 18 refs., 2 figs., 1 tab.

  6. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    International Nuclear Information System (INIS)

    A pericentric inversion of human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 → Xqter and a deletion of Xp22.3 → Xpter and was interpreted to be Xqter → Xq26.3::Xp22.3 → Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 → qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state

  7. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.; Geller, R.L.; Yen, P.H.; Rosendorff, J.; Bernstein, R.; Yoshida, A.; Shapiro, L.J.

    1987-07-01

    A pericentric inversion of human X chromosome and a recombinant X chromosome (rec(X)) derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 ..-->.. Xqter and a deletion of Xp22.3 ..-->.. Xpter and was interpreted to be Xqter ..-->.. Xq26.3::Xp22.3 ..-->.. Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 ..-->.. qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state.

  8. Independent evolution of transcriptional inactivation on sex chromosomes in birds and mammals.

    Directory of Open Access Journals (Sweden)

    Alexandra M Livernois

    Full Text Available X chromosome inactivation in eutherian mammals has been thought to be tightly controlled, as expected from a mechanism that compensates for the different dosage of X-borne genes in XX females and XY males. However, many X genes escape inactivation in humans, inactivation of the X in marsupials is partial, and the unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific inactivation of X-linked genes. The bird ZW sex chromosome system represents a third independently evolved amniote sex chromosome system with dosage compensation, albeit partial and gene-specific, via an unknown mechanism (i.e. upregulation of the single Z in females, down regulation of one or both Zs in males, or a combination. We used RNA-fluorescent in situ hybridization (RNA-FISH to demonstrate, on individual fibroblast cells, inactivation of 11 genes on the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the homogametic sex. Our results indicate that the probability of inactivation is controlled on a gene-by-gene basis (or small domains on the chicken Z and platypus X chromosomes. This regulatory mechanism must have been exapted independently to the non-homologous sex chromosomes in birds and mammals in response to an over-expressed Z or X in the homogametic sex, highlighting the universal importance that (at least partial silencing plays in the evolution on amniote dosage compensation and, therefore, the differentiation of sex chromosomes.

  9. Independent evolution of transcriptional inactivation on sex chromosomes in birds and mammals.

    Science.gov (United States)

    Livernois, Alexandra M; Waters, Shafagh A; Deakin, Janine E; Marshall Graves, Jennifer A; Waters, Paul D

    2013-01-01

    X chromosome inactivation in eutherian mammals has been thought to be tightly controlled, as expected from a mechanism that compensates for the different dosage of X-borne genes in XX females and XY males. However, many X genes escape inactivation in humans, inactivation of the X in marsupials is partial, and the unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific inactivation of X-linked genes. The bird ZW sex chromosome system represents a third independently evolved amniote sex chromosome system with dosage compensation, albeit partial and gene-specific, via an unknown mechanism (i.e. upregulation of the single Z in females, down regulation of one or both Zs in males, or a combination). We used RNA-fluorescent in situ hybridization (RNA-FISH) to demonstrate, on individual fibroblast cells, inactivation of 11 genes on the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the homogametic sex. Our results indicate that the probability of inactivation is controlled on a gene-by-gene basis (or small domains) on the chicken Z and platypus X chromosomes. This regulatory mechanism must have been exapted independently to the non-homologous sex chromosomes in birds and mammals in response to an over-expressed Z or X in the homogametic sex, highlighting the universal importance that (at least partial) silencing plays in the evolution on amniote dosage compensation and, therefore, the differentiation of sex chromosomes. PMID:23874231

  10. Chromosome banding and DNA replication patterns in bird karyotypes.

    Science.gov (United States)

    Schmid, M; Enderle, E; Schindler, D; Schempp, W

    1989-01-01

    The karyotypes of the domestic chicken (Gallus domesticus), Japanese quail (Coturnix coturnix), and griffon vulture (Gyps fulvus) were studied with a variety of banding techniques. The DNA replication patterns of bird chromosomes, analyzed by incorporation of 5-bromodeoxyuridine (BrdU) and deoxythymidine (dT), are presented here for the first time. In particular, the time sequence of replication of the ZZ/ZW sex chromosomes throughout the S-phase was meticulously analyzed. BrdU and dT incorporation are very useful methods to identify homoeologies between karyotypes, as well as rearrangements that occurred in the macroautosomes during speciation. The Z chromosomes of the three birds displayed the same replication patterns, indicating a high degree of evolutionary conservation. In the homogametic male, BrdU and dT incorporation revealed no evidence of asynchronous replication between euchromatic bands in the ZZ pair. The same was true of the three Z chromosomes in a triploid-diploid chimeric chicken embryo. Minor replication asynchronies between the homologous ZZ or ZZZ chromosomes were restricted to heterochromatic C-bands. These results confirm that, in the ZZ male/ZW female sex-determining system of birds, dosage compensation for Z-linked genes does not occur by inactivation of one of the two Z chromosomes in the homogametic male. The heterochromatic W chromosomes of the three species showed bright labeling with distamycin A/mithramycin counterstain-enhanced fluorescence and exhibited significantly delayed DNA replication. The nucleolus organizers of birds, frequently located in microchromosomes, were also distinguished by bright distamycin A/mithramycin fluorescence. PMID:2630186

  11. Chromosome differentiation patterns during cichlid fish evolution

    Directory of Open Access Journals (Sweden)

    Nirchio Mauro

    2010-06-01

    Full Text Available Abstract Background Cichlid fishes have been the subject of increasing scientific interest because of their rapid adaptive radiation which has led to an extensive ecological diversity and their enormous importance to tropical and subtropical aquaculture. To increase our understanding of chromosome evolution among cichlid species, karyotypes of one Asian, 22 African, and 30 South American cichlid species were investigated, and chromosomal data of the family was reviewed. Results Although there is extensive variation in the karyotypes of cichlid fishes (from 2n = 32 to 2n = 60 chromosomes, the modal chromosome number for South American species was 2n = 48 and the modal number for the African ones was 2n = 44. The only Asian species analyzed, Etroplus maculatus, was observed to have 46 chromosomes. The presence of one or two macro B chromosomes was detected in two African species. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene revealed a variable number of clusters among species varying from two to six. Conclusions The karyotype diversification of cichlids seems to have occurred through several chromosomal rearrangements involving fissions, fusions and inversions. It was possible to identify karyotype markers for the subfamilies Pseudocrenilabrinae (African and Cichlinae (American. The karyotype analyses did not clarify the phylogenetic relationship among the Cichlinae tribes. On the other hand, the two major groups of Pseudocrenilabrinae (tilapiine and haplochromine were clearly discriminated based on the characteristics of their karyotypes. The cytogenetic mapping of 18S ribosomal RNA (18S rRNA gene did not follow the chromosome diversification in the family. The dynamic evolution of the repeated units of rRNA genes generates patterns of chromosomal distribution that do not help follows the phylogenetic relationships among taxa. The presence of B chromosomes in cichlids is of particular interest because they may not be represented in

  12. Function and evolution of the long noncoding RNA circuitry orchestrating X-chromosome inactivation in mammals.

    Science.gov (United States)

    Furlan, Giulia; Rougeulle, Claire

    2016-09-01

    X-chromosome inactivation (XCI) is a chromosome-wide regulatory process that ensures dosage compensation for X-linked genes in Theria. XCI is established during early embryogenesis and is developmentally regulated. Different XCI strategies exist in mammalian infraclasses and the regulation of this process varies also among closely related species. In Eutheria, initiation of XCI is orchestrated by a cis-acting locus, the X-inactivation center (Xic), which is particularly enriched in genes producing long noncoding RNAs (lncRNAs). Among these, Xist generates a master transcript that coats and propagates along the future inactive X-chromosome in cis, establishing X-chromosome wide transcriptional repression through interaction with several protein partners. Other lncRNAs also participate to the regulation of X-inactivation but the extent to which their function has been maintained in evolution is still poorly understood. In Metatheria, Xist is not conserved, but another, evolutionary independent lncRNA with similar properties, Rsx, has been identified, suggesting that lncRNA-mediated XCI represents an evolutionary advantage. Here, we review current knowledge on the interplay of X chromosome-encoded lncRNAs in ensuring proper establishment and maintenance of chromosome-wide silencing, and discuss the evolutionary implications of the emergence of species-specific lncRNAs in the control of XCI within Theria. WIREs RNA 2016, 7:702-722. doi: 10.1002/wrna.1359 For further resources related to this article, please visit the WIREs website. PMID:27173581

  13. X-chromosome inactivation in Rett Syndrome human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Aaron YL Cheung

    2012-03-01

    Full Text Available Rett Syndrome (RTT is a neurodevelopmental disorder that affects girls due primarily to heterozygous mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2. Random X-chromosome inactivation (XCI results in cellular mosaicism in which some cells express wild-type MECP2 while other cells express mutant MECP2. The generation of patient-specific human induced Pluripotent Stem cells (hiPSCs facilitates the production of RTT-hiPSC-derived neurons in vitro to investigate disease mechanisms and identify novel drug treatments. The generation of RTT-hiPSCs has been reported by many laboratories, however, the XCI status of RTT-hiPSCs has been inconsistent. Some report RTT-hiPSCs retain the inactive X-chromosome (post-XCI of the founder somatic cell allowing isogenic RTT-hiPSCs that express only the wild-type or mutant MECP2 allele to be isolated from the same patient. Post-XCI RTT-hiPSCs-derived neurons retain this allele-specific expression pattern of wild-type or mutant MECP2. Conversely, others report RTT-hiPSCs in which the inactive X-chromosome of the founder somatic cell reactivates (pre-XCI upon reprogramming into RTT-hiPSCs. Pre-XCI RTT-hiPSC-derived neurons exhibit random XCI resulting in cellular mosaicism with respect to wild-type and mutant MECP2 expression. Here we review and attempt to interpret the inconsistencies in XCI status of RTT-hiPSCs generated to date by comparison to other pluripotent systems in vitro and in vivo and the methods used to analyze XCI. Finally, we discuss the relative strengths and weaknesses of post- and pre-XCI hiPSCs in the context of RTT, and other X-linked and autosomal disorders for translational medicine.

  14. Effects of LET, fluence and particle energy on inactivation, chromosomal aberrations and DNA strand breaks

    International Nuclear Information System (INIS)

    Experiments are described studying the inactivation and the induction of chromosomal aberrations in mammalian cells. In addition, experiments of the induction of single and double strand breaks of DNA in mammalian cells will be compared to the induction of single and double strand breaks of DNA in solution. (orig./MG)

  15. Chromosomal gene inactivation in the green sulfur bacterium Chlorobium tepidum by natural transformation

    DEFF Research Database (Denmark)

    Frigaard, N-U; Bryant, D A

    2001-01-01

    Conditions for inactivating chromosomal genes of Chlorobium tepidum by natural transformation and homologous recombination were established. As a model, mutants unable to perform nitrogen fixation were constructed by interrupting nifD with various antibiotic resistance markers. Growth of wild-typ...

  16. Transcriptional changes in response to X chromosome dosage in the mouse: implications for X inactivation and the molecular basis of Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Sargent Carole A

    2010-02-01

    Full Text Available Abstract Background X monosomic mice (39,XO have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO. The generally accepted hypothesis to explain this discrepancy is that the number of genes on the mouse X chromosome which escape X inactivation, and thus are expressed at higher levels in females, is very small. However this hypothesis has never been tested and only a small number of genes have been assayed for their X-inactivation status in the mouse. We performed a global expression analysis in four somatic tissues (brain, liver, kidney and muscle of adult 40,XX and 39,XO mice using the Illumina Mouse WG-6 v1_1 Expression BeadChip and an extensive validation by quantitative real time PCR, in order to identify which genes are expressed from both X chromosomes. Results We identified several genes on the X chromosome which are overexpressed in XX females, including those previously reported as escaping X inactivation, as well as new candidates. However, the results obtained by microarray and qPCR were not fully concordant, illustrating the difficulty in ascertaining modest fold changes, such as those expected for genes escaping X inactivation. Remarkably, considerable variation was observed between tissues, suggesting that inactivation patterns may be tissue-dependent. Our analysis also exposed several autosomal genes involved in mitochondrial metabolism and in protein translation which are differentially expressed between XX and XO mice, revealing secondary transcriptional changes to the alteration in X chromosome dosage. Conclusions Our results support the prediction that the mouse inactive X chromosome is largely silent, while providing a list of the genes potentially escaping X inactivation in rodents. Although the lower expression of X-linked genes in XO mice may not be relevant in the particular tissues/systems which are affected in human X chromosome monosomy, genes deregulated in XO mice are good candidates for

  17. Extreme skewing of X chromosome inactivation in mothers of homosexual men.

    Science.gov (United States)

    Bocklandt, Sven; Horvath, Steve; Vilain, Eric; Hamer, Dean H

    2006-02-01

    Human sexual preference is a sexually dimorphic trait with a substantial genetic component. Linkage of male sexual orientation to markers on the X chromosome has been reported in some families. Here, we measured X chromosome inactivation ratios in 97 mothers of homosexual men and 103 age-matched control women without gay sons. The number of women with extreme skewing of X-inactivation was significantly higher in mothers of gay men (13/97=13%) compared to controls (4/103=4%) and increased in mothers with two or more gay sons (10/44=23%). Our findings support a role for the X chromosome in regulating sexual orientation in a subgroup of gay men. PMID:16369763

  18. Lack of global meiotic sex chromosome inactivation, and paucity of tissue-specific gene expression on the Drosophila X chromosome

    Directory of Open Access Journals (Sweden)

    Nurminsky Dmitry I

    2011-05-01

    Full Text Available Abstract Background Paucity of male-biased genes on the Drosophila X chromosome is a well-established phenomenon, thought to be specifically linked to the role of these genes in reproduction and/or their expression in the meiotic male germline. In particular, meiotic sex chromosome inactivation (MSCI has been widely considered a driving force behind depletion of spermatocyte-biased X-linked genes in Drosophila by analogy with mammals, even though the existence of global MCSI in Drosophila has not been proven. Results Microarray-based study and qRT-PCR analyses show that the dynamics of gene expression during testis development are very similar between X-linked and autosomal genes, with both showing transcriptional activation concomitant with meiosis. However, the genes showing at least ten-fold expression bias toward testis are significantly underrepresented on the X chromosome. Intriguingly, the genes with similar expression bias toward tissues other than testis, even those not apparently associated with reproduction, are also strongly underrepresented on the X. Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes. Conclusions Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila. Paucity of testis-biased genes on the X appears not to be linked to reproduction or germline-specific events, but rather reflects a general underrepresentation of tissue-biased genes on this chromosome. Our analyses suggest that the activation/repression switch mechanisms that probably orchestrate the highly-biased expression of tissue-specific genes are generally not efficient on the X chromosome. This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

  19. Imprinted X chromosome inactivation: evolution of mechanisms in distantly related mammals

    Directory of Open Access Journals (Sweden)

    Shafagh A. Waters

    2015-03-01

    Full Text Available In females, X chromosome inactivation (XCI ensures transcriptional silencing of one of the two Xs (either in a random or imprinted fashion in somatic cells. Comparing this silencing between species has offered insight into different mechanisms of X inactivation, providing clues into the evolution of this epigenetic process in mammals. Long-noncoding RNAs have emerged as a common theme in XCI of therian mammals (eutherian and marsupial. Eutherian X inactivation is regulated by the noncoding RNA product of XIST, within a cis-acting master control region called the X inactivation center (XIC. Marsupials XCI is XIST independent. Instead, XCI is controlled by the long-noncoding RNA Rsx, which appears to be a functional analog of the eutherian XIST gene, insofar that its transcript coats the inactive X and represses activity of genes in cis. In this review we discuss XCI in eutherians, and contrast imprinted X inactivation in mouse and marsupials. We provide particular focus on the evolution of genomic elements that confer the unique epigenetic features that characterize the inactive X chromosome.

  20. The evolution of X chromosome inactivation in mammals: the demise of Ohno's hypothesis?

    Science.gov (United States)

    Pessia, Eugénie; Engelstädter, Jan; Marais, Gabriel A B

    2014-04-01

    Ohno's hypothesis states that dosage compensation in mammals evolved in two steps: a twofold hyperactivation of the X chromosome in both sexes to compensate for gene losses on the Y chromosome, and silencing of one X (X-chromosome inactivation, XCI) in females to restore optimal dosage. Recent tests of this hypothesis have returned contradictory results. In this review, we explain this ongoing controversy and argue that a novel view on dosage compensation evolution in mammals is starting to emerge. Ohno's hypothesis may be true for a few, dosage-sensitive genes only. If so few genes are compensated, then why has XCI evolved as a chromosome-wide mechanism? This and several other questions raised by the new data in mammals are discussed, and future research directions are proposed. PMID:24173285

  1. Reduced risk of synovial sarcoma in females: X-chromosome inactivation?

    OpenAIRE

    Bu, X; Bernstein, L; Brynes, R. K.

    2002-01-01

    Synovial sarcoma shows a characteristic t(X;18) translocation but not the expected female predominance in incidence. We speculate that, among females, one X-chromosome is inactivated and that only the translocation to an active X-chromosome leads to development of synovial sarcoma. Population-based cancer registry data from the SEER program support this hypothesis. British Journal of Cancer (2002) 87, 28–30. doi:10.1038/sj.bjc.6600362 www.bjcancer.com © 2002 Cancer Research UK

  2. X Chromosome Inactivation and Xist Evolution in a Rodent Lacking LINE-1 Activity

    Science.gov (United States)

    Cantrell, Michael A.; Carstens, Bryan C.; Wichman, Holly A.

    2009-01-01

    Dosage compensation in eutherian mammals occurs by inactivation of one X chromosome in females. Silencing of that X chromosome is initiated by Xist, a large non-coding RNA, whose coating of the chromosome extends in cis from the X inactivation center. LINE-1 (L1) retrotransposons have been implicated as possible players for propagation of the Xist signal, but it has remained unclear whether they are essential components. We previously identified a group of South American rodents in which L1 retrotransposition ceased over 8 million years ago and have now determined that at least one species of these rodents, Oryzomys palustris, still retains X inactivation. We have also isolated and analyzed the majority of the Xist RNA from O. palustris and a sister species retaining L1 activity, Sigmodon hispidus, to determine if evolution in these sequences has left signatures that might suggest a critical role for L1 elements in Xist function. Comparison of rates of Xist evolution in the two species fails to support L1 involvement, although other explanations are possible. Similarly, comparison of known repeats and potential RNA secondary structures reveals no major differences with the exception of a new repeat in O. palustris that has potential to form new secondary structures. PMID:19603076

  3. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

    OpenAIRE

    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Neal D Freedman; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X ...

  4. Bioburden assessment and gamma radiation inactivation patterns in parchment documents

    International Nuclear Information System (INIS)

    Parchment documents are part of our cultural heritage and, as historical artifacts that they are, should be preserved. The aim of this study was to validate an appropriate methodology to characterize the bioburden of parchment documents, and to assess the growth and gamma radiation inactivation patterns of the microbiota present in that material. Another goal was to estimate the minimum gamma radiation dose (Dmin) to be applied for the decontamination of parchment as an alternative treatment to the current toxic chemical and non-chemical decontamination methods. Two bioburden assessment methodologies were evaluated: the Swab Method (SM) and the Destructive Method (DM). The recovery efficiency of each method was estimated by artificial contamination, using a Cladosporium cladosporioides spore suspension. The parchment samples' microbiota was typified using morphological methods and the fungal isolates were identified by ITS-DNA sequencing. The inactivation pattern was assessed using the DM after exposure to different gamma radiation doses, and using C. cladosporioides as reference. Based on the applied methodology, parchment samples presented bioburden values lower than 5×103 CFU/cm2 for total microbiota, and lower than 10 CFU/cm2 for fungal propagules. The results suggest no evident inactivation trend for the natural parchment microbiota, especially regarding the fungal community. A minimum gamma radiation dose (Dmin) of 5 kGy is proposed for the decontamination treatment of parchment. Determining the minimal decontamination dose in parchment is essential for a correct application of gamma radiation as an alternative decontamination treatment for this type of documents avoiding the toxicity and the degradation promoted by the traditional chemical and non-chemical treatments. - Highlights: • Characterization of the microbial population of parchment documents. • Study the inactivation pattern of parchment microbiota by gamma radiation. • Assessment of the

  5. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

    Science.gov (United States)

    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

  6. No severe and global X chromosome inactivation in meiotic male germline of Drosophila

    Directory of Open Access Journals (Sweden)

    Mikhaylova Lyudmila M

    2012-06-01

    Full Text Available Abstract This article is a response to Vibranovski et al. See correspondence article http://www.biomedcentral.com/1741-7007/10/49 and the original research article http://www.biomedcentral.com/1741-7007/9/29 We have previously reported a high propensity of testis-expressed X-linked genes to activation in meiotic cells, a similarity in global gene expression between the X chromosome and autosomes in meiotic germline, and under-representation of various types of tissue-specific genes on the X chromosome. Based on our findings and a critical review of the current literature, we believe that there is no global and severe silencing of the X chromosome in the meiotic male germline of Drosophila. The term 'meiotic sex chromosome inactivation' (MSCI therefore seems misleading when used to describe the minor underexpression of the X chromosome in the testis of Drosophila, because this term erroneously implies a profound and widespread silencing of the X-linked genes, by analogy to the well-studied MSCI system in mammals, and therefore distracts from identification and analysis of the real mechanisms that orchestrate gene expression and evolution in this species.

  7. Epigenetic Pattern on the Human Y Chromosome Is Evolutionarily Conserved.

    Science.gov (United States)

    Zhang, Minjie; Wang, Chuan-Chao; Yang, Caiyun; Meng, Hao; Agbagwa, Ikechukwu O; Wang, Ling-Xiang; Wang, Yingzhi; Yan, Shi; Ren, Shancheng; Sun, Yinghao; Pei, Gang; Liu, Xin; Liu, Jiang; Jin, Li; Li, Hui; Sun, Yingli

    2016-01-01

    DNA methylation plays an important role for mammalian development. However, it is unclear whether the DNA methylation pattern is evolutionarily conserved. The Y chromosome serves as a powerful tool for the study of human evolution because it is transferred between males. In this study, based on deep-rooted pedigrees and the latest Y chromosome phylogenetic tree, we performed epigenetic pattern analysis of the Y chromosome from 72 donors. By comparing their respective DNA methylation level, we found that the DNA methylation pattern on the Y chromosome was stable among family members and haplogroups. Interestingly, two haplogroup-specific methylation sites were found, which were both genotype-dependent. Moreover, the African and Asian samples also had similar DNA methylation pattern with a remote divergence time. Our findings indicated that the DNA methylation pattern on the Y chromosome was conservative during human male history. PMID:26760298

  8. Bioburden assessment and gamma radiation inactivation patterns in parchment documents

    Science.gov (United States)

    Nunes, Inês; Mesquita, Nuno; Cabo Verde, Sandra; Carolino, Maria Manuela; Portugal, António; Botelho, Maria Luísa

    2013-07-01

    Parchment documents are part of our cultural heritage and, as historical artifacts that they are, should be preserved. The aim of this study was to validate an appropriate methodology to characterize the bioburden of parchment documents, and to assess the growth and gamma radiation inactivation patterns of the microbiota present in that material. Another goal was to estimate the minimum gamma radiation dose (Dmin) to be applied for the decontamination of parchment as an alternative treatment to the current toxic chemical and non-chemical decontamination methods. Two bioburden assessment methodologies were evaluated: the Swab Method (SM) and the Destructive Method (DM). The recovery efficiency of each method was estimated by artificial contamination, using a Cladosporium cladosporioides spore suspension. The parchment samples' microbiota was typified using morphological methods and the fungal isolates were identified by ITS-DNA sequencing. The inactivation pattern was assessed using the DM after exposure to different gamma radiation doses, and using C. cladosporioides as reference. Based on the applied methodology, parchment samples presented bioburden values lower than 5×103 CFU/cm2 for total microbiota, and lower than 10 CFU/cm2 for fungal propagules. The results suggest no evident inactivation trend for the natural parchment microbiota, especially regarding the fungal community. A minimum gamma radiation dose (Dmin) of 5 kGy is proposed for the decontamination treatment of parchment. Determining the minimal decontamination dose in parchment is essential for a correct application of gamma radiation as an alternative decontamination treatment for this type of documents avoiding the toxicity and the degradation promoted by the traditional chemical and non-chemical treatments.

  9. Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosomes is not involved in Rett syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; Dunn, M.A.; Schmeckpeper, B.J.; Naidu, S. [Johns Hophins Univ., Baltimore, MD (United States); Thomas, G. [Johns Hopkins Univ., Baltimore, MD (United States)]|[Kennedy-Kreiger Institute, Baltimore, MD (United States)

    1995-03-01

    Rett syndrome (RS), a progressive encephalopathy with onset in infancy, has been attributed to an X-linked mutation, mainly on the basis of its occurrence almost exclusively in females and its concordance in female MZ twins. The underlying mechanisms proposed are an X-linked dominant mutation with male lethality, uniparental disomy of the X chromosome, and/or some disturbance in the process of X inactivation leading to unequal distribution of cells expressing maternal or paternal alleles (referred to as a {open_quotes}nonrandom{close_quotes} or {open_quotes}skewed {close_quotes} inactivation). To determine if the X chromosome is in fact involved in RS, we studied a group of affected females including three pairs of MZ twins, two concordant for RS and one uniquely discordant for RS. Analysis of X-inactivation patterns confirms the frequent nonrandom X inactivation previously observed in MZ twins but indicates that this is independent of RS. Analysis of 29 RS females reveals not one instance of uniparental X disomy, extending the observations previously reported. Therefore, our findings contribute no support for the hypothesis that RS is an X-linked disorder. Furthermore, the concordant phenotype in most MZ females twins with RS, which has not been observed in female twins with known X-linked mutations, argues against an X mutation. 41 refs., 2 figs.

  10. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Allen, R.C.; Zoghbi, H.Y.; Moseley, A.B.; Rosenblatt, H.M.; Belmont, J.W. (Baylor College of Medicine, Houston (United States))

    1992-12-01

    The human androgen-receptor gene (HUMARA; GenBank) contains a highly polymorphic trinucleotide repeat in the first exon. The authors have found that the methylation of HpaII and HhaI sites less than 100 pb away from this polymorphic short tandem repeat (STR) correlates with X inactivation. The close proximity of the restriction-enzyme sites to the STR allows the development of a PCR assay that distinguishes between the maternal and paternal alleles and identifies their methylation status. The accuracy of this assay was tested on (a) DNA from hamster/human hybrid cell lines containing either an active or inactive human X chromosome; (b) DNA from normal males and females; and (c) DNA from females showing nonrandom patterns of X inactivation. Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27[beta] probes, which detect X inactivation patterns by Southern blot analysis. In order to demonstrate one application of this assay, the authors examined X inactivation patterns in the B lymphocytes of potential and obligate carriers of X-linked agammaglobulinemia. 42 refs., 5 figs., 1 tab.

  11. The probability to initiate X chromosome inactivation is determined by the X to autosomal ratio and X chromosome specific allelic properties.

    Directory of Open Access Journals (Sweden)

    Kim Monkhorst

    Full Text Available In female mammalian cells, random X chromosome inactivation (XCI equalizes the dosage of X-encoded gene products to that in male cells. XCI is a stochastic process, in which each X chromosome has a probability to be inactivated. To obtain more insight in the factors setting up this probability, we studied the role of the X to autosome (X ratio A ratio in initiation of XCI, and have used the experimental data in a computer simulation model to study the cellular population dynamics of XCI.To obtain more insight in the role of the XratioA ratio in initiation of XCI, we generated triploid mouse ES cells by fusion of haploid round spermatids with diploid female and male ES cells. These fusion experiments resulted in only XXY triploid ES cells. XYY and XXX ES lines were absent, suggesting cell death related either to insufficient X-chromosomal gene dosage (XYY or to inheritance of an epigenetically modified X chromosome (XXX. Analysis of active (Xa and inactive (Xi X chromosomes in the obtained triploid XXY lines indicated that the initiation frequency of XCI is low, resulting in a mixed population of XaXiY and XaXaY cells, in which the XaXiY cells have a small proliferative advantage. This result, and findings on XCI in diploid and tetraploid ES cell lines with different X ratio A ratios, provides evidence that the X ratio A ratio determines the probability for a given X chromosome to be inactivated. Furthermore, we found that the kinetics of the XCI process can be simulated using a probability for an X chromosome to be inactivated that is proportional to the X ratio A ratio. These simulation studies re-emphasize our hypothesis that the probability is a function of the concentration of an X-encoded activator of XCI, and of X chromosome specific allelic properties determining the threshold for this activator.The present findings reveal that the probability for an X chromosome to be inactivated is proportional to the X ratio A ratio. This finding

  12. DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation.

    OpenAIRE

    Kaslow, D.C.; Migeon, B R

    1987-01-01

    In marsupials and eutherian mammals, X chromosome dosage compensation is achieved by inactivating one X chromosome in female cells; however, in marsupials, the inactive X chromosomes is always paternal, and some genes on the chromosome are partially expressed. To define the role of DNA methylation in maintenance of X chromosome inactivity, we examined loci for glucose-6-phosphate dehydrogenase and hypoxanthine phosphoribosyltransferase in a North American marsupial, the opossum Didelphis virg...

  13. The Role of X-Chromosome Inactivation in Retinal Development and Disease

    Science.gov (United States)

    Fahim, Abigail T.; Daiger, Stephen P.

    2016-01-01

    The expression of X-linked genes is equalized between males and females in mammalian species through X-Chromosome inactivation (XCI). Every cell in a female mammalian embryo randomly chooses one X Chromosome for epigenetic silencing at the 8–16 cell stage, resulting in a Gaussian distribution of XCI ratios with a peak at 50:50. At the tail extremes of this distribution, X-linked recessive mutations can manifest in disease in female carriers if the mutant allele is disproportionately active. The role of XCI skewing, if any, in X-linked retinal disease is still unknown, although many have speculated that such skewing accounts for phenotypic variation in female carriers of X-linked retinitis pigmentosa (XlRP). Some investigators have used clinical findings such as tapetal-like reflex, pigmentary changes, and multifocal ERG parameters to approximate XCI patches in the retina. These studies are limited by small cohorts and the relative inaccessibility of retinal tissue for genetic and epigenetic analysis. Although blood has been used as a proxy for other tissues in determining XCI ratios, blood XCI skews with age out of proportion to other tissues and may not accurately reflect retinal XCI ratios. Future investigations in determining retinal XCI ratios and the contribution of XCI to phenotype could potentially impact prognosis for female carriers of X-linked retinal disease. PMID:26427428

  14. Pattern of Chromosomal Aberrations in Patients from North East Iran

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey

    2013-01-01

    Full Text Available Objective: Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques.Materials and Methods: In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities.Results: The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS was the most prevalent autosomal aberration in the patients (77.1%. Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA. Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner’s syndrome and 33.5% had Klinefelter’s syndrome.Conclusion: According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  15. Determining the role of skewed X-chromosome inactivation in developing muscle symptoms in carriers of Duchenne muscular dystrophy.

    Science.gov (United States)

    Viggiano, Emanuela; Ergoli, Manuela; Picillo, Esther; Politano, Luisa

    2016-07-01

    Duchenne and Becker dystrophinopathies (DMD and BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene that lead to absent or reduced expression of dystrophin in both skeletal and heart muscles. DMD/BMD female carriers are usually asymptomatic, although about 8 % may exhibit muscle or cardiac symptoms. Several mechanisms leading to a reduced dystrophin have been hypothesized to explain the clinical manifestations and, in particular, the role of the skewed XCI is questioned. In this review, the mechanism of XCI and its involvement in the phenotype of BMD/DMD carriers with both a normal karyotype or with X;autosome translocations with breakpoints at Xp21 (locus of the DMD gene) will be analyzed. We have previously observed that DMD carriers with moderate/severe muscle involvement, exhibit a moderate or extremely skewed XCI, in particular if presenting with an early onset of symptoms, while DMD carriers with mild muscle involvement present a random XCI. Moreover, we found that among 87.1 % of the carriers with X;autosome translocations involving the locus Xp21 who developed signs and symptoms of dystrophinopathy such as proximal muscle weakness, difficulty to run, jump and climb stairs, 95.2 % had a skewed XCI pattern in lymphocytes. These data support the hypothesis that skewed XCI is involved in the onset of phenotype in DMD carriers, the X chromosome carrying the normal DMD gene being preferentially inactivated and leading to a moderate-severe muscle involvement. PMID:27098336

  16. Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization.

    Science.gov (United States)

    Tan, Kun; An, Lei; Miao, Kai; Ren, Likun; Hou, Zhuocheng; Tao, Li; Zhang, Zhenni; Wang, Xiaodong; Xia, Wei; Liu, Jinghao; Wang, Zhuqing; Xi, Guangyin; Gao, Shuai; Sui, Linlin; Zhu, De-Sheng; Wang, Shumin; Wu, Zhonghong; Bach, Ingolf; Chen, Dong-Bao; Tian, Jianhui

    2016-03-22

    Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression ofRnf12to up-regulateXistsignificantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulatedRnf12/Xistexpression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications. PMID:26951653

  17. Nuclear mRNA degradation pathway(s are implicated in Xist regulation and X chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Constance Ciaudo

    2006-06-01

    Full Text Available A critical step in X-chromosome inactivation (XCI, which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s are strongly downregulated, while the levels of unspliced form(s of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process.

  18. Variations of X chromosome inactivation occur in early passages of female human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Tamar Dvash

    Full Text Available X chromosome inactivation (XCI is a dosage compensation mechanism essential for embryonic development and cell physiology. Human embryonic stem cells (hESCs derived from inner cell mass (ICM of blastocyst stage embryos have been used as a model system to understand XCI initiation and maintenance. Previous studies of undifferentiated female hESCs at intermediate passages have shown three possible states of XCI; 1 cells in a pre-XCI state, 2 cells that already exhibit XCI, or 3 cells that never undergo XCI even upon differentiation. In this study, XCI status was assayed in ten female hESC lines between passage 5 and 15 to determine whether XCI variations occur in early passages of hESCs. Our results show that three different states of XCI already exist in the early passages of hESC. In addition, we observe one cell line with skewed XCI and preferential expression of X-linked genes from the paternal allele, while another cell line exhibits random XCI. Skewed XCI in undifferentiated hESCs may be due to clonal selection in culture instead of non-random XCI in ICM cells. We also found that XIST promoter methylation is correlated with silencing of XIST transcripts in early passages of hESCs, even in the pre-XCI state. In conclusion, XCI variations already take place in early passages of hESCs, which may be a consequence of in vitro culture selection during the derivation process. Nevertheless, we cannot rule out the possibility that XCI variations in hESCs may reflect heterogeneous XCI states in ICM cells that stochastically give rise to hESCs.

  19. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation.

    OpenAIRE

    Watson, J M; Spencer, J. A.; Riggs, A D; Graves, J.A.

    1990-01-01

    Eight genes, located on the long arm of the human X chromosome and present on the marsupial X chromosome, were mapped by in situ hybridization to the chromosomes of the platypus Ornithorhynchus anatinus, one of the three species of monotreme mammals. All were located on the X chromosome. We conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a mammalian ancestor at least 150 million years ago. Since three of these g...

  20. Horizontal transfer of DNA methylation patterns into bacterial chromosomes.

    Science.gov (United States)

    Shin, Jung-Eun; Lin, Chris; Lim, Han N

    2016-05-19

    Horizontal gene transfer (HGT) is the non-inherited acquisition of novel DNA sequences. HGT is common and important in bacteria because it enables the rapid generation of new phenotypes such as antibiotic resistance. Here we show that in vivo and in vitro DNA methylation patterns can be horizontally transferred into bacterial chromosomes to program cell phenotypes. The experiments were performed using a synthetic system in Escherichia coli where different DNA methylation patterns within the cis-regulatory sequence of the agn43 gene turn on or off a fluorescent reporter (CFP). With this system we demonstrated that DNA methylation patterns not only accompany the horizontal transfer of genes into the bacterial cytoplasm but can be transferred into chromosomes by: (i) bacteriophage P1 transduction; and (ii) transformation of extracellular synthetic DNA. We also modified the experimental system by replacing CFP with the SgrS small RNA, which regulates glucose and methyl α-D-glucoside uptake, and showed that horizontally acquired DNA methylation patterns can increase or decrease cell fitness. That is, horizontally acquired DNA methylation patterns can result in the selection for and against cells that have HGT. Findings from these proof-of-concept experiments have applications in synthetic biology and potentially broad implications for bacterial adaptation and evolution. PMID:27084942

  1. Persistent Increase in Chromosome Instability in Lung Cancer : Possible Indirect Involvement of p53 Inactivation

    OpenAIRE

    Haruki, Nobuhiro; Harano, Tomoko; Masuda, Akira; Kiyono, Tohru; TAKAHASHI, TAKAO; Tatematsu, Yoshio; Shimizu, Shigeki; Mitsudomi, Tetsuya; Konishi, Hiroyuki; Osada, Hirotaka; Fujii, Yoshitaka; Takahashi, Takashi

    2001-01-01

    Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that C...

  2. Patterns of Chromosomal Evolution in Sigmodon, Evidence from Whole Chromosome Paints

    Science.gov (United States)

    Swier, V.J.; Bradley, R.D.; Rens, W.; Elder, F.F.B.; Baker, R.J.

    2009-01-01

    Of the superfamily Muroidea (31 genera, 1578 species), the Sigmodontinae (74 genera, 377 species) is the second largest subfamily in number of species and represents a significant radiation of rodent biodiversity. Only 2 of the 74 genera are found in both North and South America (Sigmodon and Oryzomys) and the remainder are exclusively from South America. In recent molecular studies, the genus Sigmodon (Cricetidae, Sigmodontinae) has been considered sister to many other South American Sigmodontines [Steppan et al., 2004]. We examine the chromosomal evolution of 9 species of Sigmodon utilizing chromosomal paints isolated from S. hispidus, proposed to be similar to the ancestral karyotype [Elder, 1980]. Utilizing a phylogenetic hypothesis of a molecular phylogeny of Sigmodon [Henson and Bradley, 2009], we mapped shared chromosomal rearrangements of taxa on a molecular tree to estimate the evolutionary position of each rearrangement. For several species (S. hirsutus, S. leucotis, S. ochrognathus, S. peruanus, and S. toltecus), the karyotype accumulated few or no changes, but in three species (S. arizonae, S. fulviventer, and S. mascotensis) numerous karyotype rearrangements were observed. These rearrangements involved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as well as the addition of interstitial DNA not identified by chromosome paints or C-banding. The hypothesis that the ancestral karyotype for this complex had a diploid number of 52, a fundamental number of 52, and a G-band pattern of which most, if not all are similar to that present in modern day S. hispidus fails to be rejected. This hypothesis remains viable as an explanation of chromosomal evolution in Sigmodontine rodents. PMID:19617697

  3. LIN-41 inactivation leads to delayed centrosome elimination and abnormal chromosome behavior during female meiosis in Caenorhabditis elegans.

    Science.gov (United States)

    Matsuura, Rieko; Ashikawa, Tomoko; Nozaki, Yuka; Kitagawa, Daiju

    2016-03-01

    During oogenesis, two successive meiotic cell divisions occur without functional centrosomes because of the inactivation and subsequent elimination of maternal centrosomes during the diplotene stage of meiosis I. Despite being a conserved phenomenon in most metazoans, the means by which this centrosome behavior is controlled during female meiosis remain elusive. Here, we conducted a targeted RNAi screening in the Caenorhabditis elegans gonad to identify novel regulators of centrosome behavior during oogenesis. We screened 513 genes known to be essential for embryo production and directly visualized GFP-γ-tubulin to monitor centrosome behavior at all stages of oogenesis. In the screening, we found that RNAi-mediated inactivation of 33 genes delayed the elimination of GFP-γ-tubulin at centrosomes during oogenesis, whereas inactivation of nine genes accelerated the process. Depletion of the TRIM-NHL protein LIN-41 led to a significant delay in centrosome elimination and to the separation and reactivation of centrosomes during oogenesis. Upon LIN-41 depletion, meiotic chromosomes were abnormally condensed and pulled toward one of the two spindle poles around late pachytene even though the spindle microtubules emanated from both centrosomes. Overall, our work provides new insights into the regulation of centrosome behavior to ensure critical meiotic events and the generation of intact oocytes. PMID:26764090

  4. Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing.

    Directory of Open Access Journals (Sweden)

    Szabolcs Szelinger

    Full Text Available In females, X chromosome inactivation (XCI is an epigenetic, gene dosage compensatory mechanism by inactivation of one copy of X in cells. Random XCI of one of the parental chromosomes results in an approximately equal proportion of cells expressing alleles from either the maternally or paternally inherited active X, and is defined by the XCI ratio. Skewed XCI ratio is suggestive of non-random inactivation, which can play an important role in X-linked genetic conditions. Current methods rely on indirect, semi-quantitative DNA methylation-based assay to estimate XCI ratio. Here we report a direct approach to estimate XCI ratio by integrated, family-trio based whole-exome and mRNA sequencing using phase-by-transmission of alleles coupled with allele-specific expression analysis. We applied this method to in silico data and to a clinical patient with mild cognitive impairment but no clear diagnosis or understanding molecular mechanism underlying the phenotype. Simulation showed that phased and unphased heterozygous allele expression can be used to estimate XCI ratio. Segregation analysis of the patient's exome uncovered a de novo, interstitial, 1.7 Mb deletion on Xp22.31 that originated on the paternally inherited X and previously been associated with heterogeneous, neurological phenotype. Phased, allelic expression data suggested an 83∶20 moderately skewed XCI that favored the expression of the maternally inherited, cytogenetically normal X and suggested that the deleterious affect of the de novo event on the paternal copy may be offset by skewed XCI that favors expression of the wild-type X. This study shows the utility of integrated sequencing approach in XCI ratio estimation.

  5. DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment

    OpenAIRE

    Borowska, Natalia; Idziak, Dominika; Hasterok, Robert

    2011-01-01

    Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the ...

  6. A novel Tth111I restriction fragment length polymorphism (RFLP) allows tracing of X-chromosome inactivation in the (Xid) hetrozygote

    Energy Technology Data Exchange (ETDEWEB)

    Shanmugam, V.; Sell, W.; Saha, B.K. [Emory Univ. of School of Medicine, Atlanta, GA (United States)] [and others

    1996-02-01

    The X-linked immunodeficiency (Xid) in CBA/N mice serves as a model for the X-linked agammaglobulinemia (XLA) syndrome in man. X-chromosome inactivation in F{sub 1} heterozygotes derived from CBA/N (X{sup xid}/X{sup xid}) and B6.Pgk-1a (X{sup +}/Y) was investigated by monitoring the methylation status of the individual Pgk-1 alleles, Pgk-1b and Pgk-1a, respectively, using a novel Tth111I RFLP. Results indicate that in circulating B lymphocytes of female heterozygotes, only the X chromosomes carrying the normal alleles (X{sup +}) are active (nonrandom inactivation of the X chromosome), whereas in non-B cells both the X chromosomes (X{sup +} and X{sup xid}) are active (random inactivation of the X chromosome). These results were further confirmed by direct evaluation of transcription of the Btk gene, the gene mutated both in Xid and in XLA. 36 refs., 2 figs., 2 tabs.

  7. Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita

    Energy Technology Data Exchange (ETDEWEB)

    Devriendt, K.; Matthijs, G.; Legius, E. [Univ. Hospital Gasthuisberg, Leuven (Belgium)] [and others

    1997-03-01

    In this study, we report on a family with X-linked dyskeratosis congenita (DC). Linkage analysis with markers in the factor VIII gene at Xq28 yielded a LOD score of 2 at a recombination of 0. Clinical manifestations of DC, such as skin lesions following the Blaschko lines, were present in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a critical role for the DC gene in bone marrow-cell and fibroblast-cell proliferation. 23 refs., 4 figs., 1 tab.

  8. Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma.

    Science.gov (United States)

    Chiu, A; Czader, M; Cheng, L; Hasserjian, R P; Wang, M; Bhagavathi, S; Hyjek, E M; Al-Ahmadie, H; Knowles, D M; Orazi, A

    2011-01-01

    Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8+ CD31+ CD34- splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8- CD31+ CD34+ cord capillaries, but very little CD8+ vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of ≤5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a

  9. Pattern of Chromosomal Aberrations in Patients from North East Iran

    OpenAIRE

    Saeedeh Ghazaey; Farzaneh Mirzaei; Mitra Ahadian; Fatemeh Keifi; Semiramis Tootian; Mohammad Reza Abbaszadegan

    2013-01-01

    Objective: Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques. Materials and Methods: In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in K...

  10. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase

    DEFF Research Database (Denmark)

    Hernández-Muñoz, Inmaculada; Lund, Anders H; van der Stoop, Petra;

    2005-01-01

    X inactivation involves the stable silencing of one of the two X chromosomes in XX female mammals. Initiation of this process occurs during early development and involves Xist (X-inactive-specific transcript) RNA coating and the recruitment of Polycomb repressive complex (PRC) 2 and PRC1 proteins...... inactivation in somatic cells. We further demonstrate that MACROH2A1 deposition is regulated by the CULLIN3/SPOP ligase complex and is actively involved in stable X inactivation, likely through the formation of an additional layer of epigenetic silencing.......X inactivation involves the stable silencing of one of the two X chromosomes in XX female mammals. Initiation of this process occurs during early development and involves Xist (X-inactive-specific transcript) RNA coating and the recruitment of Polycomb repressive complex (PRC) 2 and PRC1 proteins....... This recruitment results in an inactive state that is initially labile but is further locked in by epigenetic marks such as DNA methylation, histone hypoacetylation, and MACROH2A deposition. Here, we report that the E3 ubiquitin ligase consisting of SPOP and CULLIN3 is able to ubiquitinate the Polycomb...

  11. PATTERN OF CHROMOSOMAL ANOMALIES IN DYSMORPHIC CHILDREN AND THEIR CLINICAL CORRELATION

    OpenAIRE

    Booma, van, J.G.J.; Mohamed Ansar Ali

    2015-01-01

    BACKGROUND Chromosomal abnormalities are an important cause of congenital anomalies. OBJECTIVE To evaluate the pattern of chromosomal imbalances in congenital anomaly child and to find out the frequency of internal anomalies associated with external anomalies. METHOD A total of 75 individuals in different age groups presenting clinical profile like syndromic features, congenital anomalies and facial dysmorphism were taken. All patients underwent clinical ...

  12. Contrasting patterns of karyotype and sex chromosome evolution in Lepidoptera

    OpenAIRE

    Šíchová, Jindra

    2016-01-01

    It is known that chromosomal rearrangements play an important role in speciation by limiting gene flow within and between species. Furthermore, this effect may be enhanced by involvement of sex chromosomes that are known to undergo fast evolution compared to autosomes and play a special role in speciation due to their engagement in postzygotic reproductive isolation. The work presented in this study uses various molecular-genetic and cytogenetic techniques to describe karyotype and sex chromo...

  13. Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development

    Directory of Open Access Journals (Sweden)

    Ann-Kristin Schmälter

    2015-10-01

    Full Text Available Studying changes in nuclear architecture is a unique approach toward the understanding of nuclear remodeling during tumor development. One aspect of nuclear architecture is the orientation of chromosomes in the three-dimensional nuclear space. We studied mouse chromosome 11 in lymphocytes of [T38HxBALB/c]N mice with a reciprocal translocation between chromosome X and 11 (T38HT(X;11 exhibiting a long chromosome T(11;X and a short chromosome T(X;11 and in fast-onset plasmacytomas (PCTs induced in the same strain. We determined the three-dimensional orientation of chromosome 11 using a mouse chromosome 11 specific multicolor banding probe. We also examined the nuclear position of the small translocation chromosome T(X;11 which contains cytoband 11E2 and parts of E1. Chromosomes can point either with their centromeric or with their telomeric end toward the nuclear center or periphery, or their position is found in parallel to the nuclear border. In T38HT(X;11 nuclei, the most frequently observed orientation pattern was with both chromosomes 11 in parallel to the nuclear border (“PP”. PCT cells showed nuclei with two or more copies of chromosome 11. In PCTs, the most frequent orientation pattern was with one chromosome in parallel and the other pointing with its centromeric end toward the nuclear periphery (“CP”. There is a significant difference between the orientation patterns observed in T38HT(X;11 and in PCT nuclei (P < .0001.

  14. Evolution from XIST-Independent to XIST-Controlled X-Chromosome Inactivation: Epigenetic Modifications in Distantly Related Mammals

    Science.gov (United States)

    Koina, Edda; Gilbert, Clément; Robinson, Terence J.; Marshall Graves, Jennifer A.

    2011-01-01

    X chromosome inactivation (XCI) is the transcriptional silencing of one X in female mammals, balancing expression of X genes between females (XX) and males (XY). In placental mammals non-coding XIST RNA triggers silencing of one X (Xi) and recruits a characteristic suite of epigenetic modifications, including the histone mark H3K27me3. In marsupials, where XIST is missing, H3K27me3 association seems to have different degrees of stability, depending on cell-types and species. However, the complete suite of histone marks associated with the Xi and their stability throughout cell cycle remain a mystery, as does the evolution of an ancient mammal XCI system. Our extensive immunofluorescence analysis (using antibodies against specific histone modifications) in nuclei of mammals distantly related to human and mouse, revealed a general absence from the mammalian Xi territory of transcription machinery and histone modifications associated with active chromatin. Specific repressive modifications associated with XCI in human and mouse were also observed in elephant (a distantly related placental mammal), as was accumulation of XIST RNA. However, in two marsupial species the Xi either lacked these modifications (H4K20me1), or they were restricted to specific windows of the cell cycle (H3K27me3, H3K9me2). Surprisingly, the marsupial Xi was stably enriched for modifications associated with constitutive heterochromatin in all eukaryotes (H4K20me3, H3K9me3). We propose that marsupial XCI is comparable to a system that evolved in the common therian (marsupial and placental) ancestor. Silent chromatin of the early inactive X was exapted from neighbouring constitutive heterochromatin and, in early placental evolution, was augmented by the rise of XIST and the stable recruitment of specific histone modifications now classically associated with XCI. PMID:21541345

  15. Long-Range Periodic Patterns in Microbial Genomes Indicate Significant Multi-Scale Chromosomal Organization.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Genome organization can be studied through analysis of chromosome position-dependent patterns in sequence-derived parameters. A comprehensive analysis of such patterns in prokaryotic sequences and genome-scale functional data has yet to be performed. We detected spatial patterns in sequence-derived parameters for 163 chromosomes occurring in 135 bacterial and 16 archaeal organisms using wavelet analysis. Pattern strength was found to correlate with organism-specific features such as genome size, overall GC content, and the occurrence of known motility and chromosomal binding proteins. Given additional functional data for Escherichia coli, we found significant correlations among chromosome position dependent patterns in numerous properties, some of which are consistent with previously experimentally identified chromosome macrodomains. These results demonstrate that the large-scale organization of most sequenced genomes is significantly nonrandom, and, moreover, that this organization is likely linked to genome size, nucleotide composition, and information transfer processes. Constraints on genome evolution and design are thus not solely dependent upon information content, but also upon an intricate multi-parameter, multi-length-scale organization of the chromosome.

  16. Inactivation of normal human fibroblasts by ionising irradiation results to a similar extent from chromosomal damage and p53-dependent G1-arrest

    International Nuclear Information System (INIS)

    After ionizing irradiation, fibroblasts lose clonogenicity (1) by non-repaired DNA double-strand breaks leading to lethal chromosome aberrations and (2) by permanent G1 arrest. The aim of this study was to determine the relative contribution of these two processes. 13 normal human fibroblast strains and 3 cell lines with non-functional p53 (LFS2800, FaDu, CHO). Cells were irradiated in plateau phase followed by immediate or delayed (14 h) plating. Lethal chromosome aberrations (CA) were measured by metaphase technique, the fraction of cells permanently arrested in G1 (fG1arr) by flow cytometry and cell survival by colony assay. For normal human fibroblasts, the number of lethal chromosome aberrations increased with dose but varied substantially among the strains studied. Only for delayed but not immediate plating the surviving fraction was correlated with the number of lethal aberrations (r2 =0.69, p2 =0.19, p=0.16). When survival was converted into lethal events the ratio between these events and the number of lethal aberrations amounted to 2.00±0.05:1, indicating that chromosomal damage accounted on average for only 50% of cell killing. The remainder was attributed to cell inactivation by the p53-dependent permanent G1-arrest, since cells lacking in functional p53 (LFS2800, FaDu, CHO) were characterised by a ratio of 1.01±0.02:1. In addition, there was a negative correlation between the extent of G1-arrest and the number of CA with those cell lines showing the highest G1-arrest having the lowest number of CA indicating that there is an interaction between these two processes. For normal human fibroblasts, cell inactivation results from chromosomal damage and permanent G1 arrest to a similar extent

  17. Loss of centromeric histone H2AT120 phosphorylation accompanies somatic chromosomes inactivation in the aberrant spermatocytes of Acricotopus lucidus (Diptera, Chironomidae).

    Science.gov (United States)

    Staiber, Wolfgang

    2016-01-01

    In the germ line of the chironomid Acricotopus lucidus, two cells with quite different chromosome constitutions result from the last unequal gonial mitosis. In the male, the future primary spermatocyte receives all the germ line-limited chromosomes (=Ks) together with somatic chromosomes (=Ss), and later on undergoes meiotic divisions, while the connected aberrant spermatocyte gets only Ss and remains undivided with chromosomes inactivated in a metaphase-like condensed state. This raises the question whether the centromeres of the permanently condensed Ss of the aberrant spermatocyte remain active during meiosis of the connected regular spermatocyte. Active centromeres exhibit an epigenetic phosphorylation mark at threonine 120 of histone H2A. To visualise the centromeric H2A phosphorylation of the Ss in the aberrant spermatocyte, meiotic stages were immunostained with different anti-phospho histone H2AT120 antibodies. Clear H2AT120ph signals appear at the centromeres of the Ss during prophase, persist on the metaphase-like condensed Ss during meiosis I of the connected primary spermatocyte and disappear during transition to meiosis II. The centromeres of the Ss and Ks of the regular spermatocytes display H2AT120ph signals from prophase I to anaphase II. The loss of the H2AT120 phosphorylation detected on the centromeres of the Ss of the aberrant spermatocyte indicating their deactivation supports the idea of a programmed inactivation of the Ss to block the entry of the germ line-derived aberrant spermatocyte, lacking Ks, into meiosis, and thus to prevent the generation of sperms possessing only Ss. This mechanism would ensure the presence of the Ks in the germ line. PMID:25820679

  18. No link between X chromosome inactivation pattern and simple goiter in females

    DEFF Research Database (Denmark)

    Brix, Thomas Heiberg; Hansen, Pia Skov; Knudsen, Gun Peggy S;

    2009-01-01

    healthy control twin individuals, and then performed a within-pair comparison of XCI in 48 twin pairs discordant for SG. METHODS: DNA was extracted from peripheral blood cells. XCI analysis was performed by predigestion of DNA using the methylation-sensitive enzyme Hpall, followed by polymerase chain...... by DNA fingerprinting. RESULTS: The frequency of skewed XCI in female twins with SG, DG, and NG was 11% (8/71), 13% (6/46), and 8% (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14% (20/142, p = 0.56), 14% (13/92, p = 1...

  19. Reversal of DNA methylation with 5-azacytidine alters chromosome replication patterns in human lymphocyte and fibroblast cultures.

    OpenAIRE

    Shafer, D A; Priest, J H

    1984-01-01

    Prior studies demonstrated that developmental or induced methylation of DNA can inactivate associated gene loci. Such DNA methylation can be reversed and specific genes reactivated by treatment with 5-azacytidine (5- azaC ). The present cytogenetic studies using replication banding methods show that 5- azaC treatment also results in an increase or decrease in replication staining at one or more band locations in human lymphocyte and fibroblast chromosomes. New replication band locations are n...

  20. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals

    Energy Technology Data Exchange (ETDEWEB)

    Beskid, O. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Dusek, Z. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Solansky, I. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic); Sram, R.J. [Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 142 20 Prague 4 (Czech Republic)]. E-mail: sram@biomed.cas.cz

    2006-02-22

    The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes 1 and 4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome 1 (58.8 {+-} 32.7%, versus 73.8 {+-} 33.6% in the controls, P < 0.05), and chromosome 4 (47.0 {+-} 34.1%, versus 29.4 {+-} 32.2%, P < 0.01) were found in workers exposed to ACN. Similarly, a decrease in the proportion of cells with aberration on chromosome 1 (61.0 {+-} 24.0%, versus 73.8 {+-} 33.6%, P < 0.05) and an increase on chromosome 4 (45.6 {+-} 24.6%, versus 29.4 {+-} 32.2%, P < 0.05) were observed in workers exposed to EB. Frequency of aberrant cells (%AB.C.) as well as genomic frequency of translocations (F {sub G}/100) increased with age (P < 0.001). Aging also increased the percentage of translocations and reciprocal translocations (P < 0.05), but decreased the relative number of acentric fragments (P < 0.01). Smoking led to significantly increased F {sub G}/100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations.

  1. Chromosomal organization of simple sequence repeats in the Pacific oyster (Crassostrea gigas): (GGAT)4, (GT)7 and (TA)10 chromosome patterns

    Indian Academy of Sciences (India)

    K. Bouilly; R. Chaves; A. Leitão; A. Benabdelmouna; H. Guedes-Pinto

    2008-08-01

    Chromosome identification is essential in oyster genomic research. Fluorescence in situ hybridization (FISH) offers new opportunities for the identification of oyster chromosomes. It has been used to locate satellite DNAs, telomeres or ribosomal DNA sequences. However, regarding chromosome identification, no study has been conducted with simple sequence repeats (SSRs). FISH was used to probe the physical organization of three particular SSRs, (GGAT)4, (GT)7 and (TA)10 onto metaphase chromosomes of the Pacific oyster, Crassostrea gigas. Hybridization signals were observed in all the SSR probes, but the distribution and intensity of signals varied according to the oligonucleotide repeat. The intercalary, centromeric and telomeric bands were observed along the chromosomes, and for each particular repeat every chromosome pair presented a similar pattern, allowing karyotypic analysis with all the SSRs tested. Our study is the first in mollusks to show the application of SSR in situ hybridization for chromosome identification and karyotyping. This technique can be a useful tool for oyster comparative studies and to understand genome organization in different oyster taxa.

  2. PATTERN OF CHROMOSOMAL ANOMALIES IN DYSMORPHIC CHILDREN AND THEIR CLINICAL CORRELATION

    Directory of Open Access Journals (Sweden)

    Booma

    2015-12-01

    Full Text Available BACKGROUND Chromosomal abnormalities are an important cause of congenital anomalies. OBJECTIVE To evaluate the pattern of chromosomal imbalances in congenital anomaly child and to find out the frequency of internal anomalies associated with external anomalies. METHOD A total of 75 individuals in different age groups presenting clinical profile like syndromic features, congenital anomalies and facial dysmorphism were taken. All patients underwent clinical assessment, chest x-ray, echocardiogram and cytogenetic assessment through karyotyping. Chi-square test was used in the statistical analysis. RESULTS Out of 75 patients 40% are males, 60% are females of which chromosomal abnormalities detected 30% and 35% respectively; 62.66% have minor anomalies and major anomalies of 37.33%. Chromosomal abnormality detected includes Down’s syndrome (77.77%, satellite 13 and 22(11.11%, turners syndrome (5.55%, trisomy 19(5.55%. Most common internal anomaly is congenital heart disease, predominantly atrioventricular septal defect. It has statistical significance with consanguinity (p <0.05. CONCLUSION Frequency of Down’s syndrome is high, reflecting the need of screening in all antenatal women. Karyotyping is recommended in all dysmorphic children as it can bring to the diagnosis, treatment and prognosis and for genetic counselling of patients and families.

  3. 5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Filipe Brum Machado

    Full Text Available X-chromosome inactivation (XCI is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX and males (XY. DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG in promoter regions is a key epigenetic marker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa from inactive (Xi X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8 and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2 and Xq (AR chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic

  4. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals

    International Nuclear Information System (INIS)

    The pattern of chromosomal aberrations (CA) was studied by fluorescence in situ hybridization (FISH) technique (whole chromosomes 1 and 4 painting) in workers occupationally exposed to any of the four following conditions: acrylonitrile (ACN), ethyl benzene (EB), carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), and irradiation in nuclear power plants (NPP), respectively. Decrease in the relative frequency of translocations was observed in EB group, and an increase in reciprocal translocations in ACN and NPP-exposed groups. An increase in a relative number of insertions was registered under all four conditions (significant at ACN, EB, c-PAHs, quasisignificant at NPP-exposed groups). Significant differences in the percentage of lymphocytes with aberrations on chromosome 1 (58.8 ± 32.7%, versus 73.8 ± 33.6% in the controls, P G/100) increased with age (P G/100 (P < 0.05), but did not affect the pattern of chromosomal aberrations. Our results seem to indicate that different carcinogens may induce a different pattern of chromosomal aberrations

  5. X inactivation in Rett syndrome: A preliminary study showing partial preferential inactivation of paternal X with the M27{beta} probe

    Energy Technology Data Exchange (ETDEWEB)

    Camus, P.; Abbadi, N.; Gilgenkrantz, S. [Laboratoire de Genetique, Vandoeuvre les Nancy (France)

    1994-04-15

    Rett syndrome (RS) is a severe progressive neurological disorder occurring exclusively in females. Most cases are sporadic. The few familial cases (less than 1%) cannot be explained by a simple mode of inheritance. Several hypotheses have been proposed: X-linked male lethal mutation, maternal uniparental disomy, fresh mutation on the X chromosome, involvement of mitochondrial DNA and differential inactivation with metabolic interference of X-borne alleles. The authors have examined the pattern of X inactivation in 10 affected girls who were selected according to the clinical criteria previously described and accepted by the French Rett Scientific Committee. The X inactivation pattern was studied by analysis of methylation at the hypervariable locus DXS255 with the M27{beta} probe. The results show a more-or-less skewed inactivation of paternal X in 8 Rett females, and 2 cases of symmetrical inactivation. In control girls, inactivation was symmetrical cases and the maternal X has been preferentially inactivated in the other 2 cases. In no case was a total skewed inactivation observed. Though there was clear evidence for a preferential paternal X inactivation that was statistically significant further studies are necessary to establish a relationship between X inactivation pattern and Rett syndrome.

  6. Cell division patterns and chromosomal segregation defects in oral cancer stem cells.

    Science.gov (United States)

    Kaseb, Hatem O; Lewis, Dale W; Saunders, William S; Gollin, Susanne M

    2016-09-01

    Oral squamous cell carcinoma (OSCC) is a serious public health problem caused primarily by smoking and alcohol consumption or human papillomavirus. The cancer stem cell (CSC) theory posits that CSCs show unique characteristics, including self-renewal and therapeutic resistance. Examining biomarkers and other features of CSCs is critical to better understanding their biology. To this end, the results show that cellular SOX2 immunostaining correlates with other CSC biomarkers in OSCC cell lines and marks the rare CSC population. To assess whether CSC division patterns are symmetrical, resulting in two CSC, or asymmetrical, leading to one CSC and one cancer cell, cell size and fluorescence intensity of mitotic cells stained with SOX2 were analyzed. Asymmetrical SOX2 distribution in ≈25% of the mitoses analyzed was detected. Chromosomal instability, some of which is caused by chromosome segregation defects (CSDs), is a feature of cancer cells that leads to altered gene copy numbers. We compare chromosomal instability (as measured by CSDs) between CSCs (SOX2+) and non-CSCs (SOX2-) from the same OSCC cell lines. CSDs were more common in non-CSCs (SOX2-) than CSCs (SOX2+) and in symmetrical CSC (SOX2+) mitotic pairs than asymmetrical CSC (SOX2+/SOX2-) mitotic pairs. CSCs showed fewer and different types of CSDs after ionizing radiation treatment than non-CSCs. Overall, these data are the first to demonstrate both symmetrical and asymmetrical cell divisions with CSDs in OSCC CSC. Further, the results suggest that CSCs may undergo altered behavior, including therapeutic resistance as a result of chromosomal instability due to chromosome segregation defects. © 2016 Wiley Periodicals, Inc. PMID:27123539

  7. Ovarian Cancers Harboring Inactivating Mutations in CDK12 Display a Distinct Genomic Instability Pattern Characterized by Large Tandem Duplications.

    Science.gov (United States)

    Popova, Tatiana; Manié, Elodie; Boeva, Valentina; Battistella, Aude; Goundiam, Oumou; Smith, Nicholas K; Mueller, Christopher R; Raynal, Virginie; Mariani, Odette; Sastre-Garau, Xavier; Stern, Marc-Henri

    2016-04-01

    CDK12 is a recurrently mutated gene in serous ovarian carcinoma, whose downregulation is associated with impaired expression of DNA damage repair genes and subsequent hypersensitivity to DNA-damaging agents and PARP1/2 inhibitors. In this study, we investigated the genomic landscape associated with CDK12 inactivation in patients with serous ovarian carcinoma. We show that CDK12 loss was consistently associated with a particular genomic instability pattern characterized by hundreds of tandem duplications of up to 10 megabases (Mb) in size. Tandem duplications were characterized by a bimodal (∼0.3 and ∼3 Mb) size distribution and overlapping microhomology at the breakpoints. This genomic instability, denoted as the CDK12 TD-plus phenotype, is remarkably distinct from other alteration patterns described in breast and ovarian cancers. The CDK12 TD-plus phenotype was associated with a greater than 10% gain in genomic content and occurred at a 3% to 4% rate in The Cancer Genome Atlas-derived and in-house cohorts of patients with serous ovarian carcinoma. Moreover, CDK12-inactivating mutations together with the TD-plus phenotype were also observed in prostate cancers. Our finding provides new insight toward deciphering the function of CDK12 in genome maintenance and oncogenesis. Cancer Res; 76(7); 1882-91. ©2016 AACR. PMID:26787835

  8. X-Chromosome Inactivation Analysis in Different Cell Types and Induced Pluripotent Stem Cells Elucidates the Disease Mechanism in a Rare Case of Mucopolysaccharidosis Type II in a Female.

    Science.gov (United States)

    Řeboun, M; Rybová, J; Dobrovolný, R; Včelák, J; Veselková, T; Štorkánová, G; Mušálková, D; Hřebíček, M; Ledvinová, J; Magner, M; Zeman, J; Pešková, K; Dvořáková, L

    2016-01-01

    Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder resulting from deficiency of iduronate-2-sulphatase activity. The disease manifests almost exclusively in males; only 16 symptomatic heterozygote girls have been reported so far. We describe the results of X-chromosome inactivation analysis in a 5-year-old girl with clinically severe disease and heterozygous mutation p.Arg468Gln in the IDS gene. X inactivation analysed at three X-chromosome loci showed extreme skewing (96/4 to 99/1) in two patient's cell types. This finding correlated with exclusive expression of the mutated allele. Induced pluripotent stem cells (iPSC) generated from the patient's peripheral blood demonstrated characteristic pluripotency markers, deficiency of enzyme activity, and mutation in the IDS gene. These cells were capable of differentiation into other cell types (cardiomyocytes, neurons). In MPS II iPSC clones, the X inactivation ratio remained highly skewed in culture conditions that led to partial X inactivation reset in Fabry disease iPSC clones. Our data, in accordance with the literature, suggest that extremely skewed X inactivation favouring the mutated allele is a crucial condition for manifestation of MPS II in females. This suggests that the X inactivation status and enzyme activity have a prognostic value and should be used to evaluate MPS II in females. For the first time, we show generation of iPSC from a symptomatic MPS II female patient that can serve as a cellular model for further research of the pathogenesis and treatment of this disease. PMID:27187040

  9. Linkage disequilibrium patterns vary with chromosomal location: A case study from the von Willebrand factor region

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, W.S.; Zenger, R.; O' Brien, E.; Jorde, L.B. (Univ. of Utah School of Medicine, Salt Lake City, UT (United States)); Nyman, D. (Aland Central Sjukhus (Finland)); Eriksson, A.W. (Free Univ., Amsterdam (Netherlands)); Renlund, M.

    1994-08-01

    Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughput a population's history. As a result, disequilibrium mapping may be useful in genomic regions of <1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, the authors have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotypes for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (r[sub m] = -.76; P<.05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres. 52 refs., 3 figs., 4 tabs.

  10. Chromosome banding pattern retrieves an independent origin of 2n = 50 chromosome populations of Nannospalax xanthodon from Turkey

    Czech Academy of Sciences Publication Activity Database

    Arslan, A.; Zima, Jan

    2015-01-01

    Roč. 80, č. 5 (2015), s. 440-445. ISSN 1616-5047 Institutional support: RVO:68081766 Keywords : Karyotype * Chromosomal races * Mole rats * Anatolia Subject RIV: EG - Zoology Impact factor: 1.478, year: 2014

  11. Molecular patterns of X chromosome-linked color vision genes among 134 menof European ancestry

    International Nuclear Information System (INIS)

    The authors used Southern blot hybridization to study X chromosome-linked color vision genes encoding the apoproteins of red and green visual pigments in 134 unselected Caucasian men. One hundred and thirteen individuals (84.3%) had a normal arrangement of their color vision pigment genes. All had one red pigment gene; the number of green pigment genes ranged from one to five with a mode of two. The frequency of molecular genotypes indicative of normal color vision (84.3%) was significantly lower than had been observed in previous studies of color vision phenotypes. Color vision defects can be due to deletions of red or green pigment genes or due to formation of hybrid genes comprising portions of both red and green pigment genes. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly, 2 (1.5%) had patterns characteristic of deuteranopia, and 6 (4.5%) had protan patterns. Previously undescribed hybrid gene patterns consisting of both green and red pigment gene fragments in addition to normal red and green genes were observed in another 6 individuals (4.5%). Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests

  12. Karyotype and C-Banding Patterns of Mitotic Chromosomes in Meadow Bromegrass (Bromus riparius Rehm)

    Science.gov (United States)

    Chromosomes of meadow bromegrass, Bromus riparius, are mainly median and similar in morphology. C-bands were located at telomeric regions of the chromosomes. Majority of the chromosomes had telomeric bands either in one or both arms. Approximately 10 chromosomes had no C-bands. Karyotype of meadow b...

  13. Patterns of replication in the neo-sex chromosomes of Drosophila nasuta albomicans

    Indian Academy of Sciences (India)

    G Mahesh; N B Ramachandra; H A Ranganath

    2000-09-01

    Drosophila nasuta albomicans (with 2n = 6), contains a pair of metacentric neo-sex chromosomes. Phylogenetically these are products of centric fusion between ancestral sex (X, Y) chromosomes and an autosome (chromosome 3). The polytene chromosome complement of males with a neo-X- and neo-Y-chromosomes has revealed asynchrony in replication between the two arms of the neo-sex chromosomes. The arm which represents the ancestral X-chromosome is faster replicating than the arm which represents ancestral autosome. The latter arm of the neo-sex chromosome is synchronous with other autosomes of the complement. We conclude that one arm of the neo-X/Y is still mimicking the features of an autosome while the other arm has the features of a classical X/Y-chromosome. This X-autosome translocation differs from the other evolutionary X-autosome translocations known in certain species of Drosophila.

  14. The nucleotide excision repair (NER system of Helicobacter pylori: Role in mutation prevention and chromosomal import patterns after natural transformation

    Directory of Open Access Journals (Sweden)

    Moccia Claudia

    2012-05-01

    Full Text Available Abstract Background Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER pathway components in H. pylori mutation and recombination. Results Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype. Conclusions Our data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation.

  15. A neo-W chromosome in a tropical butterfly links colour pattern, male-killing, and speciation

    Science.gov (United States)

    Smith, David A. S.; Gordon, Ian J.; Traut, Walther; Herren, Jeremy; Collins, Steve; Martins, Dino J.; Saitoti, Kennedy; Ireri, Piera

    2016-01-01

    Sexually antagonistic selection can drive both the evolution of sex chromosomes and speciation itself. The tropical butterfly the African Queen, Danaus chrysippus, shows two such sexually antagonistic phenotypes, the first being sex-linked colour pattern, the second, susceptibility to a male-killing, maternally inherited mollicute, Spiroplasma ixodeti, which causes approximately 100% mortality in male eggs and first instar larvae. Importantly, this mortality is not affected by the infection status of the male parent and the horizontal transmission of Spiroplasma is unknown. In East Africa, male-killing of the Queen is prevalent in a narrow hybrid zone centred on Nairobi. This hybrid zone separates otherwise allopatric subspecies with different colour patterns. Here we show that a neo-W chromosome, a fusion between the W (female) chromosome and an autosome that controls both colour pattern and male-killing, links the two phenotypes thereby driving speciation across the hybrid zone. Studies of the population genetics of the neo-W around Nairobi show that the interaction between colour pattern and male-killer susceptibility restricts gene flow between two subspecies of D. chrysippus. Our results demonstrate how a complex interplay between sex, colour pattern, male-killing, and a neo-W chromosome, has set up a genetic ‘sink' that keeps the two subspecies apart. The association between the neo-W and male-killing thus provides a ‘smoking gun' for an ongoing speciation process. PMID:27440667

  16. X inactivation in females with X-linked Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2012-07-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.

  17. INCIDENCE OF DOWN’S SYNDROME WITH CHROMOSOMAL PATTERN IN THE EASTERN INDIA

    Directory of Open Access Journals (Sweden)

    Jami Sagar

    2014-07-01

    Full Text Available BACK GROUND: To study the chromosomal pattern of the Down’s syndrome patients of the eastern Indian population coming to the MKCG Medical College, Berhampur, Odisha, India. Methodology: 0.8ml of peripheral blood was collected from all the patients and cultured in RPMI 1640 medium for 72h in CO2 incubator. Then cells were harvested with colchicines and after the hypotonic treatment the slides were prepared and stained with giemsa. After that it was observed with high power microscope and reported. RESULT: From the 50 patients, 39 patients were Primary trisomy 21 (47, XX or XY+21, 6 was Mosaic Trisomy 21 (46/47, XX or XY+21, 3 was Down’s syndrome Primary amenorrohoea (47, XX, +21 and there was 2 translocation 46, XY, t (14:21 46, XY, t (21:21. The paternal age at 26-30 years were found more whereas the maternal age at 21-25 years was found more and males were more affected as compare to the females. CONCLUSION: It is tempting to speculate that, the difference in clinical features, growth retardation, abnormal dermatoglyphic patterns etc, are related to the genetic constitution of the Down’s syndrome individuals.

  18. Cloning, chromosome mapping and expression pattern of porcine PLIN and M6PRBP1 genes

    Directory of Open Access Journals (Sweden)

    Yang Zaiqing

    2008-03-01

    Full Text Available Abstract The PAT proteins, named after the three PLIN/ADRP/TIP47 (PAT proteins, PLIN for perilipin, ADRP for adipose differentiation-related protein and TIP47 for tail-interacting protein of 47 kDa, now officially named M6PRBP1 for mannose-6-phosphate receptor binding protein 1, is a set of intracellular lipid droplet binding proteins. They are localized in the outer membrane monolayer enveloping lipid droplets and are involved in the metabolism of intracellular lipid. This work describes the cloning and sequencing of porcine PLIN and M6PRBP1 cDNAs, the chromosome mapping of these two genes, as well as the expression pattern of porcine PAT genes. Sequence analysis shows that the porcine PLIN cDNA contains an open reading frame of 1551 bp encoding 516 amino acids and that the porcine M6PRBP1 cDNA contains a coding region of 1320 bp encoding 439 amino acids. Comparison of PLIN and M6PRBP1 amino-acid sequences among various species reveals that porcine and bovine proteins are the most conserved. Porcine PLIN and M6PRBP1 genes have been mapped to pig chromosomes 7 and 2, respectively, by radiation hybrid analysis using the IMpRH panel. Expression analyses in pig showed a high expression of PLIN mRNA in adipose tissue, M6PRBP1 mRNA in small intestine, kidney and spleen and ADRP mRNA in adipose tissue, lung and spleen.

  19. Adjusting breast cancer patient prognosis with non-HER2-gene patterns on chromosome 17.

    Directory of Open Access Journals (Sweden)

    Vassiliki Kotoula

    Full Text Available BACKGROUND: HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH. However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17 is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients. METHODS: Copy numbers (CN for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials. PRINCIPAL FINDINGS: HER2-genes CN strongly correlated to each other (Spearman's rho >0.6 and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN. TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154. CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS and overall survival (OS in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS. Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS. Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS. CONCLUSIONS: TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer

  20. Distinct pattern of allelic loss and inactivation of cadherin 1 and 5 genes in mammary carcinomas arising in p53+/- mice

    International Nuclear Information System (INIS)

    p53 is one of the most frequently mutated genes in mammary carcinomas (MCs). To detect tumor suppressor genes cooperating with a hetero-deficient p53 gene in mammary carcinogenesis, we first examined allelotypes in MCs from (BALB/cHeA x MSM/Ms) F1-p53+/- and (BALB/cHeA x 129/SvEv) F1-p53+/- female mice, and then surveyed down-regulated genes in the allelic loss regions. Genome-wide screening at 42 loci identified frequent (more than 30%) loss of heterozygosity (LOH) on chromosomes 5, 8, 11, 12, 14 and 18 in the MCs from either of the F1 mice. The MCs in the p53+/- mice indicated highly frequent LOH, especially on chromosomes 8, 11 and 12, distinct from other mouse tumors. More than 60% of the 38 MCs from (BALB/cHeA x MSM/Ms) F1-p53+/- mice showed LOH in a region ranging from D8Mit85 (105.0 Mb from centromere) to D8Mit113 (111.8 Mb) on chromosome 8, a region syntenic to human chromosome 16q22.1, on which LOH has been found in breast cancers. RT-PCR analyses revealed that the LOH of chromosome 8 was associated with the reduced and/or complete loss of expression of Cdh1 and Cdh5 genes in 15 (58%) and 8 (31%) of 26 MCs derived from the F1 mice, respectively. Thus, inactivation of Cdh1 and Cdh5 is likely to cooperate with the loss of p53, suggesting a possible tumor suppressive function of these genes in mammary carcinogenesis. (author)

  1. Patterns of molecular evolution of an avian neo-sex chromosome.

    Science.gov (United States)

    Pala, Irene; Hasselquist, Dennis; Bensch, Staffan; Hansson, Bengt

    2012-12-01

    Newer parts of sex chromosomes, neo-sex chromosomes, offer unique possibilities for studying gene degeneration and sequence evolution in response to loss of recombination and population size decrease. We have recently described a neo-sex chromosome system in Sylvioidea passerines that has resulted from a fusion between the first half (10 Mb) of chromosome 4a and the ancestral sex chromosomes. In this study, we report the results of molecular analyses of neo-Z and neo-W gametologs and intronic parts of neo-Z and autosomal genes on the second half of chromosome 4a in three species within different Sylvioidea lineages (Acrocephalidea, Timaliidae, and Alaudidae). In line with hypotheses of neo-sex chromosome evolution, we observe 1) lower genetic diversity of neo-Z genes compared with autosomal genes, 2) moderate synonymous and weak nonsynonymous sequence divergence between neo-Z and neo-W gametologs, and 3) lower GC content on neo-W than neo-Z gametologs. Phylogenetic reconstruction of eight neo-Z and neo-W gametologs suggests that recombination continued after the split of Alaudidae from the rest of the Sylvioidea lineages (i.e., after ~42.2 Ma) and with some exceptions also after the split of Acrocephalidea and Timaliidae (i.e., after ~39.4 Ma). The Sylvioidea neo-sex chromosome shares classical evolutionary features with the ancestral sex chromosomes but, as expected from its more recent origin, shows weaker divergence between gametologs. PMID:22826461

  2. Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

    Directory of Open Access Journals (Sweden)

    Hasmik Mkrtchyan

    Full Text Available The discovery of copy number variations (CNV in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.

  3. Exploring Codon Usage Patterns of Alternatively Spliced Genes in Human Chromosome 1

    Institute of Scientific and Technical Information of China (English)

    马飞; 庄永龙; 黄颖; 李衍达

    2004-01-01

    In this study, 414 whole protein-coding sequences (238 004 codons) of alternatively spliced genes of human chromosome 1 have been employed to explore the patterns of codon usage bias among genes. Overall codon usage data analysis indicates that G- and C-ending codons are predominant in the genes. The base usage in all three codon positions suggests a selection-mutation balance. Multivariate statistical analysis reveals that the codon usage variation has a strong positive correlation with the expressivities of the genes (r=0.5790, P<0.0001). All 27 codons identified as optimal are G- and C-ending codons.Correlation analysis shows a strong negative correlation between the gene length and codon adaptation index value (r=-0.2252, P<0.0001), and a significantly positive correlation between the gene length and Nc values (r=0.1876, P<0.0001). These results suggest that the comparatively shorter genes in the genes have higher codon usage bias to maximize translational efficiency, and selection may also contribute to the reduction of highly expressed proteins.

  4. ChromEvol: assessing the pattern of chromosome number evolution and the inference of polyploidy along a phylogeny.

    Science.gov (United States)

    Glick, Lior; Mayrose, Itay

    2014-07-01

    We announce the release of chromEvol version 2.0, a software tool for inferring the pattern of chromosome number change along a phylogeny. The software facilitates the inference of the expected number of polyploidy and dysploidy transitions along each branch of a phylogeny and estimates ancestral chromosome numbers at internal nodes. The new version features a novel extension of the model accounting for general multiplication events, other than doubling of the number of chromosomes. This allows the monoploid number (commonly referred to as x, or the base-number) of a group of interest to be inferred in a statistical framework. In addition, we devise an inference scheme, which allows explicit categorization of each terminal taxon as either diploid or polyploid. The new version also supports intraspecific variation in chromosome number and allows hypothesis testing regarding the root chromosome number. The software, alongside a detailed usage manual, is available at http://www.tau.ac.il/∼itaymay/cp/chromEvol/. PMID:24710517

  5. Use of X-Chromosome Inactivation Pattern to Analyze the Clonality of 14 Female Cases of Kaposi Sarcoma

    OpenAIRE

    Yuan, Ding; XiuJuan, Wu; Yan, Zhang; JunQin, Liang; Fang, Xiang; Shirong, Yu; Xiaojing, Kang; Yanyan, Feng; Weidong, Wu; Dong, Luo; Qingli, Lu; DeZhi, Zhang; XiongMing, Pu

    2015-01-01

    Background Kaposi sarcoma (KS) has features of both neoplastic growth and hyperplastic proliferation. It is the most common tumor seen in patients with HIV infection. Whether KS is a real tumor or a benign hyperplastic disease is not known. Material/Methods Tissues from KS and cutaneous hemangioma lesion DNA were extracted, and then digested with methylation-sensitive restriction endonuclease HpaII. Human androgen receptor gene (HUMARA) was amplified with PCR method and the product was separa...

  6. Evaluation of X-Inactivation Status and Cytogenetic Stability of Human Dermal Fibroblasts after Long-Term Culture

    OpenAIRE

    Zhi-Gang Xue; Zhan-Ping Shi; Juan Dong; Ting-Ting Liao; Yan-Peng Wang; Xue-Ping Sun; Zheng-Jie Yan; Xiao-Qiao Qian; Yu-Gui Cui; Juan Chen; Jia-Yin Liu; Guoping Fan

    2010-01-01

    Human primary fibroblasts are a popular type of somatic cells for the production of induced pluripotent stem (iPS) cells. Here we characterized biological properties of primary fibroblasts in terms of cell-growth rate, cytogenetic stability, and the number of inactive X chromosomes during long-term passaging. We produced eight lines of female human dermal fibroblasts (HDFs) and found normal karyotype and expected pattern of X chromosome inactivation (XCI) at low passages (Passage P1-5). Howev...

  7. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1992-06-01

    This project seeks to defining the chromosome segments associated with radiation induced leukemogenesis (treatment-related acute myeloid leukemia, or t-AML). Towards these goals genetic analysis of human chromosomes 5 and 7 continues to investigate correlation of treatment with balanced and unbalanced chromosomal translocations. Progress is being made in cloning the breakpoints in balanced translocations in t-AML, that is to clone the t(9;11) and t(11;19) breakpoints, to clone the t(3;21)(q26;q22) breakpoints and to determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 11 figs. 3 figs.

  8. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    This project seeks to defining the chromosome segments associated with radiation induced leukemogenesis (treatment-related acute myeloid leukemia, or t-AML). Towards these goals genetic analysis of human chromosomes 5 and 7 continues to investigate correlation of treatment with balanced and unbalanced chromosomal translocations. Progress is being made in cloning the breakpoints in balanced translocations in t-AML, that is to clone the t(9;11) and t(11;19) breakpoints, to clone the t(3;21)(q26;q22) breakpoints and to determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 11 figs. 3 figs

  9. Distinct nonrandom patterns of chromosomal deletions in giant-cell lesions of bone

    Directory of Open Access Journals (Sweden)

    Baruffi Marcelo Razera

    2002-01-01

    Full Text Available Cytogenetic analyses were performed on a bone giant cell reparative granuloma (GCRG and on three bone giant cell tumors (GCT. The present GCRG case is the second to be described cytogenetically. A modal chromosome number of 46 was observed in all samples. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes 17 and 18. Among the structural anomalies observed, there was preferential involvement of chromosomes 6 and 10. Three GCT cases presented del(10(p13 and two cases presented del(6(q25 (1 GCRG and 1 GCT. These breakpoints mapped on 10p and 6q may harbour genes of importance in the development of bone giant cell tumors.

  10. Global DNA Methylation patterns on marsupial and devil facial tumour chromosomes

    OpenAIRE

    Ingles, Emory D.; Deakin, Janine E.

    2015-01-01

    Background Despite DNA methylation being one of the most widely studied epigenetic modifications in eukaryotes, only a few studies have examined the global methylation status of marsupial chromosomes. The emergence of devil facial tumour disease (DFTD), a clonally transmissible cancer spreading through the Tasmanian devil population, makes it a particularly pertinent time to determine the methylation status of marsupial and devil facial tumour chromosomes. DNA methylation perturbations are kn...

  11. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    This document lists the major accomplishments funded by DOE in the period of January 1989 through June 1991. Specific topics covered include: studies of chromosome translocations in patients with Acute Myeloid Leukemia (AML) de novo; correlation of karyotype and therapeutic response; the relationship of specific chromosomal abnormalities to a patient's occupational history; definition of regions on chromosome 5 involved in leukemogenesis; the influence of pervious chemotherapy on leukemogenesis; identification of genes at or near breakpoints involved in leukemia and lymphoma; identification of the critical rearrangement in the 9;11 translocation; molecular analysis of translocations involving 11q23; identification of other genes (like RAS) involved in leukemogenesis; development of fluorescence in situ hybridization as a cytogenetic tool; and examination of an unequivocal case of radiation induced preleukemia. 26 refs., 8 figs., 6 tabs

  12. Distinct Patterns of Structural and Numerical Chromosomal Instability Characterize Sporadic Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jane Bayani

    2008-10-01

    Full Text Available Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN, which can generate both numerical [(N-CIN] and structural chromosomal instability [(S-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels of both (N-CIN and (S-CIN. Six tumors had a near-diploid chromosome number, two were near-tetraploid, and two were near-triploid. (N-CIN levels increased as a function of overall tumor genomic content, with near-diploid tumors exhibiting numerical instability indices ranging from 7.0 to 21.0 and near-tetraploid and triploid tumors exhibiting instability indices ranging from 24.9 to 54.9. In contrast, the extent of (S-CIN was generally more evident in the diploid tumors compared with the near-tetraploid tumors. To determine whether the associated chromosomal constitution and/or ploidy changes were influenced by mitotic segregation errors, centrosome analyses were performed on all 10 tumors. The near-diploid tumors, with the lowest numerical change, were observed to possess fewer cells with centrosome abnormalities (5.5% to 14.0%, whereas the near-tetraploid tumors possessed much higher levels of (N-CIN and were characterized by a trend of elevating percentages of cells with abnormal centrosomes (16.0% to 20.5%. These observations suggest that two distinct processes governing genome stability may be disrupted in ovarian cancer: those that impact on numerical segregation and ploidy of chromosomes and those that affect the fidelity of DNA repair and lead to structural aberrations.

  13. Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal

    OpenAIRE

    Hallast, Pille; Maisano Delser, Pierpaolo; Batini, Chiara; Zadik, Daniel; Rocchi, Mariano; Schempp, Werner; Tyler-Smith, Chris; Mark A Jobling

    2016-01-01

    The distribution of genetic diversity in great ape species is likely to have been affected by patterns of dispersal and mating. This has previously been investigated by sequencing autosomal and mitochondrial DNA (mtDNA), but large-scale sequence analysis of the male-specific region of the Y Chromosome (MSY) has not yet been undertaken. Here, we use the human MSY reference sequence as a basis for sequence capture and read mapping in 19 great ape males, combining the data with sequences extract...

  14. Global features of sequences of bacterial chromosomes, plasmids and phages revealed by analysis of oligonucleotide usage patterns

    Directory of Open Access Journals (Sweden)

    Tümmler Burkhard

    2004-07-01

    Full Text Available Abstract Background Oligonucleotide frequencies were shown to be conserved signatures for bacterial genomes, however, the underlying constraints have yet not been resolved in detail. In this paper we analyzed oligonucleotide usage (OU biases in a comprehensive collection of 155 completely sequenced bacterial chromosomes, 316 plasmids and 104 phages. Results Two global features were analyzed: pattern skew (PS and variance of OU deviations normalized by mononucleotide content of the sequence (OUV. OUV reflects the strength of OU biases and taxonomic signals. PS denotes asymmetry of OU in direct and reverse DNA strands. A trend towards minimal PS was observed for almost all complete sequences of bacterial chromosomes and plasmids, however, PS was substantially higher in separate genomic loci and several types of plasmids and phages characterized by long stretches of non-coding DNA and/or asymmetric gene distribution on the two DNA strands. Five of the 155 bacterial chromosomes have anomalously high PS, of which the chromosomes of Xylella fastidiosa 9a5c and Prochlorococcus marinus MIT9313 exhibit extreme PS values suggesting an intermediate unstable state of these two genomes. Conclusions Strand symmetry as indicated by minimal PS is a universally conserved feature of complete bacterial genomes that results from the matching mutual compensation of local OU biases on both replichors while OUV is more a taxon specific feature. Local events such as inversions or the incorporation of genome islands are balanced by global changes in genome organization to minimize PS that may represent one of the leading evolutionary forces driving bacterial genome diversification.

  15. Organization of the bacterial chromosome.

    OpenAIRE

    Krawiec, S.; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction ...

  16. Assessing multilocus introgression patterns: a case study on the mouse X chromosome in Central Europe

    Czech Academy of Sciences Publication Activity Database

    Macholán, Miloš; Baird, S. J. E.; Dufková, Petra; Munclinger, P.; Vošlajerová Bímová, Barbora; Piálek, Jaroslav

    2011-01-01

    Roč. 65, č. 5 (2011), s. 1428-1446. ISSN 0014-3820 R&D Projects: GA ČR GA206/08/0640 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z60930519 Keywords : genetic conflict * hybrid zone movement * sex biased introgression * mice * X chromosome Subject RIV: EG - Zoology Impact factor: 5.146, year: 2011

  17. Expression pattern and mapping of the murine versican gene (Cspg2) to chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Naso, M.F.; Morgan, J.L.; Buchberg, A.M. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1995-09-01

    Versican is a modular proteoglycan harboring a hyaluronan-binding domain at its amino-terminal end and a selectin-like domain at its carboxyl-terminal end, separated by a large intervening region containing the attachment sites for the glycosaminoglycan side chains. By virtue of its modular nature, versican may play a role in cellular attachment, migration, and proliferation by interacting with cell surfaces and extracellular matrix molecules. To discern the function of versican through the analysis of spontaneous and targeted genetic mutations, we have isolated a mouse versican cDNA encoding part of the hyaluronan-binding region, analyzed its mRNA expression in various adult mouse tissues and embryos, and determined the chromosomal location of the gene. Murine versican was 89% identical to human versican at the amino acid level and was highly expressed in mouse embryos at Days 13, 14, and 18. Expression was also detected in adult mouse brain, heart, lung, spleen, skeletal muscle, skin, tail, kidney, and testis. Using interspecific backcross analysis, we assigned the versican gene (Cspg2) to mouse chromosome 13, in a region that is syntenic with the long arm of human chromosome 5 where the human CSPG2 gene is located. 16 refs., 2 figs., 1 tab.

  18. Mouse Af9 Is a Controller of Embryo Patterning, Like Mll, Whose Human Homologue Fuses with AF9 after Chromosomal Translocation in Leukemia

    OpenAIRE

    Collins, Emma C.; Appert, Alexandre; Ariza-McNaughton, Linda; Pannell, Richard; Yamada, Yoshihiro; Rabbitts, Terence H.

    2002-01-01

    Chromosomal translocation t(9;11)(p22;q23) in acute myeloid leukemia fuses the MLL and AF9 genes. We have inactivated the murine homologue of AF9 to elucidate its normal role. No effect on hematopoiesis was observed in mice with a null mutation of Af9. However, an Af9 null mutation caused perinatal lethality, and homozygous mice exhibited anomalies of the axial skeleton. Both the cervical and thoracic regions were affected by anterior homeotic transformation. Strikingly, mice lacking function...

  19. Inter-chromosomal variation in the pattern of human population genetic structure

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

    Full Text Available Abstract Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC, cluster, discriminant, fixation index (FST and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2, hect domain and RLD 2 (HERC2, ectodysplasin A receptor (EDAR and solute carrier family 45, member 2 (SLC45A2. These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG and death-associated protein kinase 1 (DAPK1, which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the

  20. Escape Artists of the X Chromosome.

    Science.gov (United States)

    Balaton, Bradley P; Brown, Carolyn J

    2016-06-01

    Inactivation of one X chromosome in mammalian females achieves dosage compensation between XX females and XY males; however, over 15% of human X-linked genes continue to be expressed from the inactive X chromosome. New genomic methodologies have improved our identification and characterization of these escape genes, revealing the importance of DNA sequence, chromatin structure, and chromosome ultrastructure in regulating expression from an otherwise inactive chromosome. Study of these exceptions to the rule of silencing highlights the interconnectedness of chromatin and chromosome structure in X-chromosome inactivation (XCI). Recent advances also demonstrate the importance of these genes in sexually dimorphic disease risk, particularly cancer. PMID:27103486

  1. Mating patterns amongst Siberian reindeer herders: inferences from mtDNA and Y-chromosomal analyses.

    Science.gov (United States)

    Pakendorf, Brigitte; Novgorodov, Innokentij N; Osakovskij, Vladimir L; Stoneking, Mark

    2007-07-01

    The Evenks and Evens, who speak closely related languages belonging to the Northern Tungusic branch of the Tungusic family, are nomadic reindeer herders and hunters. They are spread over an immense territory in northeastern Siberia, and consequently different subgroups are in contact with diverse peoples speaking Samoyedic, Turkic, Mongolic, Chukotka-Kamchatkan, and Yukaghir languages. Nevertheless, the languages and culture of the Evenks and Evens are similar enough for them to have been classified as a single ethnic group in the past. This linguistic and cultural similarity indicates that they may have spread over their current area of habitation relatively recently, and thus may be closely related genetically. On the other hand, the great distances that separate individual groups of Evens and Evenks from each other might have led to preferential mating with geographic neighbors rather than with linguistically related peoples. In this study, we assess the correlation between linguistic and genetic relationship in three different subgroups of Evenks and Evens, respectively, via mtDNA and Y-chromosomal analyses. The results show that there is some evidence of a common origin based on shared mtDNA lineages and relatively similar Y-haplogroup frequencies amongst most of the Evenk and Even subgroups. However, there is little sharing of Y-chromosomal STR haplotypes, indicating that males within Evenk and Even subgroups have remained relatively isolated. There is further evidence of some female admixture in different Even subgroups with their respective geographic neighbors. However, the Tungusic groups, and especially the Evenks, show signs of genetic drift, making inferences about their prehistory difficult. PMID:17492671

  2. Cloning, tissue expression pattern, and chromosome localization of human protein kinase Bγ gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Protein kinase B (PKB) is a member of the second messenger-regulated subfamily of protein kinases, and plays a key role in cell-cycle regulation, glucose uptake and promotion of cell differentiation. Evidence shows that PKB undergoes activation in some human tumors and is involved in Ras pathway, which implies that PKB can trigger a pathway to induce oncogenic transformation. A nucleotide sequence of mouse Pkb? was used as a probe to screen homolog in a human liver cDNA library. A fragment of 1998 bp containing a 1440 bp ORF encoding 479 amino acid residues was obtained. Then the 3'-terminal of this fragment was extended to 2788 bp by 'electronic walking' screening, and the extended fragment was confirmed by PCR amplification. The protein deduced by the gene had a high identity of 83% and 78% to the human PKBγ and γ, respectively, and was designated as human PKB?. Northern hybridization detected two equally expressed transcripts of 8.5 and 6.5 kb in length in all 16 human tissues tested, with the highest expression level in brain, and lower levels with variation in the other tissues. By RH mapping, the PKBγ was placed on chromosome 1q43, between markers D1S304 and D1S2693. It is a valuable clue for cloning the candidate genes related to prostate cancer; Arrhythmogenic Right Ventricular Dysplasia (ARVD); Chediak-Higashi, NK cell Deficiency (CHS); and Hypoparathyrodism with Short Stature, Mental Retardation and Seizures which have already been mapped in this chromosomal region.

  3. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes.

    Directory of Open Access Journals (Sweden)

    Vonn Walter

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV, no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

  4. Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human Filamin A (FLNA diseases

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    Douvaras Panagiotis

    2012-02-01

    Full Text Available Abstract Background Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X-linked, filamin A gene (FLNA mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. FlnaDilp2/+ mice, heterozygous for an X-linked filamin A (Flna nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of FlnaDilp2/+ mice was affected in any way that might predict abnormal corneal epithelial maintenance. Results X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver of FlnaDilp2/+ and wild-type (WT female X-inactivation mosaics, hemizygous for the X-linked, LacZ reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of FlnaDilp2/+ and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in FlnaDilp2/+ corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually, consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. Conclusions Mosaic analysis identified no major effect of the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.

  5. Chromosomal redistribution of male-biased genes in mammalian evolution with two bursts of gene gain on the X chromosome.

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    Yong E Zhang

    Full Text Available Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI. These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution.

  6. Chromosomal Redistribution of Male-Biased Genes in Mammalian Evolution with Two Bursts of Gene Gain on the X Chromosome

    Science.gov (United States)

    Zhang, Yong E.; Vibranovski, Maria D.; Landback, Patrick; Marais, Gabriel A. B.; Long, Manyuan

    2010-01-01

    Mammalian X chromosomes evolved under various mechanisms including sexual antagonism, the faster-X process, and meiotic sex chromosome inactivation (MSCI). These forces may contribute to nonrandom chromosomal distribution of sex-biased genes. In order to understand the evolution of gene content on the X chromosome and autosome under these forces, we dated human and mouse protein-coding genes and miRNA genes on the vertebrate phylogenetic tree. We found that the X chromosome recently acquired a burst of young male-biased genes, which is consistent with fixation of recessive male-beneficial alleles by sexual antagonism. For genes originating earlier, however, this pattern diminishes and finally reverses with an overrepresentation of the oldest male-biased genes on autosomes. MSCI contributes to this dynamic since it silences X-linked old genes but not X-linked young genes. This demasculinization process seems to be associated with feminization of the X chromosome with more X-linked old genes expressed in ovaries. Moreover, we detected another burst of gene originations after the split of eutherian mammals and opossum, and these genes were quickly incorporated into transcriptional networks of multiple tissues. Preexisting X-linked genes also show significantly higher protein-level evolution during this period compared to autosomal genes, suggesting positive selection accompanied the early evolution of mammalian X chromosomes. These two findings cast new light on the evolutionary history of the mammalian X chromosome in terms of gene gain, sequence, and expressional evolution. PMID:20957185

  7. Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells.

    Science.gov (United States)

    Kara, Nihan; Hossain, Manzar; Prasanth, Supriya G; Stillman, Bruce

    2015-05-01

    Replication of eukaryotic chromosomes occurs once every cell division cycle in normal cells and is a tightly controlled process that ensures complete genome duplication. The origin recognition complex (ORC) plays a key role during the initiation of DNA replication. In human cells, the level of Orc1, the largest subunit of ORC, is regulated during the cell division cycle, and thus ORC is a dynamic complex. Upon S phase entry, Orc1 is ubiquitinated and targeted for destruction, with subsequent dissociation of ORC from chromosomes. Time lapse and live cell images of human cells expressing fluorescently tagged Orc1 show that Orc1 re-localizes to condensing chromatin during early mitosis and then displays different nuclear localization patterns at different times during G1 phase, remaining associated with late replicating regions of the genome in late G1 phase. The initial binding of Orc1 to mitotic chromosomes requires C-terminal amino acid sequences that are similar to mitotic chromosome-binding sequences in the transcriptional pioneer protein FOXA1. Depletion of Orc1 causes concomitant loss of the mini-chromosome maintenance (Mcm2-7) helicase proteins on chromatin. The data suggest that Orc1 acts as a nucleating center for ORC assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase. PMID:25784553

  8. The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

    OpenAIRE

    De La Vega, Francisco M.; Isaac, Hadar; Collins, Andrew; Scafe, Charles R.; Halldórsson, Bjarni V; Su, Xiaoping; Lippert, Ross A.; Wang, Yu; Laig-Webster, Marion; Koehler, Ryan T.; Ziegle, Janet S.; Wogan, Lewis T.; Stevens, Junko F.; Leinen, Kyle M.; Olson, Sheri J.

    2005-01-01

    The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of...

  9. The mouse lp(A3)/Edg7 lysophosphatidic acid receptor gene: genomic structure, chromosomal localization, and expression pattern.

    Science.gov (United States)

    Contos, J J; Chun, J

    2001-04-18

    The extracellular signaling molecule, lysophosphatidic acid (LPA), mediates proliferative and morphological effects on cells and has been proposed to be involved in several biological processes including neuronal development, wound healing, and cancer progression. Three mammalian G protein-coupled receptors, encoded by genes designated lp (lysophospholipid) receptor or edg (endothelial differentiation gene), mediate the effects of LPA, activating similar (e.g. Ca(2+) release) as well as distinct (neurite retraction) responses. To understand the evolution and function of LPA receptor genes, we characterized lp(A3)/Edg7 in mouse and human and compared the expression pattern with the other two known LPA receptor genes (lp(A1)/Edg2 and lp(A2)/Edg4non-mutant). We found mouse and human lp(A3) to have nearly identical three-exon genomic structures, with introns upstream of the coding region for transmembrane domain (TMD) I and within the coding region for TMD VI. This structure is similar to lp(A1) and lp(A2), indicating a common ancestral gene with two introns. We localized mouse lp(A3) to distal Chromosome 3 near the varitint waddler (Va) gene, in a region syntenic with the human lp(A3) chromosomal location (1p22.3-31.1). We found highest expression levels of each of the three LPA receptor genes in adult mouse testes, relatively high expression levels of lp(A2) and lp(A3) in kidney, and moderate expression of lp(A2) and lp(A3) in lung. All lp(A) transcripts were expressed during brain development, with lp(A1) and lp(A2) transcripts expressed during the embryonic neurogenic period, and lp(A3) transcript during the early postnatal period. Our results indicate both overlapping as well as distinct functions of lp(A1), lp(A2), and lp(A3). PMID:11313151

  10. Function of the Sex Chromosomes in Mammalian Fertility

    OpenAIRE

    Heard, Edith; Turner, James

    2011-01-01

    In female germ cells, the inactive X chromosome is reactivated before meiosis and thereafter remains active. In contrast, the X chromosome in males is inactivated during meiosis, and silencing is largely maintained during spermiogenesis.

  11. Inactivation of the Huntington's disease gene (Hdh impairs anterior streak formation and early patterning of the mouse embryo

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    Conlon Ronald A

    2005-08-01

    Full Text Available Abstract Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in

  12. Levels and patterns of nucleotide variation in domestication QTL regions on rice chromosome 3 suggest lineage-specific selection.

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    Xianfa Xie

    Full Text Available Oryza sativa or Asian cultivated rice is one of the major cereal grass species domesticated for human food use during the Neolithic. Domestication of this species from the wild grass Oryza rufipogon was accompanied by changes in several traits, including seed shattering, percent seed set, tillering, grain weight, and flowering time. Quantitative trait locus (QTL mapping has identified three genomic regions in chromosome 3 that appear to be associated with these traits. We would like to study whether these regions show signatures of selection and whether the same genetic basis underlies the domestication of different rice varieties. Fragments of 88 genes spanning these three genomic regions were sequenced from multiple accessions of two major varietal groups in O. sativa--indica and tropical japonica--as well as the ancestral wild rice species O. rufipogon. In tropical japonica, the levels of nucleotide variation in these three QTL regions are significantly lower compared to genome-wide levels, and coalescent simulations based on a complex demographic model of rice domestication indicate that these patterns are consistent with selection. In contrast, there is no significant reduction in nucleotide diversity in the homologous regions in indica rice. These results suggest that there are differences in the genetic and selective basis for domestication between these two Asian rice varietal groups.

  13. Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal.

    Science.gov (United States)

    Hallast, Pille; Maisano Delser, Pierpaolo; Batini, Chiara; Zadik, Daniel; Rocchi, Mariano; Schempp, Werner; Tyler-Smith, Chris; Jobling, Mark A

    2016-04-01

    The distribution of genetic diversity in great ape species is likely to have been affected by patterns of dispersal and mating. This has previously been investigated by sequencing autosomal and mitochondrial DNA (mtDNA), but large-scale sequence analysis of the male-specific region of the Y Chromosome (MSY) has not yet been undertaken. Here, we use the human MSY reference sequence as a basis for sequence capture and read mapping in 19 great ape males, combining the data with sequences extracted from the published whole genomes of 24 additional males to yield a total sample of 19 chimpanzees, four bonobos, 14 gorillas, and six orangutans, in which interpretable MSY sequence ranges from 2.61 to 3.80 Mb. This analysis reveals thousands of novel MSY variants and defines unbiased phylogenies. We compare these with mtDNA-based trees in the same individuals, estimating time-to-most-recent common ancestor (TMRCA) for key nodes in both cases. The two loci show high topological concordance and are consistent with accepted (sub)species definitions, but time depths differ enormously between loci and (sub)species, likely reflecting different dispersal and mating patterns. Gorillas and chimpanzees/bonobos present generally low and high MSY diversity, respectively, reflecting polygyny versus multimale-multifemale mating. However, particularly marked differences exist among chimpanzee subspecies: The western chimpanzee MSY phylogeny has a TMRCA of only 13.2 (10.8-15.8) thousand years, but that for central chimpanzees exceeds 1 million years. Cross-species comparison within a single MSY phylogeny emphasizes the low human diversity, and reveals species-specific branch length variation that may reflect differences in long-term generation times. PMID:26883546

  14. The temporal and spatial pattern of histone H3 phosphorylation at serine 28 and serine 10 is similar in plants but differs between mono- and polycentric chromosomes.

    Science.gov (United States)

    Gernand, D; Demidov, D; Houben, A

    2003-01-01

    Immunolabeling using site-specific antibodies against phosphorylated histone H3 at serine 10 or serine 28 revealed in plants an almost similar temporal and spatial pattern of both post-translational modification sites at mitosis and meiosis. During the first meiotic division the entire chromosomes are highly H3 phosphorylated. In the second meiotic division, like in mitosis, the chromosomes contain high phosphorylation levels in the pericentromeric region and very little H3 phosphorylation along the arms of monocentric species. In the polycentric plant Luzula luzuloides phosphorylation at both serine positions occurs along the whole chromosomes, whereas in monocentric species, only the pericentromeric regions showed strong signals from mitotic prophase to telophase. No phosphorylated serine 10 or serine 28 was detectable on single chromatids at anaphase II resulting from equational segregation of rye B chromosome univalents during the preceding anaphase I. In addition, we found a high level of serine 28 as well as of serine 10 phosphorylation along the entire mitotic monocentric chromosomes after treatment of mitotic cells using the phosphatase inhibitor cantharidin. These observations suggest that histone H3 phosphorylation at serine 10 and 28 is an evolutionarily conserved event and both sites are likely to be involved in the same process, such as sister chromatid cohesion. PMID:14610360

  15. Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and Alters Movement Pattern in Zebrafish.

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    Ashok Aspatwar

    Full Text Available Carbonic anhydrase related proteins (CARPs X and XI are highly conserved across species and are predominantly expressed in neural tissues. The biological role of these proteins is still an enigma. Ray-finned fish have lost the CA11 gene, but instead possess two co-orthologs of CA10. We analyzed the expression pattern of zebrafish ca10a and ca10b genes during embryonic development and in different adult tissues, and studied 61 CARP X/XI-like sequences to evaluate their phylogenetic relationship. Sequence analysis of zebrafish ca10a and ca10b reveals strongly predicted signal peptides, N-glycosylation sites, and a potential disulfide, all of which are conserved, suggesting that all of CARP X and XI are secretory proteins and potentially dimeric. RT-qPCR showed that zebrafish ca10a and ca10b genes are expressed in the brain and several other tissues throughout the development of zebrafish. Antisense morpholino mediated knockdown of ca10a and ca10b showed developmental delay with a high rate of mortality in larvae. Zebrafish morphants showed curved body, pericardial edema, and abnormalities in the head and eye, and there was increased apoptotic cell death in the brain region. Swim pattern showed abnormal movement in morphant zebrafish larvae compared to the wild type larvae. The developmental phenotypes of the ca10a and ca10b morphants were confirmed by inactivating these genes with the CRISPR/Cas9 system. In conclusion, we introduce a novel zebrafish model to investigate the mechanisms of CARP Xa and CARP Xb functions. Our data indicate that CARP Xa and CARP Xb have important roles in zebrafish development and suppression of ca10a and ca10b expression in zebrafish larvae leads to a movement disorder.

  16. Banding chromosome pattern of two species of Pimelodus (Siluriformes, Pimelodidae) from the Parana River basin of Brazil.

    Science.gov (United States)

    de Souza, Lenice; Giuliano-Caetano, Lucia; Dias, Ana Lúcia

    2004-01-01

    Cytogenetic studies were carried out on seven specimens of Pimelodus heraldoi and sixteen specimens of Pimelodus sp., both from the Parana River basin. The two species had the same diploid number of 56 chromosomes: P. heraldoi with 22M+22SM+6ST+6A and FN of 106 and Pimelodus sp. with 24M+26SM+4ST+2A and FN of 110. NORs were found at the terminal position of the long arm of one pair of ST chromosomes. C-banding (CB) showed in the two species heterochromatin distributed in various chromosomes of the complement, mainly in telomeric regions and in a pair of metacentric chromosomes with strong heterochromatic staining in both telomeres. Treatment only with the fluorochrome CMA3 confirmed in Pimelodus heraldoi and Pimelodus sp. the nucleolar chromosome pair and showed other fluorescent bands. Combined treatment with CB+CMA3 enhanced fluorescent staining of chromosomes in the two fish species evidencing several bands, including in P. heraldoi a chromosome pair showing fluorescent staining in both telomeres. PMID:19058555

  17. Cloning, tissue expression pattern characterization and chromosome localization of human peptide methionine sulfoxide reductase cDNA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Oxidation and reduction of some amino acids are one of the molecular mechanisms for regulating the function of proteins. The oxidation of methionine (Met) to methionine sulfoxide (Met(O)) results in decreasing or loss of the biological activity of related proteins. It was found that peptide methionine sulfoxide reductase (msrA) can reduce Met(O) to Met and therefore restored the biological function of the oxidized proteins. To reveal the methionine oxidation-reduction mechanism in human body, in this study, the cDNA sequence of bovine msrA was used as an information-probe to screen the human EST database. Based on a contig assembled from homologous ESTs, a 1 256-bp human MSRA cDNA was cloned from several human cDNA libraries. The cDNA contains an open reading frame (ORF) of 705 bp in length, which encodes 235 amino acid residues. Homology comparison revealed that human MSRA shares 88% and 61% identities with bovine and Escherichia coli msrA protein respectively. Expression pattern analysis revealed a single 1.6-kb transcript of human MSRA in most human tissues and with highest expression in kidney. By radiation hybrid panel mapping, the gene was localized to human chromosome 8p22-23 between markers D8S518 and D8S550. There are 2 human inherited diseases Keratolytic Winter Erythema and Microcephaly related genes in this region, it is inferred that human MSRA might be the candidate of the two diseases.

  18. An evolutionary conserved early replicating segment on the sex chromosomes of man and the great apes.

    Science.gov (United States)

    Weber, B; Schempp, W; Wiesner, H

    1986-01-01

    Replication studies on prometaphase chromosomes of man, the chimpanzee, the pygmy chimpanzee, the gorilla, and the orangutan reveal great interspecific homologies between the autosomes. The early replicating X chromosomes clearly show a high degree of conservation of both the pattern and the time course of replication. An early replicating segment on the short arm of the X chromosomes of man (Xp22.3) which escapes inactivation can be found on the X chromosomes of the great apes as well. Furthermore, the most early replicating segment on the Y chromosomes of all species tested appears to be homologous to this segment on the X chromosomes. Therefore, these early replicating segments in the great apes may correspond to the pseudoautosomal segment proposed to exist in man. From further cytogenetic characterization of the Y chromosomes it is evident that structural alterations have resulted in an extreme divergence in both the euchromatic and heterochromatic parts. It is assumed, therefore, that, in contrast to the X chromosomes, the Y chromosomes have undergone a rapid evolution within the higher primates. PMID:3096642

  19. A comparison of the chromosome G-banding pattern in two Sorex species, S. satunini and S. araneus (Mammalia, Insectivora

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    Yuri Borisov

    2012-08-01

    Full Text Available The G-banded karyotype of S. satunini was compared with the karyotype of Sorex araneus. Extensive homology was revealed. The major chromosomal rearrangements involved in the evolutionary divergence of these species have been identified as centric fusions and centromeric shifts. From the known palaeontological age of S. satunini it is obvious that the vast chromosomal polymorphism of the S. araneus group originated during the middle Pleistocene.

  20. Comparative study of mitotic chromosomes in two blowflies, Lucilia sericata and L. cluvia (Diptera, Calliphoridae, by C- and G-like banding patterns and rRNA loci, and implications for karyotype evolution

    Directory of Open Access Journals (Sweden)

    Mónica G. Chirino

    2015-03-01

    Full Text Available The karyotypes of Lucilia cluvia (Walker, 1849 and L. sericata (Meigen, 1826 from Argentina were characterized using conventional staining and the C- and G-like banding techniques. Besides, nucleolus organizer regions (NORs were detected by fluorescent in situ hybridization (FISH and silver staining technique. The chromosome complement of these species comprises five pairs of autosomes and a pair of sex chromosomes (XX/XY, female/male. The autosomes of both species have the same size and morphology, as well as C- and G-like banding patterns. The X and Y chromosomes of L. cluvia are subtelocentric and easily identified due to their very small size. In L. sericata, the X chromosome is metacentric and the largest of the complement, showing a secondary constriction in its short arm, whereas the Y is submetacentric and smaller than the X. The C-banding patterns reflect differences in chromatin structure and composition between the subtelocentric X and Y chromosomes of L. cluvia and the biarmed sex chromosomes of L. sericata. These differences in the sex chromosomes may be due to distinct amounts of constitutive heterochromatin. In L. cluvia, the NORs are placed at one end of the long-X and of the long-Y chromosome arms, whereas one of the NORs is disposed in the secondary constriction of the short-X chromosome arm and the other on the long-Y chromosome arm in L. sericata. Although the G-like banding technique does not yield G-bands like those in mammalian chromosomes, it shows a high degree chromosomal homology in both species because each pair of autosomes was correctly paired. This chromosome similarity suggests the absence of autosomal rearrangements during karyotype evolution in the two species studied.

  1. The role of background selection in shaping patterns of molecular evolution and variation: evidence from variability on the Drosophila X chromosome.

    Science.gov (United States)

    Charlesworth, Brian

    2012-05-01

    In the putatively ancestral population of Drosophila melanogaster, the ratio of silent DNA sequence diversity for X-linked loci to that for autosomal loci is approximately one, instead of the expected "null" value of 3/4. One possible explanation is that background selection (the hitchhiking effect of deleterious mutations) is more effective on the autosomes than on the X chromosome, because of the lack of crossing over in male Drosophila. The expected effects of background selection on neutral variability at sites in the middle of an X chromosome or an autosomal arm were calculated for different models of chromosome organization and methods of approximation, using current estimates of the deleterious mutation rate and distributions of the fitness effects of deleterious mutations. The robustness of the results to different distributions of fitness effects, dominance coefficients, mutation rates, mapping functions, and chromosome size was investigated. The predicted ratio of X-linked to autosomal variability is relatively insensitive to these variables, except for the mutation rate and map length. Provided that the deleterious mutation rate per genome is sufficiently large, it seems likely that background selection can account for the observed X to autosome ratio of variability in the ancestral population of D. melanogaster. The fact that this ratio is much less than one in D. pseudoobscura is also consistent with the model's predictions, since this species has a high rate of crossing over. The results suggest that background selection may play a major role in shaping patterns of molecular evolution and variation. PMID:22377629

  2. Analysis of ATP7A Gene in Patients with Menkes Disease and X Chromosome Inactivation in a Case with Menkes Disease%Menkes病患儿ATP7A基因突变及X染色体失活分析

    Institute of Scientific and Technical Information of China (English)

    赵程峰; 王静敏; 王菊莉; 黄琼辉; 邓艳华; 吴晔; 姜玉武

    2013-01-01

    Objective:To analyze and characterize the genetic features of a chinese family with Menkes disease. Familial cases of Menkes disease are rare and are due to X-chromosomal inheritance fron a carrier mother. To explain the pathogenic mechanism of the sex-limited expression of Menkes disease, we have analyzed the parental origin of mutations and the XCL status in cases with Menkes disease due to ATP7A molecular defects. Methods: Genomic DNAs from the patient and her parents were extracted using standard procedures from the peripheral blood leukocytes, PCR and DNA direct sequencing were employed to analyze all of the 7 exons of the DCX gene to determine the gene mutation. The degree of XCL and its direction relative to the X chromosome parent of origin were measured in DNA prepared from peripheral blood leucocytes by analyzing CAG repeat polymorphism in the androgen receptor gene (AR). Results:PCR detected a deletion of c.3045delT(p.T1016fsX1018),while her mother was a carrier for the mutation. The cases had a skewed XCL pattern and he favor expression of the maternal origin allele. Conclusion:The proband carried a deletion c.3045delT(p.T1016fsX1018),and his mother is normal, consistent with recessive inheritance. The skewed XCL pattern was the main XCL pattern in Menkes disease patients. The priority inactive X chromosome was mainly of maternal origin.%  目的:分析并确立1例Menkes病的ATP7A基因突变,并从X染色体失活角度探讨突变的亲源性和ATP7A的致病机制。方法:首先搜集该例临床典型Menkes病患儿及其父母的外周血提取基因组DNA,分别对患儿及父母的外周血DNA进行PCR扩增,通过DNA测序和琼脂糖凝胶电泳判定患儿突变的亲源性;用雄激素受体基因(AR)的三核苷酸多态性进行基因型分析判定X染色体失活是否发生偏斜。结果:基因诊断确诊1例Menkes病患儿,DNA直接测序检测结果为c.3045delT(p.T1016fsX1018)缺失突变,其母亲

  3. Skewed X-inactivation in cloned mice

    International Nuclear Information System (INIS)

    In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

  4. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  5. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1, 1980-Dec 31, 1980

    International Nuclear Information System (INIS)

    The relationship of the chromosome pattern in leukemic cells to prior disease and to the type of therapy are summarized. Although the karyotype seen in secondary ANLL is distinctly different from that seen in the primary malignancy, the nature of the primary disease may influence the pattern of karyotypic changes seen in the leukemic cell. This notion is very speculative and is based on limited observations. Two of three patients with leukemia following multiple myeloma were unique in that they were the only ones whose leukemic cells had more than 48 chromosomes, with +1, +6, +8, +21; this constellation of abnormalities was not seen in any of the other patients. Since most of the patients had received both radiotherapy and chemotherapy, it is difficult to determine whether specific chromosome changes are related more closely to one rather than the other of these types of therapy. It appears, however, that combined therapy is much more likely to result in abnormalities of both No. 5 and No. 7 (9/15 patients) than is either modality used alone (1/12)

  6. Further study of genetic interactions: Loss of short arm material in patients with ring chromosome 4 changes developmental pattern of del(4) (q33)

    Energy Technology Data Exchange (ETDEWEB)

    Lurie, I.W. [Univ. of Maryland, Baltimore, MD (United States)

    1995-04-10

    Segment 4q33 is not considered a probable location of a gene related with limb deficiency by Roberts and Tabin; however, the occurrence of ectrodactyly or its equivalents in at least 9 published cases of monosomy 4q33 suggests probable location of one of these genes in that region. Ulnar ray defects and/or ectrodactyly were the prevailing forms. An additional loss of the tip of 4p in patients with ring chromosome 4 leads to a change of limb deficiency type: 8 of 9 patients with r(4) and limb deficiency had radial ray defects. Therefore, interactions between a proposed {1/2} dose {open_quotes}ectrodactyly{close_quotes} gene on 4q33 and some {1/2} dosage genes on distal 4p (or disturbed cellular homeostasis due to a ring chromosome 4) can change the development pattern of limb deficiency. Possible mechanisms and significance of the phenomenon are discussed. 36 refs., 1 tab.

  7. Lack of X inactivation associated with maternal X isodisomy: Evidence for a counting mechanism prior to X inactivation during human embryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; Torchia, B.S.; Fu, S. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others

    1996-01-01

    We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/46,X,del(X) (q21.3-qter)/46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome. 41 refs., 4 figs., 2 tabs.

  8. Transposition patterns of unlinked transposed Ds elements from two T-DNA loci on tomato chromosomes 7 and 8

    Czech Academy of Sciences Publication Activity Database

    Bříza, Jindřich; Niedermeierová, Hana; Pavingerová, Daniela; Thomas, C. M.; Klimyuk, V. I.; Jones, J. D. G.

    2002-01-01

    Roč. 266, - (2002), s. 882-890. ISSN 1617-4615 R&D Projects: GA ČR GA521/96/0724 Keywords : tomato chromosomes * gene manipulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.522, year: 2002

  9. Structural organization of the inactive X chromosome in the mouse.

    Science.gov (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  10. Microgeographical distribution of two chromosomal races of house mice in Tunisia: pattern and origin of habitat partitioning.

    OpenAIRE

    N. Chatti; Ganem, G.; Benzekri, K; Catalan, J.; Britton-davidian, J; Saïd, K

    1999-01-01

    Two chromosomal races of the house mouse occur in Tunisia, a standard morph (40St) found all over the country, and a derived morph (22Rb) occurring only in central Tunisia. In this region, habitat partitioning between the two morphs was investigated by a microgeographical analysis of their distribution, assessing habitat characteristics and demographic parameters. Results showed that the 22Rb mice always occurred in the oldest sections of towns (medinas), often extending to more recent surrou...

  11. Genetic Diversity and Differentiation in Urban and Indigenous Populations of Mexico: Patterns of Mitochondrial DNA and Y-Chromosome Lineages.

    Science.gov (United States)

    González-Sobrino, Blanca Z; Pintado-Cortina, Ana P; Sebastián-Medina, Leticia; Morales-Mandujano, Fabiola; Contreras, Alejandra V; Aguilar, Yasnaya E; Chávez-Benavides, Juan; Carrillo-Rodríguez, Aurelio; Silva-Zolezzi, Irma; Medrano-González, Luis

    2016-01-01

    Aside from the admixture between indigenous people and people from overseas, populations in Mexico changed drastically after the Spanish conquest of the sixteenth century, forming an intricate history that has been underutilized in understanding the genetic population structure of Mexicans. To infer historical processes of isolation, dispersal, and assimilation, we examined the phylogeography of mitochondrial (mt) DNA and Y-chromosome lineages in 3,026 individuals from 10 urban and nine indigenous populations by identifying single nucleotide polymorphisms. A geographic array with a predominance of Amerindian lineages was observed for mtDNA, with northern indigenous populations being divergent from the central and southern indigenous populations; urban populations showed low differentiation with isolation by distance. Y-chromosome variation distinguished urban and indigenous populations through the Amerindian haplogroup Q frequency. The MtDNA and the Y-chromosome together primarily distinguished urban and indigenous populations, with different geographic arrays for both. Gene flow across geographical distance and between the urban and indigenous realms appears to have altered the pre-Hispanic phylogeography in central and southern Mexico, mainly by displacement of women, while maintaining the indigenous isolation in the north, southeast, and Zapotec regions. Most Amerindian mtDNA diversity currently occurs in urban populations and appears to be reduced among indigenous people. PMID:27050033

  12. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, July 1992--August 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1993-09-01

    Progress in identification of chromosomal transformations associated with leukemogenesis is described. In particular progress in DNA cloning of chromosomal break points in human cancer patients is described.

  13. Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes in Caenorhabditis Species.

    Science.gov (United States)

    Larson, Braden J; Van, Mike V; Nakayama, Taylor; Engebrecht, JoAnne

    2016-08-01

    During meiosis in the heterogametic sex in some species, sex chromosomes undergo meiotic sex chromosome inactivation (MSCI), which results in acquisition of repressive chromatin and transcriptional silencing. In Caenorhabditis elegans, MSCI is mediated by MET-2 methyltransferase deposition of histone H3 lysine 9 dimethylation. Here we examined the meiotic chromatin landscape in germ lines of four Caenorhabditis species; C. remanei and C. brenneri represent ancestral gonochorism, while C. briggsae and C. elegans are two lineages that independently evolved hermaphroditism. While MSCI is conserved across all four species, repressive chromatin modifications are distinct and do not correlate with reproductive mode. In contrast to C. elegans and C. remanei germ cells where X chromosomes are enriched for histone H3 lysine 9 dimethylation, X chromosomes in C. briggsae and C. brenneri germ cells are enriched for histone H3 lysine 9 trimethylation. Inactivation of C. briggsae MET-2 resulted in germ-line X chromosome transcription and checkpoint activation. Further, both histone H3 lysine 9 di- and trimethylation were reduced in Cbr-met-2 mutant germ lines, suggesting that in contrast to C. elegans, H3 lysine 9 di- and trimethylation are interdependent. C. briggsae H3 lysine 9 trimethylation was redistributed in the presence of asynapsed chromosomes in a sex-specific manner in the related process of meiotic silencing of unsynapsed chromatin. However, these repressive marks did not influence X chromosome replication timing. Examination of additional Caenorhabditis species revealed diverse H3 lysine 9 methylation patterns on the X, suggesting that the sex chromosome epigenome evolves rapidly. PMID:27280692

  14. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna-and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining SRY gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved. PMID:26690510

  15. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation

    Indian Academy of Sciences (India)

    Jennifer A. Marshall Graves

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna—and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

  16. Correlation of chromosome patterns in leukemic cells of patients with exposure to chemicals and/or radiation

    International Nuclear Information System (INIS)

    We have identified two new recurring translocations involving chromosome 5; one is a 3;5 translocation and the other involves a rearrangement between chromosomes 5 and 7. The first is t(3;5)(q25.1;q35). We studied five patients with AML and a t(3;5) in their leukemic cells. At diagnosis, four of the patients had a t(3;5) as their sole karyotypic anomaly; the remaining patient had additional structural and numerical abnormalities. Careful cytogenetic analysis indicated that the breakpoints of this rearrangement were 3q25.1 and 5q34, in contrast to the various breakpoints reported in earlier studies (3q21 to 3q25 and 5q31 to 5q35). The karyotypic, morphologic, and clinical characteristics of this group, as well as those of 15 previously reported patients with the t(3;5), were compared to identify any features that might warrant consideration of this anomaly as a specific syndrome. The median age of the group, 37 years, as younger than that of all patients with AML, 49 years. A preceding myelodysplastic syndrome was observed in three patients. We have no information regarding the occupation of most of these patients. Except for acute promyelocytic leukemia, each morphologic subtype occurred in these patients; however, the frequency of erythroleukemia (M6) was much greater than expected. 11 refs., 2 figs., 5 tabs

  17. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  18. Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis.

    OpenAIRE

    Migeon, B R; Jeppesen, P; Torchia, B.S.; Fu, S.; Dunn, M. A.; Axelman, J; Schmeckpeper, B. J.; Fantes, J; Zori, R. T.; Driscoll, D J

    1996-01-01

    We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congeni...

  19. [Chromosomal organization of the genomes of small-chromosome plants].

    Science.gov (United States)

    Muravenko, O V; Zelenin, A V

    2009-11-01

    An effective approach to study the chromosome organization in genomes of plants with small chromosomes and/or with low-informative C-banding patterns was developed in the course of investigation of the karyotypes of cotton plant, camomile, flax, and pea. To increase the resolving power of chromosome analysis, methods were worked out for revealing early replication patterns on chromosomes and for artificial impairment of mitotic chromosome condensation with the use of a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the patterns of C-banding of small chromosomes on preparations obtained with the use of 9-AMA, it is necessary to choose a length interval that must not exceed three average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA increases the resolution of differential C- and OR-banding and the precision of physical chromosome mapping by the FISH method. Of particular importance in studying small chromosomes is optimization of the computer-aided methods used to obtain and process chromosome images. The complex approach developed for analysis of the chromosome organization in plant genomes was used to study the karyotypes of 24 species of the genus Linum L. It permitted their chromosomes to be identified for the first time, and, in addition, B chromosomes were discovered and studied in the karyotypes of the species of the section Syllinum. By similarity of the karyotypes, the studied flax species were distributed in eight groups in agreement with the clusterization of these species according to the results of RAPD analysis performed in parallel. Systematic positions and phylogenetic relationships of the studied flax species were verified. Out results can serve as an important argument in favour of the proposal to develop a special program for sequencing the genome of cultivated flax (L. usitatissimum L.), which is a major representative of small-chromosome species. PMID:20058798

  20. Evolution of Sex Chromosomes in Insects

    OpenAIRE

    Kaiser, Vera B; Bachtrog, Doris

    2010-01-01

    Sex chromosomes have many unusual features relative to autosomes. Y (or W) chromosomes lack genetic recombination, are male- (female-) limited, and show an abundance of genetically inert heterochromatic DNA but contain few functional genes. X (or Z) chromosomes also show sex-biased transmission (i.e., X chromosomes show female-biased and Z-chromosomes show male-biased inheritance) and are hemizygous in the heterogametic sex. Their unusual ploidy level and pattern of inheritance imply that sex...

  1. Comparing the Prognostic Value of BAP1 Mutation Pattern, Chromosome 3 Status, and BAP1 Immunohistochemistry in Uveal Melanoma.

    Science.gov (United States)

    van de Nes, Johannes A P; Nelles, Jasmin; Kreis, Stefan; Metz, Claudia H D; Hager, Thomas; Lohmann, Dietmar R; Zeschnigk, Michael

    2016-06-01

    Uveal melanoma (UM), a tumor of the eye, can be divided into 2 major classes correlating with patients' prognosis. Gene expression profiles and chromosome 3 status are correlated with tumor classification and prognosis. Somatic BAP1 mutations are another feature largely restricted to metastatic UM. Here we performed thorough BAP1 mutation analysis including sequencing and gene dosage analysis of all BAP1 coding exons as well as methylation analysis of the promoter CpG island in a set of 66 UMs. The results were compared with the BAP1 protein expression as determined by immunohistochemistry and the tumor-related survival of the patients. BAP1 sequencing and gene dosage analysis of BAP1 exons by multiplex ligation-dependent probe amplification revealed a mutation in 33 (89%) of 37 tumors with monosomy 3 (M3) or isodisomy 3. BAP1 mutations were not detected in any of the 28 tumors with disomy 3 or partial monosomy 3 (partM3). Most of the sequence mutations (21 of 28) were frame-shift, splice-site, or nonsense mutations leading to a premature termination codon. BAP1 protein as determined by immunohistochemistry was absent in all samples with a BAP1 mutation irrespective of the functional type of mutation. Kaplan-Meier analysis revealed a highly significant association between BAP1 protein staining and patients' survival (P=0.0004). The association between BAP1 mutation status and tumor-related survival was less pronounced but still significant (P=0.0023). We conclude that BAP1 protein staining is favorable over BAP1 mutation screening by Sanger sequencing for prognostic testing of UM patients. PMID:27015033

  2. Electroencephalographic patterns during sleep in children with chromosome 15q11.2-13.1 duplications (Dup15q).

    Science.gov (United States)

    Arkilo, Dimitrios; Devinsky, Orrin; Mudigoudar, Basanagoud; Boronat, Susana; Jennesson, Melanie; Sassower, Kenneth; Vaou, Okeanis Eleni; Lerner, Jason T; Jeste, Shafali Spurling; Luchsinger, Kadi; Thibert, Ronald

    2016-04-01

    Our objective was to define the EEG features during sleep of children with neurodevelopmental disorders due to copy number gains of 15q11-q13 (Dup15q). We retrospectively reviewed continuous EEG recordings of 42 children with Dup15q (mean age: eight years, 32 with idic15), and data collected included background activity, interictal epileptiform discharges, sleep organization, and ictal activity. Three patterns were recognized: This is the first report of electroencephalographic patterns during sleep of children with Dup15q reporting alpha-delta rhythms, CSWS, and high amplitude fast frequencies. Alpha-delta rhythms are described in children with dysautonomia and/or mood disorders and CSWS in children with developmental regression. The significance of these findings in cognitive function and epilepsy for the children in our cohort needs to be determined with follow-up studies. PMID:26949155

  3. Allele-specific distribution of RNA polymerase II on female X chromosomes.

    Science.gov (United States)

    Kucera, Katerina S; Reddy, Timothy E; Pauli, Florencia; Gertz, Jason; Logan, Jenae E; Myers, Richard M; Willard, Huntington F

    2011-10-15

    While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described genome wide; however, whether or not PolII binds at transcriptionally inactive sites remains uncertain. The two X chromosomes in female cells in mammals present an opportunity to examine each of the two alleles of a given locus in both active and inactive states, depending on which X chromosome is silenced by X chromosome inactivation. Here, we investigated PolII occupancy and expression of the associated genes across the active (Xa) and inactive (Xi) X chromosomes in human female cells to elucidate the relationship of gene expression and PolII binding. We find that, while PolII in the pseudoautosomal region occupies both chromosomes at similar levels, it is significantly biased toward the Xa throughout the rest of the chromosome. The general paucity of PolII on the Xi notwithstanding, detectable (albeit significantly reduced) binding can be observed, especially on the evolutionarily younger short arm of the X. PolII levels at genes that escape inactivation correlate with the levels of their expression; however, additional PolII sites can be found at apparently silenced regions, suggesting the possibility of a subset of genes on the Xi that are poised for expression. Consistent with this hypothesis, we show that a high proportion of genes associated with PolII-accessible sites, while silenced in GM12878, are expressed in other female cell lines. PMID:21791549

  4. Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein.

    Science.gov (United States)

    Xin, Y; Yu, L; Chen, Z; Zheng, L; Fu, Q; Jiang, J; Zhang, P; Gong, R; Zhao, S

    2001-06-15

    Type A receptors of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, contain alpha, beta, delta, gamma, and rho subunits. The gamma subunit has four subtypes: gamma1, gamma2, gamma3, andgamma4. GABA(A) receptor-associated protein (GABARAP) was previously demonstrated to act as a linker protein between microtubules and the gamma2 subunit of GABA(A) receptors. However, no other linker proteins have been identified as mediating the linkage of microtubules and the remaining subunits of GABA(A) receptors. In this study we identified three human paralogues (GABARAPL1, GABARAPL2, and GABARAPL3) and two mouse orthologues (Gabarapl1 and Gabarapl2) of human GABARAP, all of which encoded 117 amino acids, as does Gabarapl. The expression patterns of GABARAPL1, GABARAPL2, and GABARAP in 16 adult tissues showed that they were expressed ubiquitously. The expression levels of GABARAPL1 as a 2.3-kb transcript were very high in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle, very low in thymus and small intestine, and moderate in other tissues tested. The unique 1.35-kb transcript of GABARAPL2 was expressed at high levels in heart, brain, testis, prostate, ovary, spleen, and skeletal muscle, at very low levels in lung, thymus, and small intestine, and moderately in other tissues tested. For GABARAP, a 1.3-kb transcript was abundantly expressed in all tested tissues with small variation. The expression patterns of Gabarapl1 and Gabarapl2 were similar to those of their counterparts in human. In addition, GABARAPL1 was localized to human chromosome 12p12.3 and GABARAPL2 to 16q22.3-q24.1 by RH mapping, while GABARAP and GABARAPL3 were found to be localized at chromosomes 17p13.2 and 15q25.1, respectively, by searching the related databases. Sequence comparison of the cDNAs and their corresponding genomic sequences shows that GABARAP, GABARAPL1, and GABARAPL2 are composed of four exons each, while GABARAPL3 is distributed only at

  5. Lack of sex chromosome specific meiotic silencing in platypus reveals origin of MSCI in therian mammals

    OpenAIRE

    Daish, Tasman J.; Casey, Aaron E.; Grutzner, Frank

    2015-01-01

    Background In therian mammals heteromorphic sex chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during meiotic prophase I while the autosomes maintain transcriptional activity. The evolution of this sex chromosome silencing is thought to result in retroposition of genes required in spermatogenesis from the sex chromosomes to autosomes. In birds sex chromosome specific silencing appears to be absent and global transcriptional reductions occur through pachytene and sex chr...

  6. Sex determining mechanisms in insects based on imprinting and elimination of chromosomes

    OpenAIRE

    Sánchez Rodríguez, Lucas

    2014-01-01

    As a rule, the sex of an individual is fixed at fertilisation, being the chromosomal constitution of the zygote a direct consequence of the chromosomal constitution of the gametes. However, there are cases in which the chromosomal differences determining sex are brought about by elimination or inactivation of chromosomes in the embryo. In Sciaridae insects, all zygotes start with the XXX constitution; the loss of either one or two X chromosomes determines whether the zygote becomes XX (fem...

  7. Cryptic mosaicism involving a second chromosome X in patients with Turner syndrome

    Directory of Open Access Journals (Sweden)

    A. Araújo

    2008-05-01

    Full Text Available The high abortion rate of 45,X embryos indicates that patients with Turner syndrome and 45,X karyotype could be mosaics, in at least one phase of embryo development or cellular lineage, due to the need for the other sex chromosome presence for conceptus to be compatible with life. In cases of structural chromosomal aberrations or hidden mosaicism, conventional cytogenetic techniques can be ineffective and molecular investigation is indicated. Two hundred and fifty patients with Turner syndrome stigmata were studied and 36 who had female genitalia and had been cytogenetically diagnosed as having "pure" 45,X karyotype were selected after 100 metaphases were analyzed in order to exclude mosaicism and the presence of genomic Y-specific sequences (SRY, TSPY, and DAZ was excluded by PCR. Genomic DNA was extracted from peripheral blood and screened by the human androgen receptor (HUMARA assay. The HUMARA gene has a polymorphic CAG repeat and, in the presence of a second chromosome with a different HUMARA allele, a second band will be amplified by PCR. Additionally, the CAG repeats contain two methylation-sensitive HpaII enzyme restriction sites, which can be used to verify skewed inactivation. Twenty-five percent (9/36 of the cases showed a cryptic mosaicism involving a second X and approximately 14% (5/36, or 55% (5/9 of the patients with cryptic mosaicism, also presented skewed inactivation. The laboratory identification of the second X chromosome and its inactivation pattern are important for the clinical management (hormone replacement therapy, and inclusion in an oocyte donation program and prognostic counseling of patients with Turner syndrome.

  8. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

    Science.gov (United States)

    Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman

    2016-08-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  9. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

    Science.gov (United States)

    Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

    2016-01-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  10. Ribosome-inactivating proteins

    OpenAIRE

    Walsh, Matthew J; Dodd, Jennifer E; Hautbergue, Guillaume M.

    2013-01-01

    Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the eukaryotic 60S ribosomal subunit. In this review, we compare archetypal RIP family members with oth...

  11. Temporal genomic evolution of bird sex chromosomes

    DEFF Research Database (Denmark)

    Wang, Zongji; Zhang, Jilin; Yang, Wei;

    2014-01-01

    driving forces of Z chromosome evolution, we analyze here 45 newly available bird genomes and four species' transcriptomes, over their course of recombination loss between the sex chromosomes. RESULTS: We show Z chromosomes in general have a significantly higher substitution rate in introns and synonymous...... evolved very recently. CONCLUSIONS: In conclusion, we uncover that the sequence and expression patterns of Z chromosome genes covary with their ages of becoming Z-linked. In contrast to the mammalian X chromosomes, such patterns are mainly driven by mutational bias and genetic drift in birds, due...... to the opposite sex-biased inheritance of Z vs. X....

  12. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, July 1991--June 1992

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1992-06-01

    This project seeks to defining the chromosome segments associated with radiation induced leukemogenesis (treatment-related acute myeloid leukemia, or t-AML). Towards these goals genetic analysis of human chromosomes 5 and 7 continues to investigate correlation of treatment with balanced and unbalanced chromosomal translocations. Progress is being made in cloning the breakpoints in balanced translocations in t-AML, that is to clone the t(9;11) and t(11;19) breakpoints, to clone the t(3;21)(q26;q22) breakpoints and to determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 11 figs. 3 figs.

  13. Distinct Patterns of Association of Variants at 11q23.3 Chromosomal Region with Coronary Artery Disease and Dyslipidemia in the Population of Andhra Pradesh, India.

    Directory of Open Access Journals (Sweden)

    Rayabarapu Pranav Chand

    Full Text Available In our attempt to comprehensively understand the nature of association of variants at 11q23.3 apolipoprotein gene cluster region, we genotyped a prioritized set of 96 informative SNPs using Fluidigm customized SNP genotyping platform in a sample of 508 coronary artery disease (CAD cases and 516 controls. We found 12 SNPs as significantly associated with CAD at P <0.05, albeit only four (rs2849165, rs17440396, rs6589566 and rs633389 of these remained significant after Benjamin Hochberg correction. Of the four, while rs6589566 confers risk to CAD, the other three SNPs reduce risk for the disease. Interaction of variants that belong to regulatory genes BUD13 and ZPR1 with APOA5-APOA4 intergenic variants is also observed to significantly increase the risk towards CAD. Further, ROC analysis of the risk scores of the 12 significant SNPs suggests that our study has substantial power to confer these genetic variants as predictors of risk for CAD, as illustrated by AUC (0.763; 95% CI: 0.729-0.798, p = <0.0001. On the other hand, the protective SNPs of CAD are associated with elevated Low Density Lipoprotein Cholesterol and Total Cholesterol levels, hence with dyslipidemia, in our sample of controls, which may suggest distinct effects of the variants at 11q23.3 chromosomal region towards CAD and dyslipidemia. It may be necessary to replicate these findings in the independent and ethnically heterogeneous Indian samples in order to establish this as an Indian pattern. However, only functional analysis of the significant variants identified in our study can provide more precise understanding of the mechanisms involved in the contrasting nature of their effects in manifesting dyslipidemia and CAD.

  14. Distinct Patterns of Association of Variants at 11q23.3 Chromosomal Region with Coronary Artery Disease and Dyslipidemia in the Population of Andhra Pradesh, India.

    Science.gov (United States)

    Pranav Chand, Rayabarapu; Kumar, Arramraju Sreenivas; Anuj, Kapadia; Vishnupriya, Satti; Mohan Reddy, Battini

    2016-01-01

    In our attempt to comprehensively understand the nature of association of variants at 11q23.3 apolipoprotein gene cluster region, we genotyped a prioritized set of 96 informative SNPs using Fluidigm customized SNP genotyping platform in a sample of 508 coronary artery disease (CAD) cases and 516 controls. We found 12 SNPs as significantly associated with CAD at P <0.05, albeit only four (rs2849165, rs17440396, rs6589566 and rs633389) of these remained significant after Benjamin Hochberg correction. Of the four, while rs6589566 confers risk to CAD, the other three SNPs reduce risk for the disease. Interaction of variants that belong to regulatory genes BUD13 and ZPR1 with APOA5-APOA4 intergenic variants is also observed to significantly increase the risk towards CAD. Further, ROC analysis of the risk scores of the 12 significant SNPs suggests that our study has substantial power to confer these genetic variants as predictors of risk for CAD, as illustrated by AUC (0.763; 95% CI: 0.729-0.798, p = <0.0001). On the other hand, the protective SNPs of CAD are associated with elevated Low Density Lipoprotein Cholesterol and Total Cholesterol levels, hence with dyslipidemia, in our sample of controls, which may suggest distinct effects of the variants at 11q23.3 chromosomal region towards CAD and dyslipidemia. It may be necessary to replicate these findings in the independent and ethnically heterogeneous Indian samples in order to establish this as an Indian pattern. However, only functional analysis of the significant variants identified in our study can provide more precise understanding of the mechanisms involved in the contrasting nature of their effects in manifesting dyslipidemia and CAD. PMID:27257688

  15. Chromosomal aberration

    International Nuclear Information System (INIS)

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G1 phase. (author)

  16. Human postmeiotic sex chromatin and its impact on sex chromosome evolution.

    Science.gov (United States)

    Sin, Ho-Su; Ichijima, Yosuke; Koh, Eitetsu; Namiki, Mikio; Namekawa, Satoshi H

    2012-05-01

    Sex chromosome inactivation is essential epigenetic programming in male germ cells. However, it remains largely unclear how epigenetic silencing of sex chromosomes impacts the evolution of the mammalian genome. Here we demonstrate that male sex chromosome inactivation is highly conserved between humans and mice and has an impact on the genetic evolution of human sex chromosomes. We show that, in humans, sex chromosome inactivation established during meiosis is maintained into spermatids with the silent compartment postmeiotic sex chromatin (PMSC). Human PMSC is illuminated with epigenetic modifications such as trimethylated lysine 9 of histone H3 and heterochromatin proteins CBX1 and CBX3, which implicate a conserved mechanism underlying the maintenance of sex chromosome inactivation in mammals. Furthermore, our analyses suggest that male sex chromosome inactivation has impacted multiple aspects of the evolutionary history of mammalian sex chromosomes: amplification of copy number, retrotranspositions, acquisition of de novo genes, and acquisition of different expression profiles. Most strikingly, profiles of escape genes from postmeiotic silencing diverge significantly between humans and mice. Escape genes exhibit higher rates of amino acid changes compared with non-escape genes, suggesting that they are beneficial for reproductive fitness and may allow mammals to cope with conserved postmeiotic silencing during the evolutionary past. Taken together, we propose that the epigenetic silencing mechanism impacts the genetic evolution of sex chromosomes and contributed to speciation and reproductive diversity in mammals. PMID:22375025

  17. The role of epigenetic inactivation of 14-3-3σin human cancer

    Institute of Scientific and Technical Information of China (English)

    Dmitri LODYGIN; Heiko HERMEKING

    2005-01-01

    Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specific promoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. The p53-regulated gene 14-3-3σ undergoes frequent epigenetic silencing in several types of cancer, including carcinoma of the breast, prostate, and skin, suggesting that the loss of 14-3-3σ expression may be causally involved in tumor progression.Functional studies demonstrated that 14-3-3σ is involved in cell-cycle control and prevents the accumulation of chromosomal damage. The recent identification of novel 14-3-3σ-associated proteins by a targeted proteomics approach implies that 14-3-3σ regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3σ expression in cancer cells.

  18. Dicentric Chromosome Formation and Epigenetics of Centromere Formation in Plants

    Institute of Scientific and Technical Information of China (English)

    Shulan Fu; Zhi Gao; James Birchler; Fangpu Han

    2012-01-01

    Plant centromeres are generally composed of tandem arrays of simple repeats that form a complex chromosome locus where the kinetochore forms and microtubules attach during mitosis and meiosis.Each chromosome has one centromere region,which is essential for accurate division of the genetic material.Recently,chromosomes containing two centromere regions (called dicentric chromosomes)have been found in maize and wheat.Interestingly,some dicentric chromosomes are stable because only one centromere is active and the other one is inactivated.Because such arrays maintain their typical structure for both active and inactive centromeres,the specification of centromere activity has an epigenetic component independent of the DNA sequence.Under some circumstances,the inactive centromeres may recover centromere function,which is called centromere reactivation.Recent studies have highlighted the important changes,such as DNA methylation and histone modification,that occur during centromere inactivation and reactivation.

  19. Ultraviolet inactivation of papain

    International Nuclear Information System (INIS)

    Flash photolysis transient spectra (lambda > 250 nm) of aqueous papain showed that the initial products are the neutral tryptophan radical Trp (lambdasub(max) 510 nm), the tryptophan triplet state 3Trp (lambdasub(max) 460 nm), the disulfide bridge electron adduct -SS-- (lambdasub(max) 420 nm) and the hydrated electron esub(aq)-. The -SS-- yield was not altered by nitrous oxide or air, indicating that the formation of this product does not involve electrons in the external medium. The original papain preparation was activated by irradiating under nitrogen. The action spectrum supports previous work attributing the low initial activity to blocking of cysteinyl site 25 with a mixed disulfide. Flask lamp irradiation in nitrogen led to activation at low starting activities and inactivation at higher starting activities, while only inactivation at the same quantum yield was observed with air saturation. The results are consistent with photoionization of an essential tryptophyl residue as the key inactivating step. (author)

  20. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1, 1980-Dec 31, 1980. [Consequences of radiotherapy and/or chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J. D.

    1980-09-01

    The relationship of the chromosome pattern in leukemic cells to prior disease and to the type of therapy are summarized. Although the karyotype seen in secondary ANLL is distinctly different from that seen in the primary malignancy, the nature of the primary disease may influence the pattern of karyotypic changes seen in the leukemic cell. This notion is very speculative and is based on limited observations. Two of three patients with leukemia following multiple myeloma were unique in that they were the only ones whose leukemic cells had more than 48 chromosomes, with +1, +6, +8, +21; this constellation of abnormalities was not seen in any of the other patients. Since most of the patients had received both radiotherapy and chemotherapy, it is difficult to determine whether specific chromosome changes are related more closely to one rather than the other of these types of therapy. It appears, however, that combined therapy is much more likely to result in abnormalities of both No. 5 and No. 7 (9/15 patients) than is either modality used alone (1/12). (ERB)

  1. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  2. Chromosome Architecture and Genome Organization

    OpenAIRE

    Giorgio Bernardi

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few...

  3. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  4. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1-December 31, 1984

    International Nuclear Information System (INIS)

    Oncogenes associated with human neoplasms are genetically mapped to the human genome. In addition, chromosomal deletions and rearrangements presumably induced by radiotherapy and/or chemotherapy for other maladys are correlated with malignant lymphomas. 27 refs., 6 figs., 2 tabs. (DT)

  5. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, January 1, 1980-December 31, 1982

    International Nuclear Information System (INIS)

    The observations that two particular translocations are consistently associated with specific differentiation stages of acute nonlymphocytic leukemia were confirmed. These are the translocation between chromosomes 8 and 21 in acute myeloblastic leukemia with maturation and the translocation between chromosomes 15 and 17 in acute promyelocytic leukemia. The observation of others that structural rearrangements involving the long arm of No. 11 are frequently seen in acute monoblastic leukemia was also confirmed. The chromosome aberrations that are observed in the great majority of patients with acute leukemia secondary to cytotoxic therapy were defined. Thus of 47 patients with secondary acute nonlymphocytic leukemia, an aneuploid clone was seen in 44, and 39 of the 44 had a loss of part or all of No. 5 and/or No. 7. I have been able to localize the region of chromosome No. 7, loss of which is important for the development of leukemia was localized. Patients with ANLL de novo whose occupational histories suggest exposure to potentially mutagenic agents have a higher frequency of aberrations involving Nos. 5 and/or 7, than do patients not so exposed. Thus 50% of exposed versus 10% of nonexposed patients had aberrations of Nos. 5 or 7

  6. X-inactivation patterns in Aicardi syndrome

    Science.gov (United States)

    Aicardi syndrome (AIC) is a severe sporadic neurodevelopmental disorder, characterized by a classic triad of agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms. Because nearly all affected individuals are female and the few known males with AIC have a 47,XXY karyotype, it i...

  7. Demasculinization of the Anopheles gambiae X chromosome

    Directory of Open Access Journals (Sweden)

    Magnusson Kalle

    2012-05-01

    Full Text Available Abstract Background In a number of organisms sex-biased genes are non-randomly distributed between autosomes and the shared sex chromosome X (or Z. Studies on Anopheles gambiae have produced conflicting results regarding the underrepresentation of male-biased genes on the X chromosome and it is unclear to what extent sexual antagonism, dosage compensation or X-inactivation in the male germline, the evolutionary forces that have been suggested to affect the chromosomal distribution of sex-biased genes, are operational in Anopheles. Results We performed a meta-analysis of sex-biased gene expression in Anopheles gambiae which provides evidence for a general underrepresentation of male-biased genes on the X-chromosome that increased in significance with the observed degree of sex-bias. A phylogenomic comparison between Drosophila melanogaster, Aedes aegypti and Culex quinquefasciatus also indicates that the Anopheles X chromosome strongly disfavours the evolutionary conservation of male-biased expression and that novel male-biased genes are more likely to arise on autosomes. Finally, we demonstrate experimentally that transgenes situated on the Anopheles gambiae X chromosome are transcriptionally silenced in the male germline. Conclusion The data presented here support the hypothesis that the observed demasculinization of the Anopheles X chromosome is driven by X-chromosome inactivation in the male germline and by sexual antagonism. The demasculinization appears to be the consequence of a loss of male-biased expression, rather than a failure in the establishment or the extinction of male-biased genes.

  8. X inactivation counting and choice is a stochastic process : evidence for involvement of an X-linked activator

    NARCIS (Netherlands)

    Monkhorst, Kim; Jonkers, Iris; Rentmeester, Eveline; Grosveld, Frank; Gribnau, Joost

    2008-01-01

    Female mammalian cells achieve dosage compensation of X-encoded genes by X chromosome inactivation (XCI). This process is thought to involve X chromosome counting and choice. To explore how this process is initiated, we analyzed XCI in tetraploid XXXX, XXXY, and XXYY embryonic stem cells and found t

  9. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  10. Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

    OpenAIRE

    Kurt Giles; Glidden, David V.; Robyn Beckwith; Rose Seoanes; David Peretz; Stephen J DeArmond; Prusiner, Stanley B.

    2008-01-01

    Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectiv...

  11. Chromosome Microarray.

    Science.gov (United States)

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  12. The demoiselle of X-inactivation: 50 years old and as trendy and mesmerising as ever.

    Directory of Open Access Journals (Sweden)

    Céline Morey

    2011-07-01

    Full Text Available In humans, sexual dimorphism is associated with the presence of two X chromosomes in the female, whereas males possess only one X and a small and largely degenerate Y chromosome. How do men cope with having only a single X chromosome given that virtually all other chromosomal monosomies are lethal? Ironically, or even typically many might say, women and more generally female mammals contribute most to the job by shutting down one of their two X chromosomes at random. This phenomenon, called X-inactivation, was originally described some 50 years ago by Mary Lyon and has captivated an increasing number of scientists ever since. The fascination arose in part from the realisation that the inactive X corresponded to a dense heterochromatin mass called the "Barr body" whose number varied with the number of Xs within the nucleus and from the many intellectual questions that this raised: How does the cell count the X chromosomes in the nucleus and inactivate all Xs except one? What kind of molecular mechanisms are able to trigger such a profound, chromosome-wide metamorphosis? When is X-inactivation initiated? How is it transmitted to daughter cells and how is it reset during gametogenesis? This review retraces some of the crucial findings, which have led to our current understanding of a biological process that was initially considered as an exception completely distinct from conventional regulatory systems but is now viewed as a paradigm "par excellence" for epigenetic regulation.

  13. Transient Microgeographic Clines during B Chromosome Invasion.

    Science.gov (United States)

    Camacho, Juan Pedro M; Shaw, Michael W; Cabrero, Josefa; Bakkali, Mohammed; Ruíz-Estévez, Mercedes; Ruíz-Ruano, Francisco J; Martín-Blázquez, Rubén; López-León, María Dolores

    2015-11-01

    The near-neutral model of B chromosome evolution predicts that the invasion of a new population should last some tens of generations, but the details on how it proceeds in real populations are mostly unknown. Trying to fill this gap, we analyze here a natural population of the grasshopper Eyprepocnemis plorans at three time points during the last 35 years. Our results show that B chromosome frequency increased significantly during this period and that a cline observed in 1992 had disappeared in 2012 once B chromosome frequency reached an upper limit at all sites sampled. This indicates that, during B chromosome invasion, transient clines for B chromosome frequency are formed at the invasion front on a microgeographic scale. Computer simulation experiments showed that the pattern of change observed for genotypic frequencies is consistent with the existence of B chromosome drive through females and selection against individuals with a high number of B chromosomes. PMID:26655780

  14. Assignment of human sprouty 4 gene to chromosome segment 5q32∼33 and analysis of its pattern of expression

    Indian Academy of Sciences (India)

    Hua Liu; Jin-Zhong Chen; Shao-Hua Gu; Jian-Liang Dai; En-Pang Zhao; Lu Huang; Wang-Xiang Xu; Yi Xie; Yu-Min Mao

    2003-04-01

    The human sprouty 4 (SPYR4) gene was localized to chromosome band 5q32∼33 by screening the Stanford radiation hybrid G3 panel using a SPRY4-specific primer pair for PCR. Northern blot analysis revealed two different mRNAs (5 kb and 2 kb) in liver, skeletal muscle, heart, lung, kidney, spleen, placenta and small intestine. Reverse transcriptase-PCR analysis showed that SPYR4 was expressed in all tested tissues to different levels.

  15. Strong Constraint on Human Genes Escaping X-Inactivation Is Modulated by their Expression Level and Breadth in Both Sexes.

    Science.gov (United States)

    Slavney, Andrea; Arbiza, Leonardo; Clark, Andrew G; Keinan, Alon

    2016-02-01

    In eutherian mammals, X-linked gene expression is normalized between XX females and XY males through the process of X chromosome inactivation (XCI). XCI results in silencing of transcription from one ChrX homolog per female cell. However, approximately 25% of human ChrX genes escape XCI to some extent and exhibit biallelic expression in females. The evolutionary basis of this phenomenon is not entirely clear, but high sequence conservation of XCI escapers suggests that purifying selection may directly or indirectly drive XCI escape at these loci. One hypothesis is that this signal results from contributions to developmental and physiological sex differences, but presently there is limited evidence supporting this model in humans. Another potential driver of this signal is selection for high and/or broad gene expression in both sexes, which are strong predictors of reduced nucleotide substitution rates in mammalian genes. Here, we compared purifying selection and gene expression patterns of human XCI escapers with those of X-inactivated genes in both sexes. When we accounted for the functional status of each ChrX gene's Y-linked homolog (or "gametolog"), we observed that XCI escapers exhibit greater degrees of purifying selection in the human lineage than X-inactivated genes, as well as higher and broader gene expression than X-inactivated genes across tissues in both sexes. These results highlight a significant role for gene expression in both sexes in driving purifying selection on XCI escapers, and emphasize these genes' potential importance in human disease. PMID:26494842

  16. High-resolution methylation analysis of the human hypoxanthine phosphoribosyltransferase gene 5{prime} region on the active and inactive X chromosomes: Correlation with binding sites for transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Hornstra, I.K.; Yang, T.P. [Univ. of Florida College of Medicine, Gainesville, FL (United States)

    1994-02-01

    DNA methylation within GC-rich promoters of constitutively expressed X-linked genes is correlated with transcriptional silencing on the inactive X chromosome in female mammals. For most X-linked genes, X chromosome inactivation results in transcriptionally active and inactive alleles occupying each female nucleus. To examine mechanisms responsible for maintaining this unique system of differential gene expression, we have analyzed the methylation of individual cytosine residues in the 5{prime} CpG island of the human hypoxanthine phosphoribosyltransferase (HPRT) gene on the active and inactive X chromosomes. These studies demonstrate the 5{prime} CpG islands of active and 5-azacytidine-reactivated alleles are essentially unmethylated while the inactive allele is hypermethylated. The inactive allele is completely methylated at nearly all CpG dinucleotides except in a 68-bp region containing four adjacent GC boxes where most CpG dinucleotides are either unmethylated or partially methylated. Curiously, these GC boxes exhibit in vivo footprints only on the active X chromosome, not on the inactive X. The methylation pattern of the inactive HPRT gene is strikingly different from that reported for the inactive X-linked human phosphoglycerate kinase gene which exhibits methylation at all CpG sites in the 5{prime} CpG island. These results suggest that the position of methylated CpG dinucleotides, the density of methylated CpGs, the length of methylated regions, and/or chromatin structure associated with methylated DNA may have a role in repressing the activity of housekeeping promoters on the inactive X chromosome. The pattern of DNA methylation on the inactive human HPRT gene may also provide insight into the process of inactivating the gene early in female embryogenesis. 55 refs., 7 figs.

  17. The chicken Z chromosome is enriched for genes with preferential expression in ovarian somatic cells

    Czech Academy of Sciences Publication Activity Database

    Mořkovský, L.; Storchová, R.; Plachý, Jiří; Ivánek, Robert; Divina, Petr; Hejnar, Jiří

    2010-01-01

    Roč. 70, č. 2 (2010), s. 129-136. ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50520514 Keywords : Z chromosome * meiotic sex chromosome inactivation * sexual antagonisms Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.311, year: 2010

  18. Role of Testis-Specific Gene Expression in Sex-Chromosome Evolution of Anopheles gambiae

    Science.gov (United States)

    Baker, Dean A.; Russell, Steven

    2011-01-01

    Gene expression in Anopheles gambiae shows a deficiency of testis-expressed genes on the X chromosome associated with an excessive movement of retrogene duplication. We suggest that the degeneration of sex chromosomes in this monandrous species is likely the result of pressures from X inactivation, dosage compensation, and sexual antagonism. PMID:21890740

  19. Contrasting Patterns of Transposable Element and Satellite Distribution on Sex Chromosomes (XY1Y2) in the Dioecious Plant Rumex acetosa

    Czech Academy of Sciences Publication Activity Database

    Šteflová, Pavlína; Tokan, Viktor; Vogel, Ivan; Lexa, M.; Macas, Jiří; Novák, Petr; Hobza, Roman; Vyskot, Boris; Kejnovský, Eduard

    2013-01-01

    Roč. 5, č. 4 (2013), s. 769-782. ISSN 1759-6653 R&D Projects: GA ČR(CZ) GAP305/10/0930; GA ČR(CZ) GAP501/10/0102; GA ČR(CZ) GAP501/12/2220 Grant ostatní: GA MŠk(CZ) ED1.1.00/02.0068 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 ; RVO:60077344 Keywords : Y-CHROMOSOME * REPETITIVE SEQUENCES * SILENE-LATIFOLIA Subject RIV: BO - Biophysics; EB - Genetics ; Molecular Biology (BC-A) Impact factor: 4.532, year: 2013

  20. Evaluating the Relationship between Spermatogenic Silencing of the X Chromosome and Evolution of the Y Chromosome in Chimpanzee and Human

    Science.gov (United States)

    Mulugeta Achame, Eskeatnaf; Baarends, Willy M.; Gribnau, Joost; Grootegoed, J. Anton

    2010-01-01

    Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals. PMID:21179482

  1. Transmission Behavior of B Chromosomes in Prochilodus lineatus (Characiformes, Prochilodontidae).

    Science.gov (United States)

    Penitente, Manolo; Daniel, Sandro N; Senhorini, José A; Foresti, Fausto; Porto-Foresti, Fábio

    2015-01-01

    The population of Prochilodus lineatus found in the Mogi-Guaçu River is karyotypically polymorphic, carrying acrocentric, metacentric, and submetacentric B chromosomes. The analysis of each B chromosome frequency in this species revealed a variation in the distribution pattern, with the metacentric type having the highest frequency (73.30%), followed by submetacentric (25.22%) and acrocentric B chromosomes (1.48%). The transmission pattern of the supernumerary chromosomes was identified by controlled crosses, and it was shown that the acro- and submetacentric B chromosomes have a transmission pattern below the Mendelian rate (kB = 0.333 and kB = 0.385, respectively), but the metacentric variant has a cumulative transmission pattern (kB = 0.587). These results indicate that the acro- and submetacentric B chromosomes are undergoing an extinction process, while the metacentric B chromosomes appear to be accumulating in frequency with each generation. PMID:26795613

  2. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae

    Directory of Open Access Journals (Sweden)

    Artoni Roberto F

    2011-07-01

    Full Text Available Abstract Background The Characidium (a Neotropical fish group have a conserved diploid number (2n = 50, but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR. In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish.

  3. Chromosomal painting and ZW sex chromosomes differentiation in Characidium (Characiformes, Crenuchidae)

    Science.gov (United States)

    2011-01-01

    Background The Characidium (a Neotropical fish group) have a conserved diploid number (2n = 50), but show remarkable differences among species and populations in relation to sex chromosome systems and location of nucleolus organizer regions (NOR). In this study, we isolated a W-specific probe for the Characidium and characterized six Characidium species/populations using cytogenetic procedures. We analyzed the origin and differentiation of sex and NOR-bearing chromosomes by chromosome painting in populations of Characidium to reveal their evolution, phylogeny, and biogeography. Results A W-specific probe for efficient chromosome painting was isolated by microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) amplification of W chromosomes from C. gomesi. The W probe generated weak signals dispersed on the proto sex chromosomes in C. zebra, dispersed signals in both W and Z chromosomes in C. lauroi and, in C. gomesi populations revealed a proximal site on the long arms of the Z chromosome and the entire W chromosome. All populations showed small terminal W probe sites in some autosomes. The 18S rDNA revealed distinctive patterns for each analyzed species/population with regard to proto sex chromosome, sex chromosome pair, and autosome location. Conclusions The results from dual-color fluorescence in situ hybridization (dual-color FISH) using W and 18S rDNA probes allowed us to infer the putative evolutionary pathways for the differentiation of sex chromosomes and NORs, from structural rearrangements in a sex proto-chromosome, followed by gene erosion and heterochromatin amplification, morphological differentiation of the sex chromosomal pair, and NOR transposition, giving rise to the distinctive patterns observed among species/populations of Characidium. Biogeographic isolation and differentiation of sex chromosomes seem to have played a major role in the speciation process in this group of fish. PMID:21787398

  4. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation: Comprehensive progress report, January 1986--June 1988

    International Nuclear Information System (INIS)

    I purchased one of the few available prototypes of the pulse field gel electrophoresis (PFGE) apparatus. We used PFGE and its various modifications to map the human Abelson protooncogene (ABL) and to show that the two alternative first exons (Ia and Ib) are separated by at least 200 kilobases (kb). This has provided the first evidence that alternative splicing from exon Ib to the common splice acceptor site (exon II) could occur over such very large distances. We are actively using vertical field gel electrophoresis, a modification of PFGE, for mapping various DNA probes on chromosome 5. Another major advance has been the development of the polymerase chain reaction (PCR). We are currently using this to define the breakpoints in the BCR gene in the 9; 22 translocation in chronic myeloid leukemia (CML) and in Ph1-positive acute lymphoblastic leukemia (ALL). I had expected to be able to describe major progress in cloning the chromosome translocation breakpoints in ANLL, and this has not occurred. Our laboratory knows how to solve the problem. We successfully cloned a new translocation breakpoint in B cell chronic lymphatic leukemia involving Nos. 14 and 19. 22 refs., 2 figs., 5 tabs

  5. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, July 1991--June 1994

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1994-06-01

    This comprehensive progress report provides a synopsis of major research accomplishments during the years of 1991-1994, including the technical aspects of the project. The objectives and accomplishments are as follows: 1. Defining the chromosome segments associated with radiation and chemically-induced leukemogenesis (treatment-related acute myeloid leukemia, t-AML); A. Continued genetic analysis of chromosomes 5 and 7, B. Correlation of treatment with balanced and unbalanced translocations. 2. Cloning the breakpoints in balanced translocations in t-AML; A. Clone the t(9;11) and t(11;19) breakpoints, B. Clone the t(3,21)(q26,q22) breakpoint, C. Determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 3. Compare the breakpoint junctions in patients who have the same translocations in t-AML and AML de novo. 4. Map the scaffold attachment regions in the genes that are involved in balanced translocations in t-AML. Plans for the continuation of present objectives and possible new objectives in consideration of past results are also provided.

  6. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Final report, January 1--December 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1998-03-01

    It has been clear for the last 15 years that cloning translocation breakpoints in both AML de novo and t-AML would provide the DNA probes required to determine whether the breakpoints in cytogenetically apparently similar translocations were identical at the level of DNA. Therefore the author has pursued an analysis of rearrangements in both types of leukemia simultaneously. She has also cloned and sequenced several translocations in acute lymphoblastic leukemia and in chronic lymphatic leukemia. Recently she cloned the breakpoint in a number of translocations involving chromosome bands 11q23 and 21q22. She has cloned the gene which she called MLL, that is located in 11q23 that is involved in the 6;11, 9;11, and 11;19 translocations that are seen in AML de novo as well as in t-AML. She has evidence that the breakpoint in 11q23 and in the t(9;11) is relatively similar in de novo and secondary AML. In addition, she has cloned the gene at the breakpoint in chromosome 21 in the t(3;21). These studies have provided DNA probes that will be very important for diagnosis and for monitoring the patient`s response to treatment.

  7. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Final report, January 1--December 31, 1997

    International Nuclear Information System (INIS)

    It has been clear for the last 15 years that cloning translocation breakpoints in both AML de novo and t-AML would provide the DNA probes required to determine whether the breakpoints in cytogenetically apparently similar translocations were identical at the level of DNA. Therefore the author has pursued an analysis of rearrangements in both types of leukemia simultaneously. She has also cloned and sequenced several translocations in acute lymphoblastic leukemia and in chronic lymphatic leukemia. Recently she cloned the breakpoint in a number of translocations involving chromosome bands 11q23 and 21q22. She has cloned the gene which she called MLL, that is located in 11q23 that is involved in the 6;11, 9;11, and 11;19 translocations that are seen in AML de novo as well as in t-AML. She has evidence that the breakpoint in 11q23 and in the t(9;11) is relatively similar in de novo and secondary AML. In addition, she has cloned the gene at the breakpoint in chromosome 21 in the t(3;21). These studies have provided DNA probes that will be very important for diagnosis and for monitoring the patient's response to treatment

  8. Chromosome Architecture and Genome Organization

    Science.gov (United States)

    Bernardi, Giorgio

    2015-01-01

    How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076

  9. Normal histone modifications on the inactive X chromosome in ICF and Rett syndrome cells: implications for methyl-CpG binding proteins

    Directory of Open Access Journals (Sweden)

    Canfield Theresa K

    2004-09-01

    Full Text Available Abstract Background In mammals, there is evidence suggesting that methyl-CpG binding proteins may play a significant role in histone modification through their association with modification complexes that can deacetylate and/or methylate nucleosomes in the proximity of methylated DNA. We examined this idea for the X chromosome by studying histone modifications on the X chromosome in normal cells and in cells from patients with ICF syndrome (Immune deficiency, Centromeric region instability, and Facial anomalies syndrome. In normal cells the inactive X has characteristic silencing type histone modification patterns and the CpG islands of genes subject to X inactivation are hypermethylated. In ICF cells, however, genes subject to X inactivation are hypomethylated on the inactive X due to mutations in the DNA methyltransferase (DNMT3B genes. Therefore, if DNA methylation is upstream of histone modification, the histones on the inactive X in ICF cells should not be modified to a silent form. In addition, we determined whether a specific methyl-CpG binding protein, MeCP2, is necessary for the inactive X histone modification pattern by studying Rett syndrome cells which are deficient in MeCP2 function. Results We show here that the inactive X in ICF cells, which appears to be hypomethylated at all CpG islands, exhibits normal histone modification patterns. In addition, in Rett cells with no functional MeCP2 methyl-CpG binding protein, the inactive X also exhibits normal histone modification patterns. Conclusions These data suggest that DNA methylation and the associated methyl-DNA binding proteins may not play a critical role in determining histone modification patterns on the mammalian inactive X chromosome at the sites analyzed.

  10. Free radical inactivation of trypsin

    International Nuclear Information System (INIS)

    Reactivities of free radical oxidants, radical OH, Br2-anion radical and Cl3COO radical and a reductant, CO2-anion radical, with trypsin and reactive protein components were determined by pulse radiolysis of aqueous solutions at pH 7, 200C. Highly reactive free radicals, radical OH, Br2-anion radical and CO2-anion radical, react with trypsin at diffusion controlled rates. Moderately reactive trichloroperoxy radical, k(Cl3COO radical + trypsin) preferentially oxidizes histidine residues. The efficiency of inactivation of trypsin by free radicals is inversely proportional to their reactivity. The yields of inactivation of trypsin by radical OH, Br2-anion radical and CO2-anion radical are low, G(inactivation) = 0.6-0.8, which corresponds to ∼ 10% of the initially produced radicals. In contrast, Cl3COO radical inactivates trypsin with ∼ 50% efficiency, i.e. G(inactivation) = 3.2. (author)

  11. Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Progress report, January 1, 1981-December 31, 1981

    International Nuclear Information System (INIS)

    The overall aim is to determine whether there is a relationship between exposure to radiation, environmental pollutants, and/or genetic background and the development of ANLL or other hematologic malignancies. I will try to define the factors that influence the development of ANLL as a second malignancy in patients who have been exposed to large doses of radiotherapy and/or chemotherapeutic agents. Two long-term goals are (1) to identify the genes that are located at the sites of consistent translocations, and then to determine the alterations in gene function that are associated with these translocations and (2) to establish the baseline frequency of various chromosome changes (mutations) in myeloid cells and then to analyze the influence of various types of environmental exposure or medical treatment on this baseline mutation rate. Ultimately, it may be possible to determine the extent of mutagenic exposure in various populations through an analysis of the leukemic cells of that populations

  12. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Science.gov (United States)

    Sankaranarayanan, Preethi; Schomay, Theodore E; Aiello, Katherine A; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq, PABPC5

  13. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    Directory of Open Access Journals (Sweden)

    Preethi Sankaranarayanan

    Full Text Available The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD, which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs. We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival

  14. hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors.

    Science.gov (United States)

    Rousseau-Merck, M F; Versteege, I; Legrand, I; Couturier, J; Mairal, A; Delattre, O; Aurias, A

    1999-07-01

    The chromatin-remodeling hSNF5/INI1 gene has recently been shown to act as a tumor suppressor gene in rhabdoid tumors (RTs). In an attempt to further characterize the main chromosomal mechanisms involved in hSNF5/INI1 inactivation in RTs, we report here the molecular cytogenetic data obtained in 12 cell lines harboring hSNF5/INI1 mutations and/or deletions in relation to the molecular genetic analysis using polymorphic markers extended to both extremities of chromosome 22q. On the whole, mitotic recombination occurring in the proximal part of chromosome 22q, as demonstrated in five cases, and nondisjunction/duplication, highly suspected in two cases (processes leading respectively to partial or complete isodisomy), appear to be major mechanisms associated with hSNF5/INI1 inactivation. Such isodisomy accompanies each of the RTs exhibiting two cytogenetically normal chromosomes 22. This results in homozygosity for the mutation at the hSNF5/INI1 locus. An alternate mechanism accounting for hSNF5/INI1 inactivation observed in these tumors is homozygous deletion in the rhabdoid consensus region. This was observed in each of the four tumors carrying a chromosome 22q abnormality and, in particular, in the three tumors with chromosomal translocations. Only one case of our series illustrates the mutation/deletion classical model proposed for the double-hit inactivation of a tumor suppressor gene. PMID:10397258

  15. Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: Methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability

    International Nuclear Information System (INIS)

    The 5' region of the gene encoding human X chromosome-linked phosphoglycerate kinase 1 (PGK1) is a promoter-containing CpG island known to be methylated at 119 of 121 CpG dinucleotides in a 450-base-pair region on the inactive human X chromosome in the hamster-human cell line X8-6T2. Here the authors report the use of polymerase chain reaction-aided genomic sequencing to determine the complete methylation pattern of this region in clones derived form X8-6T2 cells after treatment with the methylation inhibitor 5-azacytidine. They fine (i) a clone showing full expression of human phosphoglycerate kinase is fully unmethylated in this region; (ii) clones not expressing human phosphoglycerate kinase remain methylated at ∼50% of CpG sites, with a pattern of interspersed methylated (M) and unmethylated (U) sites different for each clone; (iii) singles, defined as M-U-M or U-M-U, are common; and (iv) a few CpG sites are partially methylated. The data are interpreted according to a model of multiple, autonomous CpG sites, and estimates are made for two key parameters, maintenance efficiency and de novo methylation efficiency. They also consider how the active region is kept free of methylation and suggest that transcription inhibits methylation by decreasing Em so that methylation cannot be maintained. Thus, multiple CpG sites, independent with respect to a dynamic methylation system, can stabilize two alternative states of methylation and transcription

  16. Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes

    DEFF Research Database (Denmark)

    Zhou, Qi; Wang, Jun; Huang, Ling; Nie, Wenhui; Wang, Jinhuan; Liu, Yan; Zhao, Xiangyi; Yang, Fengtang; Wang, Wen

    2008-01-01

    BACKGROUND: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation. RESULTS: We studied the intriguing case of black...... muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene...... SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles. CONCLUSION: The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals...

  17. Molecular cloning, genomic organization, chromosome mapping, tissues expression pattern and identification of a novel splicing variant of porcine CIDEb gene.

    Science.gov (United States)

    Li, YanHua; Li, AiHua; Yang, Z Q

    2016-09-01

    Cell death-inducing DNA fragmentation factor-α-like effector b (CIDEb) is a member of the CIDE family of apoptosis-inducing factors, CIDEa and CIDEc have been reported to be Lipid droplets (LDs)-associated proteins that promote atypical LD fusion in adipocytes, and responsible for liver steatosis under fasting and obese conditions, whereas CIDEb promotes lipid storage under normal diet conditions [1], and promotes the formation of triacylglyceride-enriched VLDL particles in hepatocytes [2]. Here, we report the gene cloning, chromosome mapping, tissue distribution, genetic expression analysis, and identification of a novel splicing variant of the porcine CIDEb gene. Sequence analysis shows that the open reading frame of the normal porcine CIDEb isoform covers 660bp and encodes a 219-amino acid polypeptide, whereas its alternative splicing variant encodes a 142-amino acid polypeptide truncated at the fourth exon and comprised of the CIDE-N domain and part of the CIDE-C domain. The deduced amino acid sequence of normal porcine CIDEb shows an 85.8% similarity to the human protein and 80.0% to the mouse protein. The CIDEb genomic sequence spans approximately 6KB comprised of five exons and four introns. Radiation hybrid mapping demonstrated that porcine CIDEb is located at chromosome 7q21 and at a distance of 57cR from the most significantly linked marker, S0334, regions that are syntenic with the corresponding region in the human genome. Tissue expression analysis indicated that normal CIDEb mRNA is ubiquitously expressed in many porcine tissues. It was highly expressed in white adipose tissue and was observed at relatively high levels in the liver, lung, small intestine, lymphatic tissue and brain. The normal version of CIDEb was the predominant form in all tested tissues, whereas the splicing variant was expressed at low levels in all examined tissues except the lymphatic tissue. Furthermore, genetic expression analysis indicated that CIDEb mRNA levels were

  18. Mitotic chromosome structure

    International Nuclear Information System (INIS)

    Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

  19. Mesenchymal stem cells with high telomerase expression do not actively restore their chromosome arm specific telomere length pattern after exposure to ionizing radiation

    DEFF Research Database (Denmark)

    Graakjaer, Jesper; Christensen, Rikke; Kølvrå, Steen;

    2007-01-01

    investigate the existence and maintenance of the telomere length pattern in stem cells. For this aim we studied telomere length in primary human mesenchymal stem cells (hMSC) and their telomerase-immortalised counterpart (hMSC-telo1) during extended proliferation as well as after irradiation. Telomere lengths...

  20. Degeneration of the Y chromosome in evolutionary aging models

    Science.gov (United States)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  1. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J;

    1983-01-01

    A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were...... unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2.4). Women with a known familial translocation and women 40 years or more have a relative risk of 5.7 of having an unbalanced chromosome......The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...

  2. Haploinsufficiency and the sex chromosomes from yeasts to humans

    Directory of Open Access Journals (Sweden)

    Oliver Stephen G

    2011-02-01

    Full Text Available Abstract Background Haploinsufficient (HI genes are those for which a reduction in copy number in a diploid from two to one results in significantly reduced fitness. Haploinsufficiency is increasingly implicated in human disease, and so predicting this phenotype could provide insights into the genetic mechanisms behind many human diseases, including some cancers. Results In the present work we show that orthologues of Saccharomyces cerevisiae HI genes are preferentially retained across the kingdom Fungi, and that the HI genes of S. cerevisiae can be used to predict haploinsufficiency in humans. Our HI gene predictions confirm known associations between haploinsufficiency and genetic disease, and predict several further disorders in which the phenotype may be relevant. Haploinsufficiency is also clearly relevant to the gene-dosage imbalances inherent in eukaryotic sex-determination systems. In S. cerevisiae, HI genes are over-represented on chromosome III, the chromosome that determines yeast's mating type. This may be a device to select against the loss of one copy of chromosome III from a diploid. We found that orthologues of S. cerevisiae HI genes are also over-represented on the mating-type chromosomes of other yeasts and filamentous fungi. In animals with heterogametic sex determination, accumulation of HI genes on the sex chromosomes would compromise fitness in both sexes, given X chromosome inactivation in females. We found that orthologues of S. cerevisiae HI genes are significantly under-represented on the X chromosomes of mammals and of Caenorhabditis elegans. There is no X inactivation in Drosophila melanogaster (increased expression of X in the male is used instead and, in this species, we found no depletion of orthologues to yeast HI genes on the sex chromosomes. Conclusion A special relationship between HI genes and the sex/mating-type chromosome extends from S. cerevisiae to Homo sapiens, with the microbe being a useful model for

  3. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome

    DEFF Research Database (Denmark)

    da Rocha, Simão Teixeira; Boeva, Valentina; Escamilla-Del-Arenal, Martin;

    2014-01-01

    During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2) is thought to participate in the early maintenance of the inactive state. Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate th...

  4. Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut

    International Nuclear Information System (INIS)

    developed cancer earlier, (b) perturbations in components of the chromosome segregation machinery could be involved in the initial process of carcinogenicity and (c) the importance of precocious anaphase as a screening marker for identification of mitotic checkpoint defects during early days

  5. Epigenetic inactivation and aberrant transcription of CSMD1 in squamous cell carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Scholnick Steven B

    2005-09-01

    Full Text Available Abstract Background The p23.2 region of human chromosome 8 is frequently deleted in several types of epithelial cancer and those deletions appear to be associated with poor prognosis. Cub and Sushi Multiple Domains 1 (CSMD1 was positionally cloned as a candidate for the 8p23 suppressor but point mutations in this gene are rare relative to the frequency of allelic loss. In an effort to identify alternative mechanisms of inactivation, we have characterized CSMD1 expression and epigenetic modifications in head and neck squamous cell carcinoma cell lines. Results Only one of the 20 cell lines examined appears to express a structurally normal CSMD1 transcript. The rest express transcripts which either lack internal exons, terminate abnormally or initiate at cryptic promoters. None of these truncated transcripts is predicted to encode a functional CSMD1 protein. Cell lines that express little or no CSMD1 RNA exhibit DNA methylation of a specific region of the CpG island surrounding CSMD1's first exon. Conclusion Correlating methylation patterns and expression suggests that it is modification of the genomic DNA preceding the first exon that is associated with gene silencing and that methylation of CpG dinucleotides further 3' does not contribute to inactivation of the gene. Taken together, the cell line data suggest that epigenetic silencing and aberrant splicing rather than point mutations may be contributing to the reduction in CSMD1 expression in squamous cancers. These mechanisms can now serve as a focus for further analysis of primary squamous cancers.

  6. Inactivation of bacteria in sewage sludge by gamma radiation

    International Nuclear Information System (INIS)

    The survival of certain bacterial cultures suspended in sewage sludge and exposed to gamma-radiation was studied. The inactivation patterns of most of the organisms were significantly different when irradiation was performed using sewage samples collected in the summer and monsoon seasons. The summer sample collected from the anaerobic digester afforded significant protection to both Gram negative and Gram positive organisms. This was evident by the increase in dose required to bring about a 6 log cycle reduction in viable count of the bacterial cultures, when suspended in sewage samples instead of phosphate buffer. The observations made using monsoon digester samples were quite different. This sewage sludge greatly enhanced inactivation by gamma-radiation in most cases. The effects of certain chemicals on the inactivation patterns of two organisms - Salmonella typhi and Shigella flexneri - were examined. Arsenate, mercury and lead salts sensitised S. typhi, while barium acetate and sodium sulphide protected this culture against gamma-radiation. In the case of Sh. flexneri, barium acetate and iodacetamide proved to be radioprotectors. The effects of some chemicals on the inactivation pattern of Sh. flexneri cells irradiated in sludge are also discussed. (author)

  7. XWAS: A Software Toolset for Genetic Data Analysis and Association Studies of the X Chromosome.

    Science.gov (United States)

    Gao, Feng; Chang, Diana; Biddanda, Arjun; Ma, Li; Guo, Yingjie; Zhou, Zilu; Keinan, Alon

    2015-01-01

    XWAS is a new software suite for the analysis of the X chromosome in association studies and similar genetic studies. The X chromosome plays an important role in human disease and traits of many species, especially those with sexually dimorphic characteristics. Special attention needs to be given to its analysis due to the unique inheritance pattern, which leads to analytical complications that have resulted in the majority of genome-wide association studies (GWAS) either not considering X or mishandling it with toolsets that had been designed for non-sex chromosomes. We hence developed XWAS to fill the need for tools that are specially designed for analysis of X. Following extensive, stringent, and X-specific quality control, XWAS offers an array of statistical tests of association, including: 1) the standard test between a SNP (single nucleotide polymorphism) and disease risk, including after first stratifying individuals by sex, 2) a test for a differential effect of a SNP on disease between males and females, 3) motivated by X-inactivation, a test for higher variance of a trait in heterozygous females as compared with homozygous females, and 4) for all tests, a version that allows for combining evidence from all SNPs across a gene. We applied the toolset analysis pipeline to 16 GWAS datasets of immune-related disorders and 7 risk factors of coronary artery disease, and discovered several new X-linked genetic associations. XWAS will provide the tools and incentive for others to incorporate the X chromosome into GWAS and similar studies in any species with an XX/XY system, hence enabling discoveries of novel loci implicated in many diseases and in their sexual dimorphism. PMID:26268243

  8. Genetic Multipartitions Based on D-Loop Sequences and Chromosomal Patterns in Brown Chromis, Chromis multilineata (Pomacentridae, in the Western Atlantic

    Directory of Open Access Journals (Sweden)

    Inailson Márcio Costa da Cunha

    2014-01-01

    Full Text Available Connectivity levels among Brazilian reef fish fauna populations have attracted growing interest, mainly between mainland shores and oceanic islands. The Pomacentridae, whose phylogeographic patterns are largely unknown in the Atlantic, are a family of dominant fish in reef regions. We present data on the variability and population structure of damselfish Chromis multilineata in different areas along the northeast coast of Brazil and in the waters around the oceanic islands of Fernando de Noronha (FNA and Saint Peter and Saint Paul Archipelago (SPSPA through analysis of the HVR1 mtDNA sequence of the control region. The remote SPSPA exhibits the highest level of genetic divergence among populations. Conventional and molecular cytogenetic analysis showed similar karyotype patterns (2n = 48 acrocentrics between these insular areas. Our estimates reveal three genetically different population groups of C. multilineata on the Brazilian coast. The level of genetic structure is higher than previous data suggested, indicating complex panel of interactions between the oceanic island and coastal populations of Brazil.

  9. Thermal inactivation kinetics of partially purified mango pectin methylesterase

    Directory of Open Access Journals (Sweden)

    Claudio Alonso DÍAZ-CRUZ

    2016-01-01

    Full Text Available Abstract Kinetic parameters of thermal inactivation of pectin methylesterase (PME in a partially purified mango enzyme extract were determined. The PME of mango partially purified by salting out showed different patterns of thermal inactivation, indicating the presence of a thermostable fraction at 70 °C and a thermolabile fraction at lower temperatures. The inactivation of the thermostable fraction exhibited a linear behavior that yielded a z-value of 9.44 °C and an activation energy (Ea of 245.6 kJ mol-1 K-1 using the Arrhenius model. The thermostable mango PME fraction represented 17% of total crude enzyme extract, which emphasizes the importance of residual enzyme activity after heat treatment.

  10. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae).

    Science.gov (United States)

    Lukhtanov, Vladimir A

    2014-01-01

    Lepidoptera (butterflies and moths), as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae) based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (syn)apomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819]) and between-species (e.g. the genus Agathymus Freeman, 1959) levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution. PMID:25610542

  11. Chromosome number evolution in skippers (Lepidoptera, Hesperiidae

    Directory of Open Access Journals (Sweden)

    Vladimir Lukhtanov

    2014-11-01

    Full Text Available Lepidoptera (butterflies and moths, as many other groups of animals and plants, simultaneously represent preservation of ancestral karyotype in the majority of families with a high degree of chromosome number instability in numerous independently evolved phylogenetic lineages. However, the pattern and trends of karyotype evolution in some Lepidoptera families are poorly studied. Here I provide a survey of chromosome numbers in skippers (family Hesperiidae based on intensive search and analysis of published data. I demonstrate that the majority of skippers preserve the haploid chromosome number n=31 that seems to be an ancestral number for the Hesperiidae and the order Lepidoptera at whole. However, in the tribe Baorini the derived number n=16 is the most typical state which can be used as a (synapomorphic character in further phylogenetic investigations. Several groups of skippers display extreme chromosome number variations on within-species (e.g. the representatives of the genus Carcharodus Hübner, [1819] and between-species (e.g. the genus Agathymus Freeman, 1959 levels. Thus, these groups can be used as model systems for future analysis of the phenomenon of chromosome instability. Interspecific chromosomal differences are also shown to be useful for discovering and describing new cryptic species of Hesperiidae representing in such a way a powerful tool in biodiversity research. Generally, the skipper butterflies promise to be an exciting group that will significantly contribute to the growing knowledge of patterns and processes of chromosome evolution.

  12. Compositions for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    1998-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  13. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

    Directory of Open Access Journals (Sweden)

    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

  14. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  15. Chromosome Territory Modeller and Viewer.

    Science.gov (United States)

    Tkacz, Magdalena A; Chromiński, Kornel; Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi-a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  16. Chromosome Territory Modeller and Viewer

    Science.gov (United States)

    Idziak-Helmcke, Dominika; Robaszkiewicz, Ewa; Hasterok, Robert

    2016-01-01

    This paper presents ChroTeMo, a tool for chromosome territory modelling, accompanied by ChroTeVi–a chromosome territory visualisation software that uses the data obtained by ChroTeMo. These tools have been developed in order to complement the molecular cytogenetic research of interphase nucleus structure in a model grass Brachypodium distachyon. Although the modelling tool has been initially created for one particular species, it has universal application. The proposed version of ChroTeMo allows for generating a model of chromosome territory distribution in any given plant or animal species after setting the initial, species-specific parameters. ChroTeMo has been developed as a fully probabilistic modeller. Due to this feature, the comparison between the experimental data on the structure of a nucleus and the results obtained from ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is also fully probabilistic or is subjected to certain non-random patterns. The presented tools have been written in Python, so they are multiplatform, portable and easy to read. Moreover, if necessary they can be further developed by users writing their portions of code. The source code, documentation, and wiki, as well as the issue tracker and the list of related articles that use ChroTeMo and ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license. PMID:27505434

  17. An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: Analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25

    Directory of Open Access Journals (Sweden)

    Wang Jie

    2008-02-01

    Full Text Available Abstract Background The HapMap project aimed to catalog millions of common single nucleotide polymorphisms (SNPs in the human genome in four major populations, in order to facilitate association studies of complex diseases. To examine the transferability of Han Chinese in Beijing HapMap data to the Southern Han Chinese in Shanghai, we performed comparative analyses between genotypes from over 4,500 SNPs in a 21 Mb region on chromosome 1q21-q25 in 80 unrelated Shanghai Chinese and 45 HapMap Chinese data. Results Three thousand and forty-two SNPs were analyzed after removal of SNPs that failed quality control and those not in the HapMap panel. We compared the allele frequency distributions, linkage disequilibrium patterns, haplotype frequency distributions and tagging SNP sets transferability between the HapMap population and Shanghai Chinese population. Among the four HapMap populations, Beijing Chinese showed the best correlation with Shanghai population on allele frequencies, linkage disequilibrium and haplotype frequencies. Tagging SNP sets selected from four HapMap populations at different thresholds were evaluated in the Shanghai sample. Under the threshold of r2 equal to 0.8 or 0.5, both HapMap Chinese and Japanese data showed better coverage and tagging efficiency than Caucasian and African data. Conclusion Our study supported the applicability of HapMap Beijing Chinese SNP data to the study of complex diseases among southern Chinese population.

  18. CRYPTOSPORIDIUM INACTIVATION AND REMOVAL RESEARCH

    Science.gov (United States)

    Bench- and pilot-scale tests were performed to assess the ability of conventional treatment, ozonation and chlorine dioxide to remove and inactivate Cryptosporidium oocysts. The impacts of coagulant type, coagulant dose, raw water quality, filter loading rates and filter media w...

  19. Radiation inactivation of proteolytic enzymes

    International Nuclear Information System (INIS)

    The survey was devoted to generalization of protease inactivation mechanism for different conditions of irradiation and for different kinds of enzymes. The importance of radiation conformation changes and the possible use of radiolytic processes were considered especially. The serine-, SH-, acidic-and metal-contained enzymes were described

  20. Comparative Analysis of Inactivated Wood Surfaces

    OpenAIRE

    Sernek, Milan

    2002-01-01

    A wood surface, which is exposed to a high temperature condition, can experience inactivation. Surface inactivation results in reduced ability of an adhesive to properly wet, flow, penetrate, and cure. Thus, an inactivated wood surface does not bond well with adhesives. The changes in surface chemistry, wettability, and adhesion of inactivated wood surfaces, including heartwood of yellow-poplar (Liriodendron tulipifera) and southern pine (Pinus taeda), were studied. Wood samples were dri...

  1. Comparative analysis of inactivated wood surfaces

    OpenAIRE

    Šernek, Milan

    2015-01-01

    A wood surface, which is exposed to a high temperature condition, can experience inactivation. Surface inactivation results in reduced ability of an adhesive to properly wet, flow, penetrate, and cure. Thus, an inactivated wood surface does not bond well with adhesives. The changes in surface chemistry, wettability, and adhesion of inactivated wood surfaces, including heartwood of yellow-poplar (Liriodendron tulipifera) and southern pine (Pinus taeda), were studied. Wood samples were dried fr...

  2. Chimpanzee chromosome 12 is homologous to human chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Most of the 46 human chromosomes find their counterparts in the 48 chimpanzee chromosomes except for chromosome 2 which has been hypothesized to have been derived from a centric fusion of two chimpanzee acrocentric chromosomes. These two chromosomes correspond to the human chromosomes 2p and 2g. This conclusion is based primarily on chromosome banding techniques, and the somatic cell hybridization technique has also been used. (HLW)

  3. Effective Chemical Inactivation of Ebola Virus

    Science.gov (United States)

    Haddock, Elaine; Feldmann, Friederike

    2016-01-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  4. Effective Chemical Inactivation of Ebola Virus.

    Science.gov (United States)

    Haddock, Elaine; Feldmann, Friederike; Feldmann, Heinz

    2016-07-01

    Reliable inactivation of specimens before removal from high-level biocontainment is crucial for safe operation. To evaluate efficacy of methods of chemical inactivation, we compared in vitro and in vivo approaches using Ebola virus as a surrogate pathogen. Consequently, we have established parameters and protocols leading to reliable and effective inactivation. PMID:27070504

  5. A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere

    Science.gov (United States)

    Tsabar, Michael; Haase, Julian; Harrison, Benjamin; Snider, Chloe E.; Kaminsky, Lila; Hine, Rebecca M.; Haber, James E.; Bloom, Kerry

    2016-01-01

    Transcriptional inactivation of the budding yeast centromere has been a widely used tool in studies of chromosome segregation and aneuploidy. In haploid cells when an essential chromosome contains a single conditionally inactivated centromere (GAL-CEN), cell growth rate is slowed and segregation fidelity is reduced; but colony formation is nearly 100%. Pedigree analysis revealed that only 30% of the time both mother and daughter cell inherit the GAL-CEN chromosome. The reduced segregation capacity of the GAL-CEN chromosome is further compromised upon reduction of pericentric cohesin (mcm21∆), as reflected in a further diminishment of the Mif2 kinetochore protein at GAL-CEN. By redistributing cohesin from the nucleolus to the pericentromere (by deleting SIR2), there is increased presence of the kinetochore protein Mif2 at GAL-CEN and restoration of cell viability. These studies identify the ability of cohesin to promote chromosome segregation via kinetochore assembly, in a situation where the centromere has been severely compromised. PMID:27128635

  6. A Cohesin-Based Partitioning Mechanism Revealed upon Transcriptional Inactivation of Centromere.

    Science.gov (United States)

    Tsabar, Michael; Haase, Julian; Harrison, Benjamin; Snider, Chloe E; Eldridge, Brittany; Kaminsky, Lila; Hine, Rebecca M; Haber, James E; Bloom, Kerry

    2016-04-01

    Transcriptional inactivation of the budding yeast centromere has been a widely used tool in studies of chromosome segregation and aneuploidy. In haploid cells when an essential chromosome contains a single conditionally inactivated centromere (GAL-CEN), cell growth rate is slowed and segregation fidelity is reduced; but colony formation is nearly 100%. Pedigree analysis revealed that only 30% of the time both mother and daughter cell inherit the GAL-CEN chromosome. The reduced segregation capacity of the GAL-CEN chromosome is further compromised upon reduction of pericentric cohesin (mcm21∆), as reflected in a further diminishment of the Mif2 kinetochore protein at GAL-CEN. By redistributing cohesin from the nucleolus to the pericentromere (by deleting SIR2), there is increased presence of the kinetochore protein Mif2 at GAL-CEN and restoration of cell viability. These studies identify the ability of cohesin to promote chromosome segregation via kinetochore assembly, in a situation where the centromere has been severely compromised. PMID:27128635

  7. The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus

    OpenAIRE

    Deakin, Janine E; Hore, Timothy A; Koina, Edda; Marshall Graves, Jennifer A.

    2008-01-01

    Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and “placentals”) by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation...

  8. Co-expression of a modified maize ribosome-inactivating protein and a rice basic chitinase gene in transgenic rice plants confers enhanced resistance to sheath blight.

    Science.gov (United States)

    Kim, Ju-Kon; Jang, In-Cheol; Wu, Ray; Zuo, Wei-Neng; Boston, Rebecca S; Lee, Yong-Hwan; Ahn, Il-Pyung; Nahm, Baek Hie

    2003-08-01

    Chitinases, beta-1,3-glucanases, and ribosome-inactivating proteins are reported to have antifungal activity in plants. With the aim of producing fungus-resistant transgenic plants, we co-expressed a modified maize ribosome-inactivating protein gene, MOD1, and a rice basic chitinase gene, RCH10, in transgenic rice plants. A construct containing MOD1 and RCH10 under the control of the rice rbcS and Act1 promoters, respectively, was co-transformed with a plasmid containing the herbicide-resistance gene bar as a selection marker into rice by particle bombardment. Several transformants analyzed by genomic Southern-blot hybridization demonstrated integration of multiple copies of the foreign gene into rice chromosomes. Immunoblot experiments showed that MOD1 formed approximately 0.5% of the total soluble protein in transgenic leaves. RCH10 expression was examined using the native polyacrylamide-overlay gel method, and high RCH10 activity was observed in leaf tissues where endogenous RCH10 is not expressed. R1 plants were analyzed in a similar way, and the Southern-blot patterns and levels of transgene expression remained the same as in the parental line. Analysis of the response of R2 plants to three fungal pathogens of rice, Rhizoctonia solani, Bipolaris oryzae, and Magnaporthe grisea, indicated statistically significant symptom reduction only in the case of R. solani (sheath blight). The increased resistance co-segregated with herbicide tolerance, reflecting a correlation between the resistance phenotype and transgene expression. PMID:12885168

  9. Inactivation of rabies virus by hydrogen peroxide.

    Science.gov (United States)

    Abd-Elghaffar, Asmaa A; Ali, Amal E; Boseila, Abeer A; Amin, Magdy A

    2016-02-01

    Development of safe and protective vaccines against infectious pathogens remains a challenge. Inactivation of rabies virus is a critical step in the production of vaccines and other research reagents. Beta-propiolactone (βPL); the currently used inactivating agent for rabies virus is expensive and proved to be carcinogenic in animals. This study aimed to investigate the ability of hydrogen peroxide (H2O2) to irreversibly inactivate rabies virus without affecting its antigenicity and immunogenicity in pursuit of finding safe, effective and inexpensive alternative inactivating agents. H2O2 3% rapidly inactivated a Vero cell adapted fixed rabies virus strain designated as FRV/K within 2h of exposure without affecting its antigenicity or immunogenicity. No residual infectious virus was detected and the H2O2-inactivated vaccine proved to be safe and effective when compared with the same virus harvest inactivated with the classical inactivating agent βPL. Mice immunized with H2O2-inactivated rabies virus produced sufficient level of antibodies and were protected when challenged with lethal CVS virus. These findings reinforce the idea that H2O2 can replace βPL as inactivating agent for rabies virus to reduce time and cost of inactivation process. PMID:26731189

  10. Hydrazine vapor inactivates Bacillus spores

    Science.gov (United States)

    Schubert, Wayne W.; Engler, Diane L.; Beaudet, Robert A.

    2016-05-01

    NASA policy restricts the total number of bacterial spores that can remain on a spacecraft traveling to any planetary body which might harbor life or have evidence of past life. Hydrazine, N2H4, is commonly used as a propellant on spacecraft. Hydrazine as a liquid is known to inactivate bacterial spores. We have now verified that hydrazine vapor also inactivates bacterial spores. After Bacillus atrophaeus ATCC 9372 spores deposited on stainless steel coupons were exposed to saturated hydrazine vapor in closed containers, the spores were recovered from the coupons, serially diluted, pour plated and the surviving bacterial colonies were counted. The exposure times required to reduce the spore population by a factor of ten, known as the D-value, were 4.70 ± 0.50 h at 25 °C and 2.85 ± 0.13 h at 35 °C. These inactivation rates are short enough to ensure that the bioburden of the surfaces and volumes would be negligible after prolonged exposure to hydrazine vapor. Thus, all the propellant tubing and internal tank surfaces exposed to hydrazine vapor do not contribute to the total spore count.

  11. Genome size, karyotype polymorphism and chromosomal evolution in Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Renata T Souza

    Full Text Available BACKGROUND: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL Brener. However, high allelic variation and the repetitive nature of the genome have prevented the complete linear sequence of chromosomes being determined. Determining the full complement of chromosomes and establishing syntenic groups will be important in defining the structure of T. cruzi chromosomes. A large amount of information is now available for T. cruzi and Trypanosoma brucei, providing the opportunity to compare and describe the overall patterns of chromosomal evolution in these parasites. METHODOLOGY/PRINCIPAL FINDINGS: The genome sizes, repetitive DNA contents, and the numbers and sizes of chromosomes of nine strains of T. cruzi from four lineages (TcI, TcII, TcV and TcVI were determined. The genome of the TcI group was statistically smaller than other lineages, with the exception of the TcI isolate Tc1161 (José-IMT. Satellite DNA content was correlated with genome size for all isolates, but this was not accompanied by simultaneous amplification of retrotransposons. Regardless of chromosomal polymorphism, large syntenic groups are conserved among T. cruzi lineages. Duplicated chromosome-sized regions were identified and could be retained as paralogous loci, increasing the dosage of several genes. By comparing T. cruzi and T. brucei chromosomes, homologous chromosomal regions in T. brucei were identified. Chromosomes Tb9 and Tb11 of T. brucei share regions of syntenic homology with three and six T. cruzi chromosomal bands, respectively. CONCLUSIONS: Despite genome size variation and karyotype polymorphism, T. cruzi lineages exhibit conservation of chromosome structure. Several syntenic groups are conserved among all isolates analyzed in this study. The syntenic regions are larger than expected if rearrangements occur randomly, suggesting that they are conserved owing to positive selection. Mapping of the syntenic regions on T. cruzi chromosomal bands

  12. Deficit of mitonuclear genes on the human X chromosome predates sex chromosome formation.

    Science.gov (United States)

    Dean, Rebecca; Zimmer, Fabian; Mank, Judith E

    2015-02-01

    Two taxa studied to date, the therian mammals and Caenorhabditis elegans, display underrepresentations of mitonuclear genes (mt-N genes, nuclear genes whose products are imported to and act within the mitochondria) on their X chromosomes. This pattern has been interpreted as the result of sexual conflict driving mt-N genes off of the X chromosome. However, studies in several other species have failed to detect a convergent biased distribution of sex-linked mt-N genes, leading to questions over the generality of the role of sexual conflict in shaping the distribution of mt-N genes. Here we tested whether mt-N genes moved off of the therian X chromosome following sex chromosome formation, consistent with the role of sexual conflict, or whether the paucity of mt-N genes on the therian X is a chance result of an underrepresentation on the ancestral regions that formed the X chromosome. We used a synteny-based approach to identify the ancestral regions in the platypus and chicken genomes that later formed the therian X chromosome. We then quantified the movement of mt-N genes on and off of the X chromosome and the distribution of mt-N genes on the human X and ancestral X regions. We failed to find an excess of mt-N gene movement off of the X. The bias of mt-N genes on ancestral therian X chromosomes was also not significantly different from the biases on the human X. Together our results suggest that, rather than conflict driving mt-N genes off of the mammalian X, random biases on chromosomes that formed the X chromosome could explain the paucity of mt-N genes in the therian lineage. PMID:25637223

  13. Confirmation of the synteny between human chromosome 22 and mouse chromosome 11

    Energy Technology Data Exchange (ETDEWEB)

    Claudio, J.O.; Rouleau, G.A.; Malo, D. [McGill Univ., Quebec (Canada)

    1994-09-01

    Comparative mapping based on the existence of conserved synteny between human and mouse chromosomes is a useful strategy in determining the chromosomal location of a gene. Using recombinant inbred (RI) strains of mice derived from AKR/J and DBA/2J cross (AKXD), we confirmed the existence of a small area of synteny between the chromosome 22 segment carrying the gene for neurofibromatosis type 2 (NF2) and the most proximal region of mouse chromosome 11 containing its homologue (Nf2). By analyzing the allele distribution pattern of 24 AKXD RI mice using a novel polymorphic dinucleotide (CT){sub n} repeat (D11Mcg1) in the 3{prime} untranslated region of the mouse Nf2 gene and PCR-based simple sequence repeat markers (Research Genetics), we established the chromosomal position of Nf23 on mouse chromosome 11. Minimizing the number of double recombinants in the RI strains analyzed suggests tight linkage of Nf2 to D11Mit1 and D11Mit72 which map to a region containing the genes for leukemia inhibitory factor (Lif) and neurofilament heavy chain polypeptide (Nfh). This region is syntenic to the segment carrying the genes LIF, NF2 and NEFH on human chromosome 22q. We show that D11Mcg1 will be useful for mapping of genes and closely linked loci on the proximal region of mouse chromosome 11. Our data demonstrate the predictive value of comparative mapping and confirm that human chromosome 22q12 is syntenic to the most proximal region of mouse chromosome 11.

  14. Plant sex chromosome evolution.

    Science.gov (United States)

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  15. Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome

    Institute of Scientific and Technical Information of China (English)

    Anurag Mitra; Rima Dada; Rajeev Kumar; Narmada Prasad Gupta; Kiran Kucheria; Satish Kumar Gupta

    2006-01-01

    Aim: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). Methods: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1 Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. Results: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. Conclusion:Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

  16. Ambiguous genitalia: a clinical and chromosomal study

    Directory of Open Access Journals (Sweden)

    V. Anantha Kumari

    2015-12-01

    Methods: The study is undertaken with forty cases with ages ranging from new borne to 20 yrs. Out of these 40 cases eight cases are below one year. In these cases physical examination is correlated with ultrasonography and chromosomal analysis. Results: In chromosomal analysis three persons out of forty cases were mosaics with 45, XO/46, twenty one cases who showed the chromosomal pattern as 46, XY mostly showed with no mullarian reminents. On examination palpable gonads were found in labio-scrotal sacs in seventeen cases. One of these cases was reared as girl found cytogenetically as 46, XY with the ultrasonographic impression as small uterus with no ovaries. Nineteen cases who with ambiguous genitalia showed the chromosomal pattern as 46, XX one out of these cases showed enlargement of the breast, and on examination of external genitalia found enlarged clitoris with labiamajora and minora. The child was brought up as male. Genitogram showed the absence of uterus. Conclusions: Chromosomal studies with ultrasonography can help in rearing a child male or female in young generation by surgical and Hormonal therapy. This prevents many problems in later life. This fact should be advertised openly in the public so that illiterate people should be alert. [Int J Res Med Sci 2015; 3(12.000: 3743-3748

  17. Vibrio chromosomes share common history

    OpenAIRE

    Gevers Dirk; Chang Sarah; Chang LeeAnn; Kirkup Benjamin C; Polz Martin F

    2010-01-01

    Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II) were identified from 19 sequenced Vibrionales genomes ...

  18. Meiotic behaviour of individual chromosomes in allotriploid Alstroemeria hybrids.

    Science.gov (United States)

    Kamstra, S A; de Jong, J H; Jacobsen, E; Ramanna, M S; Kuipers, A G J

    2004-07-01

    Chromosome association and chiasma formation were studied in pollen mother cells at metaphase I of four allotriplod BC1 plants (2n=3x=24) obtained from the backcross of the hybrid Alstroemeria aurea x A. inodora with its parent A. inodora. We distinguished the chromosomes of both parental species by genomic in situ hybridization (GISH), whereas the individual chromosomes were identified on the basis of their multicolour FISH banding patterns obtained after a second hybridization with two species-specific satellite repeats as probes. All the four BC1 plants possessed two genomes of A. inodora and one of A. aurea. Variable numbers of recombinant chromosomes, resulting from meiotic recombination in the interspecific hybrid, were present in these plants. The homologous A. inodora chromosomes generally formed bivalents, leaving the homoeologous A. aurea chromosomes unassociated. High frequencies of trivalents were observed for the chromosome sets that contained recombinant chromosomes, even when the recombinant segments were small. Chromosome associations in the trivalents were restricted to homologous segments. The implications of the absence of homoeologous chromosome pairing on gamete constitution and prospects for introgression in Alstroemeria are discussed. PMID:15100711

  19. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    Science.gov (United States)

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  20. Sequential cloning of chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  1. Independent sex chromosome evolution in lower vertebrates: a molecular cytogenetic overview in the Erythrinidae fish family.

    Science.gov (United States)

    Cioffi, M B; Liehr, T; Trifonov, V; Molina, W F; Bertollo, L A C

    2013-01-01

    The Erythrinidae fish family is an excellent model for analyzing the evolution of sex chromosomes. Different stages of sex chromosome differentiation from homomorphic to highly differentiated ones can be found among the species of this family. Here, whole chromosome painting, together with the cytogenetic mapping of repetitive DNAs, highlighted the evolutionary relationships of the sex chromosomes among different erythrinid species and genera. It was demonstrated that the sex chromosomes can follow distinct evolutionary pathways inside this family. Reciprocal hybridizations with whole sex chromosome probes revealed that different autosomal pairs have evolved as the sex pair, even among closely related species. In addition, distinct origins and different patterns of differentiation were found for the same type of sex chromosome system. These features expose the high plasticity of the sex chromosome evolution in lower vertebrates, in contrast to that occurring in higher ones. A possible role of this sex chromosome turnover in the speciation processes is also discussed. PMID:23919986

  2. A new chromosome was born: comparative chromosome painting in Boechera.

    Science.gov (United States)

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  3. Chromosome counts of 90Sr-induced osteosarcomas in mice. I

    International Nuclear Information System (INIS)

    From 90Sr-induced primary tumours, three transfer series were established by serial in vivo transplantation. Chromosome counts were obtained from 2 of the primary tumours and 284 transplanted tumours. The recording of abnormalities was limited to numerical chromosome deviations and the occurrence of metacentric configurations. By means of the serial tumour transplantation the numerical chromosome progression was also analysed. Though appearing at different stages of the tumour evolution, similarities in chromosome pattern were observed. (Auth.)

  4. Chimpanzee chromosome 13 is homologous to human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Sun, N. C.; Sun, C. R.Y.; Ho, T.

    1977-01-01

    Similarities between human and chimpanzee chromosomes are shown by chromosome banding techniques and somatic cell hybridization techniques. Cell hybrids were obtained from the chimpanzee lymphocyte LE-7, and the Chinese hamster mutant cell, Gal-2. Experiments showed that the ACPL, MDHs, and Gal-Act genes could be assigned to chimpanzee chromosome 13, and since these genes have been assigned to human chromosme 2p, it is suggested that chimpanzee chromosome 13 is homologous to human chromosome 2p. (HLW)

  5. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

    Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs

  6. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  7. Adaptive Evolution of Genes Duplicated from the Drosophila pseudoobscura neo-X Chromosome

    Science.gov (United States)

    Meisel, Richard P.; Hilldorfer, Benedict B.; Koch, Jessica L.; Lockton, Steven; Schaeffer, Stephen W.

    2010-01-01

    Drosophila X chromosomes are disproportionate sources of duplicated genes, and these duplications are usually the result of retrotransposition of X-linked genes to the autosomes. The excess duplication is thought to be driven by natural selection for two reasons: X chromosomes are inactivated during spermatogenesis, and the derived copies of retroposed duplications tend to be testis expressed. Therefore, autosomal derived copies of retroposed genes provide a mechanism for their X-linked paralogs to “escape” X inactivation. Once these duplications have fixed, they may then be selected for male-specific functions. Throughout the evolution of the Drosophila genus, autosomes have fused with X chromosomes along multiple lineages giving rise to neo-X chromosomes. There has also been excess duplication from the two independent neo-X chromosomes that have been examined—one that occurred prior to the common ancestor of the willistoni species group and another that occurred along the lineage leading to Drosophila pseudoobscura. To determine what role natural selection plays in the evolution of genes duplicated from the D. pseudoobscura neo-X chromosome, we analyzed DNA sequence divergence between paralogs, polymorphism within each copy, and the expression profiles of these duplicated genes. We found that the derived copies of all duplicated genes have elevated nonsynonymous polymorphism, suggesting that they are under relaxed selective constraints. The derived copies also tend to have testis- or male-biased expression profiles regardless of their chromosome of origin. Genes duplicated from the neo-X chromosome appear to be under less constraints than those duplicated from other chromosome arms. We also find more evidence for historical adaptive evolution in genes duplicated from the neo-X chromosome, suggesting that they are under a unique selection regime in which elevated nonsynonymous polymorphism provides a large reservoir of functional variants, some of which are

  8. Chromosome numbers in Bromeliaceae

    OpenAIRE

    2000-01-01

    The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. u...

  9. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed

  10. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  11. Free-radical inactivation of muscle aldolase

    International Nuclear Information System (INIS)

    Rabbit muscle aldolase has been shown to be deactivated by addition of irradiated crystals of various sugars and amino acids. Inactivation observed immediately upon dissolution is ascribed to reaction with free radicals, whereas post-dissolution inactivation is ascribed to acid-catalyzed reaction with nonradical radiolysis products. (U.S.)

  12. Gross genomic alterations and gene expression profiles of high- grade serous carcinoma of the ovary with and without BRCA1 inactivation

    International Nuclear Information System (INIS)

    BRCA1 gene inactivation causes chromosomal instability, leading to rapid accumulation of chromosomal rearrangements and mutations. The loss of BRCA1 function due to either germline/somatic mutation or epigenetic silencing is observed in most high-grade serous carcinomas of the ovary. DNA ploidy and gene expression profile were used in order to compare gross genomic alteration and gene expression pattern between cases with BRCA1 loss through mutation, BRCA1 epigenetic loss, and no BRCA1 loss in cases of high-grade serous carcinoma with known BRCA1 and BRCA 2 status. Using image cytometry and oligonucleotide microarrays, we analyzed DNA ploidy, S-phase fraction and gene expression profile of 28 consecutive cases of ovarian high-grade serous adenocarcinomas, which included 8 tumor samples with BRCA1 somatic or germline mutation, 9 samples with promoter hypermethylation of BRCA1, and 11 samples with no BRCA1 loss. None had BRCA2 mutations. The prevalence of aneuploidy and tetraploidy was not statistically different in the three groups with different BRCA1 status. The gene expression profiles were also very similar between the groups, with only two genes showing significant differential expression when comparison was made between the group with BRCA1 mutation and the group with no demonstrable BRCA1 loss. There were no genes showing significant differences in expression when the group with BRCA1 loss through epigenetic silencing was compared to either of the other two groups. In this series of 28 high-grade serous carcinomas, gross genomic alteration characterized by aneuploidy did not correlate with BRCA1 status. In addition, the gene expression profiles of the tumors showed negligible differences between the three defined groups based on BRCA1 status. This suggests that all ovarian high-grade serous carcinomas arise through oncogenic mechanisms that result in chromosomal instability, irrespective of BRCA status; the molecular abnormalities underlying this in the BRCA

  13. A novel metric for bone marrow cells chromosome pairing.

    Science.gov (United States)

    Khmelinskii, Artem; Ventura, Rodrigo; Sanches, João

    2010-06-01

    Karyotyping is a set of procedures, in the scope of the cytogenetics, that produces a visual representation of the 46 chromosomes observed during the metaphase step of the cellular division, called mitosis, paired and arranged in decreasing order of size. Automatic pairing of bone marrow cells is a difficult task because these chromosomes appear distorted, overlapped, and their images are usually blurred with undefined edges and low level of detail. In this paper, a new metric is proposed to compare this type of chromosome images toward the design of an automatic pairing algorithm for leukemia diagnostic purposes. Besides the features used in the traditional karyotyping procedures, a new feature, based on mutual information , is proposed to increase the discriminate power of the G-banding pattern dissimilarity between chromosomes and improve the performance of the classifier. The pairing algorithm is formulated as a combinatorial optimization problem where the distances between homologous chromosomes are minimized and the distances between nonhomologous ones are maximized. The optimization task is solved by using an integer programming approach. A new bone marrow chromosome dataset--Lisbon-K1 (LK1) chromosome dataset with 9200 chromosomes---was build for this study. These chromosomes have much lower quality than the classic Copenhagen, Edinburgh, and Philadelphia datasets, and its classification and pairing is therefore more difficult. Experiments using real images from the LK(1) and Grisan et al. datasets based on a leave-one-out cross-validation strategy are performed to test and validate the pairing algorithm. PMID:20172790

  14. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  15. Inactivation of RNA viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Four kinds of RNA viruses, Bluetongue virus (BT), Bovine Virus Diarrhea-Mucosal Disease virus (BVD·MD), Bovine Respiratory Syncytial virus (RS), Vesicular Stmatitis virus (VS), were subjected to various doses of gamma irradiation to determine the lethal doses. The D10 values, which are the dose necessary to decimally reduce infectivity, ranged from 1.5 to 3.4 kGy under frozen condition at dry-ice temperature, and they increased to 2.6 to 5.0 kGy under frozen condition at dry-ice temperature. Serum neutralzing antibody titer of Infectious Bovine Rhinotracheitis (IBR) was not adversely changed by the exposure to 36 kGy of gamma-rays under frozen condition. Analysis of electrophoresis patterns of the bovine serum also reveales that the serum proteins were not remarkably affected, even when exposed to 36 kGy of gamma radiation under frozen condition. The results suggested that gamma irradiation under frozen condition is an effective means for inactivating both DNA and RNA viruses without adversely affecting serum proteins and neutralizing antibody titer. (author)

  16. Effect of formaldehyde inactivation on poliovirus.

    Science.gov (United States)

    Wilton, Thomas; Dunn, Glynis; Eastwood, David; Minor, Philip D; Martin, Javier

    2014-10-01

    Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells. Importance: This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing of

  17. Mental retardation and Ullrich-Turner syndrome in cases with 45,X/46,X, +mar: Additional support for the loss of the X-inactivation center hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Cole, H.; Huang, B.; Brown, J.; Howard-Peebles, P.N.; Black, S.H.; Jackson-Cook, C. [Virginia Commonwealth Univ., Richmond, VA (United States); Salbert, B.A. [Children`s Mercy Hospital, Kansas City, MO (United States); Febles, O.R. [Hialeah Hospital, FL (United States); Stevens, C.A. [Univ. of Tennessee, Chattanooga, TN (United States)

    1994-08-15

    Four cases having mosaicism for a small marker or ring [45,X/46,X,+mar or 45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested because of minor anomalies (cases 1, 3, and 4) and/or short stature (cases 2 and 4). While all 4 cases had traits typical of Ullrich-Turner syndrome (UTS), cases 1, 3, and 4 had manifestations not usually present in UTS, including unusual facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and 4), and syndactylies (case 1). Using fluorescence in situ hybridization (FISH), each of the markers in these 4 cases was identified as having been derived from an X chromosome. Replication studies demonstrated a probable early replication pattern for the mar/r(X) in cases 1, 3, and 4, while the marker in case 2 was apparently late replicating. To date, 41 individuals having mosaicism for a small mar/r(X) chromosome have been described. Interestingly, most of the 14 individuals having a presumedly active mar/r(X) demonstrated clinical findings atypical of UTS, including abnormal facial changes (11) and MR/DD (13). MR was noted most frequently in those cases having at least 50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late replicating marker or ring. In conclusion, although the phenotype of 45,S/46,X, mar/r(X) individuals appears to be influenced by the genetic content and degree of mosaicism for the mar/r(X), the most significant factor associated with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus, our 4 cases provide further support for the hypothesis that a lack of inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and other phenotypic abnormalities seen in this subset of individuals having atypical UTS. 46 refs., 6 figs., 3 tabs.

  18. Chromosomal evolution among leaf-nosed nectarivorous bats – evidence from cross-species chromosome painting (Phyllostomidae, Chiroptera)

    Science.gov (United States)

    2013-01-01

    Background New World leaf-nosed bats, Phyllostomidae, represent a lineage of Chiroptera marked by unprecedented morphological/ecological diversity and extensive intergeneric chromosomal reorganization. There are still disagreements regarding their systematic relationships due to morphological convergence among some groups. Their history of karyotypic evolution also remains to be documented. Results To better understand the evolutionary relationships within Phyllostomidae, we developed chromosome paints from the bat species Macrotus californicus. We tested the potential of these paints as phylogenetic tools by looking for chromosomal signatures in two lineages of nectarivorous phyllostomids whose independent origins have been statistically supported by molecular phylogenies. By examining the chromosomal homologies defined by chromosome painting among two representatives of the subfamily Glossophaginae (Glossophaga soricina and Anoura cultrata) and one species from the subfamily Lonchophyllinae (Lonchophylla concava), we found chromosomal correspondence in regions not previously detected by other comparative cytogenetic techniques. We proposed the corresponding human chromosomal segments for chromosomes of the investigated species and found two syntenic associations shared by G. soricina and A. cultrata. Conclusion Comparative painting with whole chromosome-specific paints of M. californicus demonstrates an extensive chromosomal reorganization within the two lineages of nectarivorous phyllostomids, with a large number of chromosomes shared between M. californicus and G. soricina. We show that the evolution of nectar-feeding bats occurs mainly by reshuffling of chiropteran Evolutionarily Conserved Units (ECUs). Robertsonian fusions/fissions and inversions seem to be important modifiers of phyllostomid karyotypes, and autapomorphic character states are common within species. Macrotus californicus chromosome paints will be a valuable tool for documenting the pattern of

  19. Chromosomal replicons of higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Van' t Hof, J.

    1987-03-16

    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs.

  20. Chromosomal replicons of higher plants

    International Nuclear Information System (INIS)

    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs

  1. Behavior modification after inactivation of cerebellar dentate nuclei.

    Science.gov (United States)

    Peterson, Todd C; Villatoro, Lee; Arneson, Tom; Ahuja, Brittany; Voss, Stephanie; Swain, Rodney A

    2012-08-01

    Effort-based decision making occurs when subjects are given a choice between a reward available at a high response cost and a reward available at a low response cost and is altered in individuals with disorders such as autism or particular patterns of brain injury. The current study explored the relationship between effort-based decision making and reinforcement characteristics in the T maze. This was done using both normal animals and animals with bilateral inactivation of the cerebellar dentate nuclei. Rats chose between alternatives in which one arm contained high-density reinforcement (HR) and the other arm contained low-density reinforcement (LR). During training, the HR arm was obstructed and the point at which the animal no longer worked for reinforcement (breaking point) was determined. The cerebellar dentate nuclei were then transiently inactivated and once again breaking points were assessed. The results indicated that inactivation of the dentate nucleus disrupted effort-based decision making. Additionally, altering both the palatability and the magnitude of the reinforcement were assessed in an attempt to reestablish the original preinactivation breaking point. It was hypothesized that an increase in the strength or magnitude of the reinforcement would promote an increase in the breaking point of the animal even when the cerebellum was inactivated. The results indicated that with both strategies animals effectively reestablished original breaking points. The results of this study will inform the current literature regarding the modification of behavior after brain injury and further the understanding of the behavioral deficits associated with cerebellar dysfunction. PMID:22845704

  2. Cytological alteration of cultured rat liver cells by 3'-methyl-4-dimethylaminoazobenzene with special reference to chromosome changes, changes of growth patterns at a colony level and alpha-fetoprotein production.

    Directory of Open Access Journals (Sweden)

    Tokiwa,Takayoshi

    1980-06-01

    Full Text Available A near diploid clone derived from a rat liver cell line was continuously treated with various concentrations of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB in culture. By treatment with 2.8 micrograms/ml, cells with 41 chromosomes formed a mode and which then shifted to 39. The chromosome numbers of cells treated with 5.4 micrograms/ml were widely distributed at early stages, but later the mode shifted to hypotetraploid region. Untreated control cells were confirmed as near diploid. Increased plating efficiency by 3'-Me-DAB as well as the appearance of large sized colonies was obtained. The production of alpha-fetoprotein (AFP by the cells was slightly enhanced by treatment with 3'-Me-DAB. The cells treated with and without 3'-Me-DAB did not produce any tumor in rats 6 months after their intraperitoneal injection.

  3. Chromosome mapping of repetitive sequences in Anostomidae species: implications for genomic and sex chromosome evolution

    Directory of Open Access Journals (Sweden)

    da Silva Edson Lourenço

    2012-12-01

    Full Text Available Abstract Background Members of the Anostomidae family provide an interesting model system for the study of the influence of repetitive elements on genome composition, mainly because they possess numerous heterochromatic segments and a peculiar system of female heterogamety that is restricted to a few species of the Leporinus genus. The aim of this study was to isolate and identify important new repetitive DNA elements in Anostomidae through restriction enzyme digestion, followed by cloning, characterisation and chromosome mapping of this fragment. To identify repetitive elements in other Leporinus species and expand on studies of repetitive elements in Anostomidae, hybridisation experiments were also performed using previously described probes of LeSpeI repetitive elements. Results The 628-base pair (bp LeSpeII fragment was hybridised to metaphase cells of L. elongatus individuals as well as those of L. macrocephalus, L. obtusidens, L. striatus, L. lacustris, L. friderici, Schizodon borellii and S. isognathus. In L. elongatus, both male and female cells contained small clusters of LeSpeII repetitive elements dispersed on all of the chromosomes, with enrichment near most of the terminal portions of the chromosomes. In the female sex chromosomes of L. elongatus (Z2,Z2/W1W2, however, this repeated element was absent. In the remaining species, a dispersed pattern of hybridisation was observed on all chromosomes irrespective of whether or not they were sex chromosomes. The repetitive element LeSpeI produced positive hybridisations signals only in L. elongatus, L. macrocephalus and L. obtusidens, i.e., species with differentiated sex chromosomes. In the remaining species, the LeSpeI element did not produce hybridisation signals. Conclusions Results are discussed in terms of the effects of repetitive sequences on the differentiation of the Anostomidae genome, especially with respect to sex chromosome evolution. LeSpeII showed hybridisation patterns

  4. First Steps in Eukaryogenesis: Physical Phenomena in the Origin and Evolution of Chromosome Structure

    Science.gov (United States)

    Chela-Flores, Julian

    1998-04-01

    Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes.

  5. First steps in eukaryogenesis: Physical phenomena in the origin and evolution of chromosome structure

    International Nuclear Information System (INIS)

    Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna.) When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes. (author). Abstract only

  6. First steps in eukaryogenesis: Physical phenomena in the origin and evolution of chromosome structure

    International Nuclear Information System (INIS)

    Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes. (author). 65 refs

  7. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  8. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  9. Deletion of an X-inactivation boundary disrupts adjacent gene silencing.

    Directory of Open Access Journals (Sweden)

    Lindsay M Horvath

    2013-11-01

    Full Text Available In mammalian females, genes on one X are largely silenced by X-chromosome inactivation (XCI, although some "escape" XCI and are expressed from both Xs. Escapees can closely juxtapose X-inactivated genes and provide a tractable model for assessing boundary function at epigenetically regulated loci. To delimit sequences at an XCI boundary, we examined female mouse embryonic stem cells carrying X-linked BAC transgenes derived from an endogenous escape locus. Previously we determined that large BACs carrying escapee Kdm5c and flanking X-inactivated transcripts are properly regulated. Here we identify two lines with truncated BACs that partially and completely delete the distal Kdm5c XCI boundary. This boundary is not required for escape, since despite integrating into regions that are normally X inactivated, transgenic Kdm5c escapes XCI, as determined by RNA FISH and by structurally adopting an active conformation that facilitates long-range preferential association with other escapees. Yet, XCI regulation is disrupted in the transgene fully lacking the distal boundary; integration site genes up to 350 kb downstream of the transgene now inappropriately escape XCI. Altogether, these results reveal two genetically separable XCI regulatory activities at Kdm5c. XCI escape is driven by a dominant element(s retained in the shortest transgene that therefore lies within or upstream of the Kdm5c locus. Additionally, the distal XCI boundary normally plays an essential role in preventing nearby genes from escaping XCI.

  10. American marsupials chromosomes: Why study them?

    OpenAIRE

    Marta Svartman

    2009-01-01

    Marsupials, one of the three main groups of mammals, are only found in Australia and in the American continent. Studies performed in Australian marsupials have demonstrated the great potential provided by the group for the understanding of basic genetic mechanisms and chromosome evolution in mammals. Genetic studies in American marsupials are relatively scarce and cytogenetic data of most species are restricted to karyotype descriptions, usually without banding patterns. Nevertheless, the fir...

  11. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  12. An approach to automated chromosome analysis

    International Nuclear Information System (INIS)

    The methods of approach developed with a view to automatic processing of the different stages of chromosome analysis are described in this study divided into three parts. Part 1 relates the study of automated selection of metaphase spreads, which operates a decision process in order to reject ail the non-pertinent images and keep the good ones. This approach has been achieved by Computing a simulation program that has allowed to establish the proper selection algorithms in order to design a kit of electronic logical units. Part 2 deals with the automatic processing of the morphological study of the chromosome complements in a metaphase: the metaphase photographs are processed by an optical-to-digital converter which extracts the image information and writes it out as a digital data set on a magnetic tape. For one metaphase image this data set includes some 200 000 grey values, encoded according to a 16, 32 or 64 grey-level scale, and is processed by a pattern recognition program isolating the chromosomes and investigating their characteristic features (arm tips, centromere areas), in order to get measurements equivalent to the lengths of the four arms. Part 3 studies a program of automated karyotyping by optimized pairing of human chromosomes. The data are derived from direct digitizing of the arm lengths by means of a BENSON digital reader. The program supplies' 1/ a list of the pairs, 2/ a graphic representation of the pairs so constituted according to their respective lengths and centromeric indexes, and 3/ another BENSON graphic drawing according to the author's own representation of the chromosomes, i.e. crosses with orthogonal arms, each branch being the accurate measurement of the corresponding chromosome arm. This conventionalized karyotype indicates on the last line the really abnormal or non-standard images unpaired by the program, which are of special interest for the biologist. (author)

  13. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1989-01-01

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  14. Biophysics of protein-DNA interactions and chromosome organization

    OpenAIRE

    Marko, John F.

    2015-01-01

    The function of DNA in cells depends on its interactions with protein molecules, which recognize and act on base sequence patterns along the double helix. These notes aim to introduce basic polymer physics of DNA molecules, biophysics of protein-DNA interactions and their study in single-DNA experiments, and some aspects of large-scale chromosome structure. Mechanisms for control of chromosome topology will also be discussed.

  15. Chromosome Polymorphisms among Strains of Hansenula polymorpha (syn. Pichia angusta)

    OpenAIRE

    Marri, Laura; Rossolini, Gian Maria; Satta, Giuseppe

    1993-01-01

    Contour-clamped homogeneous electrophoresis and an embedded-agarose method of sample preparation were combined to carry out an analysis of the chromosome sets of nine strains of Hansenula polymorpha (syn. Pichia angusta). Chromosomal DNA molecules could be separated into a series of bands ranging, approximately, from 650 up to 2,200 kb in size. Polymorphism of the electrophoretic pattern was demonstrated among the strains investigated in this study. Cross-hybridization between H. polymorpha a...

  16. Methods of biological dosimetry employing chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    2000-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  17. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B; Vogel, F; Noer, H; Mikkelsen, M

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation with...

  18. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  19. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  20. Chromosomes, cancer and radiosensitivity

    International Nuclear Information System (INIS)

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available

  1. Chromosome Morphology in Kniphofia.

    Directory of Open Access Journals (Sweden)

    J. M. J de Wet

    1960-12-01

    Full Text Available A number of species and varieties of the genus  Kniphofia (Liliaceae were studied cytologically. The somatic chromosome number is  2n = 12 in all the species. This is also true in  Notosceptrum natalense Baker.

  2. Physical inactivation and stabilization of sludges

    International Nuclear Information System (INIS)

    High temperature conditioning of sludge is a stabilization process that insures sterilization. Both thermal pasteurization and irradiation are inactivation processes. Viruses and parasites are inactivated at 70-800C. Total bacterial destruction requires higher temperatures and/or detention time. Radio sensitivity of pathogens and pertinent treatment parameters are examined. If sludge is to be land disposed, disinfection requires irradiation doses ranging 500 Krad; if cattle feeding is considered, the required dose is 1 Mrad

  3. Microbial Inactivation by Ultrasound Assisted Supercritical Fluids

    Science.gov (United States)

    Benedito, Jose; Ortuño, Carmen; Castillo-Zamudio, Rosa Isela; Mulet, Antonio

    A method combining supercritical carbon dioxide (SC-CO2) and high power ultrasound (HPU) has been developed and tested for microbial/enzyme inactivation purposes, at different process conditions for both liquid and solid matrices. In culture media, using only SC-CO2, the inactivation rate of E. coli and S. cerevisiae increased with pressure and temperature; and the total inactivation (7-8 log-cycles) was attained after 25 and 140 min of SC-CO2 (350 bar, 36 °C) treatment, respectively. Using SC-CO2+HPU, the time for the total inactivation of both microorganisms was reduced to only 1-2 min, at any condition selected. The SC-CO2+HPU inactivation of both microorganisms was slower in juices (avg. 4.9 min) than in culture media (avg. 1.5 min). In solid samples (chicken, turkey ham and dry-cured pork cured ham) treated with SC-CO2 and SC-CO2+HPU, the inactivation rate of E. coli increased with temperature. The application of HPU to the SC-CO2 treatments accelerated the inactivation rate of E. coli and that effect was more pronounced in treatments with isotonic solution surrounding the solid food samples. The application of HPU enhanced the SC-CO2 inactivation mechanisms of microorganisms, generating a vigorous agitation that facilitated the CO2 solubilization and the mass transfer process. The cavitation generated by HPU could damage the cell walls accelerating the extraction of vital constituents and the microbial death. Thus, using the combined technique, reasonable industrial processing times and mild process conditions could be used which could result into a cost reduction and lead to the minimization in the food nutritional and organoleptic changes.

  4. Proteolytic inactivation of cytokines by Pseudomonas aeruginosa.

    OpenAIRE

    Parmely, M; Gale, A; Clabaugh, M.; Horvat, R; Zhou, W W

    1990-01-01

    Pseudomonas aeruginosa alkaline protease and elastase are thought to contribute to bacterial invasiveness, tissue damage, and immune suppression in animals and patients infected with the bacterium. This study examined the ability of the two proteases to inactivate a number of cytokines that mediate immune and inflammatory responses. Human recombinant gamma interferon (rIFN-gamma) and human recombinant tumor necrosis factor alpha were inactivated by both proteases. Murine rIFN-gamma was relati...

  5. Loss of the Y-chromosome in the primary metastasis of a male sex cord stromal tumor : Pathogenetic implications

    NARCIS (Netherlands)

    de Graaff, WE; van Echten, J; van der Veen, AY; Sleijfer, DT; Timmer, A; de Jong, B; Schraffordt Koops, H.

    1999-01-01

    The first published chromosomal pattern of the retroperitoneal lymph node metastasis of a malignant gonadal stroma cell tumor of the adult testis is presented. Karyotyping showed structural chromosomal abnormalities and loss of the Y-chromosome. This loss was confirmed in primary tumor and metastasi

  6. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  7. Major Chromosomal Rearrangements Distinguish Willow and Poplar After the Ancestral "Salicoid" Genome Duplication.

    Science.gov (United States)

    Hou, Jing; Ye, Ning; Dong, Zhongyuan; Lu, Mengzhu; Li, Laigeng; Yin, Tongming

    2016-01-01

    Populus (poplar) and Salix (willow) are sister genera in the Salicaceae family. In both lineages extant species are predominantly diploid. Genome analysis previously revealed that the two lineages originated from a common tetraploid ancestor. In this study, we conducted a syntenic comparison of the corresponding 19 chromosome members of the poplar and willow genomes. Our observations revealed that almost every chromosomal segment had a parallel paralogous segment elsewhere in the genomes, and the two lineages shared a similar syntenic pinwheel pattern for most of the chromosomes, which indicated that the two lineages diverged after the genome reorganization in the common progenitor. The pinwheel patterns showed distinct differences for two chromosome pairs in each lineage. Further analysis detected two major interchromosomal rearrangements that distinguished the karyotypes of willow and poplar. Chromosome I of willow was a conjunction of poplar chromosome XVI and the lower portion of poplar chromosome I, whereas willow chromosome XVI corresponded to the upper portion of poplar chromosome I. Scientists have suggested that Populus is evolutionarily more primitive than Salix. Therefore, we propose that, after the "salicoid" duplication event, fission and fusion of the ancestral chromosomes first give rise to the diploid progenitor of extant Populus species. During the evolutionary process, fission and fusion of poplar chromosomes I and XVI subsequently give rise to the progenitor of extant Salix species. This study contributes to an improved understanding of genome divergence after ancient genome duplication in closely related lineages of higher plants. PMID:27352946

  8. Major Chromosomal Rearrangements Distinguish Willow and Poplar After the Ancestral “Salicoid” Genome Duplication

    Science.gov (United States)

    Hou, Jing; Ye, Ning; Dong, Zhongyuan; Lu, Mengzhu; Li, Laigeng; Yin, Tongming

    2016-01-01

    Populus (poplar) and Salix (willow) are sister genera in the Salicaceae family. In both lineages extant species are predominantly diploid. Genome analysis previously revealed that the two lineages originated from a common tetraploid ancestor. In this study, we conducted a syntenic comparison of the corresponding 19 chromosome members of the poplar and willow genomes. Our observations revealed that almost every chromosomal segment had a parallel paralogous segment elsewhere in the genomes, and the two lineages shared a similar syntenic pinwheel pattern for most of the chromosomes, which indicated that the two lineages diverged after the genome reorganization in the common progenitor. The pinwheel patterns showed distinct differences for two chromosome pairs in each lineage. Further analysis detected two major interchromosomal rearrangements that distinguished the karyotypes of willow and poplar. Chromosome I of willow was a conjunction of poplar chromosome XVI and the lower portion of poplar chromosome I, whereas willow chromosome XVI corresponded to the upper portion of poplar chromosome I. Scientists have suggested that Populus is evolutionarily more primitive than Salix. Therefore, we propose that, after the “salicoid” duplication event, fission and fusion of the ancestral chromosomes first give rise to the diploid progenitor of extant Populus species. During the evolutionary process, fission and fusion of poplar chromosomes I and XVI subsequently give rise to the progenitor of extant Salix species. This study contributes to an improved understanding of genome divergence after ancient genome duplication in closely related lineages of higher plants. PMID:27352946

  9. Analysis of SINE and LINE repeat content of Y chromosomes in the platypus, Ornithorhynchus anatinus.

    Science.gov (United States)

    Kortschak, R Daniel; Tsend-Ayush, Enkhjargal; Grützner, Frank

    2009-01-01

    Monotremes feature an extraordinary sex-chromosome system that consists of five X and five Y chromosomes in males. These sex chromosomes share homology with bird sex chromosomes but no homology with the therian X. The genome of a female platypus was recently completed, providing unique insights into sequence and gene content of autosomes and X chromosomes, but no Y-specific sequence has so far been analysed. Here we report the isolation, sequencing and analysis of approximately 700 kb of sequence of the non-recombining regions of Y2, Y3 and Y5, which revealed differences in base composition and repeat content between autosomes and sex chromosomes, and within the sex chromosomes themselves. This provides the first insights into repeat content of Y chromosomes in platypus, which overall show similar patterns of repeat composition to Y chromosomes in other species. Interestingly, we also observed differences between the various Y chromosomes, and in combination with timing and activity patterns we provide an approach that can be used to examine the evolutionary history of the platypus sex-chromosome chain. PMID:19874720

  10. Chromosomal Speciation Revisited: Modes of Diversification in Australian Morabine Grasshoppers (Vandiemenella, viatica Species Group

    Directory of Open Access Journals (Sweden)

    Steven J. B. Cooper

    2011-03-01

    Full Text Available Chromosomal rearrangements can alter the rate and patterns of gene flow within or between species through a reduction in the fitness of chromosomal hybrids or by reducing recombination rates in rearranged areas of the genome. This concept, together with the observation that many species have structural variation in chromosomes, has led to the theory that the rearrangements may play a direct role in promoting speciation. Australian morabine grasshoppers (genus Vandiemenella, viatica species group are an excellent model for studying the role of chromosomal rearrangement in speciation because they show extensive chromosomal variation, parapatric distribution patterns, and narrow hybrid zones at their boundaries. This species group stimulated development of one of the classic chromosomal speciation models, the stasipatric speciation model proposed by White in 1968. Our population genetic and phylogeographic analyses revealed extensive non-monophyly of chromosomal races along with historical and on-going gene introgression between them. These findings suggest that geographical isolation leading to the fixation of chromosomal variants in different geographic regions, followed by secondary contact, resulted in the present day parapatric distributions of chromosomal races. The significance of chromosomal rearrangements in the diversification of the viatica species group can be explored by comparing patterns of genetic differentiation between rearranged and co-linear parts of the genome.

  11. Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

    Directory of Open Access Journals (Sweden)

    Tang Y Amy

    2010-05-01

    Full Text Available Abstract Background X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1 repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. Results Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. Conclusions This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous

  12. Transfer of small chromosome fragments of Agropyron elongatum to wheat chromosome via asymmetric somatic hybridization

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    The chromosome constitution of hybrids and chromatin patterns of Agropyron elongatum(Host)Neviski in F5 somatic hybrid lines Ⅱ -1-3 and I-1-9 between Triticum aestivum L.and A.Elongatum were analyzed.Based on the statistic data of pollen mother cells,F5 I-1-9 and Ⅱ-1-3 had 20-21 bivalents with a frequency of 84.66% and 85.28%,of which,89.83% and 89.57% were ring bivalents.The result indicated that both hybrid lines were basically stable in the chromosome constitution and behavior.RAPD analysis showed that the two hybrids contained biparental and integrated DNA.GISH(Genome in situ hybridization)revealed that in the form of small chromosome segments,A.Elongatum chromatin was scattered on 4-6 wheat chromosomes near by the region of centromere and telomere in the two hybrid lines.SSR analysis indicated that A.Elongatum DNA segments were distributed on the 2A,5B,6B and 2D wheat chromosomes in the hybrids,which was in accordance with the GISH results that small-segments intercalated poly-site.

  13. Peripheral blood complete remission after splenic irradiation in Mantle-Cell Lymphoma with 11q22-23 deletion and ATM inactivation

    Directory of Open Access Journals (Sweden)

    Galliano Marco

    2006-09-01

    Full Text Available Abstract Mantle Cell Lymphoma (MCL is a well-known histological and clinical subtype of B-cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (expecially Double Strand Breaks, recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response.

  14. Peripheral blood complete remission after splenic irradiation in Mantle-Cell Lymphoma with 11q22-23 deletion and ATM inactivation

    International Nuclear Information System (INIS)

    Mantle Cell Lymphoma (MCL) is a well-known histological and clinical subtype of B-cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated) inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (expecially Double Strand Breaks), recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response

  15. The single mitochondrial chromosome typical of animals has evolved into 18 minichromosomes in the human body louse, Pediculus humanus

    OpenAIRE

    Shao, Renfu; Kirkness, Ewen F.; Barker, Stephen C.

    2009-01-01

    The mitochondrial (mt) genomes of animals typically consist of a single circular chromosome that is ∼16-kb long and has 37 genes. Our analyses of the sequence reads from the Human Body Louse Genome Project and the patterns of gel electrophoresis and Southern hybridization revealed a novel type of mt genome in the sucking louse, Pediculus humanus. Instead of having all mt genes on a single chromosome, the 37 mt genes of this louse are on 18 minicircular chromosomes. Each minicircular chromosom...

  16. Biomarker for Space Radiation Risk: Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

    Science.gov (United States)

    Hada, Megumi; George, Kerry; Cucinotta, Francis A.; Wu, Honglu

    2007-01-01

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Over the years, we have studied chromosomal damage in human fibroblast, epithelia and lymphocyte cells exposed in vitro to energetic charged particles generated at several accelerator facilities in the world. We have also studied chromosome aberrations in astronaut s peripheral blood lymphocytes before and after space flight. Various fluorescence in situ hybridization painting techniques have been used to identify from only the telomere region of the chromosome to every chromosome in a human cell. We will summarize the results of the investigations, and discuss the unique radiation signatures and biomarkers for space radiation exposure.

  17. Global patterns of sequence evolution in Drosophila

    Directory of Open Access Journals (Sweden)

    Marín Ignacio

    2007-11-01

    Full Text Available Abstract Background Sequencing of the genomes of several Drosophila allows for the first precise analyses of how global sequence patterns change among multiple, closely related animal species. A basic question is whether there are characteristic features that differentiate chromosomes within a species or between different species. Results We explored the euchromatin of the chromosomes of seven Drosophila species to establish their global patterns of DNA sequence diversity. Between species, differences in the types and amounts of simple sequence repeats were found. Within each species, the autosomes have almost identical oligonucleotide profiles. However, X chromosomes and autosomes have, in all species, a qualitatively different composition. The X chromosomes are less complex than the autosomes, containing both a higher amount of simple DNA sequences and, in several cases, chromosome-specific repetitive sequences. Moreover, we show that the right arm of the X chromosome of Drosophila pseudoobscura, which evolved from an autosome 10 – 18 millions of years ago, has a composition which is identical to that of the original, left arm of the X chromosome. Conclusion The consistent differences among species, differences among X chromosomes and autosomes and the convergent evolution of X and neo-X chromosomes demonstrate that strong forces are acting on drosophilid genomes to generate peculiar chromosomal landscapes. We discuss the relationships of the patterns observed with differential recombination and mutation rates and with the process of dosage compensation.

  18. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  19. Chromosome evolution in dendropsophini (Amphibia, Anura, Hylinae).

    Science.gov (United States)

    Suárez, P; Cardozo, D; Baldo, D; Pereyra, M O; Faivovich, J; Orrico, V G D; Catroli, G F; Grabiele, M; Bernarde, P S; Nagamachi, C Y; Haddad, C F B; Pieczarka, J C

    2013-01-01

    Dendropsophini is the most species-rich tribe within Hylidae with 234 described species. Although cytogenetic information is sparse, chromosome numbers and morphology have been considered as an important character system for systematic inferences in this group. Using a diversity of standard and molecular techniques, we describe the previously unknown karyotypes of the genera Xenohyla, Scarthyla and Sphaenorhynchus and provide new information on Dendropsophus and Lysapsus. Our results reveal significant karyotype diversity among Dendropsophini, with diploid chromosome numbers ranging from 2n = 22 in S. goinorum, 2n = 24 in Lysapsus, Scinax, Xenohyla, and almost all species of Sphaenorhynchus and Pseudis, 2n = 26 in S. carneus, 2n = 28 in P. cardosoi, to 2n = 30 in all known Dendropsophus species. Although nucleolar organizer regions (NORs) and C-banding patterns show a high degree of variability, NOR positions in 2n = 22, 24 and 28 karyotypes and C-banding patterns in Lysapsus and Pseudis are informative cytological markers. Interstitial telomeric sequences reveal a diploid number reduction from 24 to 22 in Scarthyla by a chromosome fusion event. The diploid number of X. truncata corroborates the character state of 2n = 30 as a synapomorphy of Dendropsophus. PMID:24107475

  20. Chromosome instability and global gene expression patterns in proliferating human T-lymphocytes after low dose rate γ-irradiation, and genetic instability in cells from in vivo radiation-exposed persons

    International Nuclear Information System (INIS)

    Chromosomal instability (Cl), and radiation induced Cl in particular, as well as in a wider sense, genomic instability, has been of great interest lately, as it provides an explanation for the occurrence of multiple mutations during transformation of a normal cell to a malignant tumor cell. To explore this phenomenon, we developed an in vitro system to study the long term, cytogenetic effects of ionizing radiation in human T-lymphocytes. Irradiated or non-irradiated T-cells were grown for up to two months as monoclonal or bulk cell cultures in medium enriched with T-cell growth factors. Analysis of G-banded karyotypes at different time intervals demonstrated clonal aberrations in 65% of the clones derived from irradiated cells, and in only 5% of the clones from non-irradiated cells. Delayed occurrence of de novo aberrations, and a progressive development of subclones with karyotypic abnormalities of increasing complexity, was observed many cell generations after the radiation exposure. Moreover, cells exposed to γ-radiation at a low dose rate (LDR, 0.024 Gy h-1) for 5 days in G0-phase, e.g. a dose that gives the cells time to repair between subsequent hits, also demonstrated CI. Following a radiological accident in Estonia 1994, we studied the possible induction of CI in vivo. Both long term bulk cultures and single cell clones were established from one high and three low exposed persons, as well as control individuals from Estonia. Compared to our historical Swedish controls, we found CI to occur in both bulk cultures and clones, and the aberrations were more complex in the exposed individuals than in the controls, indicating that the aberrations were caused by the irradiation. However, due to the high frequency of CI in the Estonian controls, no conclusion with regard to chromosomal instability in vivo could be drawn from the study. In order to trace factors that induce and maintain the chromosomal instability, and clarify which steps are affected in the

  1. HIGH GENETIC VARIATION IN Y CHROMOSOME PATTERNS OF THE MOCOVÍ POPULATION / Alta variación genética en los patrones del cromosoma Y de la población Mocoví

    Directory of Open Access Journals (Sweden)

    Laura Angela Glesmann

    2011-12-01

    Full Text Available In numerically small ethnic groups, the loss of genetic variability in the Y chromosome is frequent, because this genomic compartment is often subjected to selective sweeps. Despite its small size, the Mocoví population retains a significant amount of genetic variation in relation to other native communities, but their Y chromosome diversity is not known in depth. The aim of this study was to analyze the genetic variability of the Y chromosome in a sample of Mocoví males from Santa Fe province (Argentina. We genotyped 11 short tandem repeats (STRs and two single nucleotide polymorphisms (SNPs: M3 and M346. The diversity observed was high, and the 25 haplotypes obtained were compared to the YHRD database, with 13 of them absent of that database. A comparison with previous data reported from other Gran Chaco native groups showed significant differences between the Mocoví and other populations of different ethnic origin. This result and other studies on molecular markers of the Mocoví prove that this ethnic group retains a high genetic diversity that clearly differentiate them from other Amerindian populations.   Keywords: Haplotypes; genetic diversity; STRs; M3; Amerindians.   Resumen La pérdida de variabilidad genética en el cromosoma Y es frecuente en grupos étnicos reducidos numéricamente, debido a que este cromosoma suele estar sometido a barridos selectivos. A pesar de ser pequeña, la población Mocoví conserva una cantidad significativa de variación genética en relación con otras comunidades nativas, pero su diversidad a nivel del cromosoma Y no se conoce en profundidad. El objetivo de este trabajo fue analizar la variabilidad genética del cromosoma Y en una muestra de varones Mocoví de la provincia de Santa Fe (Argentina. Se tipificaron 11 microsatélites (STRs y dos marcadores bialélicos (SNPs: M3 y M346. La diversidad observada fue elevada, y los 25 haplotipos obtenidos se compararon con la base de datos YHRD, donde 13

  2. Escape from X inactivation varies in mouse tissues.

    Directory of Open Access Journals (Sweden)

    Joel B Berletch

    2015-03-01

    Full Text Available X chromosome inactivation (XCI silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape genes in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a binomial model to assess allelic expression, we demonstrate a continuum between complete silencing and expression from the inactive X (Xi. The validity of the RNA-seq approach was verified using RT-PCR with species-specific primers or Sanger sequencing. Both common escape genes and genes with significant differences in XCI status between tissues were identified. Such genes may be candidates for tissue-specific sex differences. Overall, few genes (3-7% escape XCI in any of the mouse tissues examined, suggesting stringent silencing and escape controls. In contrast, an in vitro system represented by the embryonic-kidney-derived Patski cell line showed a higher density of escape genes (21%, representing both kidney-specific escape genes and cell-line specific escape genes. Allele-specific RNA polymerase II occupancy and DNase I hypersensitivity at the promoter of genes on the Xi correlated well with levels of escape, consistent with an open chromatin structure at escape genes. Allele-specific CTCF binding on the Xi clustered at escape genes and was denser in brain compared to the Patski cell line, possibly contributing to a more compartmentalized structure of the Xi and fewer escape genes in brain compared to the cell line where larger domains of escape were observed.

  3. Duplication and loss of chromosome 21 in two children with Down syndrome and acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Rogan, P.K.; Close, P.; Gannutz, L. [Pennsylvania State Univ., Hershey, PA (United States)] [and others

    1995-11-06

    Acute leukemia in Down syndrome (DS) is often associated with additional changes in the number of structure of chromosome 21. We present two DS patients whose leukemic karyotypes were associated with changes in chromosome 21 ploidy. Patient 1 developed acute lymphocytic leukemia (type L1); disomy for chromosome 21 was evident in all blast cells examined. Loss of the paternal chromosome in the leukemic clone produced maternal uniparental disomy with isodisomy over a 25-cM interval. The second patient had acute monoblastic leukemia (type M5) with tetrasomy 21 in all leukemic cells. DNA polymorphism analysis showed duplicate paternal chromosomes in the constitutional genotype. The maternal chromosome was subsequently duplicated in the leukemic clone. The distinct inheritance patterns of chromosome 21 in the blast cells of these patients would appear to indicate that leukemogenesis occurred by different genetic mechanisms in each individual. 57 refs., 2 figs., 3 tabs.

  4. Strong selective sweeps associated with ampliconic regions in great ape X chromosomes

    DEFF Research Database (Denmark)

    Nam, Kiwoong; Munch, Kasper; Hobolth, Asger;

    2014-01-01

    The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution. We here investigate natural selection on the X chromosome in all species of great apes. We find that diversity is more strongly reduced around genes on the X compared with autosomes, and that a ...... ampliconic sequences we propose that intra-genomic conflict between the X and the Y chromosomes is a major driver of X chromosome evolution.......The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution. We here investigate natural selection on the X chromosome in all species of great apes. We find that diversity is more strongly reduced around genes on the X compared with autosomes, and that a...... higher proportion of substitutions results from positive selection. Strikingly, the X exhibits several megabase long regions where diversity is reduced more than five fold. These regions overlap significantly among species, and have a higher singleton proportion, population differentiation, and...

  5. Duplication-targeted DNA methylation and mutagenesis in the evolution of eukaryotic chromosomes.

    OpenAIRE

    Kricker, M C; Drake, J W; Radman, M

    1992-01-01

    Mammalian genomes are threatened with gene inactivation and chromosomal scrambling by recombination between repeated sequences such as mobile genetic elements and pseudogenes. We present and test a model for a defensive strategy based on the methylation and subsequent mutation of CpG dinucleotides in those DNA duplications that create uninterrupted homologous sequences longer than about 0.3 kilobases. The model helps to explain both the diversity of CpG frequencies in different genes and the ...

  6. American marsupials chromosomes: why study them?

    Directory of Open Access Journals (Sweden)

    Marta Svartman

    2009-01-01

    Full Text Available Marsupials, one of the three main groups of mammals, are only found in Australia and in the American continent. Studies performed in Australian marsupials have demonstrated the great potential provided by the group for the understanding of basic genetic mechanisms and chromosome evolution in mammals. Genetic studies in American marsupials are relatively scarce and cytogenetic data of most species are restricted to karyotype descriptions, usually without banding patterns. Nevertheless, the first marsupial genome sequenced was that of Monodelphis domestica, a South American species. The knowledge about mammalian genome evolution and function that resulted from studies on M. domestica is in sharp contrast with the lack of genetic data on most American marsupial species. Here, we present an overview of the chromosome studies performed in marsupials with emphasis on the South American species.

  7. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    Directory of Open Access Journals (Sweden)

    Mohr Brigitte

    2003-01-01

    Full Text Available Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN by which chromosome findings are normalised at a resolution of 400 bands. Lost or gained chromosomes or chromosome segments are specified in detail, and ranges of chromosome breakpoint assignments are recorded. Software modules were written to summarise the recorded chromosome changes with regard to the respective chromosome involvement. To assess the degree of karyotype alterations the ploidy levels and numbers of numerical and structural changes were recorded separately, and summarised in a complex karyotype aberration score (CKAS. The SCCN and CKAS were used to analyse the extend and the spectrum of additional chromosome aberrations in 94 patients with Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia (ALL and secondary chromosome anomalies. Dosage changes of chromosomal material represented 92.1% of all additional events. Recurring regions of chromosome losses were identified. Structural rearrangements affecting (pericentromeric chromosome regions were recorded in 24.6% of the cases. Conclusions SCCN and CKAS provide unifying elements between karyotypes and computer processable data formats. They proved to be useful in the investigation of additional chromosome aberrations in Ph-positive ALL, and may represent a step towards full automation of the analysis of large and complex karyotype databases.

  8. LOSS OF HETEROZYGOSITY ON CHROMOSOME 13 IN SQUAMOUS CELL CARCINOMAS OF THE LARYNX

    Institute of Scientific and Technical Information of China (English)

    Bai Sujuan; Zhang Xue; Wang Jun; Sun Kailai; Fei Shengzhong

    1998-01-01

    Objective: To locate lost region of tumor suppressor gene on chromosome 13q in squamous cell carcinoma of the larynx (LSCC) and to provide clues and evidence for discovering and locating new suppressor gene.Methods: Loss of heterozygosity (LOH) on chromosome 13q was analyzed in 58 LSCC patients by microsatellite polymorphic sequences in loci D13S765 (13q13), RB1.20(13q14.2), D13S133 (13q14.3) and D13S318 (13q21) on chromosome 13 by PCR. Results: There weren't any LOH on chromosome 13q in 3 cases with preinvasive LSCC. Forty-five percentage (24/53) of the 53 invasive LSCC cases showed LOH at one or more loci on chromosome 13q region. The highest percentage of LOH on chromosome 13q was 52% (22/53) at D13S765locus. Conclusion: The deletion region on chromosome 13q was located near by D13S765 locus which is centromeric to RB1. In this region there is suppressor gene, which is related to the genesis and development of LSCC, possibly including RB1. The inactivation of these suppressor genes may be related to the genesis and development of invasive LSCC.

  9. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Science.gov (United States)

    MacKinnon, Ruth N.; Campbell, Lynda J.

    2011-01-01

    Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy. PMID:22567363

  10. Replication asynchrony and differential condensation of X chromosomes in female platypus (Ornithorhynchus anatinus).

    Science.gov (United States)

    Ho, Kristen K K; Deakin, Janine E; Wright, Megan L; Graves, Jennifer A Marshall; Grützner, Frank

    2009-01-01

    A common theme in the evolution of sex chromosomes is the massive loss of genes on the sex-specific chromosome (Y or W), leading to a gene imbalance between males (XY) and females (XX) in a male heterogametic species, or between ZZ and ZW in a female heterogametic species. Different mechanisms have evolved to compensate for this difference in dosage of X-borne genes between sexes. In therian mammals, one of the X chromosomes is inactivated, whereas bird dosage compensation is partial and gene-specific. In therian mammals, hallmarks of the inactive X are monoallelic gene expression, late DNA replication and chromatin condensation. Platypuses have five pairs of X chromosomes in females and five X and five Y chromosomes in males. Gene expression analysis suggests a more bird-like partial and gene-specific dosage compensation mechanism. We investigated replication timing and chromosome condensation of three of the five X chromosomes in female platypus. Our data suggest asynchronous replication of X-specific regions on X(1), X(3) and X(5) but show significantly different condensation between homologues for X(3) only, and not for X(1) or X(5). We discuss these results in relation to recent gene expression analysis of X-linked genes, which together give us insights into possible mechanisms of dosage compensation in platypus. PMID:19874719

  11. Chromosomal comparisons among and within populations of Simulium (Chirostilbia) pertinax (Diptera, Simuliidae)

    OpenAIRE

    Jairo Campos; Carlos Fernando S. de Andrade; Recco-Pimentel, Shirlei M.

    2001-01-01

    Chromosomal studies were carried on six larval populations of Simulium (Chirostilbia) pertinax from different locations in Brazil. Larvae were collected in the states of Paraná, Rio Grande do Sul, Rio de Janeiro and São Paulo. Polytene chromosome map comparisons within and among populations showed no differences in banding pattern, except for some limited polymorphism (secondary NOR and four band polymorphisms). There were no chromosomal variations associated with the resistance or susceptibi...

  12. Fluorescence in situ hybridization to chromosomes as a tool to understand human and primate genome evolution

    OpenAIRE

    Wienberg, Johannes

    2005-01-01

    For the last 15 years molecular cytogenetic techniques have been extensively used to study primate evolution. Molecular probes were helpful to distinguish mammalian chromosomes and chromosome segments on the basis of their DNA content rather than solely on morphological features such as banding patterns. Various landmark rearrangements have been identified for most of the nodes in primate phylogeny while chromosome banding still provides helpful reference maps. Fluorescence in situ hybridizat...

  13. Differential occurrence of chromosome inversion polymorphisms among Muller's elements in three species of the tripunctata group of Drosophila, including a species with fast chromosomal evolution.

    Science.gov (United States)

    Brianti, Mitsue T; Ananina, Galina; Klaczko, Louis B

    2013-01-01

    Detailed chromosome maps with reliable homologies among chromosomes of different species are the first step to study the evolution of the genetic architecture in any set of species. Here, we present detailed photo maps of the polytene chromosomes of three closely related species of the tripunctata group (subgenus Drosophila): Drosophila mediopunctata, D. roehrae, and D. unipunctata. We identified Muller's elements in each species, using FISH, establishing reliable chromosome homologies among species and D. melanogaster. The simultaneous analysis of chromosome inversions revealed a distribution pattern for the inversion polymorphisms among Muller's elements in the three species. Element E is the most polymorphic, with many inversions in each species. Element C follows; while the least polymorphic elements are B and D. While interesting, it remains to be determined how general this pattern is among species of the tripunctata group. Despite previous studies showing that D. mediopunctata and D. unipunctata are phylogenetically closer to each other than to D. roehrae, D. unipunctata shows rare karyotypic changes. It has two chromosome fusions: an additional heterochromatic chromosome pair and a pericentric inversion in the X chromosome. This especial conformation suggests a fast chromosomal evolution that deserves further study. PMID:23379335

  14. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis.

    Directory of Open Access Journals (Sweden)

    Yong-Hyun Shin

    2010-11-01

    Full Text Available Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1(-/ (- testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1(-/ (- testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/ (- ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1(-/ (- oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

  15. Refining the genetic portrait of Portuguese Roma through X-chromosomal markers

    DEFF Research Database (Denmark)

    Pereira, Vania; Gusmão, Leonor; Valente, Cristina;

    2012-01-01

    non-Gypsies. When the pattern of differentiation on the X chromosome was compared with that of autosomes, there was evidence for asymmetries in female and male effective population sizes during the admixture between Roma and non-Roma. This result supplements previous data provided by mtDNA and the Y...... chromosome, underlining the importance of using combined information from the X chromosome and autosomes to dissect patterns of genetic diversity. Following the out-of-India dispersion, the Roma acquired a complex genetic pattern that was influenced by drift and introgression with surrounding populations...

  16. Tissue-specific patterns of allelically-skewed DNA methylation

    Science.gov (United States)

    Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

    2016-01-01

    ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

  17. Molecular fundamentals of chromosomal mutagenesis

    International Nuclear Information System (INIS)

    Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages

  18. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...... impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching...

  19. Repetitive sequences associated with differentiation of W chromosome in Semaprochilodus taeniurus.

    Science.gov (United States)

    Terencio, Maria Leandra; Schneider, Carlos Henrique; Gross, Maria Claudia; Nogaroto, Viviane; de Almeida, Mara Cristina; Artoni, Roberto Ferreira; Vicari, Marcelo Ricardo; Feldberg, Eliana

    2012-12-01

    The possible origins and differentiation of a ZZ/ZW sex chromosome system in Semaprochilodus taeniurus, the only species of the family Prochilodontidae known to possess heteromorphic sex chromosomes, were examined by conventional (C-banding) and molecular (cross-species hybridization of W-specific WCP, Fluorescence in situ hybridization (FISH) with telomere (TTAGGG)n, and Rex1 probes) cytogenetic protocols. Several segments obtained by W-specific probe were cloned, and the sequences localized on the W chromosome were identified by DNA sequencing and search of nucleotide collections of the NCBI and GIRI using BLAST and CENSOR, respectively. Blocks of constitutive heterochromatin in chromosomes of S. taeniurus were observed in the centromere of all autosomal chromosomes and in the terminal, interstitial, and pericentromeric regions of the W chromosome, which did not demonstrate interstitial telomeric sites with FISH of the telomere probe. The Rex1 probe displayed a compartmentalized distribution pattern in some chromosomes and showed signs of invasion of the pericentromeric region in the W chromosome. Chromosomal painting with the W-specific WCP of S. taeniurus onto its own chromosomes showed complete staining of the W chromosome, centromeric sites, and the ends of the Z chromosome, as well as other autosomes. However, cross-species painting using this WCP on chromosomes of S. insignis, Prochilodus lineatus, and P. nigricans did not reveal a proto-W element, but instead demonstrated scattered positive signals of repetitive DNAs. Identification of the W-specific repetitive sequences showed high similarity to microsatellites and transposable elements. Classes of repetitive DNA identified in the W chromosome suggested that the genetic degeneration of this chromosome in S. taeniurus occurred through accumulation of these repetitive DNAs. PMID:23325335

  20. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  1. Reference-assisted chromosome assembly

    OpenAIRE

    Kim, Jaebum; Larkin, Denis M; Cai, Qingle; Asan,; Zhang, Yongfen; Ge, Ri-Li; Auvil, Loretta; Capitanu, Boris; Zhang, Guojie; Lewin, Harris A.; Ma, Jian

    2013-01-01

    One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed “reference-assisted chromosome assembly” (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that ou...

  2. Application and staining patterns of commercial anti-Pneumocystis carinii monoclonal antibodies.

    OpenAIRE

    Elvin, K; Linder, E.

    1993-01-01

    Commercially available monoclonal antibodies to Pneumocystis carinii were compared with respect to immunofluorescence staining patterns of human immunodeficiency virus-inactivated smears. Only the indirect staining kits were suitable for application to ethanol-inactivated samples. When antibodies from Dakopatts and Northumbria were compared, the staining of cysts and trophozoites showed different patterns.

  3. Mechanism of trypsin inactivation by intact Hymenolepis diminuta (Cestoda)

    International Nuclear Information System (INIS)

    The mechanism of trypsin inactivation by intact Hymenolepis diminuta has been investigated by biochemical and autoradiographic methods. Although worms inactivate trypsin and chymotrypsin in vitro, no inactivation of other endoproteases (subtilisin, pepsin and papain) could be demonstrated. Trypsin inactivation, as demonstrated by macromolecular substrates (azoalbumin, hemoglobin and casein), could not be detected using low molecular weight synthetic substrates such as N-p-benzoyl-DL-arginine-p-nitroanilide (BAPA) or N-p-tosyl-L-arginine methyl ester (TAME). In addition, the kinetic parameters (K/sub m/ and k3) for H. diminuta-inactivated trypsin, using BAPA as the substrate, were not different from those of the native enzyme. The number of active sites for both native and inactivated trypsin were determined by titration with p-nitro-phenyl-p'-guanidinobenzoate. Absorbance values for both titrations were found to be identical. Dialysis, heating to 50 C, or repeated freezing and thawing of the inactivated trypsin did not reverse inactivation

  4. X-chromosome workshop.

    Science.gov (United States)

    Paterson, A D

    1998-01-01

    Researchers presented results of ongoing research to the X-chromosome workshop of the Fifth World Congress on Psychiatric Genetics, covering a wide range of disorders: X-linked infantile spasms; a complex phenotype associated with deletions of Xp11; male homosexuality; degree of handedness; bipolar affective disorder; schizophrenia; childhood onset psychosis; and autism. This report summarizes the presentations, as well as reviewing previous studies. The focus of this report is on linkage findings for schizophrenia and bipolar disorder from a number of groups. For schizophrenia, low positive lod scores were obtained for markers DXS991 and DXS993 from two studies, although the sharing of alleles was greatest from brother-brother pairs in one study, and sister-sister in the other. Data from the Irish schizophrenia study was also submitted, with no strong evidence for linkage on the X chromosome. For bipolar disease, following the report of a Finnish family linked to Xq24-q27, the Columbia group reported some positive results for this region from 57 families, however, another group found no evidence for linkage to this region. Of interest, is the clustering of low positive linkage results that point to regions for possible further study. PMID:9686435

  5. Chromosome analysis and sorting

    Czech Academy of Sciences Publication Activity Database

    Doležel, Jaroslav; Kubaláková, Marie; Suchánková, Pavla; Kovářová, Pavlína; Bartoš, Jan; Šimková, Hana

    Weinheim : Wiley-VCH, 2007 - (Doležel, J.; Greilhuber, J.; Suda, J.), s. 373-403 ISBN 978-3-527-31487-4 R&D Projects: GA ČR GA521/04/0607; GA ČR GP521/05/P257; GA ČR GD521/05/H013; GA MŠk(CZ) LC06004 Grant ostatní: Mendelova zemědělská a lesnická univerzita v Brně / Agronomická fakulta(CZ) ME 844 Institutional research plan: CEZ:AV0Z5038910 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : Plant flow cytometry * chromosome sorting * flow cytogenetics Subject RIV: EB - Genetics ; Molecular Biology http://books. google .com/books?id=3cwakORieqUC&pg=PA373&lpg=PA373&dq=Chromosome+analysis+and+sorting&source=web&ots=8IyvJlBQyq&sig=_NlXyQQgBCwpj1pTC9YITvvVZqU

  6. Pulsed electric field inactivation in a microreactor

    NARCIS (Netherlands)

    Fox, M.B.

    2006-01-01

    Pulsed electric fields (PEF) is a novel, non-thermal pasteurization method which uses short, high electric field pulses to inactivate microorganisms. The advantage of a pasteurization method like PEF compared to regular heat pasteurization is that the taste, flavour, texture and nutritional value ar

  7. Inactivation of prion infectivity by ionizing rays

    International Nuclear Information System (INIS)

    Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination

  8. Inactivation of prion infectivity by ionizing rays

    Energy Technology Data Exchange (ETDEWEB)

    Gominet, M. [Ionisos, ZI les Chatinieres, F01120 Dagneux (France); Vadrot, C.; Austruy, G. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France); Darbord, J.C. [Paris V University, Central Pharmacy of Hospitals, 4 avenue de l' Observatoire, F-75006, Paris (France)], E-mail: darbord@pharmacie.univ-paris5.fr

    2007-11-15

    Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination.

  9. Inactivation of prion infectivity by ionizing rays

    Science.gov (United States)

    Gominet, M.; Vadrot, C.; Austruy, G.; Darbord, J. C.

    2007-11-01

    Inactivation of prion deposits on medical devices or prion contamination in pharmaceutical raw materials is considered as impossible by using gamma irradiation. Early, the guideline WHO/CDS/CSR/APH/2000 has described irradiation as an ineffective process. But, in 2003, S. Miekka et al. noted radiation inactivation of prions in a particular application to purify human albumin, shown by the physical denaturation of the infectious protein (PrP). The aim of our study was to determine the inactivation of prions with a scrapie model (strain C506M3) by irradiating standardised preparations. Results: Gamma irradiation was partially effective, showing a 4-5 log reduction on exposure to 50 kGy. A characteristic effect-dose curve was not observed (25, 50 and 100 kGy), only an increase in the incubation period of the murine disease (229 days with 25 kGy to 290 days with 100 kGy) compared with 170 days without irradiation. Since the inactivation was not a total one, the observed effect is significant. It is proposed that further work be undertaken with the model to investigate the application of gamma radiation known levels of prion contamination.

  10. Inactivation of Bacillus atrophaeus by OH radicals

    Science.gov (United States)

    Ono, Ryo; Yonetamari, Kenta; Tokumitsu, Yusuke; Yonemori, Seiya; Yasuda, Hachiro; Mizuno, Akira

    2016-08-01

    The inactivation of Bacillus atrophaeus by OH radicals is measured. This study aims to evaluate the bactericidal effects of OH radicals produced by atmospheric-pressure nonthermal plasma widely used for plasma medicine; however, in this study, OH radicals are produced by vacuum ultraviolet (VUV) photolysis of water vapor instead of plasma to allow the production of OH radicals with almost no other reactive species. A 172 nm VUV light from a Xe2 excimer lamp irradiates a He–H2O mixture flowing in a quartz tube to photodissociate H2O to produce OH, H, O, HO2, H2O2, and O3. The produced reactive oxygen species (ROS) flow out of the quartz tube nozzle to the bacteria on an agar plate and cause inactivation. The inactivation by OH radicals among the six ROS is observed by properly setting the experimental conditions with the help of simulations calculating the ROS densities. A 30 s treatment with approximately 0.1 ppm OH radicals causes visible inactivation.

  11. High Pressure Inactivation of HAV within Mussels

    Science.gov (United States)

    The potential of hepatitis A virus (HAV) to be inactivated within Mediterranean mussels (Mytilus galloprovincialis) and blue mussels (Mytilus edulis) by high pressure processing was evaluated. HAV was bioaccumulated within mussels to approximately 6-log10 PFU by exposure of mussels to HAV-contamina...

  12. Inactivation of papain by high LET radiations

    Energy Technology Data Exchange (ETDEWEB)

    Bisby, R.H.; Cundall, R.B.; Sims, H.E. (Salford Univ. (UK). Dept. of Biochemistry); Burns, W.G. (UKAEA Atomic Energy Research Establishment, Harwell. Chemistry Div.)

    1984-09-01

    The effect of varying LET over a wide range (0.2-1570 eV/nm) on the radiation-induced inactivation of the enzyme papain in dilute aqueous solution has been investigated. Measurements of total, reparable and non-reparable inactivation G values in oxygen, nitrous oxide and argon saturated solutions have allowed the contributions to inactivation from radicals and hydrogen peroxide to be evaluated. At high LET the results demonstrate an increasing component due to reaction of the superoxide radical, formed from oxygen produced in the track as a primary radiolysis product. This effect was not observed in our previous study with ribonuclease due to the insensitivity of ribonuclease to inactivation by superoxide and hydrogen peroxide. The results obtained with papain clearly demonstrate a maximum in G(H/sub 2/O/sub 2/) at an LET of equivalent to 140 eV/nm. Generation of O/sub 2/ within the track as a primary radiolysis product at high LET now appears to be confirmed as an important mechanism leading to reduction in the oxygen enhancement ratio for cellular systems exposed to high LET radiations (Baverstock and Burns 1981).

  13. Inactivation of human interferon by body fluids

    Science.gov (United States)

    Cesario, T. C.; Mandell, A.; Tilles, J. G.

    1973-01-01

    Description of the effects of human feces, bile, saliva, serum, and cerebrospinal fluid on interferon activity. It is shown that crude interferon is inactivated by at least 50% more than with the control medium used, when incubated for 4 hr in vitro in the presence of serum, saliva, or cerebrospinal liquid, and by close to 100% when incubated with stool extract or bile.

  14. Inactivation of Microbial Contaminants in Fresh Produce

    Science.gov (United States)

    With the microbial safety of fresh produce of increasing concern, conventional sanitizing treatments need to be supplemented with effective new interventions to inactivate human pathogens. The Produce Safety research project at the US Dept. Agriculture’s Eastern Regional Research Center develops and...

  15. Chironomus group classification according to the mapping of polytene chromosomes

    Science.gov (United States)

    Salleh, Syafinaz; Kutty, Ahmad Abas

    2013-11-01

    Chironomus is one of the important genera in Chironomidae family since they are widely diverse and abundance in aquatic ecosystem. Since Chironomus is very diverse, taxonomic work on this genus is very difficult and incomplete. Objective of this study is to form group classification of Chironomus according to the polytene chromosome mapping. The specific characteristics of polytene chromosomes in the salivary gland appeared to be particularly promising for taxonomic diagnosis of chironomid species. Chironomid larvae were collected from pristine sites at Sg. Langat and cultured in laboratory to reach fourth instar stage. The salivary glands were removed from larvae and chromosomes were stained with aceto orcein. Results showed that polytene chromosomes of Chironomus comprise of three long metacentric or submetacentric arms (BF, CD and AE arms) and one short acrocentric (G arm). In regards to nucleolar organizing region (NOR), Balbiani ring (BR), puffings and chromosome rearrangement, a number of four groups of different banding patterns were found. Two groups called as G group A and B have common NOR on arm BF and BR on arm G. However, group A has rearrangement pattern on arm CD and not in group B. This makes group B separated from group A. Another two groups called as groups C and D do not have common NOR on arm BF and also BR on arm G. Groups C and D were separated using arms G and arm AE. At arm G, only group C rearrangement pattern at unit 23c whereas group D was found to have large NOR at arm G and as well as arm AE, only group D has rearrangement pattern at unit 12c. This study indicates that chromosome arrangement could aid in revealing Chironomus diversity.

  16. Gene Inactivation in the Cyanobacterium Synechococcus sp. PCC 7002 and the Green Sulfur Bacterium Chlorobium tepidum Using In Vitro-Made DNA Constructs and Natural Transformation

    DEFF Research Database (Denmark)

    Frigaard, Niels-Ulrik; Sakuragi, Yumiko; Bryant, Donald A

    2004-01-01

    Inactivation of a chromosomal gene is a useful approach to study the function of the gene in question and can be used to produce a desired phenotype in the organism. This chapter describes how to generate such mutants of the cyanobacterium Synechococcus sp. PCC 7002 and the green sulfur bacterium...

  17. High-pressure inactivation of dried microorganisms.

    Science.gov (United States)

    Espinasse, V; Perrier-Cornet, J-M; Marecat, A; Gervais, P

    2008-01-01

    Dried microorganisms are particularly resistant to high hydrostatic pressure effects. In this study, the survival of Saccharomyces cerevisiae was studied under pressure applied in different ways. Original processes and devices were purposely developed in our laboratory for long-term pressurization. Dried and wet yeast powders were submitted to high-pressure treatments (100-150 MPa for 24-144 h at 25 degrees C) through liquid media or inert gas. These powders were also pressurized after being vacuum-packed. In the case of wet yeasts, the pressurization procedure had little influence on the inactivation rate. In this case, inactivations were mainly due to hydrostatic pressure effects. Conversely, in the case of dried yeasts, inactivation was highly dependent on the treatment scheme. No mortality was observed when dried cells were pressurized in a non-aqueous liquid medium, but when nitrogen gas was used as the pressure-transmitting fluid, the inactivation rate was found to be between 1.5 and 2 log for the same pressure level and holding time. Several hypotheses were formulated to explain this phenomenon: the thermal effects induced by the pressure variations, the drying resulting from the gas pressure release and the sorption and desorption of the gas in cells. The highest inactivation rates were obtained with vacuum-packed dried yeasts. In this case, cell death occurred during the pressurization step and was induced by shear forces. Our results show that the mechanisms at the origin of cell death under pressure are strongly dependent on the nature of the pressure-transmitting medium and the hydration of microorganisms. PMID:17573691

  18. Chromosomal comparisons among and within populations of Simulium (Chirostilbia pertinax (Diptera, Simuliidae

    Directory of Open Access Journals (Sweden)

    Jairo Campos

    2001-04-01

    Full Text Available Chromosomal studies were carried on six larval populations of Simulium (Chirostilbia pertinax from different locations in Brazil. Larvae were collected in the states of Paraná, Rio Grande do Sul, Rio de Janeiro and São Paulo. Polytene chromosome map comparisons within and among populations showed no differences in banding pattern, except for some limited polymorphism (secondary NOR and four band polymorphisms. There were no chromosomal variations associated with the resistance or susceptibility of the larvae to temephos. The chromosomal homosequentiality found among the six populations suggests that S. pertinax may be a monomorphic species.

  19. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  20. Causes of oncogenic chromosomal translocation

    OpenAIRE

    Aplan, Peter D.

    2005-01-01

    Non-random chromosomal translocations are frequently associated with a variety of cancers, especially hematologic malignancies and childhood sarcomas In addition to their diagnostic utility, chromosomal translocations are increasingly being used in the clinic to guide therapeutic decisions. However, the mechanisms which cause these translocations remain poorly understood. Illegit...

  1. [Tropical turtles chromosomes: Kinosternon leucostomum, Trachemys scripta and Staurotypus triporcatus (Testudines: Kinosternidae/Emydidae)].

    Science.gov (United States)

    Hernández-Guzmán, Javier; Indy, Jeane Rimber; Yasui, George Shigueki; Arias-Rodriguez, Lenin

    2014-06-01

    Mexico is a biodiverse country in several taxa as reptiles, that include several species of freshwater and marine turtles. Eventhough most of this group species are under protection, Tabasco State has nine native freshwater turtles, like Kinosternon leucostomum, Trachemys scripta and Staurotypus triporcatus that are very important in traditional dishes. This has resulted in a critical level of their populations, together with little biological knowledge for their conservation. Therefore, this study was dedicated to turtle cytogenetics. The study was conducted using the conventional methods for cytogenetics. The results showed the modal diploid and haploid number for K. leucostomum of 2n = 56 (2n = 56+3 microchromosomes "B") and 1n = 28 chromosomes in mitosis and meiosis, respectively. In T. scripta 2n = 50 chromosomes (2n = 50+2 microchromosomes "B") and 1n = 25 chromosomes were also characterized. Whereas in S. triporcatus we only report the 2 = 54 chromosomes (2n = 54+2 microchromosomes "B"). The karyological formula for K. leucostomum was integrated by 12 metacentric-submetacentric chromosomes "msm"/"A"+22 subtelocentric-telocentric chromosomes "stt"/"B"+22 telocentric chromosomes "T"/"C" with fundamental number (FN) of 90 chromosome arms. While T. scripta karyotype was integrated by 32 "msm/"A"+10 "stt"/"B"+8"T/"C" chromosomes, with FN of 92 arms. S. triporcatus karyotype formula was built up by 20 chromosomes "msm"/"A"+34 chromosomes "T"/"C" with FN of 74. The variation in chromosome classification, the fundamental number and the presence of supernumerary microchromosomes "B" in the studied species, were evidence of a particular chromosome cytotypes in Tabasco. We considered that the presence of microchromosomes "B" probably has different origins, and they may be very important as a pattern for the formation or separation of new species. This study also showed the absence of heterologous chromosomes between the females and males karyotypes from the studied

  2. Genetics Home Reference: ring chromosome 20 syndrome

    Science.gov (United States)

    ... 3 links) Encyclopedia: Chromosome Encyclopedia: Epilepsy Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 20 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  3. Genetics Home Reference: ring chromosome 14 syndrome

    Science.gov (United States)

    ... Encyclopedia: Chromosome Health Topic: Developmental Disabilities Health Topic: Epilepsy Genetic and Rare Diseases Information Center (1 link) Ring chromosome 14 Additional NIH Resources (2 links) National Human Genome Research Institute: Chromosome Abnormalities National Institute of ...

  4. M-Band Analysis of Chromosome Aberrations in Human Epithelial Cells Induced By Low- and High-Let Radiations

    Science.gov (United States)

    Hada, M.; Gersey, B.; Saganti, P. B.; Wilkins, R.; Gonda, S. R.; Cucinotta, F. A.; Wu, H.

    2007-01-01

    Energetic primary and secondary particles pose a health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET radiation is much more effective than low-LET radiation in the induction of various biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological endpoints are closely correlated to chromosomal damage, which can be utilized as a biomarker for radiation insult. In this study, human epithelial cells were exposed in vitro to gamma rays, 1 GeV/nucleon Fe ions and secondary neutrons whose spectrum is similar to that measured inside the Space Station. Chromosomes were condensed using a premature chromosome condensation technique and chromosome aberrations were analyzed with the multi-color banding (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of both interchromosomal (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Results of the study confirmed the observation of higher incidence of inversions for high-LET irradiation. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Half of the inversions observed in the low-LET irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, Fe ions induced a significant fraction of inversions that involved complex rearrangements of both the inter- and intrachromosome exchanges.

  5. Bacterial chromosome organization and segregation.

    Science.gov (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T

    2015-01-01

    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation. PMID:26566111

  6. A small (sSMC) chromosome 22 due to a maternal translocation between chromosomes 8 and 22: a case report.

    Science.gov (United States)

    Mundhofir, F E P; Kooper, A J A; Winarni, T I; Smits, A P T; Faradz, S M H; Hamel, B C J

    2010-01-01

    We report on a boy with partial trisomies for chromosomes 8 and 22 caused by the presence of a small supernumerary marker chromosome (sSMC), a der(22)t(8;22)(p22;q11.21), inherited from a t(8;22)(p22;q11.21) translocation carrier mother. He has mild mental retardation, unability to speak distinct words and several minor anomalies i.e. high forehead and hairline, telecanthus, upslanting palpebral fissures, depressed nasal bridge, nail hypoplasia, toe position anomaly and 5th finger clinodactyly. He has two maternal uncles and one maternal aunt with mental retardation. G-banding technique showed 47,XY,+mar whilst his mother's karyotype showed a balanced reciprocal translocation between the chromosomes 8 and 22. Fluorescence In Situ Hybridization (FISH) technique with probes for centromere 22 and 8pter were used to detect the origin of marker chromosome and confirmed the marker chromosome in the proband showing to be extra chromosomal material originated from chromosome 8 and 22. Additional genome wide microarray analysis, using the Affymetrix Nspl 250K SNP array platform was performed to further characterize the marker chromosome and resulted in a der(22)t(8;22)(p22;q11.21). Furthermore, cytogenetic analysis of three affected family members showed the same unbalanced translocation, due to 3:1 meiotic segregation. This indicated the viability of this unbalanced pattern and combined with the recurrent miscarriages by the proband's mother, the mechanism of transmitting extrachromosomal material is probably not a random process. Since, there is no similar translocation (8p;22q) reported and the chromosomal translocation largely exists of additional 8p22-8pter we compare the clinical outcomes with reported cases of 8p22-8pter triplication, although there is a part of genetic material derived from chromosome 22 present. This unique familial chromosome translocation case from Indonesia will give insight in the underlying mechanism of this recurrent chromosomal abnormality

  7. Effects of Bacterial Inactivation Methods on Downstream Proteomic Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Andy; Merkley, Eric D.; Clowers, Brian H.; Hutchison, Janine R.; Kreuzer, Helen W.

    2015-05-01

    Inactivation of pathogenic microbial samples is often necessary for the protection of researchers and to comply with local and federal regulations. By its nature, biological inactivation causes changes to microbial samples, potentially affecting observed experimental results. While inactivation induced damage to materials such as DNA has been evaluated, the effect of various inactivation strategies on proteomic data, to our knowledge, has not been discussed. To this end, we inactivated samples of Yersinia pestis and Escherichia coli by autoclave, ethanol, or irradiation treatment to determine how inactivation changes liquid chromatography tandem mass spectrometry data quality as well as apparent protein content of cells. Proteomic datasets obtained from aliquots of samples inactivated by different methods were highly similar, with Pearson correlation coefficients ranging from 0.822 to 0.985 and 0.816 to 0.985 for E. coli and Y. pestis, respectively, suggesting that inactivation had only slight impacts on the set of proteins identified. In addition, spectral quality metrics such as distributions of various database search algorithm scores remained constant across inactivation methods, indicating that inactivation does not appreciably degrade spectral quality. Though overall changes resulting from inactivation were small, there were detectable trends. For example, one-sided Fischer exact tests determined that periplasmic proteins decrease in observed abundance after sample inactivation by autoclaving (α = 1.71x10-2 for E. coli, α = 4.97x10-4 for Y. pestis) and irradiation (α = 9.43x10-7 for E. coli, α = 1.21x10-5 for Y. pestis) when compared to controls that were not inactivated. Based on our data, if sample inactivation is necessary, we recommend inactivation with ethanol treatment with secondary preference given to irradiation.

  8. Recombination of an intrachromosomal paracentric insertion of chromosome 3

    Energy Technology Data Exchange (ETDEWEB)

    Best, R.G.; Burnett, W.J.; Brock, J.K. [Univ. of South Carolina School of Medicine, Columbia, SC (United States)] [and others

    1994-09-01

    Cytogenetic studies were initiated on a newborn female due to multiple congenital anomalies including microcephaly, clinodactyly, abnormal positioning of hands, left facial palsy, heart defect, sacral dimple, and facial dysmorphic features. Facial features were described as low set rotated ears, nystagmus, and a small, flattened nose. A structural rearrangement of the long arm of chromosome 3 was observed with a complex banding pattern. Study of parental chromosomes revealed a normal male pattern for the father, and an intrachromosomal insertion on the long arm of chromosome 3 for the mother described as 46,XX,dir ins(3)(q21q23q26.2). Further characterization of the proband`s structurally abnormal chromosome 3 revealed a karyotype best described as: 46,XX,rec(3),dupq23{r_arrow}q26.2::q21{r_arrow}q23,dir ins(3)(q21q23q26.2), which is a partial duplication of both the inserted segment as well as the intervening segment between the inserted segment and the insertion site. This would appear to be the result of a three-strand double cross-over within the insertion loop. Molecular cytogenetic studies are presently underway to further elucidate chromosome structure of the proband and her mother.

  9. ADN et chromosomes

    OpenAIRE

    Hayes, Hélène

    2000-01-01

    Chaque chromosome contient une seule molécule d’ADN. L’ADN déroulé d’un noyau de cellule humaine mesurerait environ 1,8 m : chaque molécule d’ADN est enroulée et compactée en plusieurs étapes, grâce à l’association de différentes protéines, et loge dans le noyau de 6 µm de diamètre. Le degré de condensation de l’ADN est variable selon les régions chromosomiques et les régions les moins condensées sont les plus riches en gènes. L’ADN est composé d’une variété de séquences codantes ou non et ré...

  10. X-Chromosome dosage compensation.

    Science.gov (United States)

    Meyer, Barbara J

    2005-01-01

    In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the

  11. Chromosome evolution in malaria mosquitoes inferred from physically mapped genome assemblies.

    Science.gov (United States)

    Sharakhov, Igor V; Artemov, Gleb N; Sharakhova, Maria V

    2016-04-01

    Polymorphic inversions in mosquitoes are distributed nonrandomly among chromosomes and are associated with ecological, behavioral, and physiological adaptations related to pathogen transmission. Despite their significance, the patterns and mechanism of genome rearrangements are not well understood. Recent sequencing and physical mapping of the genomes for 16 Anopheles mosquito species provided an opportunity to study chromosome evolution at the highest resolution. New studies revealed that fixed rearrangement accumulated [Formula: see text]3 times faster on the X chromosome than on autosomes. The highest densities of transposable elements (TEs) and satellites of different sizes have also been found on the X chromosome, suggesting a mechanism for the inversion generation. The high rate of X chromosome rearrangements is in sharp contrast with the paucity of polymorphic inversions on the X in the majority of anopheline species. This paper highlights the advances in understanding chromosome evolution in malaria vectors and discusses possible future directions in studying mechanisms and biological roles of genome rearrangements. PMID:27021248

  12. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  13. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  14. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  15. Mitotic chromosome condensation in vertebrates

    International Nuclear Information System (INIS)

    Work from several laboratories over the past 10–15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292–301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories—a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307–316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119–1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579–589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different

  16. Inactivation and reactivation of B. megatherium phage.

    Science.gov (United States)

    NORTHROP, J H

    1955-11-20

    Preparation of Reversibly Inactivated (R.I.) Phage.- If B. megatherium phage (of any type, or in any stage of purification) is suspended in dilute salt solutions at pH 5-6, it is completely inactivated; i.e., it does not form plaques, or give rise to more phage when mixed with a sensitive organism (Northrop, 1954). The inactivation occurs when the phage is added to the dilute salt solution. If a suspension of the inactive phage in pH 7 peptone is titrated to pH 5 and allowed to stand, the activity gradually returns. The inactivation is therefore reversible. Properties of R.I. Phage.- The R.I. phage is adsorbed by sensitive cells at about the same rate as the active phage. It kills the cells, but no active phage is produced. The R.I. phage therefore has the properties of phage "ghosts" (Herriott, 1951) or of colicines (Gratia, 1925), or phage inactivated by ultraviolet light (Luria, 1947). The R.I. phage is sedimented in the centrifuge at the same rate as active phage. It is therefore about the same size as the active phage. The R.I. phage is most stable in pH 7, 5 per cent peptone, and may be kept in this solution for weeks at 0 degrees C. The rate of digestion of R.I. phage by trypsin, chymotrypsin, or desoxyribonuclease is about the same as that of active phage (Northrop, 1955 a). Effect of Various Substances on the Formation of R.I. Phage.- There is an equilibrium between R.I. phage and active phage. The R.I. form is the stable one in dilute salt solution, pH 5 to 6.5 and at low temperature (6.5, in dilute salt solution, the R.I. phage changes to the active form. The cycle, active right harpoon over left harpoon inactive phage, may be repeated many times at 0 degrees C. by changing the pH of the solution back and forth between pH 7 and pH 6. Irreversible inactivation is caused by distilled water, some heavy metals, concentrated urea or quanidine solutions, and by l-arginine. Reversible inactivation is prevented by all salts tested (except those causing

  17. Chromosomal variation and systematics of Myoxids

    Directory of Open Access Journals (Sweden)

    Jan Zima

    1995-05-01

    Full Text Available Abstract A synopsis of cytogenetic studies performed on various species and populations of myoxids is presented. Interspecific phylogenetic relationships derived from chromosomal data are evaluated and the evolutionary importance of intraspecific karyotypic variation is discussed. New data on the karyotypes of Dryomys nitedula from Asia and Muscardinus avellanarius from Europe are presented and discussed with special emphasis on the contrasting pattern of chromosomal differentiation in Eliomys vs. Dryomys and other myoxids. A bibliography of myoxid cytogenetics and karyology is compiled. Riassunto Variazione cromosomica e sistematica dei Mioxidi - Viene presentata una sinossi degli studi citogenetici effettuati su varie specie e popolazioni di Mioxidi. Vengono valutate le relazioni filogenetiche interspecifiche derivate da dati cromosomici e viene discussa l'importanza evolutiva della variazione cariotipica intraspecifica. Vengono presentati nuovi dati sui cariotipi di Dryomys nitedula asiatico e di Muscardinus avellanurius europeo e discussi con particolare enfasi sul contrastante pattern di differenziamento cromosomico di Eliomys rispetto a Dryomys ed altri Mioxidi. Viene compilata una bibliografia su citogenetica e cariologia dei Mioxidi.

  18. Inactivation in ShakerB K+ channels: a test for the number of inactivating particles on each channel.

    OpenAIRE

    Gomez-Lagunas, F; Armstrong, C M

    1995-01-01

    Fast inactivation in ShakerB K channels results from pore-block caused by "ball peptides" attached to the inner part of each K channel. We have examined the question of how many functional inactivating balls are on each channel and how this number affects inactivation and recovery from inactivation. To that purpose we expressed ShakerB in the insect cell line Sf9 and gradually removed inactivation by perfusing the cell interior with the hydrolytic enzyme papain under whole cell patch clamp. I...

  19. Immunogenicity of UV-inactivated measles virus

    International Nuclear Information System (INIS)

    By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 105 to 106 HadU50/ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.)

  20. Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

    Science.gov (United States)

    Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

    2013-01-01

    The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat. PMID:23884766

  1. Inactivation of Anandamide Signaling: A Continuing Debate

    Directory of Open Access Journals (Sweden)

    Wael E. Houssen

    2010-10-01

    Full Text Available Since the first endocannabinoid anandamide was identified in 1992, extensive research has been conducted to characterize the elements of the tightly controlled endocannabinoid signaling system. While it was established that the activity of endocannabinoids are terminated by a two-step process that includes cellular uptake and degradation, there is still a continuing debate about the mechanistic role of these processes in inactivating anandamide signals.

  2. Inactivation of Bacillus anthracis by Gamma irradiation

    Directory of Open Access Journals (Sweden)

    N. Natalia

    2013-09-01

    Full Text Available The use of Bacillus anthracis as a biological weapon heighlightened awareness of the need for validated methods for the inactivation of B. anthracis spores. Ionizing radiation is capable of causing a variety of chemical changes and biological effects on bacteria which can be due both to direct interactions with critical cell components and to indirect actions on bacteria by molecular entities formed as a result of radiolysis of other molecules in the bacterial cell. This study determined the gamma irradiation dose for inactivating B. anthracis spores and its biological effects on the bacterial characteristics. Gamma irradiation was conducted at the IRKA irradiator at the National Nuclear Energy Agency, Jakarta and cobalt-60 was used as the source of ionizing radiation (capacity of ca. 134,044 Kci. Freeze dried culture of B. anthracis in glass ampoules was irradiated using variable doses of 30, 20 and 10 KGy. Viability, biochemical and protease enzyme characteristics of B. anthracis were evaluated before and after irradiation. The ability of B. anthracis to degrade gelatin, haemoglobin and bovine immunoglobulin G was also tested. The results showed that ionizing radiation was able to inactivate or kill 11,05 x 108 cfu B. anthracis by 95.37%, 99.58% and 99.99 at respective doses of 10, 20 and 30 KGy. Bacterial spores appear to be less susceptible to irradiation than the vegetative cells, because of their specific structure. The survive spores irradiated at 30kGy shows some biochemical characteristic changes. The survivors failed to degrade methyl -D-glucopyranoside and arbutine. The ability of B. anthracis protease to degrade gelatin, haemoglobin and bovine immunoglobulin G was not affected by irradiation. These findings showed that a gamma irradiation at 30 KGy effectively inactivates B. anthracis spores without changing the protease activities.

  3. Radiation-induced inactivation of proteolytic enzymes

    Science.gov (United States)

    Orlova, M. A.

    1993-05-01

    Data on the mechanism of the inactivation of proteases under various conditions and the possible applications of these processes are surveyed. Serine, sulfhydryl, acid, and metal containing proteases are considered. Attention is concentrates on the conformation changes in radiolytic processes: their dependence on the pH of the medium and the correlations with the change in the aminoacid composition of the enzymes. The bibliography includes 90 references.

  4. Photodynamic inactivation of antibiotic-resistant pathogens

    International Nuclear Information System (INIS)

    Nowadays methicillin-resistant strain Staphylococcus aureus (MRSA) is one of the most widespread multiresistant bacteria. Photodynamic inactivation (PDI) of microorganisms by photosensitizers (PS) may be an effective and alternative therapeutic option against antibiotic resistant bacteria. The effectiveness of new PS cationic porphyrin Zn-TBut4PyP was tested on two strains of S. aureus (MRSA and methicillin-sensitive S. aureus). It is shown that Zn-TBut4PyP has high photodynamic activity against both strains

  5. Chromosome conservation in squamate reptiles revealed by comparative chromosome painting

    Czech Academy of Sciences Publication Activity Database

    Giovannotti, M.; Pokorná, Martina; Kratochvíl, L.; Caputo, V.; Olmo, E.; Ferguson-Smith, M. A.; Rens, W.

    Manchester : ICCS, 2011. 78-78. [Intarnational Chromosome Conference /18./. 29.08.2011-02.09.2011, Manchester] Institutional research plan: CEZ:AV0Z50450515 Keywords : squamate reptiles Subject RIV: EG - Zoology

  6. Numerous transitions of sex chromosomes in Diptera.

    Directory of Open Access Journals (Sweden)

    Beatriz Vicoso

    2015-04-01

    Full Text Available Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot, but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes. Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

  7. Rapid inactivation of SARS-like coronaviruses.

    Energy Technology Data Exchange (ETDEWEB)

    Kapil, Sanjay (Kansas State University, Manhattan, KS); Oberst, R. D. (Kansas State University, Manhattan, KS); Bieker, Jill Marie; Tucker, Mark David; Souza, Caroline Ann; Williams, Cecelia Victoria

    2004-03-01

    Chemical disinfection and inactivation of viruses is largely understudied, but is very important especially in the case of highly infectious viruses. The purpose of this LDRD was to determine the efficacy of the Sandia National Laboratories developed decontamination formulations against Bovine Coronavirus (BCV) as a surrogate for the coronavirus that causes Severe Acute Respiratory Syndrome (SARS) in humans. The outbreak of SARS in late 2002 resulted from a highly infectious virus that was able to survive and remain infectious for extended periods. For this study, preliminary testing with Escherichia coli MS-2 (MS-2) and Escherichia coli T4 (T4) bacteriophages was conducted to develop virucidal methodology for verifying the inactivation after treatment with the test formulations following AOAC germicidal methodologies. After the determination of various experimental parameters (i.e. exposure, concentration) of the formulations, final testing was conducted on BCV. All experiments were conducted with various organic challenges (horse serum, bovine feces, compost) for results that more accurately represent field use condition. The MS-2 and T4 were slightly more resistant than BCV and required a 2 minute exposure while BCV was completely inactivated after a 1 minute exposure. These results were also consistent for the testing conducted in the presence of the various organic challenges indicating that the test formulations are highly effective for real world application.

  8. Radical inactivation of a biological sulphydryl molecule

    International Nuclear Information System (INIS)

    Reactive species produced from the free radical-induced chain oxidation of low molecular weight sulphydryl-containing molecules in aerated solutions deactivate the sulphydryl-containing enzyme papain, forming both reparable mixed disulphides and non-reparable products. This inactivation is highly efficient for penicillamine and glutathione, but almost negligible with cysteine, which is a protector of papain for [cysteine] / [papain] >= 5 under all conditions used. In the case of glutathione, superoxide dismutase caused only a small reduction in the inactivation and peroxide yields were small, implying that the deactivating species are not .O2- but RSOO. radicals or products from them. For penicillamine, however, dimutase was highly effective and the peroxide yields were relatively large, demonstrating that .O2- or a radical with similar capabilities for forming H2O2 and being deactivated by dismutase was involved. Although in the presence of dismutase penicillamine is a better protector of non-reparable papain inactivation than glutathione, it suffers from a deficiency in that the papain-penicillamine mixed disulphide, which is always formed, cannot be repaired by spontaneous reaction with RSH molecules. (author)

  9. Mechanism of inactivating microorganisms with ionizing radiation

    International Nuclear Information System (INIS)

    The inactivation of microorganisms with a high dose of ionizing radiation is characterized by the exponential function of the dose N/sub D/=N0exp(-kD) where N0 is the number of microorganisms before irradiation and N/sub D/ the number of microorganisms after irradiation with dose D and k is the constant characterizing the strain resistance. Microorganisms differ by their sensitivity to radiation. Important for their inactivation are irradiation conditions (the presence of O2, temperature, pressure, pH, etc.). The efficiency of sterilization is assessed by the inactivation coefficient, t.e., the relation between the initial and the final concentration of cells irradiated with the given dose. The value of this coefficient is usually 104 to 108. For routine control of the sterilization process biological indicators are used, i.e., monitors, contaminated with a high number of germs of the standard resistant strain Bacillus sphaericus C/sub I/A. (E.F.)

  10. Spare PRELI gene loci: failsafe chromosome insurance?

    Directory of Open Access Journals (Sweden)

    Wenbin Ma

    Full Text Available BACKGROUND: LEA (late embryogenesis abundant proteins encode conserved N-terminal mitochondrial signal domains and C-terminal (A/TAEKAK motif repeats, long-presumed to confer cell resistance to stress and death cues. This prompted the hypothesis that LEA proteins are central to mitochondria mechanisms that connect bioenergetics with cell responses to stress and death signaling. In support of this hypothesis, recent studies have demonstrated that mammalian LEA protein PRELI can act as a biochemical hub, which upholds mitochondria energy metabolism, while concomitantly promoting B cell resistance to stress and induced death. Hence, it is important to define in vivo the physiological relevance of PRELI expression. METHODS AND FINDINGS: Given the ubiquitous PRELI expression during mouse development, embryo lethality could be anticipated. Thus, conditional gene targeting was engineered by insertion of flanking loxP (flox/Cre recognition sites on PRELI chromosome 13 (Chr 13 locus to abort its expression in a tissue-specific manner. After obtaining mouse lines with homozygous PRELI floxed alleles (PRELI(f/f, the animals were crossed with CD19-driven Cre-recombinase transgenic mice to investigate whether PRELI inactivation could affect B-lymphocyte physiology and survival. Mice with homozygous B cell-specific PRELI deletion (CD19-Cre/Chr13 PRELI(-/- bred normally and did not show any signs of morbidity. Histopathology and flow cytometry analyses revealed that cell lineage identity, morphology, and viability were indistinguishable between wild type CD19-Cre/Chr13 PRELI(+/+ and CD19-Cre/Chr13 PRELI(-/- deficient mice. Furthermore, B cell PRELI gene expression seemed unaffected by Chr13 PRELI gene targeting. However, identification of additional PRELI loci in mouse Chr1 and Chr5 provided an explanation for the paradox between LEA-dependent cytoprotection and the seemingly futile consequences of Chr 13 PRELI gene inactivation. Importantly, PRELI expression

  11. Familial transmission of a deletion of chromosome 21 derived from a translocation between chromosome 21 and an inverted chromosome 22.

    Science.gov (United States)

    Aviv, H; Lieber, C; Yenamandra, A; Desposito, F

    1997-06-27

    Chromosome analysis of a newborn boy with Down syndrome resulted in the identification of a family with an unusual derivative chromosome 22. The child has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization (FISH) studies show that the derivative chromosome is chromosome 22 with evidence of both paracentric and pericentric inversions, joined to the long arm of chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy 21 extending from 21q21.2 to 21q terminus in the patient. The child's mother, brother, maternal aunt, and maternal grandmother are all carriers of the derivative chromosome. All have 45 chromosomes, with one normal chromosome 21, one normal chromosome 22, and the derivative chromosome 22. The rearrangement results in the absence of the short arm, the centromere, and the proximal long arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative chromosome in this family have normal physical appearance, mild learning disabilities and poor social adjustment. PMID:9182781

  12. Meiosis and chromosome painting of sex chromosome systems in Ceboidea.

    Science.gov (United States)

    Mudry, M D; Rahn, I M; Solari, A J

    2001-06-01

    The identity of the chromosomes involved in the multiple sex system of Alouatta caraya (Aca) and the possible distribution of this system among other Ceboidea were investigated by chromosome painting of mitotic cells from five species and by analysis of meiosis at pachytene in two species. The identity of the autosome #7 (X2) involved in the multiple system of Aca and its breakage points were demonstrated by both meiosis and chromosome painting. These features are identical to those described by Consigliere et al. [1996] in Alouatta seniculus sara (Assa) and Alouatta seniculus arctoidea (Asar). This multiple system was absent in the other four Ceboidea species studied here. However, data from the literature strongly suggest the presence of this multiple in other members of this genus. The presence of this multiple system among several species and subspecies that show high levels of chromosome rearrangements may suggest a special selective value of this multiple. The meiotic features of the sex systems of Aca and Cebus apella paraguayanus (Cap) are strikingly different at pachytene, as the latter system is similar to the sex pair of man and other primates. The relatively large genetic distances between species presently showing this multiple system suggest that its origin is not recent. Other members of the same genus should be investigated at meiosis and by chromosome painting in order to know the extent and distribution of this complex sex-chromosome system. PMID:11376445

  13. Karyological characterization of the endemic Iberian rock lizard, Iberolacerta monticola (Squamata, Lacertidae): insights into sex chromosome evolution.

    Science.gov (United States)

    Rojo, V; Giovannotti, M; Naveira, H; Nisi Cerioni, P; González-Tizón, A M; Caputo Barucchi, V; Galán, P; Olmo, E; Martínez-Lage, A

    2014-01-01

    Rock lizards of the genus Iberolacerta constitute a promising model to examine the process of sex chromosome evolution, as these closely related taxa exhibit remarkable diversity in the degree of sex chromosome differentiation with no clear phylogenetic segregation, ranging from cryptic to highly heteromorphic ZW chromosomes and even multiple chromosome systems (Z1Z1Z2Z2/Z1Z2W). To gain a deeper insight into the patterns of karyotype and sex chromosome evolution, we performed a cytogenetic analysis based on conventional staining, banding techniques and fluorescence in situ hybridization in the species I. monticola, for which previous cytogenetic investigations did not detect differentiated sex chromosomes. The karyotype is composed of 2n = 36 acrocentric chromosomes. NORs and the major ribosomal genes were located in the subtelomeric region of chromosome pair 6. Hybridization signals of the telomeric sequences (TTAGGG)n were visualized at the telomeres of all chromosomes and interstitially in 5 chromosome pairs. C-banding showed constitutive heterochromatin at the centromeres of all chromosomes, as well as clear pericentromeric and light telomeric C-bands in several chromosome pairs. These results highlight some chromosomal markers which can be useful to identify species-specific diagnostic characters, although they may not accurately reflect the phylogenetic relationships among the taxa. In addition, C-banding revealed the presence of a heteromorphic ZW sex chromosome pair, where W is smaller than Z and almost completely heterochromatic. This finding sheds light on sex chromosome evolution in the genus Iberolacerta and suggests that further comparative cytogenetic analyses are needed to understand the processes underlying the origin, differentiation and plasticity of sex chromosome systems in lacertid lizards. PMID:24296524

  14. Chromosome fragility in Freemartin cattle

    Directory of Open Access Journals (Sweden)

    V. Barbieri

    2010-04-01

    Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

  15. Methods for chromosome-specific staining

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel

    1995-01-01

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogenous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include methods for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes.

  16. Chromosome evolution in Neotropical butterflies

    OpenAIRE

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O.; Brown, Keith S., Jr.

    2013-01-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results i...

  17. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  18. Chromosome evolution in Neotropical butterflies.

    Science.gov (United States)

    Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O; Brown, Keith S

    2013-06-01

    We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results in the context of chromosome numbers of over 1400 Neotropical butterfly species and subspecies derived from about 3000 populations published here and in earlier papers of a series. The overall results show that many Neotropical groups are characterized by karyotype instability with several derived modal numbers or none at all, while almost all taxa of Lepidoptera studied from the other parts of the world have one of n = 29-31 as modal numbers. Possibly chromosome number changes become fixed in the course of speciation driven by biotic interactions. Population subdivision and structuring facilitate karyotype change. Factors that stabilize chromosome numbers include hybridization among species sharing the same number, migration, sexual selection and possibly the distribution of chromosomes within the nucleus. PMID:23865963

  19. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    OpenAIRE

    Mohr Brigitte; Jauch Anna; Heinze Barbara; Fonatsch Christa; Balz Harald; Bradtke Jutta; Schoch Claudia; Rieder Harald

    2003-01-01

    Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN) by which chromosome findings are normalised at a resolution...

  20. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

    Science.gov (United States)

    Zody, Michael C; Garber, Manuel; Adams, David J; Sharpe, Ted; Harrow, Jennifer; Lupski, James R; Nicholson, Christine; Searle, Steven M; Wilming, Laurens; Young, Sarah K; Abouelleil, Amr; Allen, Nicole R; Bi, Weimin; Bloom, Toby; Borowsky, Mark L; Bugalter, Boris E; Butler, Jonathan; Chang, Jean L; Chen, Chao-Kung; Cook, April; Corum, Benjamin; Cuomo, Christina A; de Jong, Pieter J; DeCaprio, David; Dewar, Ken; FitzGerald, Michael; Gilbert, James; Gibson, Richard; Gnerre, Sante; Goldstein, Steven; Grafham, Darren V; Grocock, Russell; Hafez, Nabil; Hagopian, Daniel S; Hart, Elizabeth; Norman, Catherine Hosage; Humphray, Sean; Jaffe, David B; Jones, Matt; Kamal, Michael; Khodiyar, Varsha K; LaButti, Kurt; Laird, Gavin; Lehoczky, Jessica; Liu, Xiaohong; Lokyitsang, Tashi; Loveland, Jane; Lui, Annie; Macdonald, Pendexter; Major, John E; Matthews, Lucy; Mauceli, Evan; McCarroll, Steven A; Mihalev, Atanas H; Mudge, Jonathan; Nguyen, Cindy; Nicol, Robert; O'Leary, Sinéad B; Osoegawa, Kazutoyo; Schwartz, David C; Shaw-Smith, Charles; Stankiewicz, Pawel; Steward, Charles; Swarbreck, David; Venkataraman, Vijay; Whittaker, Charles A; Yang, Xiaoping; Zimmer, Andrew R; Bradley, Allan; Hubbard, Tim; Birren, Bruce W; Rogers, Jane; Lander, Eric S; Nusbaum, Chad

    2006-04-20

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. PMID:16625196

  1. Distribution of Telomeric Sequences (TTAGGG)n in Rearranged Chromosomes of Phyllotine Rodents (Cricetidae, Sigmodontinae).

    Science.gov (United States)

    Lanzone, Cecilia; Labaroni, Carolina; Suárez, Natalia; Rodríguez, Daniela; Herrera, Macarena L; Bolzán, Alejandro D

    2015-01-01

    Phyllotines are sigmodontine rodents endemic to South America with broad genetic variability, Robertsonian polymorphisms being the most frequent. Moreover, this taxon includes a species with multiple sex chromosomes, which is infrequent in mammals. However, molecular cytogenetic techniques have never been applied to phyllotines to elucidate their karyotypic evolution. We studied the chromosomes of 4 phyllotine species using FISH with a pantelomeric probe (TTAGGG)n. Graomys griseoflavus, Eligmodontia puerulus, and E. morgani are polymorphic for Robertsonian translocations, whereas Salinomys delicatus possesses XX/ XY1Y2 sex chromosomes. Telomeric signals were detected at both ends of all chromosomes of the studied species. In S. delicatus interstitial telomeric sequences (ITS) were observed in the 3 major chromosome pairs, which are equidistant from one of the telomeres in these chromosomes. These results suggest that ITS are important in the reshuffling of the highly derived karyotype of S. delicatus. Considering the phylogeny of phyllotines, the Robertsonian rearrangements of G. griseoflavus, E. puerulus, and E. morgani possibly represent chromosome fusions which have occurred independently. The pericentromeric regions of the biarmed chromosomes of these species do not contain telomeric sequences characteristic for strict fusions of recent origin, suggesting a common pattern of telomeric repeat loss during chromosomal evolution of these rodents. PMID:27035350

  2. Partial trisomy 11q involving chromosome 1 detected by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, M.; Bereziouk, O.; McCorquodale, D.J. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    Partial trisomy 11q was detected in an infant delivered 3-4 weeks prematurely. The phenotype included slanted palpebral fissures, high arched palate, developmental delay, microcephaly, and cardiac defects, all of which occur in the majority of cases with this syndrome. Other features included a column-shaped skull, preauricular pit, single palmar crease, short, broad great toes, flat occiput, unilateral kidney agenesis, and strabismus. Chromosomes obtained from peripheral blood cells revealed the presence of extra material on the long arm of chromosome 1. The G-banding pattern of this extra material indicated that it might be derived from chromosome 1 or 11. Chromosomal {open_quotes}paints{close_quotes} showed that it was not chromosome 1 material, but was chromosome 11 material extending from band q21 to qter. Partial trisomy 11q arising from translocation of the 11q material to chromosome 2, 3, 4, 5, 6, 9, 10, 13, 17, 21, 22, and X has been reported previously, whereas translocation to chromosome 1 has not. The chromosome to which the 11q material is translocated does not alter the most frequent features of the partial trisomy 11q syndrome, but may influence other less common features.

  3. Chromosome mapping of repetitive sequences in four Serrasalmidae species (Characiformes).

    Science.gov (United States)

    Ribeiro, Leila Braga; Matoso, Daniele Aparecida; Feldberg, Eliana

    2014-03-01

    The Serrasalmidae family is composed of a number of commercially interesting species, mainly in the Amazon region where most of these fishes occur. In the present study, we investigated the genomic organization of the 18S and 5S rDNA and telomeric sequences in mitotic chromosomes of four species from the basal clade of the Serrasalmidae family: Colossoma macropomum, Mylossoma aureum, M. duriventre, and Piaractus mesopotamicus, in order to understand the chromosomal evolution in the family. All the species studied had diploid numbers 2n = 54 and exclusively biarmed chromosomes, but variations of the karyotypic formulas were observed. C-banding resulted in similar patterns among the analyzed species, with heterochromatic blocks mainly present in centromeric regions. The 18S rDNA mapping of C. macropomum and P. mesopotamicus revealed multiple sites of this gene; 5S rDNA sites were detected in two chromosome pairs in all species, although not all of them were homeologs. Hybridization with a telomeric probe revealed signals in the terminal portions of chromosomes in all the species and an interstitial signal was observed in one pair of C. macropomum. PMID:24688290

  4. Chromosomal evolution in the South American Riodinidae (Lepidoptera: Papilionoidea).

    Science.gov (United States)

    Brown, Keith S; von Schoultz, Barbara; Saura, Anja O; Saura, Anssi

    2012-08-01

    We give the haploid chromosome numbers of 173 species or subspecies of Riodinidae as well as of 17 species or subspecies of neotropical Lycaenidae for comparison. The chromosome numbers of riodinids have thus far been very poorly known. We find that their range of variation extends from n = 9 to n = 110 but numbers above n = 31 are rare. While lepidopterans in general have stable chromosome numbers, or variation is limited at most a subfamily or genus, the entire family Riodinidae shows variation within genera, tribes and subfamilies with no single modal number. In particular, a stepwise pattern with chromosome numbers that are about even multiples is seen in several unrelated genera. We propose that this variation is attributable to the small population sizes, fragmented populations with little migration, and the behavior of these butterflies. Small and isolated riodinid populations would allow for inbreeding to take place. Newly arisen chromosomal variants could become fixed and contribute to reproductive isolation and speciation. In contrast to the riodinids, the neotropical Lycaenidae (Theclinae and Polyommatinae) conform to the modal n = 24 that characterizes the family. PMID:22967142

  5. Chromosomal abnormalities among children born with conotruncal cardiac defects

    Science.gov (United States)

    Lammer, Edward J.; Chak, Jacqueline S.; Iovannisci, David M.; Schultz, Kathleen; Osoegawa, Kazutoyo; Yang, Wei; Carmichael, Suzan L.; Shaw, Gary M.

    2010-01-01

    BACKGROUND Conotruncal heart defects comprise 25%-30% of non-syndromic congenital heart defects. This study describes the frequency of chromosome abnormalities and microdeletion 22q11 associated with conotruncal heart malformations. METHODS From a population base of 974,579 infants/fetuses delivered, 622 Californian infants/fetuses were ascertained with a defect of aortico-pulmonary septation. Infants whose primary cardiac defect was tetralogy of Fallot (n=296) or D-transposition of the great vessels (n=189) were screened for microdeletions of 22q11. RESULTS Fourteen (2.3%) of the 622 infants/fetuses had chromosomal abnormalities. Thirty infants, 10% of those whose primary defect was tetralogy of Fallot, had chromosome 22q11 microdeletions. Right aortic arch, abnormal branching patterns of the major arteries arising from the thoracic aorta, and pulmonary artery abnormalities were observed more frequently in these children. CONCLUSIONS We found an unusual number of infants with an extra sex chromosome and a conotruncal defect. Infants with tetralogy of Fallot due to 22q11 microdeletion showed more associated vascular anomalies than infants with tetralogy but no 22q11 microdeletion. Although these associated vascular anomalies provide clues as to which infants with tetralogy of Fallot are more likely to carry the microdeletion, the overall risk of 10% among all infants with tetralogy of Fallot warrants chromosome analysis and FISH testing routinely. PMID:19067405

  6. Chromosome mapping of repetitive sequences in four Serrasalmidae species (Characiformes

    Directory of Open Access Journals (Sweden)

    Leila Braga Ribeiro

    2014-01-01

    Full Text Available The Serrasalmidae family is composed of a number of commercially interesting species, mainly in the Amazon region where most of these fishes occur. In the present study, we investigated the genomic organization of the 18S and 5S rDNA and telomeric sequences in mitotic chromosomes of four species from the basal clade of the Serrasalmidae family: Colossoma macropomum, Mylossoma aureum, M. duriventre, and Piaractus mesopotamicus, in order to understand the chromosomal evolution in the family. All the species studied had diploid numbers 2n = 54 and exclusively biarmed chromosomes, but variations of the karyotypic formulas were observed. C-banding resulted in similar patterns among the analyzed species, with heterochromatic blocks mainly present in centromeric regions. The 18S rDNA mapping of C. macropomum and P. mesopotamicus revealed multiple sites of this gene; 5S rDNA sites were detected in two chromosome pairs in all species, although not all of them were homeologs. Hybridization with a telomeric probe revealed signals in the terminal portions of chromosomes in all the species and an interstitial signal was observed in one pair of C. macropomum.

  7. Abundance of female-biased and paucity of male-biased somatically expressed genes on the mouse X-chromosome

    Directory of Open Access Journals (Sweden)

    Reinius Björn

    2012-11-01

    Full Text Available Abstract Background Empirical evaluations of sexually dimorphic expression of genes on the mammalian X-chromosome are needed to understand the evolutionary forces and the gene-regulatory mechanisms controlling this chromosome. We performed a large-scale sex-bias expression analysis of genes on the X-chromosome in six different somatic tissues from mouse. Results Our results show that the mouse X-chromosome is enriched with female-biased genes and depleted of male-biased genes. This suggests that feminisation as well as de-masculinisation of the X-chromosome has occurred in terms of gene expression in non-reproductive tissues. Several mechanisms may be responsible for the control of female-biased expression on chromosome X, and escape from X-inactivation is a main candidate. We confirmed escape in case of Tmem29 using RNA-FISH analysis. In addition, we identified novel female-biased non-coding transcripts located in the same female-biased cluster as the well-known coding X-inactivation escapee Kdm5c, likely transcribed from the transition-region between active and silenced domains. We also found that previously known escapees only partially explained the overrepresentation of female-biased X-genes, particularly for tissue-specific female-biased genes. Therefore, the gene set we have identified contains tissue-specific escapees and/or genes controlled by other sexually skewed regulatory mechanisms. Analysis of gene age showed that evolutionarily old X-genes (>100 myr, preceding the radiation of placental mammals are more frequently female-biased than younger genes. Conclusion Altogether, our results have implications for understanding both gene regulation and gene evolution of mammalian X-chromosomes, and suggest that the final result in terms of the X-gene composition (masculinisation versus feminisation is a compromise between different evolutionary forces acting on reproductive and somatic tissues.

  8. Inactivation of Enteric Viruses in Minimally Processed Berries and Herbs▿

    OpenAIRE

    Butot, S.; Putallaz, T.; Amoroso, R; Sánchez, G.

    2009-01-01

    Several hepatitis A virus (HAV) and human norovirus (HuNoV) outbreaks due to consumption of contaminated berries and vegetables have recently been reported. Model experiments were performed to determine the effectiveness of freeze-drying, freeze-drying combined with heating, and steam blanching for inactivation of enteric viruses that might be present on the surface of berries and herbs. Inactivation of HAV and inactivation of feline calicivirus, a surrogate for HuNoV, were assessed by viral ...

  9. MILT DILUTION EFFECTIVENESS ON PIKEPERCH (SANDER LUCIOPERCA) SPERM DNA INACTIVATION

    OpenAIRE

    B. KORBULY; A. GROZEA; ADA CEAN; I. BĂNĂŢEAN - DUNEA; N. PĂCALĂ; A. VĂLEAN

    2013-01-01

    Percid fishes, including pikeperch (Sander lucioperca) have recently become the subject of intense research. In order to obtain gynogenetic all female pikeperch populations, normal pikeperch eggs are fertilized with inactivated sperm. Because pikeperch semen has a high viscosity, milt has to be diluted in an immobilizing solution before DNA inactivation. The aim of this study was to assess milt diluting solutions effectiveness in order to inactivate sperm DNA with UV irradiation, to produce m...

  10. Molecular and Physiological Effects of Mycobacterial oxyR Inactivation

    OpenAIRE

    Pagán-Ramos, Eileen; Master, Sharon S.; Pritchett, Christopher L.; Reimschuessel, Renate; Trucksis, Michele; Timmins, Graham S.; Deretic, Vojo

    2006-01-01

    The majority of slow-growing mycobacteria have a functional oxyR, the central regulator of the bacterial oxidative stress response. In contrast, this gene has been inactivated during the evolution of Mycobacterium tuberculosis. Here we inactivated the oxyR gene in Mycobacterium marinum, an organism used to model M. tuberculosis pathogenesis. Inactivation of oxyR abrogated induction of ahpC, a gene encoding alkylhydroperoxide reductase, normally activated upon peroxide challenge. The absence o...

  11. Inactivation of human norovirus using chemical sanitizers.

    Science.gov (United States)

    Kingsley, David H; Vincent, Emily M; Meade, Gloria K; Watson, Clytrice L; Fan, Xuetong

    2014-02-01

    The porcine gastric mucin binding magnetic bead (PGM-MB) assay was used to evaluate the ability of chlorine, chlorine dioxide, peroxyacetic acid, hydrogen peroxide, and trisodium phosphate to inactivate human norovirus within 10% stool filtrate. One-minute free chlorine treatments at concentrations of 33 and 189 ppm reduced virus binding in the PGM-MB assay by 1.48 and 4.14 log₁₀, respectively, suggesting that chlorine is an efficient sanitizer for inactivation of human norovirus (HuNoV). Five minute treatments with 5% trisodium phosphate (pH~12) reduced HuNoV binding by 1.6 log₁₀, suggesting that TSP, or some other high pH buffer, could be used to treat food and food contact surfaces to reduce HuNoV. One minute treatments with 350 ppm chlorine dioxide dissolved in water did not reduce PGM-MB binding, suggesting that the sanitizer may not be suitable for HuNoV inactivation in liquid form. However a 60-min treatment with 350 ppm chlorine dioxide did reduce human norovirus by 2.8 log₁₀, indicating that chlorine dioxide had some, albeit limited, activity against HuNoV. Results also suggest that peroxyacetic acid has limited effectiveness against human norovirus, since 1-min treatments with up to 195 ppm reduced human norovirus binding by treatment of up to 60 min resulted in minimal binding reduction (~0.1 log₁₀) suggesting that H₂O₂ is not a good liquid sanitizer for HuNoV. Overall this study suggests that HuNoV is remarkably resistant to several commonly used disinfectants and advocates for the use of chlorine (sodium hypochlorite) as a HuNoV disinfectant wherever possible. PMID:24334094

  12. Inactivation of Effector Caspases through Nondegradative Polyubiquitylation

    DEFF Research Database (Denmark)

    Ditzel, Mark; Broemer, Meike; Tenev, Tencho;

    2008-01-01

    Ubiquitin-mediated inactivation of caspases has long been postulated to contribute to the regulation of apoptosis. However, detailed mechanisms and functional consequences of caspase ubiquitylation have not been demonstrated. Here we show that the Drosophila Inhibitor of Apoptosis 1, DIAP1, blocks...... reduces the caspase's proteolytic velocity. Disruption of drICE ubiquitylation, either by mutation of DIAP1's E3 activity or drICE's ubiquitin-acceptor lysines, abrogates DIAP1's ability to neutralize drICE and suppress apoptosis in vivo. We also show that DIAP1 rests in an "inactive" conformation that...

  13. Ribosome-Inactivating and Related Proteins

    OpenAIRE

    Joachim Schrot; Alexander Weng; Matthias F. Melzig

    2015-01-01

    Ribosome-inactivating proteins (RIPs) are toxins that act as N-glycosidases (EC 3.2.2.22). They are mainly produced by plants and classified as type 1 RIPs and type 2 RIPs. There are also RIPs and RIP related proteins that cannot be grouped into the classical type 1 and type 2 RIPs because of their different sizes, structures or functions. In addition, there is still not a uniform nomenclature or classification existing for RIPs. In this review, we give the current status of all known plant ...

  14. Radiation Inactivation of Viruses in Infected Products

    International Nuclear Information System (INIS)

    Full text: The effects of gamma radiation on foot-and-mouth disease virus in vitro and in situ have been studied. The data so far obtained show that a dose of 2 Mrad is required to inactivate virus in infected animal carcasses. But the dose may adversely affect the organoleptic quality of the meat. Experiments in vitro and in situ are necessary to study the effects of ionizing radiation on other viruses, such as rinderpest, swine fever and African swine fever-viruses, associated with animal products. Radiation may offer a possible means of eliminating the virus titre in many animal products and solve consequent quarantine problems. (author)

  15. The chromosomes of the Didelphidae (Marsupialia) and their evolutionary significance

    Science.gov (United States)

    Reig, O.; Gardner, A.L.; Bianchi, N.O.; Patton, J.L.

    1977-01-01

    One hundred and seventy-seven specimens of American didelphids, representing 9 genera and 22 species have been studied for their chromosomal constitution. Didelphids are very conservative in chromosomal complements. All of the studied species can be sorted into one of three kinds of karyotypes: 2n= 14 (three species of Didelphis, one of Lutreolina, two of Philander, and one of Chironectes), 2n = 14 (eight species of Marmosa, one of Metachirus, three of Caluromys, and one of Dromiciops), and 2n= 18 (three species of Monodelphis). These karyotypes are stable, showing only minor variations within each basic pattern. It is concluded that chromosomals evolution in the Didelphidae proceededs from low numbers to higher numbers by a process of centromeric fissioning complemented by some pericentric inversions and/or translocations. The pattern of karyotypic stability is consistent with bradytely at the organismic level of evolution. This is explained by a low rate of regulatory genetic evolution promoted by epistatic selection favouring the retention of chromosomal arrangements highly advantageous for overall adaptation.

  16. Heterochromatin differentiation in holocentric chromosomes of Rhynchospora (Cyperaceae

    Directory of Open Access Journals (Sweden)

    André L.L. Vanzela

    2000-06-01

    Full Text Available Holocentric chromosomes of six species of Rhynchospora, R. ciliata, R. pubera, R. riparia and R. barbata (2n = 10, R. nervosa (2n = 30 and R. globosa (2n = 36, were stained with CMA3/DAPI fluorochromes or treated with C-banding and sequentially stained with Giemsa or CMA3/DAPI. Variability in banding pattern was found among the species studied. Heterochromatin was observed on terminal and interstitial chromosome regions, indicating that the holocentric chromosomes of Rhynchospora show a heterochromatin distribution pattern similar to those plant monocentric chromosomes.Cromossomos holocêntricos de seis espécies de Rhynchospora (R. ciliata, R. pubera, R. riparia e R. barbata (2n = 10, R. nervosa (2n = 30 and R. globosa (2n = 36 foram corados com os fluorocromos CMA3/DAPI ou tratados para bandeamento C e seqüencialmente corados com Giemsa ou CMA3/DAPI. Variabilidade no padrão de bandas foi encontrada entre as espécies estudadas. A heterocromatina foi observada em regiões terminais e intersticiais dos cromossomos, indicando que os cromossomos holocêntricos de Rhynchospora mostram um padrão de distribuição de heterocromatina similar àqueles dos cromossomos monocêntricos de plantas.

  17. Inactivation of virus in solution by cold atmospheric pressure plasma: identification of chemical inactivation pathways

    Science.gov (United States)

    Aboubakr, Hamada A.; Gangal, Urvashi; Youssef, Mohammed M.; Goyal, Sagar M.; Bruggeman, Peter J.

    2016-05-01

    Cold atmospheric pressure plasma (CAP) inactivates bacteria and virus through in situ production of reactive oxygen and nitrogen species (RONS). While the bactericidal and virucidal efficiency of plasmas is well established, there is limited knowledge about the chemistry leading to the pathogen inactivation. This article describes a chemical analysis of the CAP reactive chemistry involved in the inactivation of feline calicivirus. We used a remote radio frequency CAP produced in varying gas mixtures leading to different plasma-induced chemistries. A study of the effects of selected scavengers complemented with positive control measurements of relevant RONS reveal two distinctive pathways based on singlet oxygen and peroxynitrous acid. The first mechanism is favored in the presence of oxygen and the second in the presence of air when a significant pH reduction is induced in the solution by the plasma. Additionally, smaller effects of the H2O2, O3 and \\text{NO}2- produced were also found. Identification of singlet oxygen-mediated 2-imidazolone/2-oxo-His (His  +14 Da)—an oxidative modification of His 262 comprising the capsid protein of feline calicivirus links the plasma induced singlet oxygen chemistry to viral inactivation.

  18. Comparative study on the mechanisms of rotavirus inactivation by sodium dodecyl sulfate and ethylenediaminetetraacetate

    Energy Technology Data Exchange (ETDEWEB)

    Ward, R.L. (Sandia Labs., Albuquerque, NM); Ashley, C.S.

    1980-06-01

    This report describes a comparative study on the effects of the anionic detergent sodium dodecyl sulfate and the chelating agent ethylenediaminetetraacetate on purified rotavirus SA-11 particles. Both chemicals readily inactivated rotavirus at quite low concentrations and under very mild conditions. In addition, both agents modified the viral capsid and prevented the adsorption of inactivated virions to cells. Capsid damage by ethylenediaminetetraacetate caused a shift in the densities of rotavirions from about l.35 to about 1.37 g/ml and a reduction in their sedimentation coefficients. Sodium dodcyl sulfate, on the other hand, did not detectably alter either of these physical properties of rotavirions. Both agents caused some alteration of the isoelectric points of the virions. Finally, analysis of rotavirus proteins showed that ethylenediaminetetraacetate caused the loss of two protein peaks from the electrophoretic pattern of virions but sodium dodecyl sulfate caused the loss of only one of these same protein peaks.

  19. Comparative cytogenetics of six Indo-Pacific moray eels (Anguilliformes: Muraenidae) by chromosomal banding and fluorescence in situ hybridization.

    Science.gov (United States)

    Coluccia, E; Deidda, F; Cannas, R; Lobina, C; Cuccu, D; Deiana, A M; Salvadori, S

    2015-09-01

    A comparative cytogenetic analysis, using both conventional staining techniques and fluorescence in situ hybridization, of six Indo-Pacific moray eels from three different genera (Gymnothorax fimbriatus, Gymnothorax flavimarginatus, Gymnothorax javanicus, Gymnothorax undulatus, Echidna nebulosa and Gymnomuraena zebra), was carried out to investigate the chromosomal differentiation in the family Muraenidae. Four species displayed a diploid chromosome number 2n = 42, which is common among the Muraenidae. Two other species, G. javanicus and G. flavimarginatus, were characterized by different chromosome numbers (2n = 40 and 2n = 36). For most species, a large amount of constitutive heterochromatin was detected in the chromosomes, with species-specific C-banding patterns that enabled pairing of the homologous chromosomes. In all species, the major ribosomal genes were localized in the guanine-cytosine-rich region of one chromosome pair, but in different chromosomal locations. The (TTAGGG)n telomeric sequences were mapped onto chromosomal ends in all muraenid species studied. The comparison of the results derived from this study with those available in the literature confirms a substantial conservation of the diploid chromosome number in the Muraenidae and supports the hypothesis that rearrangements have occurred that have diversified their karyotypes. Furthermore, the finding of two species with different diploid chromosome numbers suggests that additional chromosomal rearrangements, such as Robertsonian fusions, have occurred in the karyotype evolution of the Muraenidae. PMID:26242690

  20. Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W. (San Francisco, CA); Pinkel, Daniel (Lafayette, CA); Kallioniemi, Olli-Pekka (Turku, FI); Kallioniemi, Anne (Tampere, FI); Sakamoto, Masaru (Tokyo, JP)

    2009-10-06

    Methods and compositions for staining based upon nucleic acid sequence that employ .[.nudeic.]. .Iadd.nucleic .Iaddend.acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  1. Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W.; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Kallioniemi, Anne; Sakamoto, Masaru

    2008-09-09

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  2. Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17

    Science.gov (United States)

    Gray, Joe W.; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Kallioniemi, Anne; Sakamoto, Masaru

    2002-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nudeic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  3. Epilepsy and ring chromosome 20: case report

    Directory of Open Access Journals (Sweden)

    Gomes Marleide da Mota

    2002-01-01

    Full Text Available We present the clinical, electroencephalographic, neuroimaging (brain magnetic resonance image - MRI and spectroscopy by MRI and cytogenetic findings of a young male patient with a rare cytogenetic anomaly characterised by a de novo 46,XY,r(20(p13q13.3 karyotype. He presents with mental retardation, emotional liability, and strabismus, without any other significant dysmorphies. There are brain anomalies characterised by corpus callosum, uvula, nodule and cerebellum pyramid hypoplasias, besides arachnoid cysts in the occipital region. He had seizures refractory to pharmacotherapy and long period of confusional status with or without a motor component. The authors recognised that the EEG pattern was not fixed but changed over time, specially for bursts of slow waves with great amplitude accompanied or not by sharp components, and bursts of theta waves sharply contoured. Previously, epilepsy solely has been assigned to region 20q13. However, the important structural cerebral alterations present in our case has not been reported associated to such chromosomal abnormality and may indicate possible new chromosomal sites where such atypical neurological characteristics could be mapped.

  4. Retrospective dosimetry using chromosome painting

    International Nuclear Information System (INIS)

    Chromosome aberration frequency measured in peripheral lymphocytes of persons exposed to ionizing radiation has been used since 1960s for dose assessment. Suspected overexposure is usually evaluated by the frequency of dicentrics and centric rings using an appropriate in vitro calibration curve. However, these chromosome aberrations are unstable with time after exposure and dose reconstruction may encounter uncertainties when the time between the exposure and the analysis is considerable or even unknown. It appears that translocations persist with time after exposure and may be used as an indication of acute past overexposures. Moreover, they appear to accumulate the cytogenetical information, which correlates with the dose received under fractionated, chronic or even occupational exposure conditions. Translocations may be detected using G-banding, which allows to score the total amount of radiation induced translocations but it is a time consuming method, or by Chromosome Painting, a method base on the Fluorescence in situ Hybridization (FISH) technique, painting only some chromosome pairs with specific whole chromosome probes and then extrapolating the observed translocation frequencies to the full genome. The latter method allows a faster aberration scoring than G-banding and appears to be the most promissory tool for biodosimetry, particularly when it is necessary to assess low doses and consequently to score a large number of metaphases, e.g. radiation workers exposed within dose limits. As with the unstable chromosome aberration, it is necessary an in vitro calibration curve based on the frequency of stable chromosome aberrations to assess doses. Our laboratory performed calibration curves for Co60 γ-rays based on the frequencies of unstable (dicentrics and centric rings detected by conventional Giemsa staining) and stable chromosome aberrations (translocations and inversions, detected by G-banding). In order to minimize the interlaboratory variability, we

  5. The Reduction of Chromosome Number in Meiosis Is Determined by Properties Built into the Chromosomes

    OpenAIRE

    Paliulis, Leocadia V.; Nicklas, R. Bruce

    2000-01-01

    In meiosis I, two chromatids move to each spindle pole. Then, in meiosis II, the two are distributed, one to each future gamete. This requires that meiosis I chromosomes attach to the spindle differently than meiosis II chromosomes and that they regulate chromosome cohesion differently. We investigated whether the information that dictates the division type of the chromosome comes from the whole cell, the spindle, or the chromosome itself. Also, we determined when chromosomes can switch from ...

  6. Mean expression of the X chromosome is associated with neuronal density

    Directory of Open Access Journals (Sweden)

    James Thomas Swingland

    2012-11-01

    Full Text Available Neurodegenerative diseases are characterised by neuronal loss. Neuronal loss causes a varying density of neurons across samples which confounds results from gene expression studies. Chromosome X is known to be specifically important in brain. We hypothesised the existence of a chromosomal signature of gene expression associated with the X-chromosome for neurological conditions not normally associated with that chromosome. The hypothesis was investigated using microarray datasets from studies on Parkinson's disease, Alzheimer's disease and Huntington's disease. Data were analysed using Chromowave, an analytical tool for detecting spatially extended expression changes across chromosomes. To examine associations with neuronal density, expressions from a set of neuron specific genes were extracted. The association between these genes and the expression patterns extracted by Chromowave was then analyzed. We observed an extended pattern of low expression of ChrX consistent in all the neurodegenerative disease brain datasets. There was a strong correlation between mean ChrX expression and the pattern extracted from the autosomal neuronal specific genes, but no correlation with mean autosomal expression. No chromosomal patterns associated with the neuron specific genes were found on other chromosomes. The chromosomal expression pattern was not present in datasets from blood cells. The ChrX:Autosome expression ratio was also higher in neuronal cells than in tissues with a mix of cell types.The results suggest that a loss of neurons manifests in gene expression experiments primarily as a reduction in mean expression of genes along ChrX. The most likely explanation for this finding relates to the documented general up-regulation of ChrX in brain tissue which, this work suggests, occurs primarily in neurons. The purpose and mechanisms behind this cell specific higher expression warrant further research, which may also help elucidate connectio

  7. p31comet-Induced Cell Death Is Mediated by Binding and Inactivation of Mad2.

    Directory of Open Access Journals (Sweden)

    Hyun-Jin Shin

    Full Text Available Mad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer. p31comet is a Mad2-interacting protein that serves as a spindle checkpoint silencer at mitosis. In this study, we showed that p31comet-induced apoptosis and senescence occur via counteraction of Mad2 activity. Upon retroviral transduction of p31comet, the majority of human cancer cell lines tested lost the ability to form colonies in a low-density seeding assay. Cancer cells with p31comet overexpression underwent distinct apoptosis and/or senescence, irrespective of p53 status, confirming the cytotoxicity of p31comet. Interestingly, both cytotoxic and Mad2 binding activities were eliminated upon deletion of the C-terminal 30 amino acids of p31comet. Point mutation or deletion of the region affecting Mad2 binding additionally abolished cytotoxic activity. Consistently, wild-type Mad2 interacting with p31comet, but not its non-binding mutant, inhibited cell death, indicating that the mechanism of p31comet-induced cell death involves Mad2 inactivation. Our results clearly suggest that the regions of p31comet affecting interactions with Mad2, including the C-terminus, are essential for induction of cell death. The finding that p31comet-induced cell death is mediated by interactions with Mad2 that lead to its inactivation is potentially applicable in anticancer therapy.

  8. Guided by RNAs: X-inactivation as a model for lncRNA function.

    Science.gov (United States)

    Froberg, John E; Yang, Lin; Lee, Jeannie T

    2013-10-01

    The recent revolution in sequencing technology has helped to reveal a large transcriptome of long non-coding RNAs (lncRNAs). A major challenge in the years to come is to determine what biological functions, if any, they serve. Although the purpose of these transcripts is largely unknown at present, existing examples suggest that lncRNAs play roles in a wide variety of biological processes. Exemplary cases are lncRNAs within the X-inactivation center. Indeed, lncRNAs dominate control of random X-chromosome inactivation (XCI). The RNA-based regulatory mechanisms of XCI include recruitment of chromatin modifiers, formation of RNA-based subnuclear compartments, and regulation of transcription by antisense transcription. XCI and lncRNAs now also appear to be very relevant in the development and progression of cancer. This perspective focuses on new insights into lncRNA-dependent regulation of XCI, which we believe serve as paradigms for understanding lncRNA function more generally. PMID:23816838

  9. Disabled-1 is a large common fragile site gene, inactivated in multiple cancers.

    Science.gov (United States)

    McAvoy, Sarah; Zhu, Yu; Perez, Damon S; James, C David; Smith, David I

    2008-02-01

    Common fragile sites (CFS) are large, genomically unstable regions, which are hot-spots for deletions and other alterations, especially in cancer cells. Several have been shown to contain genes that span large genomic regions, such as FHIT (1.5 Mb), WWOX (1.0 Mb), GRID2 (1.36 Mb), PARK2 (1.3 Mb), and RORA (730 kb). These genes are frequently inactivated in multiple different cancers, and FHIT and WWOX are shown to function as tumor suppressors. The disabled-1 gene (DAB1) is one of the human homologs of the Drosophila disabled locus, which in mammals is involved in neuronal migration and lamination in the developing cerebral cortex. Mice DAB1 inactivation results in the neurological mutant Scrambler, having similarities to mice with the inactivation of PARK2 (Quaker), GRID2 (Lurcher), and RORA (Staggerer). We were interested in whether DAB1 was another large CFS gene that could have cancer development importance. We demonstrated here that the human DAB1 gene (spanning 1.25 Mb) mapped within FRA1B CFS region on chromosomal band 1p32.2. Real-time RT-PCR analysis revealed that the expression level of DAB1 was decreased in many human cancer samples, including primary tumor tissues and cancer-derived cell lines, from several different cancers, especially in brain and endometrial cancer. Additionally, the introduction of an over-expression DAB1 plasmid into two different cell lines, having insignificant endogenous DAB1 expression, resulted in decreased cell growth. In summary, DAB1 is another gene that resides within an unstable CFS region and might play a role in human tumorigenesis. These data may provide further linkage between neurological development and cancer. PMID:18008369

  10. Separate Location of Parental Chromosomes in Squashed Metaphases of Hybrid between Hordeum vulgare L. and Four Polyploid, Alien Species

    DEFF Research Database (Denmark)

    Jensen, J.; Linde-Laursen, Ib

    1984-01-01

    In 38 squashed, somatic metaphases of four hybrids between diploid Hordeum vulgare and two tetra-and two hexaploid alien species, each of the H. vulgare chromosomes was identifed, and differentiated from the chromosomes of the other parental species, by its Giemsa C-banding pattern. The H. vulgare...

  11. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  12. Radiation-induced chromosomal instability

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, S. [GSI, Biophysics, Darmstadt (Germany)

    1999-03-01

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/{mu}m) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  13. Dean flow fractionation of chromosomes

    Science.gov (United States)

    Hockin, Matt; Sant, Himanshu J.; Capecchi, Mario; Gale, Bruce K.

    2016-03-01

    Efforts to transfer intact mammalian chromosomes between cells have been attempted for more than 50 years with the consistent result being transfer of sub unit length pieces regardless of method. Inertial microfluidics is a new field that has shown much promise in addressing the fractionation of particles in the 2-20 μm size range (with unknown limits) and separations are based upon particles being carried by curving confined flows (within a spiral shaped, often rectangular flow chamber) and migrating to stable "equilibrium" positions of varying distance from a chamber wall depending on the balance of dean and lift forces. We fabricated spiral channels for inertial microfluidic separations using a standard soft lithography process. The concentration of chromosomes, small contaminant DNA and large cell debris in each outlets were evaluated using microscope (60X) and a flow cytometer. Using Dean Flow Fractionation, we were able to focus 4.5 times more chromosomes in outlet 2 compared to outlet 4 where most of the large debris is found. We recover 16% of the chromosomes in outlet #1- 50% in 2, 23% in 3 and 11% in 4. It should be noted that these estimates of recovery do not capture one piece of information- it actually may be that the chromosomes at each outlet are physically different and work needs to be done to verify this potential.

  14. The status of dosage compensation in the multiple X chromosomes of the platypus.

    Directory of Open Access Journals (Sweden)

    Janine E Deakin

    Full Text Available Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and "placentals" by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation operates in the third mammal lineage, the egg-laying monotremes, is of considerable interest, since the platypus has a complex sex chromosome system in which five X and five Y chromosomes share considerable genetic homology with the chicken ZW sex chromosome pair, but not with therian XY chromosomes. The assignment of genes to four platypus X chromosomes allowed us to examine X dosage compensation in this unique species. Quantitative PCR showed a range of compensation, but SNP analysis of several X-borne genes showed that both alleles are transcribed in a heterozygous female. Transcription of 14 BACs representing 19 X-borne genes was examined by RNA-FISH in female and male fibroblasts. An autosomal control gene was expressed from both alleles in nearly all nuclei, and four pseudoautosomal BACs were usually expressed from both alleles in male as well as female nuclei, showing that their Y loci are active. However, nine X-specific BACs were usually transcribed from only one allele. This suggests that while some genes on the platypus X are not dosage compensated, other genes do show some form of compensation via stochastic transcriptional inhibition, perhaps representing an ancestral system that evolved to be more tightly controlled in placental mammals such as human and mouse.

  15. Certain patterns of DNA double strand breaks in membrane-attached superstructure units cause cell killing: a radiation action model

    International Nuclear Information System (INIS)

    The discovery that the chromosomal DNA is arranged in membrane-attached superstructure units (MASSUs) is the key for the understanding of the action of ionizing radiations on mammalian cells. Concerning X-rays the following hypothesis is proved true: The appearance of K ≥ 2 double-strand breaks (DSBs) in any MASSU of a G1 cell, respectively, in both MASSUs of any sister MASSU pair of a S cell results in its inactivation (k = actual number of DSBs per MASSU). DSB patterns in the MASSUs characterized by less DSBs will be repaired by recombination with homologous MASSUs. In G1 cells it occurs by the recombination with the homologous MASSU of the homologous chromosome. In the replicated MASSUs of S cells it probably happens by the succession of the following mechanisms: recombination repair of MASSUs with one DSB using the sister MASSU as a matrix (sister chromatid exchange), establishment of 1 intact genome by the substitution of the heavily damaged MASSUs (k ≥ 2) by the intact or repaired sister MASSU at the common attachment point, and degradation of the heavily damaged or abundant MASSUs. Thus the dependence of the form and the steepness of the dose survival curves on the cell cycle stages is interpreted by a universally valid radiation action mechanism. (author)

  16. Live cell imaging of the nascent inactive X chromosome during the early differentiation process of naive ES cells towards epiblast stem cells.

    Directory of Open Access Journals (Sweden)

    Aurélia Guyochin

    Full Text Available Random X-chromosome inactivation ensures dosage compensation in mammals through the transcriptional silencing of one of the two X chromosomes present in each female cell. Silencing is initiated in the differentiating epiblast of the mouse female embryos through coating of the nascent inactive X chromosome by the non-coding RNA Xist, which subsequently recruits the Polycomb Complex PRC2 leading to histone H3-K27 methylation. Here we examined in mouse ES cells the early steps of the transition from naive ES cells towards epiblast stem cells as a model for inducing X chromosome inactivation in vitro. We show that these conditions efficiently induce random XCI. Importantly, in a transient phase of this differentiation pathway, both X chromosomes are coated with Xist RNA in up to 15% of the XX cells. In an attempt to determine the dynamics of this process, we designed a strategy aimed at visualizing the nascent inactive X-chromosome in live cells. We generated transgenic female XX ES cells expressing the PRC2 component Ezh2 fused to the fluorescent protein Venus. The fluorescent fusion protein was expressed at sub-physiological levels and located in nuclei of ES cells. Upon differentiation of ES cell towards epiblast stem cell fate, Venus-fluorescent territories appearing in interphase nuclei were identified as nascent inactive X chromosomes by their association with Xist RNA. Imaging of Ezh2-Venus for up to 24 hours during the differentiation process showed survival of some cells with two fluorescent domains and a surprising dynamics of the fluorescent territories across cell division and in the course of the differentiation process. Our data reveal a strategy for visualizing the nascent inactive X chromosome and suggests the possibility for a large plasticity of the nascent inactive X chromosome.

  17. Pulvinar inactivation disrupts selection of movement plans.

    Science.gov (United States)

    Wilke, Melanie; Turchi, Janita; Smith, Katy; Mishkin, Mortimer; Leopold, David A

    2010-06-23

    The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions. PMID:20573910

  18. Ribosome Inactivating Proteins from Plants Inhibiting Viruses

    Institute of Scientific and Technical Information of China (English)

    Inderdeep Kaur; R C Gupta; Munish Puri

    2011-01-01

    Many plants contain ribosome inactivating proteins (RIPs) with N-glycosidase activity,which depurinate large ribosomal RNA and arrest protein synthesis.RIPs so far tested inhibit replication of mRNA as well as DNA viruses and these proteins,isolated from plants,are found to be effective against a broad range of viruses such as human immunodeficiency virus (HIV),hepatitis B virus (HBV) and herpes simplex virus (HSV).Most of the research work related to RIPs has been focused on antiviral activity against HIV; however,the exact mechanism of antiviral activity is still not clear.The mechanism of antiviral activity was thought to follow inactivation of the host cell ribosome,leading to inhibition of viral protein translation and host cell death.Enzymatic activity of RIPs is not hmited to depurination of the large rRNA,in addition they can depurinate viral DNA as well as RNA.Recently,Phase Ⅰ/Ⅱ clinical trials have demonstrated the potential use of RIPs for treating patients with HIV disease.The aim of this review is to focus on various RIPs from plants associated with anti-HIV activity.

  19. Chromosome analysis of three species of Myoxidae

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Civitelli

    1995-05-01

    Full Text Available Abstract Karyotype analysis was carried out on three species of dormice: Myoxus glis, 4 populations from Northern and Southern Italy and from Turkey; Dryomys nitedula, 4 populations from Northern and Southern Italy, from Israel and from Turkey; Myomimus roachi, 1 specimen from Turkey. Myoxus glis shows 2n=62; comparison of our specimens from different localities shows complete correspondence between karyotypes, both for the autosomes and the heterochromosomes. Dryomys nitedula shows 2n=48. All populations we studied, show the same karyotypic pattern, except for the NOR-bearing chromosomes. Myomimus roachi, here studied for the first time, shows 2n=44. All the autosomes are biarmed of decreasing size. The X-chromosome is a medium size metacentric, while the Y-chromosome is the smallest one. All the three species we studied, show one pair of NOR-bearing chromosomes, Ag-NORs always correspond to the secondary constriction. Differences in the fundamental number and in heterochromosome morphology, have been observed by other authors, in different European populations. This variability is analysed and discussed. Riassunto Analisi cromosomica in tre specie di Myoxidae - L'analisi cromosomica è stata condotta su popolazioni europee di tre specie di Myoxidae: Myoxus glis, 4 popolazioni provenienti dal Nord e Sud Italia, e dalla Turchia; Dryomys nitedula, 4 popolazioni provenienti dal Nord e Sud Italia, da Israele e dalla Turchia; Myomimus roachi, 1 esemplare, proveniente dalla Turchia. Myoxus glis presenta 2n=62. Gli esemplari, provenienti dalle diverse popolazioni, mostrano corrispondenza nella morfologia sia degli autosomi che degli eterocromosomi. Dryomys nitedula presenta 2n=48. La morfologia dei cromosomi nei cariotipi appare corrispondente mentre diversa è la localizzazione degli Ag-NOR.

  20. Chromosome painting in the manatee supports Afrotheria and Paenungulata

    Directory of Open Access Journals (Sweden)

    Zori Roberto T

    2007-01-01

    Full Text Available Abstract Background Sirenia (manatees, dugongs and Stellar's sea cow have no evolutionary relationship with other marine mammals, despite similarities in adaptations and body shape. Recent phylogenomic results place Sirenia in Afrotheria and with elephants and rock hyraxes in Paenungulata. Sirenia and Hyracoidea are the two afrotherian orders as yet unstudied by comparative molecular cytogenetics. Here we report on the chromosome painting of the Florida manatee. Results The human autosomal and X chromosome paints delimited a total of 44 homologous segments in the manatee genome. The synteny of nine of the 22 human autosomal chromosomes (4, 5, 6, 9, 11, 14, 17, 18 and 20 and the X chromosome were found intact in the manatee. The syntenies of other human chromosomes were disrupted in the manatee genome into two to five segments. The hybridization pattern revealed that 20 (15 unique associations of human chromosome segments are found in the manatee genome: 1/15, 1/19, 2/3 (twice, 3/7 (twice, 3/13, 3/21, 5/21, 7/16, 8/22, 10/12 (twice, 11/20, 12/22 (three times, 14/15, 16/19 and 18/19. Conclusion There are five derived chromosome traits that strongly link elephants with manatees in Tethytheria and give implicit support to Paenungulata: the associations 2/3, 3/13, 8/22, 18/19 and the loss of the ancestral eutherian 4/8 association. It would be useful to test these conclusions with chromosome painting in hyraxes. The manatee chromosome painting data confirm that the associations 1/19 and 5/21 phylogenetically link afrotherian species and show that Afrotheria is a natural clade. The association 10/12/22 is also ubiquitous in Afrotheria (clade I, present in Laurasiatheria (clade IV, only partially present in Xenarthra (10/12, clade II and absent in Euarchontoglires (clade III. If Afrotheria is basal to eutherians, this association could be part of the ancestral eutherian karyotype. If afrotherians are not at the root of the eutherian tree, then the 10

  1. Inactivating the spindle checkpoint kinase Bub1 during embryonic development results in a global shutdown of proliferation

    Directory of Open Access Journals (Sweden)

    Taylor Stephen S

    2009-09-01

    Full Text Available Abstract Background Bub1 is a component of the spindle assembly checkpoint, a surveillance mechanism that maintains chromosome stability during M-phase. Bub1 is essential during the early stages of embryogenesis, with homozygous BUB1-null mice dying shortly after day E3.5. Bub1 is also required later during embryogenesis; inactivation of BUB1 on day E10.5 appears to rapidly block all further development. However, the mechanism(s responsible for this phenotype remain unclear. Findings Here we show that inactivating BUB1 on day E10.5 stalls embryogenesis within 48 hours. This is accompanied by a global shutdown of proliferation, widespread apoptosis and haemorrhaging. Conclusion Our results suggest that Bub1 is required throughout the developing embryo for cellular proliferation. Therefore, Bub1 has been shown to be essential in all scenarios analyzed thus far in mice: proliferation of cultured fibroblasts, spermatogenesis, oogenesis and both early and late embryonic development. This likely reflects the fact that Bub1 has dual functions during mitosis, being required for both SAC function and chromosome alignment.

  2. Adults with Chromosome 18 Abnormalities.

    Science.gov (United States)

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child. PMID:25403900

  3. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  4. Genome sequence comparative analysis of long arm and short arm of human X chromosome.

    Science.gov (United States)

    Li, Zhan-Jun; Song, Shu-Xia; Zhai, Yu; Hou, Jie; Han, Li-Zhi; Wang, Xiu-Fang

    2005-01-01

    30% of the genes tested on Xp escaped inactivation, whereas less than 3% of the genes on Xq escaped inactivation. To investigate the molecular mechanism involved in the propagation and maintenance of X chromosome inactivation and escape, the long arm and short arm of the X chromosome were compared for RNA binding density. Nucleotide sequences on the X chromosome were divided into 50 kb per segment that was recorded as a set of frequency values of 7-nucleotide (7 nt) strings using all possible 7 nt strings (4(7) = 16 384). 120 genes highly expressed in the tonsil germinal center B cells were selected for calculating the 7 nt string frequency values of all introns (intron 7nt). Intron 7nt was considered RNAs (RNA population) that simulated the total of small RNA fragments in cells. Knowing the 7 nt frequency values of DNA segments and the intron 7nt, we can calculate the binding density of DNA segments to the intron 7nt that was termed as RNA binding density. The RNA binding density was determined by the amount of complement sequences. The more amount of complement sequences, the more density of RNA binding. The RNA binding density simulated the total of small RNA fragments bound to the DNA segment. Several principal characteristics were observed for the first time: (1) The mean value of RNA binding density of DNA segments on Xp was significantly higher than that on Xq ( P < 0.001); (2) The numbers of DNA segments highly binding RNAs were more on Xp than on Xq (P < 0.001); (3) The clusters of RNA highly binding DNA segments were associated with regions in which genes escape inactivation. It has been suggested that RNAs activate genes and the interaction of RNA-DNA in cells are extensive, for example, RNAs increase DNase I sensitivity of DNA, there is plenty of nonprotein-coding RNAs in cells, the binding specificity of DNA-RNA is far higher than that of DNA-protein and the affinity of DNA with RNA is increased, as compared with DNA. The nonrandom properties of

  5. Making chromosome abnormalities treatable conditions.

    Science.gov (United States)

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

    Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p-, 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions. PMID:26351122

  6. Restriction enzyme buffers and 5-azacytidine induce loss of protein and banding in plant metaphase chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Olszewska, M.J.; Gernand, D.; Luchniak, P.; Sakowicz, T. [Lodz Univ. (Poland)

    1995-12-31

    The incubation of root meristem of `Vicia faba` L. with 5-azacytidine for 72 h (5 cell cycles) resulted in shorter DNA fragments after digestion with a restriction enzyme Sau3A. under the same condition `in situ` digestion of metaphase chromosomes with Sau3A revealed a stronger banding (C-banding-like) pattern in 5-azacytidine-treated chromosomes than in the control. This difference could hardly be attributed to the euchromatin demethylation as 5-azacytidine caused a loss of chromosomal proteins; similar effect was found as a result of incubation with some restriction endonuclease buffers which did not diminish the labelling with {sup 3}H-thymidine. After 5-azacytidine administration the entrance of cells into mitosis was delayed, the metaphase chromosomes were under condensed and the pattern of DNA replication remained unchanged. (author). 27 refs, 4 figs, 2 tabs.

  7. Restriction enzyme buffers and 5-azacytidine induce loss of protein and banding in plant metaphase chromosomes

    International Nuclear Information System (INIS)

    The incubation of root meristem of 'Vicia faba' L. with 5-azacytidine for 72 h (5 cell cycles) resulted in shorter DNA fragments after digestion with a restriction enzyme Sau3A. under the same condition 'in situ' digestion of metaphase chromosomes with Sau3A revealed a stronger banding (C-banding-like) pattern in 5-azacytidine-treated chromosomes than in the control. This difference could hardly be attributed to the euchromatin demethylation as 5-azacytidine caused a loss of chromosomal proteins; similar effect was found as a result of incubation with some restriction endonuclease buffers which did not diminish the labelling with 3H-thymidine. After 5-azacytidine administration the entrance of cells into mitosis was delayed, the metaphase chromosomes were under condensed and the pattern of DNA replication remained unchanged. (author). 27 refs, 4 figs, 2 tabs

  8. Using Chromosomes to Teach Evolution: Chromosomal Rearrangements in Speciation Events.

    Science.gov (United States)

    Offner, Susan

    1994-01-01

    Uses diagrams to aid in discussing how the English map of the human chromosomes, published by Offner in 1993, can be used to illustrate some important questions in evolution, as well as give students a glimpse into some of the mechanisms underlying evolutionary change. (ZWH)

  9. US Naval nuclear powering submarine inactivation, disposal and recycling

    International Nuclear Information System (INIS)

    The US NAVY report dealing with the problem of American nuclear submarine inactivation after service life ending is discussed. 31 submarines were inactivated in 1993 accomplishing the treaty on strategic weapons reduction. The technologies of dismantling, weapon, components and equipment removing, submarine hull cutting, transportation of nuclear compartments contaminated with residual radioactivity and their disposal in Hanford are described. 3 figs

  10. Mechanism of Inactivation in Voltage-Gated Na(+) Channels.

    Science.gov (United States)

    Gawali, V S; Todt, H

    2016-01-01

    Voltage-gated Na(+) channels (VGSCs) initiate action potentials thereby giving rise to rapid transmission of electrical signals along cell membranes and between cells. Depolarization of the cell membrane causes VGSCs to open but also gives rise to a nonconducting state termed inactivation. Inactivation of VGSCs serves a critical physiologic function as it determines the extent of excitability of neurons and of muscle cells. Depending on the time course of development and removal of inactivation both "fast-" and "slow"-inactivated states have been described. Evidence from mutagenesis studies suggests that fast inactivation is produced by a block of the internal vestibule by a tethered inactivation particle that has been mapped to the internal linker between domains III and IV. The motion of this linker may be regulated by parts of the internal C-terminus. The molecular mechanism of slow inactivation is less clear. However, aside from a high number of mutagenesis studies, the recent availability of 3D structures of crystallized prokaryotic VGSCs offers insights into the molecular motions associated with slow inactivation. One possible scenario is that slow movements of the voltage sensors are transmitted to the external vestibule giving rise to a conformational change of this region. This molecular rearrangement is transmitted to the S6 segments giving rise to collapse of the internal vestibule. PMID:27586291

  11. Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to High and Low LET Radiations

    Science.gov (United States)

    Hada, M.; Wilkins, R.; Saganti, P. B.; Gersey, B.; Cucinotta, F. A.; Wu, H.

    2006-01-01

    Energetic heavy ions pose a health risk to astronauts in extended ISS and future Mars missions. High-LET heavy ions are particularly effective in causing various biological effects including cell inactivation, genetic mutations and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human epithelial cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells (CH184B5F5/M10) were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory, high energy neutron at the Los Alamos Nuclear Science Center (LANSCE) or Cs-137-gamma radiation source at the University of Texas, MD Anderson Cancer Center. After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). The results of the mBAND study showed a higher ratio of inversion involved with interchromosomal exchange in heavy ions compared to -ray irradiation. Analysis of chromosome aberrations using mBAND has the potential to provide useful information on human cell response to space-like radiation.

  12. Molecular mapping of chromosomes 17 and X. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1989-12-31

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  13. An integrated linkage, chromosome, and genome map for the yellow fever mosquito Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Vladimir A Timoshevskiy

    Full Text Available BACKGROUND: Aedes aegypti, the yellow fever mosquito, is an efficient vector of arboviruses and a convenient model system for laboratory research. Extensive linkage mapping of morphological and molecular markers localized a number of quantitative trait loci (QTLs related to the mosquito's ability to transmit various pathogens. However, linking the QTLs to Ae. aegypti chromosomes and genomic sequences has been challenging because of the poor quality of polytene chromosomes and the highly fragmented genome assembly for this species. METHODOLOGY/PRINCIPAL FINDINGS: Based on the approach developed in our previous study, we constructed idiograms for mitotic chromosomes of Ae. aegypti based on their banding patterns at early metaphase. These idiograms represent the first cytogenetic map developed for mitotic chromosomes of Ae. aegypti. One hundred bacterial artificial chromosome clones carrying major genetic markers were hybridized to the chromosomes using fluorescent in situ hybridization. As a result, QTLs related to the transmission of the filarioid nematode Brugia malayi, the avian malaria parasite Plasmodium gallinaceum, and the dengue virus, as well as sex determination locus and 183 Mbp of genomic sequences were anchored to the exact positions on Ae. aegypti chromosomes. A linear regression analysis demonstrated a good correlation between positions of the markers on the physical and linkage maps. As a result of the recombination rate variation along the chromosomes, 12 QTLs on the linkage map were combined into five major clusters of QTLs on the chromosome map. CONCLUSION: This study developed an integrated linkage, chromosome, and genome map-iMap-for the yellow fever mosquito. Our discovery of the localization of multiple QTLs in a few major chromosome clusters suggests a possibility that the transmission of various pathogens is controlled by the same genomic loci. Thus, the iMap will facilitate the identification of genomic determinants of

  14. Characterization of chromosome structures of Falconinae (Falconidae, Falconiformes, Aves) by chromosome painting and delineation of chromosome rearrangements during their differentiation

    OpenAIRE

    Nishida, Chizuko; Ishijima, Junko; KOSAKA, Ayumi; Tanabe, Hideyuki; Habermann, Felix A.; Griffin, Darren K.; MATSHUDA, Yoichi; 秀之, 田辺

    2008-01-01

    Karyotypes of most bird species are characterized by around 2n = 80 chromosomes, comprising 7–10 pairs of large- and medium-sized macrochromosomes including sex chromosomes and numerous morphologically indistinguishable microchromosomes. The Falconinae of the Falconiformes has a different karyotype from the typical avian karyotype in low chromosome numbers, little size difference between macrochromosomes and a smaller number of microchromosomes. To characterize chromosome structures of Falcon...

  15. Characterization of chromosome structures of Falconinae (Falconidae, Falconiformes, Aves) by chromosome painting and delineation of chromosome rearrangements during their differentiation

    OpenAIRE

    Nishida, Chizuko; Ishijima, Junko; KOSAKA, Ayumi; Tanabe, Hideyuki; Habermann, Felix A.; Griffin, Darren K.; Matsuda, Yoichi

    2008-01-01

    Karyotypes of most bird species are characterized by around 2n = 80 chromosomes, comprising 7Y10 pairs of large- and medium-sized macrochromosomes including sex chromosomes and numerous morphologically indistinguishable microchromosomes. The Falconinae of the Falconiformes has a different karyotype from the typical avian karyotype in low chromosome numbers, little size difference between macrochromosomes and a smaller number of microchromosomes. To characterize chromosome structures of Falcon...

  16. Cytogenetic analysis of Aegilops chromosomes, potentially usable in triticale (X Triticosecale Witt.) breeding.

    Science.gov (United States)

    Kwiatek, M; Wiśniewska, H; Apolinarska, B

    2013-05-01

    Chromosome identification using fluorescence in situ hybridization (FISH) is widely used in cytogenetic research. It is a diagnostic tool helpful in chromosome identification. It can also be used to characterize alien introgressions, when exercised in a combination with genomic in situ hybridization (GISH). This work aims to find chromosome identification of Aegilops species and Aegilops × Secale amphiploids, which can be used in cereal breeding as a source of favourable agronomic traits. Four diploid and two tetraploid Aegilops species and three Aegilops × Secale hybrids were analysed using FISH with pSc119.2, pAs1, 5S rDNA and 25S rDNA clones to differentiate the U-, M-, S(sh)- and D-subgenome chromosomes of Aegilops genus. Additionally, GISH for chromosome categorization was carried out. Differences in the hybridization patterns allowed to identify all U-, M-, S(sh)- and D-subgenome chromosomes. Some differences in localization of the rDNA, pSc119.2 and pAs1 sequences between analogue subgenomes in diploid and tetraploid species and Aegilops × Secale hybrids were detected. The hybridization pattern of the M and S genome was more variable than that of the U and D genome. An importance of the cytogenetic markers in plant breeding and their possible role in chromosome structure, function and evolution is discussed. PMID:23378244

  17. Energy-dependent inactivation of citrate lyase in Enterobacter aerogenes.

    Science.gov (United States)

    Kulla, H; Gottschalk, G

    1977-12-01

    Enterobacter aerogenes was grown in continous culture with ammonia as the growth-limiting substrate, and changes in citrate lyase and citrate synthase activities were monitored after growth shifts from anaerobic growth on citrate to aerobic growth on citrate, aerobic growth on glucose, anaerobic growth on glucose, and anaerobic growth on glucose plus nitrate. Citrate lyase was inactivated during aerobic growth on glucose and during anaerobic growth with glucose plus nitrate. Inactivation did not occur during anaerobic growth on glucose, and as a result of the simultaneous presence of citrate lyase and citrate synthase, growth difficulties were observed. Citrate lyase inactivation consisted of deacetylation of the enzyme. The corresponding deacetylase could not be demonstrated in cell extracts, and it is concluded that, as in a number of other inactivations, electron transport to oxygen or nitrate was required for inactivation. PMID:924971

  18. Modelling and application of the inactivation of microorganism

    International Nuclear Information System (INIS)

    Prevention of consuming contaminated food with toxic microorganisms causing infections and consideration of food protection and new microbial inactivation methods are obligatory situations. Food microbiology is mainly related with unwanted microorganisms spoiling foods during processing and transporting stages and causing diseases. Determination of pathogen microorganisms is important for human health to define and prevent dangers and elongate shelf life. Inactivation of pathogen microorganisms can provide food security and reduce nutrient losses. Microbial inactivation which is using methods of food protection such as food safety and fresh. With this aim, various methods are used such as classical thermal processes (pasteurisation, sterilisation), pressured electrical field (PEF), ionised radiation, high pressure, ultrasonic waves and plasma sterilisation. Microbial inactivation modelling is a secure and effective method in food production. A new microbiological application can give useful results for risk assessment in food, inactivation of microorganisms and improvement of shelf life. Application and control methods should be developed and supported by scientific research and industrial applications

  19. Inactivation of Chikungunya virus by 1,5 iodonapthyl azide

    Directory of Open Access Journals (Sweden)

    Sharma Anuj

    2012-12-01

    Full Text Available Abstract Background Chikungunya virus (CHIKV is an arthropod borne alphavirus of the family Togaviridae. CHIKV is a reemerging virus for which there is no safe prophylactic vaccine. A live attenuated strain of CHIKV, CHIK181/25, was previously demonstrated to be highly immunogenic in humans, however, it showed residual virulence causing transient arthralgia. Findings In this study, we demonstrate the complete inactivation of CHIKV181/25 by 1,5 iodonapthyl azide (INA. No cytopathic effect and virus replication was observed in cells infected with the INA-inactivated CHIKV. However, a reduction in the INA-inactivated CHIK virus-antibody binding capacity was observed by western blot analysis. Conclusion INA completely inactivated CHIKV and can further be explored for developing an inactivated-CHIKV vaccine.

  20. Pathogen Inactivation of red cells: challenges and opportunities

    Institute of Scientific and Technical Information of China (English)

    Stephen J. Wagner

    2006-01-01

    @@ Introduction Virus inactivation methods for blood have been explored as a means to further reduce the risk from tested agents and to decrease the risk of emerging or variant agents for whom no deferral or effective screening methods are available. Although inactivation methods promise to reduce transfusion-related infectious disease risk, these methods are not perfect. Most techniques for pathogen reduction will not kill bacterial spores, or inactivate bacterial endotoxin, prion protein, or certain non-enveloped viruses whose tightly packed capsid proteins prevent access of the virucidal agent to its nucleic acid target. In addition,various inactivation methods have been known to decrease blood cell yield, affect blood cell recovery or survival, and may pose risk to recipients or blood center workers. My presentation today will review two methods for pathogen inactivation of red cells.

  1. Chlorophyll mediated photodynamic inactivation of blue laser on Streptococcus mutans

    Science.gov (United States)

    Astuti, Suryani Dyah; Zaidan, A.; Setiawati, Ernie Maduratna; Suhariningsih

    2016-03-01

    Photodynamic inactivation is an inactivation method in microbial pathogens that utilize light and photosensitizer. This study was conducted to investigate photodynamic inactivation effects of low intensity laser exposure with various dose energy on Streptococcus mutans bacteria. The photodynamic inactivation was achieved with the addition of chlorophyll as photosensitizers. To determine the survival percentage of Streptococcus mutans bacteria after laser exposure, the total plate count method was used. For this study, the wavelength of the laser is 405 nm and variables of energy doses are 1.44, 2.87, 4.31, 5.74, 7.18, and 8.61 in J/cm2. The results show that exposure to laser with energy dose of 7.18 J/cm2 has the best photodynamic inactivation with a decrease of 78% in Streptococcus

  2. Primary infertility in a phenotypic male with 46XX chromosomal constitution.

    OpenAIRE

    Tan, T. T.; Khalid, B A

    1993-01-01

    The case of a 32 year old male with normal male adrenarchal hair pattern, bilateral gynaecomastia, a small phallus, hypospadias and bilateral poorly developed testes presenting with primary infertility secondary to azoospermia and a pelvic cyst is described. Repeated chromosomal analysis showed 46XX chromosomal constitution. Laparotomy revealed a simple cyst between the urinary bladder and the rectum. XX male syndrome is a rare cause of male infertility. The majority of cases is due to interc...

  3. Chromosomal Analysis of Couples with Repeated Spontaneous Abortions in Northeastern Iran

    OpenAIRE

    Saeedeh Ghazaey; Fatemeh Keify; Farzaneh Mirzaei; Masumeh Maleki; Semiramis Tootian; Mitra Ahadian; Mohammad Reza Abbaszadegan

    2015-01-01

    Background: Cytogenetic study of reproductive wastage is an important aspect in determining the genetic background of early embryogenesis. Approximately 15 to 20% of all pregnancies in humans are terminated as recurrent spontaneous abortions (RSAs). The aim of this study was to detect chromosome abnormalities in couples with RSAs and to compare our results with those reported previously. Materials and Methods: In this retrospective study, the pattern of chromosomal aberrations ...

  4. Multitude multicolor chromosome banding (mMCB) - a comprehensive one-step multicolor FISH banding method.

    Science.gov (United States)

    Weise, A; Heller, A; Starke, H; Mrasek, K; Kuechler, A; Pool-Zobel, B L; Claussen, U; Liehr, T

    2003-01-01

    Multicolor chromosome banding (MCB) using one single chromosome-specific MCB probe set per experiment was previously reported as powerful tool in molecular cytogenetics for the characterization of all kinds of human marker chromosomes. However, a quick analysis of karyotypes with highly complex chromosomal changes was hampered by the problem that up to 24 MCB experiments were necessary for a comprehensive karyotype description. To overcome that limitation the 138 available region-specific microdissection-derived libraries for all human chromosomes were combined to one single probe set, called multitude MCB (mMCB). A typical fluorescence banding pattern along the human karyotype is produced, which can be evaluated either by transforming these profiles into chromosome region-specific pseudo-colors or more reliably by studying the fluorescence profiles. The mMCB probe set has been applied on chromosomes of normal male and female probands, two primary myelodysplastic syndromes and two solid tumor cell lines. Additionally, a cell line of Gorilla gorilla (GGO) studied previously by single chromosome-specific MCB was reevaluated by the mMCB method. All results were in concordance with those obtained in parallel or by other cytogenetic and molecular cytogenetic approaches indicating that mMCB is a powerful multicolor FISH banding tool for fast characterization of complex karyotypes. PMID:15004461

  5. Embryonic hybrid cells: a powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes

    Directory of Open Access Journals (Sweden)

    SEROV OLEG

    2001-01-01

    Full Text Available The properties of embryonic hybrid cells obtained by fusion of embryonic stem (ES or teratocarcinoma (TC cells with differentiated cells are reviewed. Usually, ES-somatic or TC-somatic hybrids retain pluripotent capacity at high levels quite comparable or nearly identical with those of the pluripotent partner. When cultured in vitro, ES-somatic- and TC-somatic hybrid cell clones, as a rule, lose the chromosomes derived from the somatic partner; however, in some clones the autosomes from the ES cell partner were also eliminated, i.e. the parental chromosomes segregated bilaterally in the ES-somatic cell hybrids. This opens up ways for searching correlation between the pluripotent status of the hybrid cells and chromosome segregation patterns and therefore for identifying the particular chromosomes involved in the maintenance of pluripotency. Use of selective medium allows to isolate in vitro the clones of ES-somatic hybrid cells in which "the pluripotent" chromosome can be replaced by "the somatic" counterpart carrying the selectable gene. Unlike the TC-somatic cell hybrids, the ES-somatic hybrids with a near-diploid complement of chromosomes are able to contribute to various tissues of chimeric animals after injection into the blastocoel cavity. Analysis of the chimeric animals showed that the "somatic" chromosome undergoes reprogramming during development. The prospects for the identification of the chromosomes that are involved in the maintenance of pluripotency and its cis- and trans-regulation in the hybrid cell genome are discussed.

  6. The role of DNA cluster damage and chromosome aberrations in radiation-induced cell killing: a theoretical approach

    International Nuclear Information System (INIS)

    The role played by DNA cluster damage and chromosome aberrations in radiation-induced cell killing was investigated, assuming that certain chromosome aberrations (dicentrics, rings and large deletions, or 'lethal aberrations') lead to clonogenic inactivation and that chromosome aberrations are due to micrometre-scale rejoining of chromosome fragments derived from DNA cluster lesions (CLs). The CL yield and the threshold distance governing fragment rejoining were left as model parameters. The model, implemented as a Monte Carlo code called BIANCA (Biophysical Analysis of Cell death and chromosome Aberrations), provided simulated survival curves that were compared with survival data on AG1522 and V79 cells exposed to different radiation types, including heavy ions. The agreement between simulation outcomes and experimental data suggests that lethal aberrations are likely to play an important role in cell killing not only for AG1522 cells exposed to X rays, as already reported by others, but also for other radiation types and other cells. Furthermore, the results are consistent with the hypothesis that the critical DNA lesions leading to cell death and chromosome aberrations are double-strand break clusters ( possibly involving the ∼1000- 10 000 bp scale) and that the effects of such clusters are modulated by micrometre-scale proximity effects during DNA damage processing. (authors)

  7. Mathematical glimpse on the Y chromosome degeneration

    Science.gov (United States)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  8. Regulation of Brassinosteroid Biosynthesis and Inactivation

    Institute of Scientific and Technical Information of China (English)

    Baolin Zhao; Jia Li

    2012-01-01

    Brassinosteroids (BRs) are a group of naturally-occurring steroidal phytohormones playing fundamental roles during normal plant growth and development.Using a combination of experimental approaches,including analytical chemistry,genetics,and biochemistry,the major BR biosynthetic pathway has been largely elucidated.The least-understood knowledge in the BR research field is probably the molecular mechanisms controlling the bioactive levels of BRs in response to various developmental and environmental cues.In this review,we focus our discussion on a recently-proposed,8-step predominant BR biosynthetic pathway,several newly-identified transcription factors regulating the expression of key enzymes that catalyze BR biosynthesis,and up-to-date information about the mechanisms that plants use to inactivate unnecessary BRs.

  9. Protein inactivations during novel bioseparation techniques.

    Science.gov (United States)

    Sadana, A

    1994-02-01

    An analysis is presented for the quantitative and qualitative inactivation of proteins and other bioproducts during their separation utilizing the reverse micellar and the aqueous two-phase extraction techniques. Information on the influence of different parameters on the quantitative yields of the bioproducts separated is available, and more information is being gathered to provide further physical insights into improving the quantitative yields. However, very little information is available on the qualitative nature of the bioproducts separated utilizing either the reverse micelle or the aqueous two-phase extraction technique. More information is definitely required on the qualitative nature of the bioproducts separated by the above techniques to assist in their proper evaluation as effective bioseparation techniques. PMID:7764586

  10. Ribosome-Inactivating and Related Proteins

    Directory of Open Access Journals (Sweden)

    Joachim Schrot

    2015-05-01

    Full Text Available Ribosome-inactivating proteins (RIPs are toxins that act as N-glycosidases (EC 3.2.2.22. They are mainly produced by plants and classified as type 1 RIPs and type 2 RIPs. There are also RIPs and RIP related proteins that cannot be grouped into the classical type 1 and type 2 RIPs because of their different sizes, structures or functions. In addition, there is still not a uniform nomenclature or classification existing for RIPs. In this review, we give the current status of all known plant RIPs and we make a suggestion about how to unify those RIPs and RIP related proteins that cannot be classified as type 1 or type 2 RIPs.

  11. UV inactivation of pathogenic and indicator microorganisms

    International Nuclear Information System (INIS)

    Survival was measured as a function of the dose of germicidal UV light for the bacteria Escherichia coli, Salmonella typhi, Shigella sonnei, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis spores, the enteric viruses poliovirus type 1 and simian rotavirus SA11, the cysts of the protozoan Acanthamoeba castellanii, as well as for total coliforms and standard plate count microorganisms from secondary effluent. The doses of UV light necessary for a 99.9% inactivation of the cultured vegetative bacteria, total coliforms, and standard plate count microorganisms were comparable. However, the viruses, the bacterial spores, and the amoebic cysts required about 3 to 4 times, 9 times, and 15 times, respectively, the dose required for E. coli. These ratios covered a narrower relative dose range than that previously reported for chlorine disinfection of E. coli, viruses, spores, and cysts

  12. UV inactivation of pathogenic and indicator microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Chang, J.C.; Ossoff, S.F.; Lobe, D.C.; Dorfman, M.H.; Dumais, C.M.; Qualls, R.G.; Johnson, J.D.

    1985-06-01

    Survival was measured as a function of the dose of germicidal UV light for the bacteria Escherichia coli, Salmonella typhi, Shigella sonnei, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis spores, the enteric viruses poliovirus type 1 and simian rotavirus SA11, the cysts of the protozoan Acanthamoeba castellanii, as well as for total coliforms and standard plate count microorganisms from secondary effluent. The doses of UV light necessary for a 99.9% inactivation of the cultured vegetative bacteria, total coliforms, and standard plate count microorganisms were comparable. However, the viruses, the bacterial spores, and the amoebic cysts required about 3 to 4 times, 9 times, and 15 times, respectively, the dose required for E. coli. These ratios covered a narrower relative dose range than that previously reported for chlorine disinfection of E. coli, viruses, spores, and cysts.

  13. Esterase resistant to inactivation by heavy metals

    KAUST Repository

    El, Dorry Hamza

    2014-09-25

    EstATII is an esterase that a halotolerant, thermophilic and resistant to a spectrum of heavy metals including toxic concentration of metals. It was isolated from the lowest convective layer of the Atlantis II Red Sea brine pool. The Atlantis II brine pool is an extreme environment that possesses multiple harsh conditions such as; high temperature, salinity, pH and high concentration of metals, including toxic heavy metals. A fosmid metagenomic library using DNA isolated from the lowest convective layer this pool was used to identify EstATII. Polynucleotides encoding EstATII and similar esterases are disclosed and can be used to make EstATII. EstATII or compositions or apparatuses that contain it may be used in various processes employing lipases/esterases especially when these processes are performed under harsh conditions that inactivate other kinds of lipases or esterases.

  14. CHROMOSOMAL MULTIPLICITY IN BURKHOLDERIA CEPACIA

    Science.gov (United States)

    We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...

  15. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David

    2014-01-01

    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...

  16. Ion channels to inactivate neurons in Drosophila

    Directory of Open Access Journals (Sweden)

    James J L Hodge

    2009-08-01

    Full Text Available Ion channels are the determinants of excitability; therefore, manipulation of their levels and properties provides an opportunity for the investigator to modulate neuronal and circuit function. There are a number of ways to suppress electrical activity in Drosophila neurons, for instance, over-expression of potassium channels (i.e. Shaker Kv1, Shaw Kv3, Kir2.1 and DORK that are open at resting membrane potential. This will result in increased potassium efflux and membrane hyperpolarisation setting resting membrane potential below the threshold required to fire action potentials. Alternatively over-expression of other channels, pumps or co-transporters that result in a hyperpolarised membrane potential will also prevent firing. Lastly, neurons can be inactivated by, disrupting or reducing the level of functional voltage-gated sodium (Nav1 paralytic or calcium (Cav2 cacophony channels that mediate the depolarisation phase of action potentials. Similarly, strategies involving the opposite channel manipulation should allow net depolarisation and hyperexcitation in a given neuron. These changes in ion channel expression can be brought about by the versatile transgenic (i.e. Gal4/UAS based systems available in Drosophila allowing fine temporal and spatial control of (channel transgene expression. These systems are making it possible to electrically inactivate (or hyperexcite any neuron or neural circuit in the fly brain, and much like an exquisite lesion experiment, potentially elucidate whatever interesting behaviour or phenotype each network mediates. These techniques are now being used in Drosophila to reprogram electrical activity of well-defined circuits and bring about robust and easily quantifiable changes in behaviour, allowing different models and hypotheses to be rapidly tested.

  17. Rabies virus inactivation by binary ethylenimine: new method for inactivated vaccine production.

    OpenAIRE

    Larghi, O P; Nebel, A E

    1980-01-01

    The inactivation dynamics of rabies virus (PV strain) by binary ethylenimine, and the immunogenic properites and the stability of the vaccines prepared using this agent, were studied. Binary ethylenimine at a final concentration of 0.01 M was prepared wtih 2-bromoethylamine hydrobromide in alkaline solutions, either separately from or in suspensions of rabies virus propagated in BHK cells. The infectivity of virus suspensions containing more than 108 plaque-forming units per 0.1 ml was inacti...

  18. Use of antinucleoside antibodies to probe the organization of chromosomes denatured by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ultraviolet irradiation of methanol:acetic acid-fixed human and mouse metaphase chromosomes rendered them capable of binding antibodies specific for purine or pyrimidine bases. Since these antibodies react with single-stranded but not with native DNA, our results indicate that UV irradiation generated single-stranded regions in chromosomal DNA. Using an indirect immunofluorescence technique to detect antibody binding, highly characteristic, nonrandom patterns of antibody binding were observed. Antibodies to adenosine (anti-A) and thymidine (anti-T) produced identical patterns of binding which in most respects matched the chromosome banding patterns produced by quinacrine. However, additional foci of intense fluorescence were seen in the paracentromeric regions of constitutive heterochromatin on chromosomes 1, 9 and 16, regions which had been shown by in situ DNA--RNA hybridization to be the locations of AT-rich human satellite DNA. Antibodies to cytidine were also bound to the same region of chromosome 9. In mouse chromosome preparations, both anti-A and anti-T produced bright fluorescence of the region containing centromeric heterochromatin, which had been shown to be the location of the AT-rich satellite DNA of this species. (U.S.)

  19. Multicolor spectral karyotyping of human chromosomes.

    Science.gov (United States)

    Schröck, E; du Manoir, S; Veldman, T; Schoell, B; Wienberg, J; Ferguson-Smith, M A; Ning, Y; Ledbetter, D H; Bar-Am, I; Soenksen, D; Garini, Y; Ried, T

    1996-07-26

    The simultaneous and unequivocal discernment of all human chromosomes in different colors would be of significant clinical and biologic importance. Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization. By means of computer separation (classification) of spectra, spectrally overlapping chromosome-specific DNA probes could be resolved, and all human chromosomes were simultaneously identified. PMID:8662537

  20. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH SPERM DISORDERS

    OpenAIRE

    L. Y. Pylyp; L. A. Spinenko; V. D. Zukin; N. M. Bilko

    2013-01-01

    Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intrac...

  1. Evolution of sex chromosomes ZW of Schistosoma mansoni inferred from chromosome paint and BAC mapping analyses.

    Science.gov (United States)

    Hirai, Hirohisa; Hirai, Yuriko; LoVerde, Philip T

    2012-12-01

    Chromosomes of schistosome parasites among digenetic flukes have a unique evolution because they exhibit the sex chromosomes ZW, which are not found in the other groups of flukes that are hermaphrodites. We conducted molecular cytogenetic analyses for investigating the sex chromosome evolution using chromosome paint analysis and BAC clones mapping. To carry this out, we developed a technique for making paint probes of genomic DNA from a single scraped chromosome segment using a chromosome microdissection system, and a FISH mapping technique for BAC clones. Paint probes clearly identified each of the 8 pairs of chromosomes by a different fluorochrome color. Combination analysis of chromosome paint analysis with Z/W probes and chromosome mapping with 93 BAC clones revealed that the W chromosome of Schistosoma mansoni has evolved by at least four inversion events and heterochromatinization. Nine of 93 BAC clones hybridized with both the Z and W chromosomes, but the locations were different between Z and W chromosomes. The homologous regions were estimated to have moved from the original Z chromosome to the differentiated W chromosome by three inversions events that occurred before W heterohcromatinization. An inversion that was observed in the heterochromatic region of the W chromosome likely occurred after W heterochromatinization. These inversions and heterochromatinization are hypothesized to be the key factors that promoted the evolution of the W chromosome of S. mansoni. PMID:22831897

  2. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  3. A case of trisomy of chromosome 15

    OpenAIRE

    Coldwell, S; Fitzgerald, B.; Semmens, J.M.; Ede, R; Bateman, C

    1981-01-01

    We describe a case of trisomy of chromosome 15 in an infant who presented at birth with numerous abnormalities. As far as we are aware this chromosomal abnormality has not been described before. On the basis of this one case there appear to be no features which are specific to this chromosomal abnormality.

  4. STRUCTURAL CHROMOSOME DIVERSIFICATION IN TWO SOUTHERN ATLANTIC MARINE CATFISHES (ARIIDAE

    Directory of Open Access Journals (Sweden)

    Washington Candeia de Araújo

    2016-03-01

    Full Text Available Siluriforms is one of the most diverse groups of the Neotropical ichthyofauna. About 1,750 species occurs exclusively in the Americas. In view the high number of species, geographical widespread and morphological similarities, there are still many questions about the relationship among some families and species. One of the two families in this Order that inhabit the marine environment, Ariidae shows numerous taxonomic uncertainties. Cytogenetic analysis in Atlantic species are still incipient. To evaluate the karyotype diversity and infer the evolutionary history of this clade are presented here chromosomal data of species Cathorops spixii and Sciades sp. distributed in the northeastern Brazil coastline. Both species have the same diploid number 2n=56, but with marked differences between chromosomal formulas. In fact, C. spixii shows 12m+16sm+24st+4a (NF=108 and Sciades sp. presents 14m+10sm+22st+10a (NF=102. Both species have multiple NORs (nucleolar organizer regions, localized in the terminal portion of two chromosome pairs. The karyotypic patterns of these and other species of Ariidae indicates that pericentric inversion represent that the main mechanism involved in chromosomal diversity of the family. Taxonomic uncertainty in some taxa and the occurrence of interpopulational karyotypic variations in species Ariidae, raise detailed analyzes using the mapping of repetitive sequences in order to identify possible cryptic species in this family along the Brazilian coast. Keywords: Cathorops spixii, Sciades sp., pericentric inversions, fish cytogenetics, marine catfishes.

  5. Expression reduction in mammalian X chromosome evolution refutes Ohno’s hypothesis of dosage compensation

    Science.gov (United States)

    Lin, Fangqin; Xing, Ke; Zhang, Jianzhi; He, Xionglei

    2012-01-01

    Susumu Ohno proposed in 1967 that, during the origin of mammalian sex chromosomes from a pair of autosomes, per-allele expression levels of X-linked genes were doubled to compensate for the degeneration of their Y homologs. This conjecture forms the foundation of the current evolutionary model of sex chromosome dosage compensation, but has been tested in mammals only indirectly via a comparison of expression levels between X-linked and autosomal genes in the same genome. The test results have been controversial, because examinations of different gene sets led to different conclusions that either support or refute Ohno’s hypothesis. Here we resolve this uncertainty by directly comparing mammalian X-linked genes with their one-to-one orthologs in species that diverged before the origin of the mammalian sex chromosomes. Analyses of RNA sequencing data and proteomic data provide unambiguous evidence for expression halving (i.e., no change in per-allele expression level) of X-linked genes during evolution, with the exception of only ∼5% of genes that encode members of large protein complexes. We conclude that Ohno’s hypothesis is rejected for the vast majority of genes, reopening the search for the evolutionary force driving the origin of chromosome-wide X inactivation in female mammals. PMID:22753487

  6. Expression reduction in mammalian X chromosome evolution refutes Ohno's hypothesis of dosage compensation.

    Science.gov (United States)

    Lin, Fangqin; Xing, Ke; Zhang, Jianzhi; He, Xionglei

    2012-07-17

    Susumu Ohno proposed in 1967 that, during the origin of mammalian sex chromosomes from a pair of autosomes, per-allele expression levels of X-linked genes were doubled to compensate for the degeneration of their Y homologs. This conjecture forms the foundation of the current evolutionary model of sex chromosome dosage compensation, but has been tested in mammals only indirectly via a comparison of expression levels between X-linked and autosomal genes in the same genome. The test results have been controversial, because examinations of different gene sets led to different conclusions that either support or refute Ohno's hypothesis. Here we resolve this uncertainty by directly comparing mammalian X-linked genes with their one-to-one orthologs in species that diverged before the origin of the mammalian sex chromosomes. Analyses of RNA sequencing data and proteomic data provide unambiguous evidence for expression halving (i.e., no change in per-allele expression level) of X-linked genes during evolution, with the exception of only ∼5% of genes that encode members of large protein complexes. We conclude that Ohno's hypothesis is rejected for the vast majority of genes, reopening the search for the evolutionary force driving the origin of chromosome-wide X inactivation in female mammals. PMID:22753487

  7. Sequential Cross-Species Chromosome Painting among River Buffalo, Cattle, Sheep and Goat: A Useful Tool for Chromosome Abnormalities Diagnosis within the Family Bovidae

    Science.gov (United States)

    Pauciullo, Alfredo; Perucatti, Angela; Cosenza, Gianfranco; Iannuzzi, Alessandra; Incarnato, Domenico; Genualdo, Viviana; Di Berardino, Dino; Iannuzzi, Leopoldo

    2014-01-01

    The main goal of this study was to develop a comparative multi-colour Zoo-FISH on domestic ruminants metaphases using a combination of whole chromosome and sub-chromosomal painting probes obtained from the river buffalo species (Bubalus bubalis, 2n = 50,XY). A total of 13 DNA probes were obtained through chromosome microdissection and DOP-PCR amplification, labelled with two fluorochromes and sequentially hybridized on river buffalo, cattle (Bos taurus, 2n = 60,XY), sheep (Ovis aries, 2n = 54,XY) and goat (Capra hircus, 2n = 60,XY) metaphases. The same set of paintings were then hybridized on bovine secondary oocytes to test their potential use for aneuploidy detection during in vitro maturation. FISH showed excellent specificity on metaphases and interphase nuclei of all the investigated species. Eight pairs of chromosomes were simultaneously identified in buffalo, whereas the same set of probes covered 13 out 30 chromosome pairs in the bovine and goat karyotypes and 40% of the sheep karyotype (11 out of 27 chromosome pairs). This result allowed development of the first comparative M-FISH karyotype within the domestic ruminants. The molecular resolution of complex karyotypes by FISH is particularly useful for the small chromosomes, whose similarity in the banding patterns makes their identification very difficult. The M-FISH karyotype also represents a practical tool for structural and numerical chromosome abnormalities diagnosis. In this regard, the successful hybridization on bovine secondary oocytes confirmed the potential use of this set of probes for the simultaneous identification on the same germ cell of 12 chromosome aneuploidies. This is a fundamental result for monitoring the reproductive health of the domestic animals in relation to management errors and/or environmental hazards. PMID:25330006

  8. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

    Directory of Open Access Journals (Sweden)

    Marco Barchi

    2008-05-01

    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  9. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

    Directory of Open Access Journals (Sweden)

    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  10. The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

    OpenAIRE

    Wienberg, Johannes; Jauch, Anna; Lüdecke, H J; Senger, G; Horsthemke, B; Claussen, U; Cremer, Thomas; Arnold, N.; Lengauer, Christoph

    1994-01-01

    Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of ...

  11. Effect of light irradiation wavelength on the inactivation of penicillium

    International Nuclear Information System (INIS)

    Characteristics of the Inactivation inactivity of Penicillium implicatum, one of the most common fungi in the environment, were examined under the specified light irradiation on the basis of the action spectrum. The Penicillium implicatum spores were spread on PDA plates. Each plate was irradiated using three kinds of light sources. Monochromatic light was simultaneously irradiated on the plates every 20 nm in the range of 260 to 500 nm. The irradiation energy was measured by wavelength. UVA and UVB fluorescent lamps were also used to irradiate the plates under the measurement of irradiation energy. After the exposure to light, the plates were cultivated for one week at 25 deg C. Viable fungal colonies were counted. Characteristic curbs of the inactivation rate of Penicillium implicatum versus irradiation energy showed the shortest wavelength of 260 nm was the most effective in the inactivation. It is due to the fact that the wavelength is close to the absorption of DNA. Moreover, from the examination of wavelength dependency of the inactivation rate under irradiation of a constant energy, 2 kJ/m2, it was observed that the wavelength in the visible light range was also effective in the inactivation to some extent. On the other hand, irradiation with a UVB fluorescent lamp resulted in inactivation of all Penicillium spores at about 3 kJ/m2. In the case of the UVA fluorescent lamp, about 80 kJ/m2 caused the inactivation of all the spores. (author)

  12. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

  13. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

  14. Gamma-ray inactivation of biotin in dilute aqueous solution

    International Nuclear Information System (INIS)

    The relative roles of the radicals produced by water radiolysis in the inactivation of biotin in aqueous solution were investigated. The effects of nitrous oxide and isopropanol used as selective free radical scavengers allowed the inactivation efficiencies per unit G-value of OH, H, and esub(aq)- to be estimated; these efficiencies were 0.73, 0.10, and 0.02 in neutral solution, respectively. Hydrogen gas and hydrogen peroxide unaffected the activity of biotin. G0-Value for biotin inactivation in oxygen-free neutral solution was 2.08. Under these conditions the hydroxyl radical attack was found to be responsible for the large part of inactivation. On the other hand, in oxygenated neutral solution, G0-value was 4.16. This large increase of inactivation in oxygenated solution suggested that, although hydrated electrons were considerably ineffective as an inactivating species in oxygen-free solution, superoxide ions would be much more effective in causing inactivation of biotin in oxygenated solution. A rate constant for the reaction of biotin with hydroxyl radical was 1.34 x 1010M-1 sec-1 as determined by the PNDA method. (auth.)

  15. Application of gaseous ozone for inactivation of Bacillus subtilis spores.

    Science.gov (United States)

    Aydogan, Ahmet; Gurol, Mirat D

    2006-02-01

    The effectiveness of gaseous ozone (O3) as a disinfectant was tested on Bacillus subtilis spores, which share the same physiological characteristics as Bacillus anthracis spores that cause the anthrax disease. Spores dried on surfaces of different carrier material were exposed to O3 gas in the range of 500-5000 ppm and at relative humidity (RH) of 70-95%. Gaseous O3 was found to be very effective against the B. subtilis spores, and at O3 concentrations as low as 3 mg/L (1500 ppm), approximately 3-log inactivation was obtained within 4 hr of exposure. The inactivation curves consisted of a short lag phase followed by an exponential decrease in the number of surviving spores. Prehydration of the bacterial spores has eliminated the initial lag phase. The inactivation rate increased with increasing O3 concentration but not >3 mg/L. The inactivation rate also increased with increase in RH. Different survival curves were obtained for various surfaces used to carry spores. Inactivation rates of spores on glass, a vinyl floor tile, and office paper were nearly the same. Whereas cut pile carpet and hardwood flooring surfaces resulted in much lower inactivation rates, another type of carpet (loop pile) showed significant enhancement in the inactivation of the spores. PMID:16568801

  16. Virus-specific thermostability and heat inactivation profiles of alphaviruses.

    Science.gov (United States)

    Park, So Lee; Huang, Yan-Jang S; Hsu, Wei-Wen; Hettenbach, Susan M; Higgs, Stephen; Vanlandingham, Dana L

    2016-08-01

    Serological diagnosis is a critical component for disease surveillance and is important to address the increase in incidence and disease burden of alphaviruses, such as the chikungunya (CHIKV) and Ross River (RRV) viruses. The gold standard for serological diagnosis is the plaque reduction neutralization test (PRNT), which demonstrates the neutralizing capacity of serum samples after the removal of complement activity and adventitious viruses. This procedure is normally performed following inactivation of the virus at 56°C for 30min. Although this protocol has been widely accepted for the inactivation of envelope RNA viruses, recent studies have demonstrated that prolonged heat inactivation is required to completely inactivate two alphaviruses, Western equine encephalitis virus and CHIKV. Incomplete inactivation of viruses poses a laboratory biosafety risk and can also lead to spurious test results. Despite its importance in ensuring the safety of laboratory personnel as well as test integrity, systematic investigation on the thermostability of alphaviruses has not been performed. In this study, the temperature tolerance and heat inactivation profiles of RRV, Barmah Forest, and o'nyong-nyong viruses were determined. Variations in thermostability were observed within the Semliki forest serocomplex. Therefore, evidence-based heat inactivation procedures for alphaviruses are recommended. PMID:27079828

  17. Epigenetic Histone Marks of Extended Meta-Polycentric Centromeres of Lathyrus and Pisum Chromosomes.

    Science.gov (United States)

    Neumann, Pavel; Schubert, Veit; Fuková, Iva; Manning, Jasper E; Houben, Andreas; Macas, Jiří

    2016-01-01

    Species of the legume genera Lathyrus and Pisum possess chromosomes that exhibit a unique structure of their centromeric regions, which is clearly apparent during metaphase by the formation of extended primary constrictions which span up to a third of the length of the chromosome. In addition, these species express two different variants of the CenH3 protein which are co-localized in multiple domains along the poleward surface of the primary constrictions. Here, we show that the constrictions represent a distinct type of chromatin differing from the chromosome arms. In metaphase, histone phosphorylation patterns including H3S10ph, H3S28ph, and H3T3ph were observed along the entire constriction, in a way similar to holocentric chromosomes. On the other hand, distribution of phosphorylated H2AT120 was different from that previously reported from either, holocentric and monocentric chromosomes, occurring at chromatin surrounding but not overlapping CenH3 domains. Since some of these phosphorylations play a role in chromatid cohesion, it can be assumed that they facilitate correct chromosome segregation by ensuring that multiple separate CenH3 domains present on the same chromatid are oriented toward the same pole. The constrictions also displayed distinct patterns of histone methylation marks, being enriched in H3K9me2 and depleted in H3K4me3 and H3K27me2 compared to the chromosome arms. Super-resolution fluorescence microscopy revealed that although both CenH3 protein variants are present in all CenH3 domains detected on metaphase chromosomes, they are only partially co-localized while there are chromatin subdomains which are mostly made of only one CenH3 variant. Taken together, these data revealed specific features of extended primary constrictions of Lathyrus and Pisum and support the idea that they may represent an intermediate stage between monocentric and holocentric chromosomes. PMID:26973677

  18. Epigenetic histone marks of extended meta-polycentric centromeres of Lathyrus and Pisum chromosomes

    Directory of Open Access Journals (Sweden)

    Pavel eNeumann

    2016-03-01

    Full Text Available Species of the legume genera Lathyrus and Pisum possess chromosomes that exhibit a unique structure of their centromeric regions, which is clearly apparent during metaphase by the formation of extended primary constrictions which span up to a third of the length of the chromosome. In addition, these species express two different variants of the CenH3 protein which are co-localized in multiple domains along the poleward surface of the primary constrictions. Here we show that the constrictions represent a distinct type of chromatin differing from the chromosome arms. In metaphase, histone phosphorylation patterns including H3S10ph, H3S28ph and H3T3ph were observed along the entire constriction, in a way similar to holocentric chromosomes. On the other hand, distribution of phosphorylated H2AT120 was different from that previously reported from either, holocentric and monocentric chromosomes, occurring at chromatin surrounding but not overlapping CenH3 domains. Since some of these phosphorylations play a role in chromatid cohesion, it can be assumed that they facilitate correct chromosome segregation by ensuring that multiple separate CenH3 domains present on the same chromatid are oriented towards the same pole. The constrictions also displayed distinct patterns of histone methylation marks, being enriched in H3K9me2 and depleted in H3K4me3 and H3K27me2 compared to the chromosome arms. High resolution fluorescence microscopy revealed that although both CenH3 protein variants are present in all CenH3 domains detected on metaphase chromosomes, they are only partially co-localized while there are chromatin subdomains which are mostly made of only one CenH3 variant. Taken together, these data revealed specific features of extended primary constrictions of Lathyrus and Pisum and support the idea that they may represent an intermediate stage between monocentric and holocentric chromosomes.

  19. Holoprosencephaly due to numeric chromosome abnormalities.

    Science.gov (United States)

    Solomon, Benjamin D; Rosenbaum, Kenneth N; Meck, Jeanne M; Muenke, Maximilian

    2010-02-15

    Holoprosencephaly (HPE) is the most common malformation of the human forebrain. When a clinician identifies a patient with HPE, a routine chromosome analysis is often the first genetic test sent for laboratory analysis in order to assess for a structural or numerical chromosome anomaly. An abnormality of chromosome number is overall the most frequently identified etiology in a patient with HPE. These abnormalities include trisomy 13, trisomy 18, and triploidy, though several others have been reported. Such chromosome number abnormalities are almost universally fatal early in gestation or in infancy. Clinical features of specific chromosome number abnormalities may be recognized by phenotypic manifestations in addition to the HPE. PMID:20104610

  20. Novel insights into mitotic chromosome condensation

    Science.gov (United States)

    Piskadlo, Ewa; Oliveira, Raquel A.

    2016-01-01

    The fidelity of mitosis is essential for life, and successful completion of this process relies on drastic changes in chromosome organization at the onset of nuclear division. The mechanisms that govern chromosome compaction at every cell division cycle are still far from full comprehension, yet recent studies provide novel insights into this problem, challenging classical views on mitotic chromosome assembly. Here, we briefly introduce various models for chromosome assembly and known factors involved in the condensation process (e.g. condensin complexes and topoisomerase II). We will then focus on a few selected studies that have recently brought novel insights into the mysterious way chromosomes are condensed during nuclear division.