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Sample records for chromosomes human x

  1. The DNA sequence of the human X chromosome

    Science.gov (United States)

    Ross, Mark T.; Grafham, Darren V.; Coffey, Alison J.; Scherer, Steven; McLay, Kirsten; Muzny, Donna; Platzer, Matthias; Howell, Gareth R.; Burrows, Christine; Bird, Christine P.; Frankish, Adam; Lovell, Frances L.; Howe, Kevin L.; Ashurst, Jennifer L.; Fulton, Robert S.; Sudbrak, Ralf; Wen, Gaiping; Jones, Matthew C.; Hurles, Matthew E.; Andrews, T. Daniel; Scott, Carol E.; Searle, Stephen; Ramser, Juliane; Whittaker, Adam; Deadman, Rebecca; Carter, Nigel P.; Hunt, Sarah E.; Chen, Rui; Cree, Andrew; Gunaratne, Preethi; Havlak, Paul; Hodgson, Anne; Metzker, Michael L.; Richards, Stephen; Scott, Graham; Steffen, David; Sodergren, Erica; Wheeler, David A.; Worley, Kim C.; Ainscough, Rachael; Ambrose, Kerrie D.; Ansari-Lari, M. Ali; Aradhya, Swaroop; Ashwell, Robert I. S.; Babbage, Anne K.; Bagguley, Claire L.; Ballabio, Andrea; Banerjee, Ruby; Barker, Gary E.; Barlow, Karen F.; Barrett, Ian P.; Bates, Karen N.; Beare, David M.; Beasley, Helen; Beasley, Oliver; Beck, Alfred; Bethel, Graeme; Blechschmidt, Karin; Brady, Nicola; Bray-Allen, Sarah; Bridgeman, Anne M.; Brown, Andrew J.; Brown, Mary J.; Bonnin, David; Bruford, Elspeth A.; Buhay, Christian; Burch, Paula; Burford, Deborah; Burgess, Joanne; Burrill, Wayne; Burton, John; Bye, Jackie M.; Carder, Carol; Carrel, Laura; Chako, Joseph; Chapman, Joanne C.; Chavez, Dean; Chen, Ellson; Chen, Guan; Chen, Yuan; Chen, Zhijian; Chinault, Craig; Ciccodicola, Alfredo; Clark, Sue Y.; Clarke, Graham; Clee, Chris M.; Clegg, Sheila; Clerc-Blankenburg, Kerstin; Clifford, Karen; Cobley, Vicky; Cole, Charlotte G.; Conquer, Jen S.; Corby, Nicole; Connor, Richard E.; David, Robert; Davies, Joy; Davis, Clay; Davis, John; Delgado, Oliver; DeShazo, Denise; Dhami, Pawandeep; Ding, Yan; Dinh, Huyen; Dodsworth, Steve; Draper, Heather; Dugan-Rocha, Shannon; Dunham, Andrew; Dunn, Matthew; Durbin, K. James; Dutta, Ireena; Eades, Tamsin; Ellwood, Matthew; Emery-Cohen, Alexandra; Errington, Helen; Evans, Kathryn L.; Faulkner, Louisa; Francis, Fiona; Frankland, John; Fraser, Audrey E.; Galgoczy, Petra; Gilbert, James; Gill, Rachel; Glöckner, Gernot; Gregory, Simon G.; Gribble, Susan; Griffiths, Coline; Grocock, Russell; Gu, Yanghong; Gwilliam, Rhian; Hamilton, Cerissa; Hart, Elizabeth A.; Hawes, Alicia; Heath, Paul D.; Heitmann, Katja; Hennig, Steffen; Hernandez, Judith; Hinzmann, Bernd; Ho, Sarah; Hoffs, Michael; Howden, Phillip J.; Huckle, Elizabeth J.; Hume, Jennifer; Hunt, Paul J.; Hunt, Adrienne R.; Isherwood, Judith; Jacob, Leni; Johnson, David; Jones, Sally; de Jong, Pieter J.; Joseph, Shirin S.; Keenan, Stephen; Kelly, Susan; Kershaw, Joanne K.; Khan, Ziad; Kioschis, Petra; Klages, Sven; Knights, Andrew J.; Kosiura, Anna; Kovar-Smith, Christie; Laird, Gavin K.; Langford, Cordelia; Lawlor, Stephanie; Leversha, Margaret; Lewis, Lora; Liu, Wen; Lloyd, Christine; Lloyd, David M.; Loulseged, Hermela; Loveland, Jane E.; Lovell, Jamieson D.; Lozado, Ryan; Lu, Jing; Lyne, Rachael; Ma, Jie; Maheshwari, Manjula; Matthews, Lucy H.; McDowall, Jennifer; McLaren, Stuart; McMurray, Amanda; Meidl, Patrick; Meitinger, Thomas; Milne, Sarah; Miner, George; Mistry, Shailesh L.; Morgan, Margaret; Morris, Sidney; Müller, Ines; Mullikin, James C.; Nguyen, Ngoc; Nordsiek, Gabriele; Nyakatura, Gerald; O’Dell, Christopher N.; Okwuonu, Geoffery; Palmer, Sophie; Pandian, Richard; Parker, David; Parrish, Julia; Pasternak, Shiran; Patel, Dina; Pearce, Alex V.; Pearson, Danita M.; Pelan, Sarah E.; Perez, Lesette; Porter, Keith M.; Ramsey, Yvonne; Reichwald, Kathrin; Rhodes, Susan; Ridler, Kerry A.; Schlessinger, David; Schueler, Mary G.; Sehra, Harminder K.; Shaw-Smith, Charles; Shen, Hua; Sheridan, Elizabeth M.; Shownkeen, Ratna; Skuce, Carl D.; Smith, Michelle L.; Sotheran, Elizabeth C.; Steingruber, Helen E.; Steward, Charles A.; Storey, Roy; Swann, R. Mark; Swarbreck, David; Tabor, Paul E.; Taudien, Stefan; Taylor, Tineace; Teague, Brian; Thomas, Karen; Thorpe, Andrea; Timms, Kirsten; Tracey, Alan; Trevanion, Steve; Tromans, Anthony C.; d’Urso, Michele; Verduzco, Daniel; Villasana, Donna; Waldron, Lenee; Wall, Melanie; Wang, Qiaoyan; Warren, James; Warry, Georgina L.; Wei, Xuehong; West, Anthony; Whitehead, Siobhan L.; Whiteley, Mathew N.; Wilkinson, Jane E.; Willey, David L.; Williams, Gabrielle; Williams, Leanne; Williamson, Angela; Williamson, Helen; Wilming, Laurens; Woodmansey, Rebecca L.; Wray, Paul W.; Yen, Jennifer; Zhang, Jingkun; Zhou, Jianling; Zoghbi, Huda; Zorilla, Sara; Buck, David; Reinhardt, Richard; Poustka, Annemarie; Rosenthal, André; Lehrach, Hans; Meindl, Alfons; Minx, Patrick J.; Hillier, LaDeana W.; Willard, Huntington F.; Wilson, Richard K.; Waterston, Robert H.; Rice, Catherine M.; Vaudin, Mark; Coulson, Alan; Nelson, David L.; Weinstock, George; Sulston, John E.; Durbin, Richard; Hubbard, Tim; Gibbs, Richard A.; Beck, Stephan; Rogers, Jane; Bentley, David R.

    2009-01-01

    The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. PMID:15772651

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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

  3. Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

    International Nuclear Information System (INIS)

    Jordan, R.; Schwartz, J.L.

    1994-01-01

    Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by 60 Co γ rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab

  4. A worldwide phylogeography for the human X chromosome.

    Directory of Open Access Journals (Sweden)

    Simone S Santos-Lopes

    Full Text Available BACKGROUND: We reasoned that by identifying genetic markers on human X chromosome regions where recombination is rare or absent, we should be able to construct X chromosome genealogies analogous to those based on Y chromosome and mitochondrial DNA polymorphisms, with the advantage of providing information about both male and female components of the population. METHODOLOGY/PRINCIPAL FINDINGS: We identified a 47 Kb interval containing an Alu insertion polymorphism (DXS225 and four microsatellites in complete linkage disequilibrium in a low recombination rate region of the long arm of the human X chromosome. This haplotype block was studied in 667 males from the HGDP-CEPH Human Genome Diversity Panel. The haplotypic diversity was highest in Africa (0.992+/-0.0025 and lowest in the Americas (0.839+/-0.0378, where no insertion alleles of DXS225 were observed. Africa shared few haplotypes with other geographical areas, while those exhibited significant sharing among themselves. Median joining networks revealed that the African haplotypes were numerous, occupied the periphery of the graph and had low frequency, whereas those from the other continents were few, central and had high frequency. Altogether, our data support a single origin of modern man in Africa and migration to occupy the other continents by serial founder effects. Coalescent analysis permitted estimation of the time of the most recent common ancestor as 182,000 years (56,700-479,000 and the estimated time of the DXS225 Alu insertion of 94,400 years (24,300-310,000. These dates are fully compatible with the current widely accepted scenario of the origin of modern mankind in Africa within the last 195,000 years and migration out-of-Africa circa 55,000-65,000 years ago. CONCLUSIONS/SIGNIFICANCE: A haplotypic block combining an Alu insertion polymorphism and four microsatellite markers on the human X chromosome is a useful marker to evaluate genetic diversity of human populations and

  5. Implications for x-chromosome regulation from studies of human x-chromosome DNA

    International Nuclear Information System (INIS)

    Wolf, S.F.; Migeon, B.R.

    1983-01-01

    It is clear that there must be multiple events involved in the regulation of the mammalian X chromosome. The initial event, occurring about the time of implantation results in inactivation of all but a single X chromosome in diploid cells. A popular working hypothesis is that DNA modification, such as methylation or sequence rearrangement, might be responsible for maintenance of the inactive state. Methylation is particularly attractive, since the preference for methylating half-methylated sites might result in perpetuation of the differentiated state. In this paper we discuss several facets of our studies of X inactivation; specifically, our general strategy, studies of X DNA methylation, and studies of loci that escape inactivation. 47 references, 8 figures, 2 tables

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Chromosome painting analysis of X-ray-induced aberrations in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Matsuoka, A.; Hayashi, M.; Yamazaki, N.; Sofuni, T.

    1994-01-01

    Chromosomal rearrangements in human lymphocytes induced by X-rays (0, 0.5, 1.0 and 2.0 Gray) were analyzed using chromosome painting. DNA probes for human chromosomes 1, 3 or 4 alone, and a combination of 1 and 4, were used for analysis. The frequency of cells with rearrangements, i.e. reciprocal translocations, dicentrics, insertions, tricentrics and fragments, involving chromosome 4 increased with dose in both 48 and 72 h cultures. The number of translocations per cell also increased with dose at 48 and 72 h. Dicentrics increased with dose in 48 h but not in 72 h cultures. The estimated genomic frequency of aberrations per cell was comparable with results in banded cells. No difference was shown on the detection efficiency of chromosome rearrangements among the various DNA probes used. Since this technique does not necessarily require well-spread metaphases for analysis, it is possible to increase the number of analyzable metaphases compared with the banding technique. Chromosome painting is a simpler, more objective and practical method for detecting chromosome rearrangements than conventional banding analyses. (Author)

  8. Chromosomes and irradiation: in vitro study of the action of X-rays on human lymphocytes

    International Nuclear Information System (INIS)

    Mouriquand, C.; Patet, J.; Gilly, C.; Wolff, C.

    1966-01-01

    Radioinduced chromosomal aberrations were studied in vitro on leukocytes of human peripheral blood after x irradiation at 25, 50, 100, 200, and 300 R. The numeric and structural anomalies were examined on 600 karyotypes. The relationship between these disorders and the dose delivered to the blood are discussed. An explanation on their mechanism of formation is tentatively given. (authors) [fr

  9. Three-dimensional visualization of a human chromosome using coherent x-ray diffraction

    International Nuclear Information System (INIS)

    Nishino, Yoshinori; Ishikawa, Tetsuya; Takahashi, Yukio; Imamoto, Naoko; Maeshima, Kazuhiro

    2010-01-01

    We succeeded in observing a human chromosome in two- and three-dimensions using x-ray diffraction microscopy. X-ray diffraction microscopy is a lens-less imaging technique utilizing coherent x-ray diffraction, and can overcome various limitations in conventional lens-based x-ray microscopy. Biological applications of the method have been limited to 2D observation, and 3D observation has been long waited. We found that the reconstructed chromosome images contain high-density axial structure, which has not been observed under unstained or unlabeled conditions. The result experimentally demonstrates the effectiveness of x-ray diffraction microscopy in observing internal structures of unstained biological samples with high image contrast. (author)

  10. Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease.

    Science.gov (United States)

    Cantone, Irene; Fisher, Amanda G

    2017-11-05

    X-chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human embryonic stem (ES) cells and induced pluripotent stem cells hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies. We outline our recent results using mouse ES cells to reprogramme female human fibroblasts by cell-cell fusion. We show that pluripotent reprogramming induces widespread and rapid chromatin remodelling in which the human Xi loses XIST and H3K27m3 enrichment and selected Xi genes become reactivated, ahead of mitotic division. Using RNA sequencing to map the extent of human Xi reactivation, and chromatin-modifying drugs to potentiate reactivation, we outline how this approach could be used to better design strategies to re-express human X-linked loci. As cell fusion induces the expression of human pluripotency genes that represent both the 'primed' and 'naive' states, this approach may also offer a fresh opportunity to segregate human pluripotent states with distinct Xi expression profiles, using single-cell-based approaches.This article is part of the themed issue 'X-chromosome inactivation: a tribute to Mary Lyon'. © 2017 The Author(s).

  11. 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

    2016-08-02

    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.

  12. Fluorescent in-situ hybridization of cattle and sheep chromosomes with cloned human fragile-X DNA

    DEFF Research Database (Denmark)

    Ali, Ahmd; Thomsen, Preben Dybdahl; Babar, M.E.

    2009-01-01

    An extensive study on spontaneous and 5-Fluorodeoxyuridine induced fragile sites identified Xq31 in cattle (Bos taurus) and (Xq24, Xq26) in sheep (Ovis aries) in addition to several autosomal fragile sites (under publication). A ZOO-FISH study using three cloned human fragile-X probes with CCG....../CGG(n) trinucleotide repeat sequence was carried out to determine homology between human and bovine fragile-X. The hybridisation results showed only a weak signal on a human chromosome that was not an X with all three fragile site probes. No signals were detected in sheep chromosomes. The signal of all three human...... fragile-X probes on cattle chromosomes was however, medium-prominent sub-centromeric signal on two homologues. BrdU administration in 12 h before harvesting identified these homologues to be chromosome number 5. In addition retrospective slides of cattle and sheep chromosomes used for fragile site studies...

  13. Types of structural chromosome aberrations and their incidences in human spermatozoa X-irradiated in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kamiguchi, Yujiroh; Tateno, Hiroyuki; Mikamo, Kazuya (Asahikawa Medical College (Japan). Department of Biological Sciences)

    1990-02-01

    The authors studied the effects of in vitro X-irradiation on human sperm chromosomes, using our interspecific in vitro fertilization system between human spermatozoa and zona-free hamster oocytes. 28 semen samples from 5 healthy men were exposed to 0.23, 0.45, 0.91 and 1.82 Gy of X-rays. Totals of 2098 and 2862 spermatozoa were karyotyped in the control and the irradiated groups, respectively. The indicence of spermatozoa with X-ray-induced structural chromosome aberrations (Y) increased linearly with increasing dosage (D), being best expressed by the equation, Y = 0.08 + 34.52 D. The incidence of breakage-type aberrations was moe than 9 times higher than that of exchange-type aberrations. Both of them showed linear dose-dependent increases, which were expressed by the regression lines, Y = -0.014 + 0.478 D and Y -0.010 + 0.057 D, respectively. The incidence of chromosome-ltype aberrations was about 6 times higher than that of chromatid-type aberrations. Their dose-dependent increases were expressed by the regression lines, Y = -0.015 + 0.462 D and Y = -0.006 + 0.079 D, respectively. These results are discussed in relation to the previous data obtained with {gamma}-rays. The repair mechanism of X-ray-induced sperm DNA lesions is also discussed. (author). 21 refs.; 4 figs.; 4 tabs.

  14. Evaluating the relationship between spermatogenic silencing of the X chromosome and evolution of the Y chromosome in chimpanzee and human

    NARCIS (Netherlands)

    E. Mulugeta (Eskeatnaf); W.M. Baarends (Willy); J.H. Gribnau (Joost); J.A. Grootegoed (Anton)

    2010-01-01

    textabstractChimpanzees 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

  15. Frequencies of X-ray and fast neutron induced chromosome translocations in human peripheral blood lymphocytes as detected by in situ hybridization using chromosome specific DNA libraries

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Darroudi, F.; Vermeulen, S.; Wiegant, J.

    1992-01-01

    DNA libraries of six human chromosomes were used to detect translocations in human lymphocytes induced by different doses of X-rays and fast neutrons. Results show that with X-rays, one can detect about 1.5 to 2.0 fold more translocations in comparison to dicentrics, whereas following fast neutron irradiation, the difference between these two classes of aberrations are significantly different at high doses. In addition, triple fluorescent in situ hybridization technique was used to study the frequencies of radiation-induced translocations involving a specific chromosome. Chromosome number 1 was found to be involved in translocations more frequently than chromosomes number 2, 3, 4, 8 and X. (author). 10 refs., 1 fig., 2 tabs

  16. Loss of heterozygosity on the X chromosome in human breast cancer.

    Science.gov (United States)

    Loupart, M L; Adams, S; Armour, J A; Walker, R; Brammar, W; Varley, J

    1995-08-01

    The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

  17. Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile X syndrome.

    Science.gov (United States)

    Verdyck, Pieter; Berckmoes, Veerle; De Vos, Anick; Verpoest, Willem; Liebaers, Inge; Bonduelle, Maryse; De Rycke, Martine

    2015-10-01

    Fragile X syndrome (FXS), the most common inherited intellectual disability syndrome, is caused by expansion and hypermethylation of the CGG repeat in the 5' UTR of the FMR1 gene. This expanded repeat, also known as the rare fragile site FRAXA, causes X chromosome fragility in cultured cells from patients but only when induced by perturbing pyrimidine synthesis. We performed preimplantation genetic diagnosis (PGD) on 595 blastomeres biopsied from 442 cleavage stage embryos at risk for FXS using short tandem repeat (STR) markers. In six blastomeres, from five embryos an incomplete haplotype was observed with loss of all alleles telomeric to the CGG repeat. In all five embryos, the incomplete haplotype corresponded to the haplotype carrying the CGG repeat expansion. Subsequent analysis of additional blastomeres from three embryos by array comparative genomic hybridization (aCGH) confirmed the presence of a terminal deletion with a breakpoint close to the CGG repeat in two blastomeres from one embryo. A blastomere from another embryo showed the complementary duplication. We conclude that a CGG repeat expansion at FRAXA causes X chromosome fragility in early human IVF embryos at risk for FXS. © 2015 Wiley Periodicals, Inc.

  18. Structure, organization, and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal crossing-over and an ancestral pentamer repeat shared with the human X chromosome.

    Science.gov (United States)

    Waye, J S; Willard, H F

    1986-09-01

    The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were approximately 98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.

  19. Report of the Fourth International Workshop on human X chromosome mapping 1993

    Energy Technology Data Exchange (ETDEWEB)

    Schlessinger, D.; Mandel, J.L.; Monaco, A.P.; Nelson, D.L.; Willard, H.F. [eds.

    1993-12-31

    Vigorous interactive efforts by the X chromosome community have led to accelerated mapping in the last six months. Seventy-five participants from 12 countries around the globe contributed progress reports to the Fourth International X Chromosome Workshop, at St. Louis, MO, May 9-12, 1993. It became clear that well over half the chromosome is now covered by YAC contigs that are being extended, verified, and aligned by their content of STSs and other markers placed by cytogenetic or linkage mapping techniques. The major aim of the workshop was to assemble the consensus map that appears in this report, summarizing both consensus order and YAC contig information.

  20. Chromosome aberrations induced by low doses of X-rays in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Ziemba-Zoltowska, B.; Bocian, E.; Rosiek, O.; Sablinski, J.

    1980-01-01

    Curves derived from the dose-response data for the yield of aberrations in human lymphocytes can be represented by a quadratic equation at all but low dose ranges. A calibration curve has therefore been determined at a low dose range of X-radiation (11.5 to 57.5 rad). The frequencies of dicentrics plus centric rings, and of acentrics were better fitted by linear dose-response models than quadratic. The linearity of the relationship indicated that asymmetrical chromosome exchanges at low doses of radiation are produced predominantly by a single track mechanism. A dose-response curve for dicentrics plus centric rings (5 to 60 rad) has also been derived by pooling published data with the results of this study. This calibration curve is relevant to cytogenetic dosimetry in radiological protection. (UK)

  1. Chromosome aberrations in human peripheral lymphocytes induced by single or fractionated X-irradiation

    International Nuclear Information System (INIS)

    Ivanov, B.; Leonard, A.; Deknyudt, G.

    1980-01-01

    Investigated is the effect of single (125 and 250 R) and fractionated (2x125 R) irradiation on the output of chromosome aberrations in lymphocytes of human peripheral blood kept between irradiations at the temperature of 5 deg C. The single irradiation is carried out immediately after vein-puncture. In the case of fractionated irradiation the first dose of 125R is given after vein-puncture, the second, in the interval of 2, 8 and 24 hours. Blood is cultivated immediately after two irradiations in order to prepare metaphase plates for cytogenic analysis. Repair processes in cell heritage structures are not realised in blood irradiated by fractions which is kept at 5 deg C between irradiations. On the contrary, chromosome fragments, interstitial deletions, aberrant cells and cell breaks are found in a large amount in blood irradiated by fractions. They have appeared with the authentically high statistic difference as compared with the cells irradiated one time with the same dose. This effect is probably attained due to blood preservation

  2. X chromosome and suicide.

    Science.gov (United States)

    Fiori, L M; Zouk, H; Himmelman, C; Turecki, G

    2011-02-01

    Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90  kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

  3. Frequency and distribution analysis of chromosomal translocations induced by x-ray in human lymphocytes

    International Nuclear Information System (INIS)

    Lopez Hidalgo, Juana Ines

    2000-01-01

    The characteristic of ionizing radiation suggests that induced chromosomal damage in the form of translocations would appear to be randomly distributed. However, the outcome of tests performed in vitro and in vivo (irradiated individuals) are contradictories. The most translocation-related chromosomes, as far as some studies reveal on one hand, appear to be less involved in accordance with others. These data, together with those related to molecular mechanisms involved in translocations production suggest that in G 0 -irradiated cells, the frequency and distribution of this kind of chromosomal rearrangement, does not take place at random. They seem to be affected by in-nucleus chromosome distribution, by each chromosome's DNA length and functional features, by the efficiency of DNA repair mechanisms, and by inter individual differences. The objective of this study was to establish the frequency pattern of each human chromosome involved in radio-induced translocations, as well as to analyze the importance the chromosome length, the activity of DNA polymerase- dependant repair mechanisms, and inter individual differences within the scope of such distribution. To achieve the goals, peripheral blood lymphocytes from healthy donors were irradiated in presence and absence of 2'-3' dideoxithimidine (ddThd), a Β - DNA polymerase inhibitor, which takes part in the base repair mechanism (B E R). The results showed that: The presence of ddThd during the irradiation increase the basal frequency of radioinduced translocations in 60 %. This result suggests that ddThd repair synthesis inhibition can be in itself a valid methodology for radiation-induced bases damage assessment, damage which if not BER-repaired may result in translocation-leading double strand breaks. A statistically significant correlation between translocation frequency and chromosome length, in terms of percentage of genome, has been noticed both in (basal) irradiation and in irradiation with ddThd inhibitor

  4. Effect of caffeine posttreatment on X-ray-induced chromosomal aberrations in human blood lymphocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, A T [Rijksuniversiteit Leiden (Netherlands). Dept. of Radiation Genetics and Chemical Mutagenesis; Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands)); Obe, G [Rijksuniversiteit Leiden (Netherlands). Dept. of Radiation Genetics and Chemical Mutagenesis; Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands); Freie Univ. Berlin (Germany, F.R.). Inst. fuer Genetik); Dulout, F N [Rijksuniversiteit Leiden (Netherlands). Dept. of Radiation Genetics and Chemical Mutagenesis; Instituto Multidisciplinario de Biologia Celular, La Plata (Argentinia))

    1980-01-01

    The potentiating effect of caffeine on X-ray-induced chromosomal aberrations in human blood lymphocytes has been investigated, with special reference to cell cycle stages (G0 and G2). Both quantitative and qualitative differences in the yield of chromosomal aberrations were detected in caffeine-posttreated cells, depending on the cell stage irradiated. The studies on caffeine potentiating effects on X-irradiated G0 lymphocytes from normal adults, newborns, Down syndrome patients, and an ataxia telangiectasia patient pointed to interindividual variations in the response to caffeine potentiation among normal probands and a very profound effect in ataxia cells.

  5. The effect of caffeine posttreatment on X-ray-induced chromosomal aberrations in human blood lymphocytes in vitro

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Obe, G.

    1980-01-01

    The potentiating effect of caffeine on X-ray-induced chromosomal aberrations in human blood lymphocytes has been investigated, with special reference to cell cycle stages (G0 and G2). Both quantitative and qualitative differences in the yield of chromosomal aberrations were detected in caffeine-posttreated cells, depending on the cell stage irradiated. The studies on caffeine potentiating effects on X-irradiated G0 lymphocytes from normal adults, newborns, Down syndrome patients, and an ataxia telangiectasia patient pointed to interindividual variations in the response to caffeine potentiation among normal probands and a very profound effect in ataxia cells. (orig.) [de

  6. Intergenic DNA sequences from the human X chromosome reveal high rates of global gene flow

    Directory of Open Access Journals (Sweden)

    Wall Jeffrey D

    2008-11-01

    Full Text Available Abstract Background Despite intensive efforts devoted to collecting human polymorphism data, little is known about the role of gene flow in the ancestry of human populations. This is partly because most analyses have applied one of two simple models of population structure, the island model or the splitting model, which make unrealistic biological assumptions. Results Here, we analyze 98-kb of DNA sequence from 20 independently evolving intergenic regions on the X chromosome in a sample of 90 humans from six globally diverse populations. We employ an isolation-with-migration (IM model, which assumes that populations split and subsequently exchange migrants, to independently estimate effective population sizes and migration rates. While the maximum effective size of modern humans is estimated at ~10,000, individual populations vary substantially in size, with African populations tending to be larger (2,300–9,000 than non-African populations (300–3,300. We estimate mean rates of bidirectional gene flow at 4.8 × 10-4/generation. Bidirectional migration rates are ~5-fold higher among non-African populations (1.5 × 10-3 than among African populations (2.7 × 10-4. Interestingly, because effective sizes and migration rates are inversely related in African and non-African populations, population migration rates are similar within Africa and Eurasia (e.g., global mean Nm = 2.4. Conclusion We conclude that gene flow has played an important role in structuring global human populations and that migration rates should be incorporated as critical parameters in models of human demography.

  7. The X chromosome in space.

    Science.gov (United States)

    Jégu, Teddy; Aeby, Eric; Lee, Jeannie T

    2017-06-01

    Extensive 3D folding is required to package a genome into the tiny nuclear space, and this packaging must be compatible with proper gene expression. Thus, in the well-hierarchized nucleus, chromosomes occupy discrete territories and adopt specific 3D organizational structures that facilitate interactions between regulatory elements for gene expression. The mammalian X chromosome exemplifies this structure-function relationship. Recent studies have shown that, upon X-chromosome inactivation, active and inactive X chromosomes localize to different subnuclear positions and adopt distinct chromosomal architectures that reflect their activity states. Here, we review the roles of long non-coding RNAs, chromosomal organizational structures and the subnuclear localization of chromosomes as they relate to X-linked gene expression.

  8. Report of the fifth international workshop on human X chromosome mapping

    Energy Technology Data Exchange (ETDEWEB)

    Willard, H.F.; Cremers, F.; Mandel, J.L.; Monaco, A.P.; Nelson, D.L.; Schlessinger, D.

    1994-12-31

    A high-quality integrated genetic and physical map of the X chromosome from telomere to telomere, based primarily on YACs formatted with probes and STSs, is increasingly close to reality. At the Fifth International X Chromosome Workshop, organized by A.M. Poustka and D. Schlessinger in Heidelberg, Germany, April 24--27, 1994, substantial progress was recorded on extension and refinement of the physical map, on the integration of genetic and cytogenetic data, on attempts to use the map to direct gene searches, and on nascent large-scale sequencing efforts. This report summarizes physical and genetic mapping information presented at the workshop and/or published since the reports of the fourth International X Chromosome Workshop. The principle aim of the workshop was to derive a consensus map of the chromosome, in terms of physical contigs emphasizing the location of genes and microsatellite markers. The resulting map is presented and updates previous versions. This report also updates the list of highly informative microsatellites. The text highlights the working state of the map, the genes known to reside on the X, and the progress toward integration of various types of data.

  9. Delayed cell death, giant cell formation and chromosome instability induced by X-irradiation in human embryo cells

    International Nuclear Information System (INIS)

    Roy, K.; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami

    1999-01-01

    We studied X-ray-induced delayed cell death, delayed giant cell formation and delayed chromosome aberrations in normal human embryo cells to explore the relationship between initial radiation damage and delayed effect appeared at 14 to 55 population doubling numbers (PDNs) after X-irradiation. The delayed effect was induced in the progeny of X-ray survivors in a dose-dependent manner and recovered with increasing PDNs after X-irradiation. Delayed plating for 24 h post-irradiation reduced both acute and delayed lethal damage, suggesting that potentially lethal damage repair (PLDR) can be effective for relieving the delayed cell death. The chromosome analysis revealed that most of the dicentrics (more than 90%) observed in the progeny of X-ray survivors were not accompanied with fragments, in contrast with those observed in the first mitosis after X-irradiation. The present results indicate that the potentiality of genetic instability is determined during the repair process of initial radiation damage and suggest that the mechanism for formation of delayed chromosome aberrations by radiation might be different from that of direct radiation-induced chromosome aberrations. (author)

  10. X-ray-induced breakage and rejoining of human interphase chromosomes

    International Nuclear Information System (INIS)

    Cornforth, M.N.; Bedford, J.S.

    1983-01-01

    A method was developed for the high-resolution measurement of breaks in prematurely condensed chromosomes at the G 1 phase of the cell cycle. The dose response for fragments (breaks) produced immediately after x-irradiation of confluent cultures of normal human cells was linear down to 10.9 rad (0.109 Gy) and extrapolated to zero effect at zero dose. The curve had a slope of 0.063 breaks per cell per rad, which is at least an order of magnitude greater than that for breaks scored in the same cells after they have progressed to mitosis following subculture. When incubated at 37 0 C half of the breaks disappeared in 2 hours. A slower, perhaps nonrejoining component was apparent at later incubation times. The initial rate of break rejoining was similar to the rate of increase in survival after incubation because of the repair of potentially lethal damage and is also in close agreement with recently reported values for the rejoining of double-strand breakage in DNA

  11. Sensitivity of human peripheral lymphocyte chromosomes to various X-ray doses and subsequent storage in Plexiglass or glass containers

    International Nuclear Information System (INIS)

    Ivanov, B.; Bulanova, M.; Geogieva, I.

    1979-01-01

    A study was performed to determine whether chromosomal aberrations produced in vitro by various X-ray doses in human lymphocytes were affected by post-irradiation storage of the blood in plastic or glass containers. Following X-ray doses of up to 400 R, the yields of cells with aberrations and the incidence of dicentrics, rings, interstitial deletions, symmetrical changes and chromosome fragments increased with dose. After storage of the irradiated lymphocytes in either Plexiglass or glass, the values for exchange aberrations, deletions and aberrant cells were compared. The only statistically significant difference was a slight increase in the percentage of aberrant cells stored in the plastic containers at the 400 R dose level. It was concluded that plastics appear to have a sensitizing effect on the genetic structure of the peripheral lymphocyte and thus the use of this material to store blood in biological dosimetry studies should be discouraged. (U.K.)

  12. Persistence of X-ray-induced chromosomal rearrangements in long-term cultures of human diploid fibroblasts

    International Nuclear Information System (INIS)

    Kano, Y.; Little, J.B.

    1984-01-01

    As part of a long-term study of mechanisms of human cell neoplastic transformation, the authors have examined the change in the frequencies of X-ray-induced chromosome rearrangements in density-inhibited human foreskin fibroblasts as a function of subculture time. In nonproliferating cells, the frequency of chromosomal aberrations declined within 24 to 48 hr but still remained at a relatively high level up to 43 days after irradiation. Aberrations disappeared rapidly, however, when the cells were allowed to proliferate, indicating that these lesions are lethal to dividing cells. The frequency of induced translocations, as determined by analysis of G-banded karyotypes, was dose dependent and remained stable up to 20 mean population doublings after irradiation. When subculture of density-inhibited cultures was delayed for 4 hr after irradiation (confluent holding), the frequency of chromosomal aberrations in the first mitosis declined, whereas the translocation frequencies at later passage were elevated as compared with cells subcultured immediately. This correlates with the reported increase in the frequency of transformation under similar conditions. These findings support the hypothesis that chromosomal rearrangements induced by DNA damage may be involved in the initiation of cancer

  13. A History of the Discovery of Random X Chromosome Inactivation in the Human Female and its Significance

    Directory of Open Access Journals (Sweden)

    Sophia Balderman

    2011-07-01

    Full Text Available Genetic determinants of sex in placental mammals developed by the evolution of primordial autosomes into the male and female sex chromosomes. The Y chromosome determines maleness by the action of the gene SRY, which encodes a protein that initiates a sequence of events prompting the embryonic gonads to develop into testes. The X chromosome in the absence of a Y chromosome results in a female by permitting the conversion of the embryonic gonads into ovaries. We trace the historical progress that resulted in the discovery that one X chromosome in the female is randomly inactivated in early embryogenesis, accomplishing approximate equivalency of X chromosome gene dosage in both sexes. This event results in half of the somatic cells in a tissue containing proteins encoded by the genes of the maternal X chromosome and half having proteins encoded by the genes of the paternal X chromosome, on average, accounting for the phenotype of a female heterozygote with an X chromosome mutation. The hypothesis of X chromosome inactivation as a random event early in embryogenesis was first described as a result of studies of variegated coat color in female mice. Similar results were found in women using the X chromosome-linked gene, glucose-6-phosphate dehydrogenase, studied in red cells. The random inactivation of the X chromosome-bearing genes for isoenzyme types A and B of glucose-6-phosphate dehydrogenase was used to establish the clonal origin of neoplasms in informative women with leiomyomas. Behind these discoveries are the stories of the men and women scientists whose research enlightened these aspects of X chromosome function and their implication for medicine.

  14. Aberrant patterns of X chromosome inactivation in a new line of human embryonic stem cells established in physiological oxygen concentrations.

    Science.gov (United States)

    de Oliveira Georges, Juliana Andrea; Vergani, Naja; Fonseca, Simone Aparecida Siqueira; Fraga, Ana Maria; de Mello, Joana Carvalho Moreira; Albuquerque, Maria Cecília R Maciel; Fujihara, Litsuko Shimabukuro; Pereira, Lygia Veiga

    2014-08-01

    One of the differences between murine and human embryonic stem cells (ESCs) is the epigenetic state of the X chromosomes in female lines. Murine ESCs (mESCs) present two transcriptionally active Xs that will undergo the dosage compensation process of XCI upon differentiation, whereas most human ESCs (hESCs) spontaneously inactivate one X while keeping their pluripotency. Whether this reflects differences in embryonic development of mice and humans, or distinct culture requirements for the two kinds of pluripotent cells is not known. Recently it has been shown that hESCs established in physiological oxygen levels are in a stable pre-XCI state equivalent to that of mESCs, suggesting that culture in low oxygen concentration is enough to preserve that epigenetic state of the X chromosomes. Here we describe the establishment of two new lines of hESCs under physiological oxygen level and the characterization of the XCI state in the 46,XX line BR-5. We show that a fraction of undifferentiated cells present XIST RNA accumulation and single H3K27me foci, characteristic of the inactive X. Moreover, analysis of allele specific gene expression suggests that pluripotent BR-5 cells present completely skewed XCI. Our data indicate that physiological levels of oxygen are not sufficient for the stabilization of the pre-XCI state in hESCs.

  15. Rejoining of x-ray induced chromosome breaks in human cells and its relationship to cellular repair

    International Nuclear Information System (INIS)

    Cornforth, M.N.

    1985-01-01

    A method was developed to improve the resolution for measuring breaks produced in interphase chromosomes by X-rays following the induction of premature chromosome condensation (PCC). It is based on the principle of 5-BrdU incorporation into the DNA of HeLa mitotic cells, which act as inducers of PCC when they are fused to diploid human fibroblasts. After a modified Fluorescence Plus Giemsa (FPG) protocol, the PCC stain intensely, while the mitotic inducer chromosomes stain faintly. The dose response for density inhibited (G 0 ) human cells was linear from 10.9 to 600 rad, with a slope of 0.06 breaks per cell per rad. Upon incubation at 37 0 C, half of the breaks disappeared in 2 hours. Following a dose of 600 rad the initial rate of break rejoining mirrored the rate of increase in survival from post-irradiation incubation, due to the repair of potentially lethal damage (PLD). The X-ray induced PCC rejoining characteristics from two ataxia telangiectasia (A-T) cell lines were compared to profiles obtained with normal cells. Both normal and A-T cells apparently sustained the same initial level of radiation damage, and both cell types rejoined breaks at the same rate. However, while normal cells eventually rejoined all but about 5% of the breaks produced by 600 rad, the A-T lines were left with 5-6 times the level of residual damage. These experiments demonstrate that progression of cells into S phase is not a necessary condition for the measured frequency of chromosome fragments observed in X-irradiated A-T cells

  16. Female human pluripotent stem cells rapidly lose X chromosome inactivation marks and progress to a skewed methylation pattern during culture.

    Science.gov (United States)

    Geens, M; Seriola, A; Barbé, L; Santalo, J; Veiga, A; Dée, K; Van Haute, L; Sermon, K; Spits, C

    2016-04-01

    Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation? We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapid loss of histone H3 lysine 27 trimethylation (H3K27me3) and long non-coding X-inactive specific transcript (XIST) expression during culture, often accompanied by erosion of XCI-specific methylation, and a frequent loss of random XCI in the cultures. Variable XCI patterns have been reported in female hPSC, not only between different hPSC lines, but also between sub-passages of the same cell line, however the reasons for this variability remain unknown. Moreover, while non-random XCI-linked DNA methylation patterns have been previously reported, their origin and extent have not been investigated. We investigated the XCI patterns in 23 human pluripotent stem cell (hPSC) lines, during long-term culture and after differentiation, by gene expression analysis, histone modification assessment and study of DNA methylation. The presence and location of H3K27me3 was studied by immunofluorescence, XIST expression by real-time PCR, and mono- or bi-allelic expression of X-linked genes was studied by sequencing of cDNA. XCI-specific DNA methylation was analysed using methylation-sensitive restriction and PCR, and more in depth by massive parallel bisulphite sequencing. All hPSC lines showed XCI, but we found a rapid loss of XCI marks during the early stages of in vitro culture. While this loss of XCI marks was accompanied in several cases by an extensive erosion of XCI-specific methylation, it did not result in X chromosome reactivation. Moreover, lines without strong erosion of methylation frequently displayed non-random DNA methylation, which occurred independently from the loss of XCI marks. This bias in X chromosome DNA methylation did not appear as a passenger event driven by clonal culture

  17. Micromechanics of human mitotic chromosomes

    International Nuclear Information System (INIS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F

    2011-01-01

    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

  18. Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation

    International Nuclear Information System (INIS)

    Purrott, R.J.; Reeder, E.

    1976-01-01

    Unstimulated (G 0 ) human peripheral blood lymphocytes were exposed at 37degC to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the expected additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yield originally reported by Lane. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls

  19. Selfish X chromosomes and speciation.

    Science.gov (United States)

    Patten, Manus M

    2017-12-27

    In two papers published at about the same time almost thirty years ago, Frank (Evolution, 45, 1991a, 262) and Hurst and Pomiankowski (Genetics, 128, 1991, 841) independently suggested that divergence of meiotic drive systems-comprising genes that cheat meiosis and genes that suppress this cheating-might provide a general explanation for Haldane's rule and the large X-effect in interspecific hybrids. Although at the time, the idea was met with skepticism and a conspicuous absence of empirical support, the tide has since turned. Some of the clearest mechanistic explanations we have for hybrid male sterility involve meiotic drive systems, and several other cases of hybrid sterility are suggestive of a role for meiotic drive. In this article, I review these ideas and their descendants and catalog the current evidence for the meiotic drive model of speciation. In addition, I suggest that meiotic drive is not the only intragenomic conflict to involve the X chromosome and contribute to hybrid incompatibility. Sexually and parentally antagonistic selection pressures can also pit the X chromosome and autosomes against each other. The resulting intragenomic conflicts should lead to co-evolution within populations and divergence between them, thus increasing the likelihood of incompatibilities in hybrids. I provide a sketch of these ideas and interpret some empirical patterns in the light of these additional X-autosome conflicts. © 2017 John Wiley & Sons Ltd.

  20. Kinetics of the formation of chromosome aberrations in x-irradiated human lymphocytes: Analysis by premature chromosome condensation with delayed fusion

    International Nuclear Information System (INIS)

    Greinert, R.; Detzler, E.; Volkmer, B.

    1995-01-01

    Human lymphocytes irradiated with graded doses of up to 5 Gy of 150 kV X rays were fused with mitotic CHO cells after delay times ranging from 0 to 14 h after irradiation. The yields of dicentrics seen under PCC conditions, using C-banding for centromere detection, and of excess acentric fragments observed in the PCC experiment were determined by image analysis. At 4 Gy the time course of the yield of dicentrics shows an early plateau for delay times up to 2 h, then an S-shaped rise and a final plateau which is reached after a delay time of about 8 to 10 h. Whereas the dose-yield curve measured at zero delay time is strictly linear, the shape of the curve obtained for 8 h delay time is linear-quadratic. The linear yield component, αD is formed entirely in the fast process manifested in the early plateau, while component βD 2 is developed slowly in the subsequent hours. Analysis of the kinetics of the rise of the S-shaped curve for yield as a function of time leads to the postulate of an open-quotes intermediate productclose quotes of pairwise DNA lesion interaction, still fragile when subjected to the stress of PCC, but gradually processed into a stable dicentric chromosome. It is concluded that the observed difference in the kinetics of the α and β components explains a number of earlier results, especially the disappearance of the β component at high LET, and opens possibilities for chemical and physical modification of the β component during the extended formation process after irradiation observed here. 22 refs., 4 figs

  1. Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes: analysis by premature chromosome condensation with delayed fusion.

    Science.gov (United States)

    Greinert, R; Detzler, E; Volkmer, B; Harder, D

    1995-11-01

    Human lymphocytes irradiated with graded doses of up to 5 Gy of 150 kV X rays were fused with mitotic CHO cells after delay times ranging from 0 to 14 h after irradiation. The yields of dicentrics seen under PCC conditions, using C-banding for centromere detection, and of excess acentric fragments observed in the PCC experiment were determined by image analysis. At 4 Gy the time course of the yield of dicentrics shows an early plateau for delay times up to 2 h, then an S-shaped rise and a final plateau which is reached after a delay time of about 8 to 10 h. Whereas the dose-yield curve measured at zero delay time is strictly linear, the shape of the curve obtained for 8 h delay time is linear-quadratic. The linear yield component, alpha D, is formed entirely in the fast process manifested in the early plateau, while component beta D2 is developed slowly in the subsequent hours. Analysis of the kinetics of the rise of the S-shaped curve for yield as a function of time leads to the postulate of an "intermediate product" of pairwise DNA lesion interaction, still fragile when subjected to the stress of PCC, but gradually processed into a stable dicentric chromosome. It is concluded that the observed difference in the kinetics of the alpha and beta components explains a number of earlier results, especially the disappearance of the beta component at high LET, and opens possibilities for chemical and physical modification of the beta component during the extended formation process after irradiation observed here.

  2. Generation of an approximately 2.4 Mb human X centromere-based minichromosome by targeted telomere-associated chromosome fragmentation in DT40.

    Science.gov (United States)

    Mills, W; Critcher, R; Lee, C; Farr, C J

    1999-05-01

    A linear mammalian artificial chromosome (MAC) will require at least three types of functional element: a centromere, two telomeres and origins of replication. As yet, our understanding of these elements, as well as many other aspects of structure and organization which may be critical for a fully functional mammalian chromosome, remains poor. As a way of defining these various requirements, minichromosome reagents are being developed and analysed. Approaches for minichromosome generation fall into two broad categories: de novo assembly from candidate DNA sequences, or the fragmentation of an existing chromosome to reduce it to a minimal size. Here we describe the generation of a human minichromosome using the latter, top-down, approach. A human X chromosome, present in a DT40-human microcell hybrid, has been manipulated using homologous recombination and the targeted seeding of a de novo telomere. This strategy has generated a linear approximately 2.4 Mb human X centromere-based minichromosome capped by two artificially seeded telomeres: one immediately flanking the centromeric alpha-satellite DNA and the other targeted to the zinc finger gene ZXDA in Xp11.21. The chromosome retains an alpha-satellite domain of approximately 1. 8 Mb, a small array of gamma-satellite repeat ( approximately 40 kb) and approximately 400 kb of Xp proximal DNA sequence. The mitotic stability of this minichromosome has been examined, both in DT40 and following transfer into hamster and human cell lines. In all three backgrounds, the minichromosome is retained efficiently, but in the human and hamster microcell hybrids its copy number is poorly regulated. This approach of engineering well-defined chromosome reagents will allow key questions in MAC development (such as whether a lower size limit exists) to be addressed. In addition, the 2.4 Mb minichromosome described here has potential to be developed as a vector for gene delivery.

  3. Radiation hybrid mapping of human chromosome 18

    International Nuclear Information System (INIS)

    Francke, U.; Moon, A.J.; Chang, E.; Foellmer, B.; Strauss, B.; Haschke, A.; Chihlin Hsieh; Geigl, E.M.; Welch, S.

    1990-01-01

    The authors have generated a Chinese hamster V79/380-6 HPRT minus x human leukocyte hybrid cell line (18/V79) with chromosome 18 as the only human chromosome that is retained at high frequency without specific selection. Hybrid cells were selected in HAT medium, and 164 individual colonies were isolated. Of 110 colonies screened for human DNA by PCR amplification using a primer specific for human Alu repeats 67 (61%) were positive. These were expanded in culture for large-scale DNA preparations. Retesting expanded clones by PCR with Alu and LINE primers has revealed unique patterns of amplification products. In situ hybridization of biotin labelled total human DNA to metaphase spreads from various hybrids revealed the presence of one or more human DNA fragments integrated in hamster chromosomes. The authors have generated a resource that should allow the construction of a radiation map, to be compared with the YAC contig map also under construction in their laboratory

  4. Statistics for X-chromosome associations.

    Science.gov (United States)

    Özbek, Umut; Lin, Hui-Min; Lin, Yan; Weeks, Daniel E; Chen, Wei; Shaffer, John R; Purcell, Shaun M; Feingold, Eleanor

    2018-06-13

    In a genome-wide association study (GWAS), association between genotype and phenotype at autosomal loci is generally tested by regression models. However, X-chromosome data are often excluded from published analyses of autosomes because of the difference between males and females in number of X chromosomes. Failure to analyze X-chromosome data at all is obviously less than ideal, and can lead to missed discoveries. Even when X-chromosome data are included, they are often analyzed with suboptimal statistics. Several mathematically sensible statistics for X-chromosome association have been proposed. The optimality of these statistics, however, is based on very specific simple genetic models. In addition, while previous simulation studies of these statistics have been informative, they have focused on single-marker tests and have not considered the types of error that occur even under the null hypothesis when the entire X chromosome is scanned. In this study, we comprehensively tested several X-chromosome association statistics using simulation studies that include the entire chromosome. We also considered a wide range of trait models for sex differences and phenotypic effects of X inactivation. We found that models that do not incorporate a sex effect can have large type I error in some cases. We also found that many of the best statistics perform well even when there are modest deviations, such as trait variance differences between the sexes or small sex differences in allele frequencies, from assumptions. © 2018 WILEY PERIODICALS, INC.

  5. Chromosomes and irradiation: in vitro study of the action of X-rays on human lymphocytes; Chromosomes et radiations: etude in vitro de l'action des rayons X sur les lymphocytes humains

    Energy Technology Data Exchange (ETDEWEB)

    Mouriquand, C; Patet, J; Gilly, C; Wolff, C

    1966-07-01

    Radioinduced chromosomal aberrations were studied in vitro on leukocytes of human peripheral blood after x irradiation at 25, 50, 100, 200, and 300 R. The numeric and structural anomalies were examined on 600 karyotypes. The relationship between these disorders and the dose delivered to the blood are discussed. An explanation on their mechanism of formation is tentatively given. (authors) [French] L'etude in vitro des anomalies chromosomiques radioinduites a ete pratiquee sur des leucocytes de sang peripherique preleve chez 4 sujets et irradie aux doses de 25, 50, 100, 200, 300 R. Les aberrations numeriques et structurales ont ete examinees sur 600 caryotypes. Les rapports entre ces anomalies et les doses appliquees sont etudies. Une hypothese sur leur mecanisme de formation est avancee. (auteurs)

  6. Comment of the paper 'Chromosome aberrations induced by low doses of X-rays in human lymphocytes in vitro'

    International Nuclear Information System (INIS)

    Merkle, W.; Paretzke, H.G.

    1981-01-01

    This comment points out some problems in the statistical evaluation of the data of Ziemba-Zoltowska, E. Bocian, O. Rosiek and J. Sablinski (1980) on chromosome aberrations in irradiated human lymphocytes; comments are made on results derived from a an iteratively reweighted least squares procedure instead of the ordinary unweighted least squares method to establish first and second order dose-response curves for dicentric and centric rings. (U.K.)

  7. Detailed ordering of markers localizing to the Xq26-Xqter region of the human X chromosome by the use of an interspecific Mus spretus mouse cross

    International Nuclear Information System (INIS)

    Avner, P.; Amar, L.; Arnaud, D.; Hanauer, A.; Cambrou, J.

    1987-01-01

    Five probes localizing to the Xq26-Xqter region of the human X chromosome have been genetically mapped on the mouse X chromosome using an interspecific cross involving Mus spretus to a contiguous region lying proximally to the Tabby (Ta) locus. Pedigree and recombinational analysis establish the marker order as being Hprt-FIX-c11-G6PD-St14-1. The size of this contiguous region is such that the X-linked muscular dystrophy (mdx) mouse mutation probably maps within this segment. This in turn suggests that it is highly improbable that the mouse mdx locus represents a model for Duchenne muscular dystrophy (DMD). It is, however, compatible with the idea that this mutation may correspond in man to Emery Dreifuss muscular dystrophy. The high frequency of restriction fragment length polymorphisms found in this interspecific system for all the human cross-reacting probes examined up until now, using only a limited number of restriction enzymes, suggests that the Mus spretus mapping system may be of great potential value for establishing the linkage relationships existing in man when conserved chromosomal regions are concerned and human/mouse cross-reacting probes are available or can be obtained

  8. Evaluation of rate of unstable chromosomal changes in human blood irradiated by X-rays: establishment of dose-response curve

    International Nuclear Information System (INIS)

    Mendonça, J.C.G.; Mendes, M.E.; Melo, A.M.M.A.; Silva, L.M.; Andrade, A.M.G.; Hwang, S.F.; Lima, F.F.

    2017-01-01

    Since the discovery of ionizing radiation, and consequently of its properties, there has been an increasing in its use, which in turn has raised concerns about the biological damage that it could cause in exposed individuals. As a result, cytogenetic dosimetry has emerged: a method that can be used as a complement or, in the absence of physical dosimetry, relating the frequency of chromosomal changes found in the blood of the exposed individual and the dose absorbed through dose-response calibration curves. This work aimed to verify the frequencies of the unstable chromosomal changes in human blood lymphocytes irradiated by X-rays of 250 kVp with different absorbed doses and later establish the dose-response calibration curves. The irradiation was performed at the CRCN-NE/CNEN-PE, Brazil metrology service on a PANTAK X-ray machine, model HF 320. The blood samples had their lymphocytes cultured in culture media and, after the processing, the metaphases were obtained. The chromosomal alterations analyzed were chromosomes dicentric, ring and isolated actinic fragments. There was an increase in frequencies of all chromosomal changes with increased absorbed dose. The calibration curves of dicentric and dicentric + rings presented good adjustments with the values of the coefficients Y = 0.0013 + 0.0271D + 0.0556D 2 (X 2 = 10.36 / GL = 6) and Y = 0.0013 + 0.0263D + 0.0640D 2 (X 2 = 7.43 / GL = 6), respectively. The establishment of these curves enables the Laboratory of Biological Dosimetry of the CRCN/NE/CNEN-PE to estimate the dose absorbed by occupationally exposed individuals and in cases of radiological accidents

  9. X-chromosome inactivation and escape

    Indian Academy of Sciences (India)

    2015-11-06

    Nov 6, 2015 ... tion and cancer in mice after a long period of time (Yildirim et al. 2013). ... chromosome of man has a short pairing seg- ment, that is not normally ..... Lyon M. F. 1988 The William Allan memorial award address: X-chromosome ...

  10. 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.

  11. 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.

  12. 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 - others: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

  13. Human X-chromosome inactivation pattern distributions fit a model of genetically influenced choice better than models of completely random choice

    Science.gov (United States)

    Renault, Nisa K E; Pritchett, Sonja M; Howell, Robin E; Greer, Wenda L; Sapienza, Carmen; Ørstavik, Karen Helene; Hamilton, David C

    2013-01-01

    In eutherian mammals, one X-chromosome in every XX somatic cell is transcriptionally silenced through the process of X-chromosome inactivation (XCI). Females are thus functional mosaics, where some cells express genes from the paternal X, and the others from the maternal X. The relative abundance of the two cell populations (X-inactivation pattern, XIP) can have significant medical implications for some females. In mice, the ‘choice' of which X to inactivate, maternal or paternal, in each cell of the early embryo is genetically influenced. In humans, the timing of XCI choice and whether choice occurs completely randomly or under a genetic influence is debated. Here, we explore these questions by analysing the distribution of XIPs in large populations of normal females. Models were generated to predict XIP distributions resulting from completely random or genetically influenced choice. Each model describes the discrete primary distribution at the onset of XCI, and the continuous secondary distribution accounting for changes to the XIP as a result of development and ageing. Statistical methods are used to compare models with empirical data from Danish and Utah populations. A rigorous data treatment strategy maximises information content and allows for unbiased use of unphased XIP data. The Anderson–Darling goodness-of-fit statistics and likelihood ratio tests indicate that a model of genetically influenced XCI choice better fits the empirical data than models of completely random choice. PMID:23652377

  14. Replication of chromosomal and episomal DNA in X-ray-damaged human cells: A cis- or trans-acting mechanism

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Rose, R.; Mitchell, D.L.

    1990-01-01

    Episomal plasmids and viruses in mammalian cells present small targets for X-ray-induced DNA damage. At doses up to 100 Gy, DNA strand breaks or endonuclease III-sensitive sites were not discernible in 10.3-kb Epstein-Barr virus-based plasmid DNA or in 4.9-kb defective simian virus 40 DNA. DNA replication in these small molecules, however, was inhibited strongly by X-ray doses of greater than or equal to 20 Gy, decreasing to only 20 to 40% of control values. Inhibition was relieved slightly by growth in caffeine but was increased by growth in 3-aminobenzamide. Inhibition of DNA replication in episomal DNA molecules that are too small to sustain significant damage directly to their DNA may be due to either (a) a trans-acting diffusible factor that transfers the consequences of DNA breakage to episomes and to other replicating molecules, (b) a cis-acting mechanism in which episomes are structurally linked to genomic chromatin, and replication of both episomal and chromosomal replicons is under common control, or (c) radiation damage on other cellular structures unrelated to DNA. The resolution of these cellular mechanisms may shed light on the X-ray-resistant replication in ataxia-telangiectasia and may suggest strategies for molecular characterization of potential trans- or cis-acting factors

  15. [Architecture of the X chromosome, expression of LIM kinase 1, and recombination in the agnostic mutants of Drosophila: a model of human Williams syndrome].

    Science.gov (United States)

    Savvateeva-Popova, E V; Peresleni, A I; Sharagina, L M; Medvedeva, A V; Korochkina, S E; Grigor'eva, I V; Diuzhikova, N A; Popov, A V; Baricheva, E M; Karagodin, D; Heisenberg, M

    2004-06-01

    As the Human Genome and Drosophila Genome Projects were completed, it became clear that functions of human disease-associated genes may be elucidated by studying the phenotypic expression of mutations affecting their structural or functional homologs in Drosophila. Genomic diseases were identified as a new class of human disorders. Their cause is recombination, which takes place at gene-flanking duplicons to generate chromosome aberrations such as deletions, duplications, inversions, and translocations. The resulting imbalance of the dosage of developmentally important genes arises at a frequency of 10(-3) (higher than the mutation rate of individual genes) and leads to syndromes with multiple manifestations, including cognitive defects. Genomic DNA fragments were cloned from the Drosophila melanogaster agnostic locus, whose mutations impair learning ability and memory. As a result, the locus was exactly localized in X-chromosome region 11A containing the LIM kinase 1 (LIMK1) gene (CG1848), which is conserved among many species. Hemizygosity for the LIMK1 gene, which is caused by recombination at neighboring extended repeats, underlies cognitive disorders in human Williams syndrome. LIMK1 is a component of the integrin signaling cascade, which regulates the functions of the actin cytoskeleton, synaptogenesis, and morphogenesis in the developing brain. Immunofluorescence analysis revealed LIMK1 in all subdomains of the central complex and the visual system of Drosophila melanogaster. Like in the human genome, the D. melanogaster region is flanked by numerous repeats, which were detected by molecular genetic methods and analysis of ectopic chromosome pairing. The repeats determined a higher rate of spontaneous and induced recombination. including unequal crossing over, in the agnostic gene region. Hence, the agnostic locus was considered as the first D. melanogaster model suitable for studying the genetic defect associated with Williams syndrome in human.

  16. X-linked gene expression and X-chromosome inactivation: marsupials, mouse, and man compared.

    Science.gov (United States)

    VandeBerg, J L; Robinson, E S; Samollow, P B; Johnston, P G

    1987-01-01

    The existence of paternal X inactivation in Australian and American marsupial species suggests that this feature of X-chromosome dosage compensation is not a recent adaptation, but probably predates the evolutionary separation of the Australian and American marsupial lineages. Although it is theoretically possible that the marsupial system is one of random X inactivation with p greater than 0.99 and q less than 0.01 and dependent on parental source, no instance of random X inactivation (p = q or p not equal to q) has ever been verified in any tissue or cell type of any marsupial species. Therefore, we conclude that the most fundamental difference in X inactivation of marsupials and eutherians is whether the inactive X is the paternal one or is determined at random (with p = q in most but not all cases). The only other unequivocal difference between eutherians and marsupials is that both X chromosomes are active in mice and human oocytes, but not in kangaroo oocytes. Apparently, the inactive X is reactivated at a later meiotic stage or during early embryogenesis in kangaroos. X-chromosome inactivation takes place early in embryogenesis of eutherians and marsupials. Extraembryonic membranes of mice exhibit paternal X inactivation, whereas those of humans seem to exhibit random X inactivation with p greater than q (i.e., preferential paternal X inactivation). In general, extraembryonic membranes of marsupial exhibit paternal X inactivation, but the Gpd locus is active on both X chromosomes in at least some cells of kangaroo yolk sac. It is difficult to draw any general conclusion because of major differences in embryogeny of mice, humans, and marsupials, and uncertainties in interpreting the data from humans. Other differences between marsupials and eutherians in patterns of X-linked gene expression and X-chromosome inactivation seem to be quantitative rather than qualitative. Partial expression of some genes on the inactive X is characteristic of marsupials, with

  17. Molecular mapping of chromosomes 17 and X

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

    Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition of new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping clones from a larger genome.

  18. MECHANISMS IN ENDOCRINOLOGY: Aberrations of the X chromosome as cause of male infertility.

    Science.gov (United States)

    Röpke, Albrecht; Tüttelmann, Frank

    2017-11-01

    Male infertility is most commonly caused by spermatogenetic failure, clinically noted as oligo- or a-zoospermia. Today, in approximately 20% of azoospermic patients, a causal genetic defect can be identified. The most frequent genetic causes of azoospermia (or severe oligozoospermia) are Klinefelter syndrome (47,XXY), structural chromosomal abnormalities and Y-chromosomal microdeletions. Consistent with Ohno's law, the human X chromosome is the most stable of all the chromosomes, but contrary to Ohno's law, the X chromosome is loaded with regions of acquired, rapidly evolving genes, which are of special interest because they are predominantly expressed in the testis. Therefore, it is not surprising that the X chromosome, considered as the female counterpart of the male-associated Y chromosome, may actually play an essential role in male infertility and sperm production. This is supported by the recent description of a significantly increased copy number variation (CNV) burden on both sex chromosomes in infertile men and point mutations in X-chromosomal genes responsible for male infertility. Thus, the X chromosome seems to be frequently affected in infertile male patients. Four principal X-chromosomal aberrations have been identified so far: (1) aneuploidy of the X chromosome as found in Klinefelter syndrome (47,XXY or mosaicism for additional X chromosomes). (2) Translocations involving the X chromosome, e.g. nonsyndromic 46,XX testicular disorders of sex development (XX-male syndrome) or X-autosome translocations. (3) CNVs affecting the X chromosome. (4) Point mutations disrupting X-chromosomal genes. All these are reviewed herein and assessed concerning their importance for the clinical routine diagnostic workup of the infertile male as well as their potential to shape research on spermatogenic failure in the next years. © 2017 European Society of Endocrinology.

  19. Effects of inhibitors of DNA repair on the frequencies of chromosomal aberrations induced by x-rays or alkylating agents in cultured human lymphocytes

    International Nuclear Information System (INIS)

    Kihlman, B.A.; Andersson, H.C.

    1986-01-01

    In the first part of this presentation the authors give examples of the synergistic enhancements that are obtained with various inhibitor combinations in G/sub 2/. The second part of the presentation deals with the effects of two agents, also well known for their capacity to potentiate the frequency of chromosomal aberrations induced by physical and chemical agents, but with a different mechanism of action. These agents are caffeine and 3-aminobenzamide (3AB). Caffeine has for decades been used as an inhibitor of DNA repair although its mechanism of action has not been fully understood. 3AB has more recently come into focus as an efficient inhibitor of the synthesis of poly-(ADP-ribose), a substance believed to be of importance in connection with the repair of certain types of DNA damage. The results presented do not quite fit in with the general idea about the mode of action of these agents. All experiments were carried out with whole-blood cultures of human lymphocytes. When inhibitors were used as post-treatments, chromosomal aberrations were induced by X-rays or by the alkylating agents thiotepa (TT) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). X-rays were generated by a Siemens Stabilipan 200 apparatus, at a dose rate of 0.5 Gy/min. The tube (TR 200f) was operated at 180 kV, 10 mA and the radiation filtered through 4 mm Al

  20. Molecular nature of X-ray-induced mutations compared with that of spontaneous ones in human c-hprt gene integrated into mammalian chromosomal DNA

    International Nuclear Information System (INIS)

    Kimura, Hiroshi; Kato, Takesi.

    1992-01-01

    X-ray-induced mutations were analysed at molecular levels in comparison with spontaneous mutations. Altered sequences were determined tentatively of 30 independent X-ray-induced mutations in a cDNA of the human hprt gene which was integrated into mammalian chromosome as a part of a shuttle vector. Mutations consisted of base substitutions (37 %), frameshifts (27 %), deletions (27 %) and others (10 %). All these mutational events were distributed randomly over the gene without there being hot spots. The spectrum and distribution of X-ray-induced mutations resembled those of spontaneous mutations. Among base substitutions, transversions were predominant and base substitution mutations occurred more at A:T sites than at G:C sites, which is also the case in spontaneous mutations. Most of the frameshift and deletion mutations induced by X-rays, as well as those spontaneously arising, were characterized by the existence of short direct repeats of several identical bases in a row at the sites of the mutations. A slippage misalignment mechanism in replication well accounts for the generation of these classes of mutations. Judging from the data accumulated so far, it can be concluded that X-ray-induced mutations at molecular levels are similar to those spontaneously occurring. (author)

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

    DEFF Research Database (Denmark)

    Machiela, Mitchell J; Zhou, Weiyin; Karlins, Eric

    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-chrom...

  2. X-Chromosomal short tandem repeat loci in the Turkish population ...

    African Journals Online (AJOL)

    In this study, we aimed to demonstrate the importance and utility of polymorphic short tandem repeat (STR) found on the human X chromosome and to provide the first allelic frequency data of X-STR (X chromosomal) loci in the Turkish population. Blood samples were taken from unrelated individuals (135 males and 129 ...

  3. 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

  4. Monoamine oxidase deficiency in males with an X chromosome deletion.

    Science.gov (United States)

    Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G

    1989-01-01

    Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

  5. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  6. Influence of X chromosome and hormones on human brain development: a magnetic resonance imaging and proton magnetic resonance spectroscopy study of Turner syndrome

    NARCIS (Netherlands)

    Cutter, William J.; Daly, Eileen M.; Robertson, Dene M. W.; Chitnis, Xavier A.; van Amelsvoort, Therese A. M. J.; Simmons, Andrew; Ng, Virginia W. K.; Williams, Benjamin S.; Shaw, Phillip; Conway, Gerard S.; Skuse, David H.; Collier, David A.; Craig, Michael; Murphy, Declan G. M.

    2006-01-01

    Women with Turner syndrome (TS; 45,X) lack a normal second X chromosome, and many are prescribed exogenous sex and growth hormones (GH). Hence, they allow us an opportunity to investigate genetic and endocrine influences on brain development. We examined brain anatomy and metabolism in 27 adult

  7. Generation of a panel of somatic cell hybrids containing unselected fragments of human chromosome 10 by X-ray irradiation and cell fusion: Application to isolating the MEN2A region in hybrid cells

    International Nuclear Information System (INIS)

    Goodfellow, P.J.; Povey, S.; Nevanlinna, H.A.; Goodfellow, P.N.

    1990-01-01

    We have used X-ray irradiation and cell fusion to generate somatic cell hybrids containing fragments of human chromosome 10. Our experiments were directed towards isolating the region of the MEN2A gene in hybrids and to use those as the source of DNA for cloning and mapping new markers from near the MEN2A locus. A number of hybrid clones containing human sequences that are tightly linked to the MEN2A gene were identified. Some 25% of our hybrids, however, proved to contain more than one human chromosome 10-derived fragment or showed evidence of deletions and/or rearrangements. A detailed analysis of the human content of X-ray irradiation hybrids is required to assess the integrity and number of human fragments retained. Despite retention of multiple human-derived fragments, these hybrids will prove useful as cloning and mapping resources

  8. Human oocyte chromosome analyses need a standardized ...

    Indian Academy of Sciences (India)

    Studies of DNA polymorphisms in human trisomic abor- tions and liveborn have ... Keywords. human oocyte chromosomes; cytogenetic analysis; aneuploidy; nondisjunction; predivision. Journal of .... oocytes and giant embryos. Hum. Reprod.

  9. The study of human Y chromosome variation through ancient DNA.

    Science.gov (United States)

    Kivisild, Toomas

    2017-05-01

    High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

  10. Comparative study of dose-response curve for chromosome aberrations induced in human lymphocytes by {sup 60}Co and X-Rays

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Mendonça, Julyanne C.G.; Andrade, Aida M.G.; Silva, Laís M.; Hwang, Suy; Melo, Ana M.M.A.; Santos, Neide; Lima, Fabiana F., E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2017-11-01

    Biodosimetry represents a biological marker to the estimation of health risks after accidental overexposure to ionizing radiation. Chromosomal dicentric in peripheral blood lymphocytes have been the most reliable biomarker of exposure to IR during the last several decades. This technique could be used to support physical dosimetry or when it is impossible to achieve it. A reliable measurement of the absorbed dose is critical for medical decision, including the assessment of long-term health consequences. The aim of this research is to compare dose-response curves for dicentric aberration induced in human lymphocytes by {sup 60}Co and X-Rays. For both quality of radiation, the samples were exposed to at least eight different absorbed doses. The X-rays with dose rate of 0,275 Gy/min at Laboratory of Metrology (CRCN/NE - PE - Brazil) and the second one was exposed to cobalt source with dose rate of 0.055 Gy/min ({sup 60}Co Gammacell 220) located at Department of Nuclear Energy (UFPE-DEN-BRASIL). Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. The frequencies of dicentrics were counted in more than 18.000 metaphases for this comparison. After that, all frequencies and distributions of dicentrics were tested to analyze their conformity with Poisson distribution and then each quality of radiation were used for build the calibration curves using Dose Estimate program. These results showed that both curves followed the Poisson distribution and coefficients of each one are: YX-rays = 0,0013 (± 0,0006) + 0,0271 (± 0,0086)⁎D + 0,0556(±0,0050))⁎D{sup 2} and Y{sub Co-60} = 0,0014 (± 0,0010) + 0,0081 (± 0,0073))⁎D + 0,0451 (± 0,0046))⁎D{sup 2} (Y = frequency of dicentrics and D = absorbed dose). It was expected that there was no significant difference between this two types of radiation because both were low LET. We believed that dose rate have been a principal factor to produce this

  11. Chromosomal aberrations in children exposed to diagnostic x-rays

    International Nuclear Information System (INIS)

    Nordenson, I.; Beckman, G.; Beckman, L.; Lemperg, R.

    1980-01-01

    Among children who have received high x-ray doses congenital dislocation of the hip joint is the predominating diagnosis. In a series of 9 children who had received high x-ray doses (8 with luxation of the hip joint and one with achondroplasia) a significant increase of chromosomal aberrations was found. The increase concerned mainly chromosome type aberrations. The shorter the time since the last x-ray investigation the higher was the frequency of chromosome type aberrations. (author)

  12. X1X1X2X2/X1X2Y sex chromosome systems in the Neotropical Gymnotiformes electric fish of the genus Brachyhypopomus

    Directory of Open Access Journals (Sweden)

    Adauto Lima Cardoso

    2015-06-01

    Full Text Available Several types of sex chromosome systems have been recorded among Gymnotiformes, including male and female heterogamety, simple and multiple sex chromosomes, and different mechanisms of origin and evolution. The X1X1X2X2/X1X2Y systems identified in three species of this order are considered homoplasic for the group. In the genus Brachyhypopomus, only B. gauderio presented this type of system. Herein we describe the karyotypes of Brachyhypopomus pinnicaudatus and B. n. sp. FLAV, which have an X1X1X2X2/X1X2Y sex chromosome system that evolved via fusion between an autosome and the Y chromosome. The morphology of the chromosomes and the meiotic pairing suggest that the sex chromosomes of B. gauderio and B. pinnicaudatus have a common origin, whereas in B . n. sp. FLAV the sex chromosome system evolved independently. However, we cannot discard the possibility of common origin followed by distinct processes of differentiation. The identification of two new karyotypes with an X1X1X2X2/X1X2Y sex chromosome system in Gymnotiformes makes it the most common among the karyotyped species of the group. Comparisons of these karyotypes and the evolutionary history of the taxa indicate independent origins for their sex chromosomes systems. The recurrent emergence of the X1X1X2X2/X1X2Y system may represent sex chromosomes turnover events in Gymnotiformes.

  13. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content

    NARCIS (Netherlands)

    Hughes, Jennifer F.; Skaletsky, Helen; Pyntikova, Tatyana; Graves, Tina A.; van Daalen, Saskia K. M.; Minx, Patrick J.; Fulton, Robert S.; McGrath, Sean D.; Locke, Devin P.; Friedman, Cynthia; Trask, Barbara J.; Mardis, Elaine R.; Warren, Wesley C.; Repping, Sjoerd; Rozen, Steve; Wilson, Richard K.; Page, David C.

    2010-01-01

    The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome(1,2). Little is known about the recent evolution of the Y chromosome because only

  14. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis.

    Science.gov (United States)

    Phillips, Carolyn M; Wong, Chihunt; Bhalla, Needhi; Carlton, Peter M; Weiser, Pinky; Meneely, Philip M; Dernburg, Abby F

    2005-12-16

    The him-8 gene is essential for proper meiotic segregation of the X chromosomes in C. elegans. Here we show that loss of him-8 function causes profound X chromosome-specific defects in homolog pairing and synapsis. him-8 encodes a C2H2 zinc-finger protein that is expressed during meiosis and concentrates at a site on the X chromosome known as the meiotic pairing center (PC). A role for HIM-8 in PC function is supported by genetic interactions between PC lesions and him-8 mutations. HIM-8 bound chromosome sites associate with the nuclear envelope (NE) throughout meiotic prophase. Surprisingly, a point mutation in him-8 that retains both chromosome binding and NE localization fails to stabilize pairing or promote synapsis. These observations indicate that stabilization of homolog pairing is an active process in which the tethering of chromosome sites to the NE may be necessary but is not sufficient.

  15. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis

    International Nuclear Information System (INIS)

    Phillips, Carolyn M.; Wong, Chihunt; Bhalla, Needhi; Carlton, Peter M.; Weiser, Pinky; Meneely, Philip M.; Dernburg, Abby F.

    2005-01-01

    The him-8 gene is essential for proper meiotic segregation of the X chromosomes in C. elegans. Here we show that loss of him-8 function causes profound X-chromosome-specific defects in homolog pairing and synapsis.him-8 encodes a C2H2 zinc finger protein that is expressed during meiosis and concentrates at a site on the X chromosome known as themeiotic Pairing Center (PC). A role for HIM-8 in PC function is supported by genetic interactions between PC lesions and him-8 mutations. HIM-8-bound chromosome sites associate with the nuclear envelope (NE)throughout meiotic prophase. Surprisingly, a point mutation in him-8 that retains both chromosome binding and NE localization fails to stabilize pairing or promote synapsis. These observations indicate that stabilization of homolog pairing is an active process in which the tethering of chromosome sites to the NE may be necessary but is not sufficient

  16. Effect of post-treatments with caffeine during G2 on the frequencies of chromosome-type aberrations produced by X-rays in human lymphocytes during G0 and G1

    International Nuclear Information System (INIS)

    Tanzarella, C.; De Salvia, R.; Degrassi, F.; Palitti, F.; Andersson, H.C.; Hansson, K.; Kihlman, B.A.

    1986-01-01

    Human lymphocytes were irradiated with X-rays in G 0 and G 1 , grown in the presence of 5-bromodeoxyuridine, and harvested at different times from 48 to 80 h after stimulation. Some cultures were exposed to 2.5-5 mM caffeine during the last 3 h before harvesting. The frequencies of chromosome-type aberrations were scored in first division (M 1 ) metaphases. The post-treatment with caffeine increased the frequencies of mitoses and chromosome-type aberrations in irradiated cultures. The results suggest that cells carrying chromosome-type aberrations are delayed in G 2 and that caffeine increases the frequencies of aberrations in dividing cells by removing this G 2 -block. (author)

  17. Human Chromosome 7: DNA Sequence and Biology

    OpenAIRE

    Scherer, Stephen W.; Cheung, Joseph; MacDonald, Jeffrey R.; Osborne, Lucy R.; Nakabayashi, Kazuhiko; Herbrick, Jo-Anne; Carson, Andrew R.; Parker-Katiraee, Layla; Skaug, Jennifer; Khaja, Razi; Zhang, Junjun; Hudek, Alexander K.; Li, Martin; Haddad, May; Duggan, Gavin E.

    2003-01-01

    DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate gene...

  18. Neocentric X-chromosome in a girl with Turner-like syndrome

    Directory of Open Access Journals (Sweden)

    Hemmat Morteza

    2012-06-01

    Full Text Available Abstract Background Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea. Result G-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm and a normal X chromosome. The other cell line (16% of cells exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the “all human centromeres” probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq, required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study. Conclusion To our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.

  19. X-Chromosome short tandem repeat, advantages and typing ...

    African Journals Online (AJOL)

    Microsatellites of the X-chromosome have been increasingly studied in recent years as a useful tool in forensic analysis. This review describes some details of X-chromosomal short tandem repeat (STR) analysis. Among them are: microsatellites, amplification using polymerase chain reaction (PCR) of STRs, PCR product ...

  20. Cloning an expressed gene shared by the human sex chromosomes

    International Nuclear Information System (INIS)

    Darling, S.M.; Banting, G.S.; Pym, B.; Wolfe, J.; Goodfellow, P.N.

    1986-01-01

    The existence of genes shared by mammalian sex chromosomes has been predicted on both evolutionary and functional grounds. However, the only experimental evidence for such genes in humans is the cell-surface antigen encoded by loci on the X and Y chromosomes (MIC2X and MIC2Y, respectively), which is recognized by the monoclonal antibody 12E7. Using the bacteriophage λgt11 expression system in Escherichia coli and immunoscreening techniques, the authors have isolated a cDNA clone whose primary product is recognized by 12E7. Southern blot analysis using somatic cell hybrids containing only the human X or Y chromosomes shows that the sequences reacting with the cDNA clone are localized to the sex chromosomes. In addition, the clone hybridizes to DNAs isolated from mouse cells that have been transfected with human DNA and selected for 12E7 expression on the fluorescence-activated cell sorter. The authors conclude that the cDNA clone encodes the 12E7 antigen, which is the primary product of the MIC2 loci. The clone was used to explore sequence homology between MIC2X and MIC2Y; these loci are closely related, if not identical

  1. Structure of the human chromosome interaction network.

    Directory of Open Access Journals (Sweden)

    Sergio Sarnataro

    Full Text Available New Hi-C technologies have revealed that chromosomes have a complex network of spatial contacts in the cell nucleus of higher organisms, whose organisation is only partially understood. Here, we investigate the structure of such a network in human GM12878 cells, to derive a large scale picture of nuclear architecture. We find that the intensity of intra-chromosomal interactions is power-law distributed. Inter-chromosomal interactions are two orders of magnitude weaker and exponentially distributed, yet they are not randomly arranged along the genomic sequence. Intra-chromosomal contacts broadly occur between epigenomically homologous regions, whereas inter-chromosomal contacts are especially associated with regions rich in highly expressed genes. Overall, genomic contacts in the nucleus appear to be structured as a network of networks where a set of strongly individual chromosomal units, as envisaged in the 'chromosomal territory' scenario derived from microscopy, interact with each other via on average weaker, yet far from random and functionally important interactions.

  2. Time course of enhancement of chromosomal aberration production in human lyphocytes by post-treatment with aphidicolin following X-radiation

    International Nuclear Information System (INIS)

    Bender, M.A.

    1989-01-01

    The authors have shown earlier that the DNA polymerase inhibitor, aphidicolin, enhances the production of chromosomal aberration by X-rays when administered as a post-treatment. The effect is marked in metaphases collected for the first hour or two following irradiation. Because the yield of X-ray-induced chromosome aberrations falls rapidly with increasing irradiation-fixation interval in G 2 cells it is possible that a difference in yield between cells post-treated with a drug like aphidicolin and those not-treated could arise simply through alteration of the time required for post-treated cells to reach metaphase. The results of the present experiments agree with those of the earlier one in that the X-ray and X-ray plus 1.5 h 5 x 10 -5 M aphidicolin post-treatment-induced chromatid aberration yield fall very rapidly with increasing X-ray-fixation interval, with the marked excess caused by the post-treatment rapidly disappearing and the yield for post-treated samples fixed between 3 and 6 h post-irradiation becoming no greater than those for samples treated with X-rays alone. The answer to the question of whether the yields increase again at later irradiation-fixation intervals, though complicated by the greater delay in aphidicolin post-treated samples and by admixture at later fixation times of metaphases that were in G 1 when irradiated, appears clearly to be yes. (author). 15 refs.; 3 figs.; 3 figs.; 2 tabs

  3. Chromosome Aberrations Induced in Human Peripheral Blood by 2-MeV X-Irradiation to the Whole Body and In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Buckton, Karin E.; Langlands, A. O.; Smith, P. G.; Looby, P. C.; Woodcock, G. E. [Medical Research Council, Clinical and Population Cytogenetics Research Unit, Western General Hospital Edinburgh (United Kingdom); McLelland, J. [Edinburgh Royal Infirmary and Western General Hospital, Edinburgh (United Kingdom)

    1969-11-15

    In recent years it has proved possible to correlate the incidence of ring and dicentric chromosomes in cultured human peripheral blood lymphocytes with given radiation doses both in vitro and following partial or whole body irradiation exposure in vivo In the present study a comparison is made between the yield of aberrations in six men with advanced cancer who received whole body irradiation in doses varying between 36 and 50 rads and the yield of aberrations in samples of their blood drawn before exposure and irradiated in vitro simultaneously to the same dose A comparison is also made between the yield of aberrations following in vitro irradiation to much higher doses of blood derived from these same cancer patients and blood from non cancer controls The significance of these findings is discussed with reference to biological dosimetry using chromosome aberrations as the parameter for both external and internal irradiation Apart from such a practical application it also appears possible to develop this technique to study the sensitivity of cells to chromosome breakage by radiation in selected populations such as mongols or persons with Fancom s anaemia where there is a higher than normal incidence of malignant disease. (author)

  4. BRCA1-mediated repression of select X chromosome genes

    Directory of Open Access Journals (Sweden)

    Ropers H Hilger

    2004-09-01

    Full Text Available Abstract Recently BRCA1 has been implicated in the regulation of gene expression from the X chromosome. In this study the influence of BRCA1 on expression of X chromosome genes was investigated. Complementary DNA microarrays were used to compare the expression levels of X chromosome genes in 18 BRCA1-associated ovarian cancers to those of the 13 "BRCA1-like" and 14 "BRCA2-like" sporadic tumors (as defined by previously reported expression profiling. Significance was determined using parametric statistics with P

  5. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

    Directory of Open Access Journals (Sweden)

    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  6. The complete sequence of human chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, State; Gordon, Laurie A.; Scott, Duncan; Xie, Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael; Bajorek, Eva; Black, Stacey; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan, Yee Man; Denys, Mirian; Detter, Chris; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstenin, David; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Israni, Sanjay; Jett, Jamie; Kadner, Kristen; Kimbal, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou, Yunian; Martinez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar, Richard; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James; Ramirez, Lucia; Rash, Sam; Retterer, James; Rodriguez, Alex; Rogers, Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy; Wu, Kevin; Yang, Joan; Dickson, Mark; Cheng, Jan-Fang; Eichler, Evan E.; Olsen, Anne; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, Susan M.; Myers, Richard M.; Rubin, Edward M.

    2004-04-15

    Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding and syntenic conservation with non-mammalian vertebrates, suggesting they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-encoding genes including the protocadherin and interleukin gene families and the first complete versions of each of the large chromosome 5 specific internal duplications. These duplications are very recent evolutionary events and play a likely mechanistic role, since deletions of these regions are the cause of debilitating disorders including spinal muscular atrophy (SMA).

  7. Mouse Chromosome Engineering for Modeling Human Disease

    OpenAIRE

    van der Weyden, Louise; Bradley, Allan

    2006-01-01

    Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

  8. Study of 25 X-chromosome SNPs in the Portuguese

    DEFF Research Database (Denmark)

    Pereira, Vania; Tomas Mas, Carmen; Amorim, António

    2011-01-01

    The importance of X-chromosome markers in individual identifications, population genetics, forensics and kinship testing is getting wide recognition. In this work, we studied the distributions of 25 X-chromosome single nucleotide polymorphisms (X-SNPs) in population samples from Northern, Central...... and Southern Portugal (n=305). The data were also compared with previous data from the Mediterranean area confirming a general genetic homogeneity among populations in the region. The X-SNP distribution in the three Portuguese regional samples did not show any significant substructure and the X...

  9. Dosage compensation and demasculinization of X chromosomes in Drosophila.

    Science.gov (United States)

    Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

    2010-08-24

    The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. Natural Selection Reduced Diversity on Human Y Chromosomes

    Science.gov (United States)

    Wilson Sayres, Melissa A.; Lohmueller, Kirk E.; Nielsen, Rasmus

    2014-01-01

    The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area. PMID:24415951

  11. Chromosome aberration induction in human diploid fibroblast and epithelial cells

    International Nuclear Information System (INIS)

    Scott, D.

    1986-01-01

    The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

  12. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

    Science.gov (United States)

    Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

    2011-03-03

    The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

  13. Genetic Analysis of Eight X-Chromosomal Short Tandem Repeat ...

    African Journals Online (AJOL)

    X-Chromosome short tandem repeat (STR) typing can complement existing DNA profiling protocols and can also offer useful information in cases of complex kinship analysis. This is the first population study of 8 X-linked STRs in Iraq. The purpose of this work was to provide a basic data of allele and haplotype frequency for ...

  14. Human oocyte chromosome analysis: complicated cases and major ...

    Indian Academy of Sciences (India)

    Human oocyte chromosome analysis: complicated cases and major ... dardized even after more than 20 years of research, making it difficult to draw .... (c) Part of a metaphase with a chromosome break in the centromeric region (arrows).

  15. European gene mapping project (EUROGEM) : Breakpoint panels for human chromosomes based on the CEPH reference families

    NARCIS (Netherlands)

    Attwood, J; Bryant, SP; Bains, R; Povey, R; Povey, S; Rebello, M; Kapsetaki, M; Moschonas, NK; Grzeschik, KH; Otto, M; Dixon, M; Sudworth, HE; Kooy, RF; Wright, A; Teague, P; Terrenato, L; Vergnaud, G; Monfouilloux, S; Weissenbach, J; Alibert, O; Dib, C; Faure, S; Bakker, E; Pearson, NM; Vossen, RHAM; Gal, A; MuellerMyhsok, B; Cann, HM; Spurr, NK

    Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 17; 18, 20 and X were constructed from genotypes from the CEPH reference families. Each recombinant chromosome included has a breakpoint well-supported with reference to defined quantitative criteria. The panels

  16. X-ray induction of mitotic and meiotic chromosome aberrations

    International Nuclear Information System (INIS)

    Yao, K.T.S.

    1980-01-01

    In 1964 six pairs of rat kangaroo (Potorous tridactylis) were obtained from Australia. The tissues of these animals were used to initiate cell lines. Since this species has a low chromosome number of six pairs, each pair with its own distinctive morphology, it is particularly favorable for cytogenetic research. In cell cultures derived from the corneal endothelial tissues of one animal there emerged a number of haploid cells. The number of haploid cells in the cultures reached as high as 20% of the total mitotic configurations. The in vitro diploid and haploid mixture cell cultures could be a resemblance or a coincidence to the mixture existence of the diploid primary spermatocytes and the haploid secondary spermatocytes (gametes) in the in vivo testicular tissues of the male animals. It would be interesting to compare reactions of the haploid and diploid cell mixture, either in the cultures or in the testes, to x-ray exposure. Two other studies involving x-ray effects on Chinese hamster oocyte maturation and meiotic chromosomes and the x-ray induction of Chinese hamster spermatocyte meiotic chromosome aberrations have been done in this laboratory. A review of these three studies involving diploid and haploid chromosomes may lead to further research in the x-ray induction of chromosome aberrations

  17. Clinical utility of the X-chromosome array.

    Science.gov (United States)

    Zarate, Yuri A; Dwivedi, Alka; Bartel, Frank O; Bellomo, M Allison; Cathey, Sara S; Champaigne, Neena L; Clarkson, L Kate; Dupont, Barbara R; Everman, David B; Geer, Joseph S; Gordon, Barbara C; Lichty, Angie W; Lyons, Michael J; Rogers, R Curtis; Saul, Robert A; Schroer, Richard J; Skinner, Steven A; Stevenson, Roger E

    2013-01-01

    Previous studies have limited the use of specific X-chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X-chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X-linked conditions. A total of 59 studies were ordered with 27 copy number variants detected in 25 patients (25/59 = 42%). The findings were deemed pathogenic/likely pathogenic (16/59 = 27%), benign (4/59 = 7%) or uncertain (7/59 = 12%). We place particular emphasis on the utility of this test for the diagnostic evaluation of families affected with X-linked conditions and how it compares to whole genome arrays in this setting. In conclusion, the X-chromosome array frequently detects genomic alterations of the X chromosome and it has advantages when evaluating some specific X-linked conditions. However, careful interpretation and correlation with clinical findings is needed to determine the significance of such changes. When the X-chromosome array was used to confirm a suspected X-linked condition, it had a yield of 63% (12/19) and was useful in the evaluation and risk assessment of patients and families. Copyright © 2012 Wiley Periodicals, Inc.

  18. Molecular mapping of chromosomes 17 and X. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Barker, D.F.

    1991-01-15

    Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition of new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping@ clones from a larger genome.

  19. Late-replicating X-chromosome: replication patterns in mammalian females

    Directory of Open Access Journals (Sweden)

    Tunin Karen

    2002-01-01

    Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.

  20. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi; Fukuda, Nana; Ikeo, Kazuho; Gojobori, Takashi

    2013-01-01

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly

  1. Accelerated pseudogenization on the neo-X chromosome in Drosophila miranda

    KAUST Repository

    Nozawa, Masafumi; Onizuka, Kanako; Fujimi, Mai; Ikeo, Kazuho; Gojobori, Takashi

    2016-01-01

    Y chromosomes often degenerate via the accumulation of pseudogenes and transposable elements. By contrast, little is known about X-chromosome degeneration. Here we compare the pseudogenization process between genes on the neo-sex chromosomes

  2. Radiation hybrids from human chromosome 3: A basis for the construction of region and specific sublibraries

    International Nuclear Information System (INIS)

    Atchison, L.; Cosmis, R.L.; Atchison, M.L.

    1990-01-01

    The authors are interested in identifying genes on human chromosome involved in disease processes. To date at least 20 different loci on this chromosome are implicated with various disease states. DNA libraries containing clones derived from a small chromosomal subregion implicated in a particular disease would greatly assist these studies. They have utilized the radiation hybrid (RH) technique to generate a series of somatic cell hybrids that contain small segments of human chromosome 3 as the only human genetic material. A Chinese hamster-human cell hybrid (Q314-2) containing only human chromosome 3 was used to prepare radiation hybrids. Cells were lethally X-irradiated with 6,000 rads and fused to Urd(??) Chinese hamster cells by PEG 1000 treatment. The majority of hybrids (>72%) analyzed retained portions of chromosome 3. The amount of chromosome 3 in each hybrid ranged from nearly all of the chromosome to very little. Currently these hybrids are being further characterized with single copy probes of known map location in order to isolate regions of chromosome 3 that contain specific disease locus. These reduced hybrids can then be used for the construction of region specific libraries and for the generation of new DNA probes from the specific region of interest

  3. Identification of the facultative heterochromatic X chromosome in females of 25 rodent species.

    Science.gov (United States)

    Kanda, N; Yosida, T H

    1979-01-01

    Treatment of the chromosomes of 25 rodent species with a 50 degrees C hypotonic solution and Giemsa staining permitted identification of the heterochromatic X chromosome in 24 species. With this technique, the facultative of the heterochromatic X chromosome or the facultative portion of large, composite-type X chromosoms is stained darker than the other chromosomes, allowing it to be distinguished from the homologous euchromatic X chromosome in female metaphase cells. Intense staining of the single X chromosome was not observed in male metaphase cells. It is suggested that this differential staining of one of the two X chromosomes might be due to qualitative differences in chromosomal proteins rather than to differences in the degree of chromosomal condensation or in DNA base sequence.

  4. X-chromosome inactivation in development and cancer.

    Science.gov (United States)

    Chaligné, Ronan; Heard, Edith

    2014-08-01

    X-chromosome inactivation represents an epigenetics paradigm and a powerful model system of facultative heterochromatin formation triggered by a non-coding RNA, Xist, during development. Once established, the inactive state of the Xi is highly stable in somatic cells, thanks to a combination of chromatin associated proteins, DNA methylation and nuclear organization. However, sporadic reactivation of X-linked genes has been reported during ageing and in transformed cells and disappearance of the Barr body is frequently observed in cancer cells. In this review we summarise current knowledge on the epigenetic changes that accompany X inactivation and discuss the extent to which the inactive X chromosome may be epigenetically or genetically perturbed in breast cancer. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. Distribution of X-ray induced chromosome rearrangement breaks along the polytene chromosomes of Anopheles messeae

    International Nuclear Information System (INIS)

    Pleshkova, G.N.

    1983-01-01

    Distribution of chromosomal aberrations localization along polytene chromosomes (aoutosomes) of salivary glands of malarial mosquito. Anopheles messeae is presented. Induced aberrations in F 1 posterity from X-ray irradiated fecundated females are studied. Poipts of breaks of inversions and trapslocations are localized separately. There are no considerable dif-- ferences in the distribution character of two types of aberrations. Over the length of autosomes the breaks are more frequent in distal halves, their frequency in proximal parts anally in near centromeric regions of chromosomes is reduced. Concentration of breaks in certain ''hot points'' of the chromosomes is pointed out. Comparison of distribution of actual and expected frequencies of break points according to chi 2 criterion revealed highly fiducial discrepancies, testifying to uneven participation of different regions of chromosomes in aberration formation. Similarities and differences of the data obtained from analogous ones, demonstrated in Drosophila, as well as possible reasons for the distribution unevennes are discussed. On the basis of analysis of intrinsic and literature data a supposition is made that the ''hot points'' (break concentrations) can be considered as localizaion markers of intercalary heterochromatin

  6. Repair of chromosome damage induced by X-irradiation during G2 phase in a line of normal human fibroblasts and its malignant derivative

    International Nuclear Information System (INIS)

    Parshad, R.; Gantt, R.; Sanford, K.K.; Jones, G.M.; Tarone, R.E.

    1982-01-01

    A line of normal human skin fibroblasts (KD) differed from its malignant derivative (HUT-14) in the extent of cytogenetic damage induced by X-irradiation during G2 phase. Malignant cells had significantly more chromatid breaks and gaps after exposure to 25, 50, or 100 rad. The gaps may represent single-strand breaks. Results from alkaline elution of cellular DNA immediately after irradiation showed that the normal and malignant cells in asynchronous population were equally sensitive to DNA single-strand breakage by X-irradiation. Caffeine or beta-cytosine arabinoside (ara-C), inhibitors of DNA repair, when added directly following G2 phase exposure, significantly increased the incidence of radiation-induced chromatid damage in the normal cells. In contrast, similar treatment of the malignant cells had little influence. Ara-C differed from caffeine in its effects; whereas both agents increased the frequency of chromatid breaks and gaps, only ara-C increased the frequency of gaps to the level observed in the irradiated malignant cells. Addition of catalase, a scavenger of the derivative free hydroxyl radical (.OH), to the cultures of malignant cells before, during, and following irradiation significantly reduced the chromatid damage; and catalase prevented formation of chromatid gaps. The DNA damage induced by X-ray during G2 phase in the normal KD cells was apparently repaired by a caffeine- and ara-C-sensitive mechanism(s) that was deficient or absent in their malignant derivatives

  7. Repair of chromosome damage induced by X-irradiation during G2 phase in a line of normal human fibroblasts and its malignant derivative

    International Nuclear Information System (INIS)

    Parshad, R.; Gantt, R.; Sanford, K.K.; Jones, G.M.; Tarone, R.E.

    1982-01-01

    A line of normal human skin fibroblasts (KD) differed from its malignant derivative (HUT-14) in the extent of cytogenetic damage induced by X-irradiation during G 2 phase. Malignant cells had significantly more chromatid breaks and gaps after exposure to 25, 50, or 100 rad. Results from alkaline elution of cellular DNA immediately after irradiation showed that the normal and malignant cells in asynchronous population were equally sensitive to DNA single-strand breakage by X-irradiation. Caffeine or #betta#-cytosine arabinoside (ara-C), inhibitors of DNA repair, when added directly following G 2 phase exposure, significantly increased the incidence of radiation-induced chromatid damage in the normal cells. In contrast, similar treatment of the malignant cells had little influence. Ara-C differed from caffeine in its effects; whereas both agents increased the frequency of chromatid breaks and gaps, only ara-C increased the frequency of gaps to the level observed in the irradiated malignant cells. Addition of catalase, which destroys H 2 O 2 , or mannitol, a scavenger of the derivative free hydroxyl radical (.OH), to the cultures of malignant cells before, during, and following irradiation significantly reduced the chromatid damage; and catalase prevented formation of chromatid gaps. The DNA damage induced by X-ray during G 2 phase in the normal KD cells was apparently repaired by a caffeine- and ara-C-sensitive mechanism(s) that was deficient or absent in their malignant derivatives

  8. Flow cytometry measurements of human chromosome kinetochore labeling

    International Nuclear Information System (INIS)

    Fantes, J.A.; Green, D.K.; Malloy, P.; Sumner, A.T.

    1989-01-01

    A method for the preparation and measurement of immunofluorescent human chromosome centromeres in suspension is described using CREST antibodies, which bind to the centromeric region of chromosomes. Fluorescein isothiocyanate (FITC)-conjugated antihuman antibodies provide the fluorescent label. Labeled chromosomes are examined on microscope slides and by flow cytometry. In both cases a dye which binds to DNA is added to provide identification of the chromosome groups. Sera from different CREST patients vary in their ability to bind to chromosome arms in addition to the centromeric region. Flow cytometry and microfluorimetry measurements have shown that with a given CREST serum the differences in kinetochore fluorescence between chromosomes are only minor. Flow cytometry experiments to relate the number of dicentric chromosomes, induced by in vitro radiation of peripheral blood cells to the slightly increased number of chromosomes with above-average kinetochore fluorescence did not produce decisive radiation dosimetry results

  9. 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...... with ampliconic sequences we propose that intra-genomic conflict between the X and the Y chromosomes is a major driver of X chromosome evolution....

  10. Chromosomal localization of the human diazepam binding inhibitor gene

    International Nuclear Information System (INIS)

    DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

    1988-01-01

    The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes

  11. X-Inactivation: Xist RNA Uses Chromosome Contacts to Coat the X

    OpenAIRE

    Leung, Karen N.; Panning, Barbara

    2014-01-01

    The mechanisms by which Xist RNA associates with the X chromosome to mediate alterations in chromatin structure remain mysterious. Recent genome-wide Xist RNA distribution studies suggest that this long noncoding RNA uses 3-dimensional chromosome contacts to move to its sites of action.

  12. X-inactivation: Xist RNA uses chromosome contacts to coat the X.

    Science.gov (United States)

    Leung, Karen N; Panning, Barbara

    2014-01-20

    The mechanisms by which Xist RNA associates with the X chromosome to mediate alterations in chromatin structure remain mysterious. Recent genome-wide Xist RNA distribution studies suggest that this long noncoding RNA uses 3-dimensional chromosome contacts to move to its sites of action. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Evaluation of rate of unstable chromosomal changes in human blood irradiated by X-rays: establishment of dose-response curve; Avaliação da taxa de alterações cromossômicas instáveis em sangue humano irradiado por Raios x: estabelecimento de curva dose-resposta

    Energy Technology Data Exchange (ETDEWEB)

    Mendonça, J.C.G.; Mendes, M.E.; Melo, A.M.M.A., E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Silva, L.M.; Andrade, A.M.G.; Hwang, S.F.; Lima, F.F. [Centro Regional de Ciências Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil). Lab. de Dosimetria Biológica

    2017-07-01

    Since the discovery of ionizing radiation, and consequently of its properties, there has been an increasing in its use, which in turn has raised concerns about the biological damage that it could cause in exposed individuals. As a result, cytogenetic dosimetry has emerged: a method that can be used as a complement or, in the absence of physical dosimetry, relating the frequency of chromosomal changes found in the blood of the exposed individual and the dose absorbed through dose-response calibration curves. This work aimed to verify the frequencies of the unstable chromosomal changes in human blood lymphocytes irradiated by X-rays of 250 kVp with different absorbed doses and later establish the dose-response calibration curves. The irradiation was performed at the CRCN-NE/CNEN-PE, Brazil metrology service on a PANTAK X-ray machine, model HF 320. The blood samples had their lymphocytes cultured in culture media and, after the processing, the metaphases were obtained. The chromosomal alterations analyzed were chromosomes dicentric, ring and isolated actinic fragments. There was an increase in frequencies of all chromosomal changes with increased absorbed dose. The calibration curves of dicentric and dicentric + rings presented good adjustments with the values of the coefficients Y = 0.0013 + 0.0271D + 0.0556D{sup 2} (X{sup 2} = 10.36 / GL = 6) and Y = 0.0013 + 0.0263D + 0.0640D{sup 2} (X{sup 2} = 7.43 / GL = 6), respectively. The establishment of these curves enables the Laboratory of Biological Dosimetry of the CRCN/NE/CNEN-PE to estimate the dose absorbed by occupationally exposed individuals and in cases of radiological accidents.

  14. Survivin and chromosome instability induced by X-irradiation

    International Nuclear Information System (INIS)

    Shen Bo; Ju Guizhi; Liu Yang

    2006-01-01

    Objective: To explore the biological effect of survivin on chromosome instability induced by X-ray irradiation. Methods: Immunocytochemistry was used to detect the expression of sutvivin in HeLa cells. Carrier pSUPER-SVV was transfected into HeLa cells to interfere the expression of survivin. Flow cytometry assay was applied to detect the occurrence of polyploid at 0 h, 4 h, 12 h, and 48 h after the HeLa cells transfected with pSUPER-SVV and irradiated with 4 Gy X-rays irradiation, and compared with the group irradiated with 4 Gy X-rays but no transfection. Results: The expression of survivin was down-regulated by transfecting with small hair RNA, its depression rate was estimated to be about 32.16% at 48 h after transfection. The occurrence of polyploid giant cells was higher in the 4 Gy X-ray irradiated group at 48 h after the irradiation than the control groups (P<0.001). Being expression of survivin interfered, the occurrence at 12 h or 48 h after irradiation, however, was about two times higher than that in the control group. Conclusion: X-ray irradiation can induce chromosome instability in HeLa cells and the effect could be enhanced by interfering the expression of surviving. It was suggested that survivin plays an important role in maintaining the stability of chromosome. (authors)

  15. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

    Directory of Open Access Journals (Sweden)

    Laurence D Hurst

    2015-12-01

    Full Text Available X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE and data from the Functional Annotation of the Mammalian Genome (FANTOM5 project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds, as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased

  16. Scanning conductance microscopy investigations on fixed human chromosomes

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Lange, Jacob Moresco; Jensen, Linda Boye

    2008-01-01

    Scanning conductance microscopy investigations were carried out in air on human chromosomes fixed on pre-fabricated SiO2 surfaces with a backgate. The point of the investigation was to estimate the dielectric constant of fixed human chromosomes in order to use it for microfluidic device...... optimization. The phase shift caused by the electrostatic forces, together with geometrical measurements of the atomic force microscopy (AFM) cantilever and the chromosomes were used to estimate a value,for the dielectric constant of different human chromosomes....

  17. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

    KAUST Repository

    Hurst, Laurence D.

    2015-12-18

    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression

  18. 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

  19. X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.

    Directory of Open Access Journals (Sweden)

    Tanmoy Bhattacharyya

    2014-02-01

    Full Text Available Hybrid sterility (HS belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes.

  20. X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.

    Science.gov (United States)

    Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri

    2014-02-01

    Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm) allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes.

  1. X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids

    Science.gov (United States)

    Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri

    2014-01-01

    Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2Mmm allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes. PMID:24516397

  2. Chromosome aberrations: plants to human and Feulgen to FISH

    International Nuclear Information System (INIS)

    Natarajan, A.T.

    2005-01-01

    Chromosome aberrations and their impact on human health have been recognized for a long time. In the 1950s, in India, studies on induced chromosome aberrations in plants were initiated by Swaminathan and his students. I trace here the impact of these initial studies on further developments in this field. The studies which were started in plants have been extended to mammals (including human) and the simple squash and solid staining have been improved by molecular cytogenetic techniques, thus enabling accurate identification and quantification of different types of chromosome aberrations. These studies have also thrown light on the mechanisms of chromosome aberration formation, especially following exposure to ionizing radiation. (author)

  3. Induction of chromosomal aberrations in human lymphocytes by fission neutrons

    International Nuclear Information System (INIS)

    Silva, Marcia Augusta da; Coelho, Paulo Rogerio Pinto; Bartolini, Paolo; Okazaki, Kayo

    2009-01-01

    Chromosome aberrations induced by sparsely ionizing radiation (low-LET) are well known and cytogenetic analyses of irradiated human lymphocytes have been widely applied to biological dosimetry. However, much less is known about chromosome aberrations induced by densely ionizing radiation (high LET), such as that of alpha particles or neutrons. Such particles induce DNA strand breaks, as well as chromosome breakage and rearrangements of high complexity. This damage is more localized and less efficiently repaired than after X- or γ-ray irradiation. This preferential production of complex aberrations by densely ionizing radiation is related to the unique energy deposition patterns, which produces highly localized multiple DNA damage at the chromosomal level. A better knowledge of the interactions between different types of radiation and cellular DNA is of importance, not only from the radiobiological viewpoint but also for dosimetric and therapeutic purposes. The objective of the present study was to analyse the cytogenetic effects of fission neutrons on peripheral blood lymphocytes in order to evaluate structural and numerical aberrations and number of cells in the different mitotic cycles. So, blood samples from five healthy donors, 22-25 years old, of both sexes, were irradiated in the Research Reactor IEA-R1 of our Institute (IPEN/CNEN-SP) with thermal and fast neutrons at doses of 0.2; 0.3; 0.5 and 1.0 Gy. The γ contribution to the total absorbed dose was about 30%. These doses were monitored by thermoluminescent dosemeters: LiF-600 (for neutrons) and LiF-700 (for γ-rays). The data concerning structural aberrations were evaluated with regard to three parameters: percentage of cells with aberrations, number of aberrations/cell and number of dicentric/cell. The cytogenetic results showed an increase in the three parameters after irradiation with neutrons, as a function of radiation dose. Apparently, there was no influence of neutrons on the kinetics of cellular

  4. Study of ionizing radiation effect on human spermatozoa chromosomes

    International Nuclear Information System (INIS)

    Rousseaux, S.

    1990-02-01

    The purpose of this thesis is to study the radio-induced chromosomal aberrations in spermatozoa. After a brief recall on ionizing radiations, the author reviews the radio-induced chromosomal anomalies on somatic cells and on germinal line cells and spermatozoa. The author presents the technical aspects of human spermatozoa karyotype and finally studies the radio induced chromosomal anomalies of sperm to patients undergoing a radiotherapy. 13 tabs., 28 figs., 28 photos

  5. Chromosomes of older humans are more prone to aminopterine-induced breakage

    International Nuclear Information System (INIS)

    Esposito, D.; Fassina, G.; Szabo, P.; Weksler, M.; De Angelis, P.; Siniscalco, M.; Rodgers, L.

    1989-01-01

    The authors have adopted a simplified version of the cell hybrid cotransfer method to test the hypothesis that human lymphocytes derived from elderly individuals have a higher chromosome instability. Peripheral blood lymphocytes from old male individuals and young controls were fused with a Chinese hamster cell line (CHO-YH21), yielding 10 HAT-resistant rodent-human clones from the old propositi and 22 from the young controls. Both series of hybrid clones were analyzed with respect to the retention of the enzyme glucose-6-phosphate dehydrogenase and the surface antigen MIC2 identified by monoclonal antibody 12E7, two human X chromosome-linked markers located at opposite ends of the X chromosome. Cell hybrid clones with an X chromosome from a young control retained both markers in about 70% of the cells. In contrast, cell hybrid clones with an X chromosome from an old donor retained the MIC2 marker in only 30% of their cells. Slot-blot hybridization studies have established that the observed loss of the MIC2 marker is due to loss of the coding gene, not to suppression of its expression. T lymphocytes from old donors were also found to have an LD 50 for aminopterine significantly lower than the concentration of this drug in the HAT medium used to grow the hybrids. They speculate that the higher rate of chromosomal breakage and of marker loss observed along the old-age X chromosomes could be the result of molecular scars accumulated with aging at sites of constitutive chromosomal fragility

  6. Chromosome

    Science.gov (United States)

    ... St Louis, MO: Elsevier; 2017:chap 69. Taber's Medical Dictionary Online. Chromosome. www.tabers.com/tabersonline/view/Tabers-Dictionary/753321/all/chromosome?q=Chromosome&ti=0 . Accessed June 11, 2017.

  7. Conformation regulation of the X chromosome inactivation center: a model.

    Directory of Open Access Journals (Sweden)

    Antonio Scialdone

    2011-10-01

    Full Text Available X-Chromosome Inactivation (XCI is the process whereby one, randomly chosen X becomes transcriptionally silenced in female cells. XCI is governed by the Xic, a locus on the X encompassing an array of genes which interact with each other and with key molecular factors. The mechanism, though, establishing the fate of the X's, and the corresponding alternative modifications of the Xic architecture, is still mysterious. In this study, by use of computer simulations, we explore the scenario where chromatin conformations emerge from its interaction with diffusing molecular factors. Our aim is to understand the physical mechanisms whereby stable, non-random conformations are established on the Xic's, how complex architectural changes are reliably regulated, and how they lead to opposite structures on the two alleles. In particular, comparison against current experimental data indicates that a few key cis-regulatory regions orchestrate the organization of the Xic, and that two major molecular regulators are involved.

  8. Chromosomal mosaicism in human preimplantation embryos: a systematic review.

    NARCIS (Netherlands)

    Echten-Arends, J. van; Mastenbroek, S.; Sikkema-Raddatz, B.; Korevaar, J.C.; Heineman, M.J.; Veen, F. van der; Repping, S.

    2011-01-01

    BACKGROUND: Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is

  9. Chromosomal mosaicism in human preimplantation embryos : a systematic review

    NARCIS (Netherlands)

    van Echten-Arends, Jannie; Mastenbroek, Sebastiaan; Sikkema-Raddatz, Birgit; Korevaar, Johanna C.; Heineman, Maas Jan; van der Veen, Fulco; Repping, Sjoerd

    2011-01-01

    BACKGROUND: Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is

  10. The distribution of chromosome aberrations among chromosomes of karyotype in exposed human lymphocyte

    International Nuclear Information System (INIS)

    Que Tran; Tien Hoang Hung

    1997-01-01

    Induced chromosome aberrations (ch. ab.) in exposed Human peripheral blood lymphocyte have been used to assay radio.bio.doses, because of their characters such as: the maintaining Go phase in cell cycle in body, the distribution of cell in blood system and the distribution of ch. ab. in exposed cells of body and among chromosomes of karyotype. The frequency of ch. ab. reflected the quantity of radiation dose, dose rate and radiation energy. The dependence between radiation dose and frequency of ch. ab. was illustrated by the mathematic equations. The distribution of induced ch. ab. among the cells exposed to uniform radiation fields was Poisson's, but the distribution of ch. ab. among chromosomes in karyotype depended on radiation field and mononucleotid sequence of DNA molecular of each chromosome. The minimum influence of mononucleotid sequence of DNA molecular in inform ch. ab. will be advantageous state for dose-assessments. The location of induced ch. ab. in exposed Human lymphocyte had been determined by karyotype analyses. The data of statistic analyse had improved that the number of ch. ab. depended on the size of chromosomes in karyotype. The equal distribution of ch. ab.among chromosomes in karyotype provided the objectiveness and the accuracy of using the chromosomal aberrant analysis technique on bio-dosimetry. (author)

  11. Human artificial chromosomes with alpha satellite-based de novo centromeres show increased frequency of nondisjunction and anaphase lag.

    Science.gov (United States)

    Rudd, M Katharine; Mays, Robert W; Schwartz, Stuart; Willard, Huntington F

    2003-11-01

    Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres require specialized chromatin that consists of alpha satellite DNA complexed with epigenetically modified histones and centromere-specific proteins. While several types of alpha satellite DNA have been used to assemble de novo centromeres in artificial chromosome assays, the extent to which they fully recapitulate normal centromere function has not been explored. Here, we have used two kinds of alpha satellite DNA, DXZ1 (from the X chromosome) and D17Z1 (from chromosome 17), to generate human artificial chromosomes. Although artificial chromosomes are mitotically stable over many months in culture, when we examined their segregation in individual cell divisions using an anaphase assay, artificial chromosomes exhibited more segregation errors than natural human chromosomes (P artificial chromosomes missegregate over a fivefold range, the data suggest that variable centromeric DNA content and/or epigenetic assembly can influence the mitotic behavior of artificial chromosomes.

  12. Dielectrophoretic manipulation of human chromosomes in microfluidic channels: extracting chromosome dielectric properties

    DEFF Research Database (Denmark)

    Clausen, Casper Hyttel; Dimaki, Maria; Buckley, Sonia

    2011-01-01

    An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method...... of manipulation combined with a custom designed microfluidic system containing the required electrodes for dielectrophoresis experiments. Our results show that although this system is presently not able to distinguish between the different chromosomes, it can provide average data for the dielectric properties...... of human chromosomes in polyamine buffer. These can then be used to optimize system designs for further characterization and even sorting. The experimental data from the dielectrophoretic manipulation were combined with theoretical calculations to extract a range of values for the permittivity...

  13. Rapid evolution of cancer/testis genes on the X chromosome

    Directory of Open Access Journals (Sweden)

    Simpson Andrew J

    2007-05-01

    Full Text Available Abstract Background Cancer/testis (CT genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole. Results To shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes. Conclusion Given their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.

  14. The role of sex chromosomes in mammalian germ cell differentiation: can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes?

    Directory of Open Access Journals (Sweden)

    Teruko Taketo

    2015-06-01

    Full Text Available The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.

  15. Increased frequency of spontaneous and X-ray-induced chromosomal aberrations in lymphocytes from neonates and the influence of caffeine

    International Nuclear Information System (INIS)

    Karsdon, J.; Rijn, J. van; Berger, H.

    1989-01-01

    The authors have examined lymphocytes from human preterm (PT) and fullterm (FT) babies for an effect of gestational age (GA) on chromosomal aberrations either occurring spontaneously or indiced by treatment with X-rays alone; or with caffeine supplementation in comparison to the lymphocytes of healthy adults. (AD). Per cent of abnormal cells (% Abn) was used as an indicator of chromosome sensitivy to the different treatments. PT babies had significantly higher spontaneous and X-ray-induced % Abn values than AD, but were comparable to FT. After X-iradiation + caffeine the yield of aberrations in any 2 groups was not significantly different. Chromosomal sensitivity may resuult from factors other than GA. This in vitro model may permit study of the mechanisms of chromosomal damage repair and prevention of free radical damage of DNA during the perinatal period. (author). 33 refs.; 1 fig.; 3 tabs

  16. Chromosomal localization of the human and mouse hyaluronan synthase genes

    Energy Technology Data Exchange (ETDEWEB)

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

    1997-05-01

    We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

  17. Preparation and bivariate analysis of suspensions of human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    van den Engh, G.J.; Trask, B.J.; Gray, J.W.; Langlois, R.G.; Yu, L.C.

    1985-01-01

    Chromosomes were isolated from a variety of human cell types using a HEPES-buffered hypotonic solution (pH 8.0) containing KCl, MgSO/sub 4/ dithioerythritol, and RNase. The chromosomes isolated by this procedure could be stained with a variety of fluorescent stains including propidium iodide, chromomycin A3, and Hoeschst 33258. Addition of sodium citrate to the stained chromosomes was found to improve the total fluorescence resolution. High-quality bivariate Hoeschst vs. chromomycin fluorescence distributions were obtained for chromosomes isolated from a human fibroblast cell strain, a human colon carcinoma cell line, and human peripheral blood lymphocyte cultures. Good flow karyotypes were also obtained from primary amniotic cell cultures. The Hoeschst vs. chromomycin flow karyotypes of a given cell line, made at different times and at dye concentrations varying over fourfold ranges, show little variation in the relative peak positions of the chromosomes. The size of the DNA in chromosomes isolated using this procedure ranges from 20 to 50 kilobases. The described isolation procedure is simple, it yields high-quality flow karyotypes, and it can be used to prepare chromosomes from clinical samples. 22 references, 7 figures, 1 table.

  18. Chromosomal radiosensitivity of human leucocytes in relation to sampling time

    International Nuclear Information System (INIS)

    Buul, P.P.W. van; Natarajan, A.T.

    1980-01-01

    Frequencies of chromosomal aberrations after irradiation with X-rays of peripheral blood lymphocytes in vitro were determined at different times after initiation of cultures. In each culture, the kinetics of cell multiplication was followed by using BrdU labelling and differential staining of chromosomes. The results indicate that the mixing up of first and second cell cycle cells at later sampling times cannot explain the observed variation in the frequencies of chromosomal aberrations but that donor-to-donor variation is a predominant factor influencing yields of aberrations. The condition of a donor seems to be most important because repeats on the same donor also showed marked variability. (orig.)

  19. Chromosome-Centric Human Proteome Project Allies with Developmental Biology: A Case Study of the Role of Y Chromosome Genes in Organ Development.

    Science.gov (United States)

    Meyfour, Anna; Pooyan, Paria; Pahlavan, Sara; Rezaei-Tavirani, Mostafa; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2017-12-01

    One of the main goals of Chromosome-Centric Human Proteome Project is to identify protein evidence for missing proteins (MPs). Here, we present a case study of the role of Y chromosome genes in organ development and how to overcome the challenges facing MPs identification by employing human pluripotent stem cell differentiation into cells of different organs yielding unprecedented biological insight into adult silenced proteins. Y chromosome is a male-specific sex chromosome which escapes meiotic recombination. From an evolutionary perspective, Y chromosome has preserved 3% of ancestral genes compared to 98% preservation of the X chromosome based on Ohno's law. Male specific region of Y chromosome (MSY) contains genes that contribute to central dogma and govern the expression of various targets throughout the genome. One of the most well-known functions of MSY genes is to decide the male-specific characteristics including sex, testis formation, and spermatogenesis, which are majorly formed by ampliconic gene families. Beyond its role in sex-specific gonad development, MSY genes in coexpression with their X counterparts, as single copy and broadly expressed genes, inhibit haplolethality and play a key role in embryogenesis. The role of X-Y related gene mutations in the development of hereditary syndromes suggests an essential contribution of sex chromosome genes to development. MSY genes, solely and independent of their X counterparts and/or in association with sex hormones, have a considerable impact on organ development. In this Review, we present major recent findings on the contribution of MSY genes to gonad formation, spermatogenesis, and the brain, heart, and kidney development and discuss how Y chromosome proteome project may exploit developmental biology to find missing proteins.

  20. Experimental observation of G banding verifying X-ray workers' chromosome translocation detected by FISH

    International Nuclear Information System (INIS)

    Sun Yuanming; Li Jin; Wang Qin; Tang Weisheng; Wang Zhiquan

    2002-01-01

    Objective: FISH is the most effective way of detecting chromosome aberration and many factors affect its accuracy. G-banding is used to verify the results of early X-ray workers' chromosome translocation examined by FISH. Methods: The chromosome translocations of early X-ray workers have been analysed by FISH (fluorescence in situ hybridization) and G-banding, yields of translocation treated with statistics. Results: The chromosome aberrations frequencies by tow methods are closely related. Conclusion: FISH is a feasible way to analyse chromosome aberrations of X-ray workers and reconstruct dose

  1. Analysis of B chromosome nondisjunction induced by the r-X1 deficiency in maize.

    Science.gov (United States)

    Tseng, Shih-Hsuan; Peng, Shu-Fen; Cheng, Ya-Ming

    2017-11-20

    The maize B chromosome typically undergoes nondisjunction during the second microspore division. For normal A chromosomes, the r-X1 deficiency in maize can induce nondisjunction during the second megaspore and first microspore divisions. However, it is not known whether the r-X1 deficiency also induces nondisjunction of the maize B chromosome during these cell divisions. To answer this question, chromosome numbers were determined in the progeny of r-X1/R-r female parents carrying two B chromosomes. Some of the r-X1-lacking progeny (21.2%) contained zero or two B chromosomes. However, a much higher percentage of the r-X1-containing progeny (43.4%) exhibited zero or two B chromosomes, but none displayed more than two B chromosomes. Thus, the results indicated that the r-X1 deficiency could also induce nondisjunction of the B chromosome during the second megaspore division; moreover, the B chromosome in itself could undergo nondisjunction during the same division. In addition, pollen grains from plants with two B chromosomes lacking or exhibiting the r-X1 deficiency were compared via pollen fluorescence in situ hybridization (FISH) using a B chromosome-specific probe. The results revealed that the r-X1 deficiency could induce the occurrence of B chromosome nondisjunction during the first microspore division and that the B chromosome in itself could undergo nondisjunction during the same division at a lower frequency. Our data shed more light on the behavior of the maize B chromosome during cell division.

  2. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    International Nuclear Information System (INIS)

    Ejima, Yosuke

    1988-01-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G 0 or G 1 phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases. (author)

  3. Human hereditary diseases associated with elevated frequency of chromosome aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Ejima, Yosuke; Ikushima, Takaji (ed.)

    1988-07-01

    Human recessive diseases collectively known as chromosome breakage syndromes include Fanconi's anemia, Bloom's syndrome and ataxia telangiectasia. Cells from these patients show chromosome instabilities both spontaneously and following treatments with radiations or certain chemicals, where defects in DNA metabolisms are supposed to be involved. Cells from patients with ataxia telangiectasia are hypersensitive to ionizing radiations, though DNA replication is less affected than in normal cells. Chromatid-type as well as chromosom-type aberrations are induced in cells irradiated in G/sub 0/ or G/sub 1/ phases. These unusual responses to radiations may provide clues for understanding the link between DNA replicative response and cellular radiosensitivity. Alterations in cellular radiosensitivity or spontaneous chromosome instabilities are observed in some patients with congenital chromosome anomalies or dominant diseases, where underlying defects may be different from those in recessive diseases.

  4. Caenorhabditis elegans histone methyltransferase MET-2 shields the male X chromosome from checkpoint machinery and mediates meiotic sex chromosome inactivation.

    Directory of Open Access Journals (Sweden)

    Paula M Checchi

    2011-09-01

    Full Text Available Meiosis is a specialized form of cellular division that results in the precise halving of the genome to produce gametes for sexual reproduction. Checkpoints function during meiosis to detect errors and subsequently to activate a signaling cascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpoint response that can in turn trigger germline apoptosis. In a heterogametic germ line, however, sex chromosomes proceed through meiosis with unsynapsed regions and are not recognized by checkpoint machinery. We conducted a directed RNAi screen in Caenorhabditis elegans to identify regulatory factors that prevent recognition of heteromorphic sex chromosomes as unpaired and uncovered a role for the SET domain histone H3 lysine 9 histone methyltransferase (HMTase MET-2 and two additional HMTases in shielding the male X from checkpoint machinery. We found that MET-2 also mediates the transcriptional silencing program of meiotic sex chromosome inactivation (MSCI but not meiotic silencing of unsynapsed chromatin (MSUC, suggesting that these processes are distinct. Further, MSCI and checkpoint shielding can be uncoupled, as double-strand breaks targeted to an unpaired, transcriptionally silenced extra-chromosomal array induce checkpoint activation in germ lines depleted for met-2. In summary, our data uncover a mechanism by which repressive chromatin architecture enables checkpoint proteins to distinguish between the partnerless male X chromosome and asynapsed chromosomes thereby shielding the lone X from inappropriate activation of an apoptotic program.

  5. A Genealogical Look at Shared Ancestry on the X Chromosome.

    Science.gov (United States)

    Buffalo, Vince; Mount, Stephen M; Coop, Graham

    2016-09-01

    Close relatives can share large segments of their genome identical by descent (IBD) that can be identified in genome-wide polymorphism data sets. There are a range of methods to use these IBD segments to identify relatives and estimate their relationship. These methods have focused on sharing on the autosomes, as they provide a rich source of information about genealogical relationships. We hope to learn additional information about recent ancestry through shared IBD segments on the X chromosome, but currently lack the theoretical framework to use this information fully. Here, we fill this gap by developing probability distributions for the number and length of X chromosome segments shared IBD between an individual and an ancestor k generations back, as well as between half- and full-cousin relationships. Due to the inheritance pattern of the X and the fact that X homologous recombination occurs only in females (outside of the pseudoautosomal regions), the number of females along a genealogical lineage is a key quantity for understanding the number and length of the IBD segments shared among relatives. When inferring relationships among individuals, the number of female ancestors along a genealogical lineage will often be unknown. Therefore, our IBD segment length and number distributions marginalize over this unknown number of recombinational meioses through a distribution of recombinational meioses we derive. By using Bayes' theorem to invert these distributions, we can estimate the number of female ancestors between two relatives, giving us details about the genealogical relations between individuals not possible with autosomal data alone. Copyright © 2016 by the Genetics Society of America.

  6. Structure and chromosomal localization of the human lymphotoxin gene

    International Nuclear Information System (INIS)

    Nedwin, G.E.; Jarrett-Nedwin, J.; Smith, D.H.; Naylor, S.L.; Sakaguchi, A.Y.; Goeddel, D.V.; Gray, P.W.

    1987-01-01

    The authors have isolated, sequenced, and determined the chromosomal localization of the gene encoding human lymphotoxin (LT). The single copy gene was isolated from a human genomic library using a /sup 32/P-labeled 116 bp synthetic DNA fragment whose sequence was based on the NH/sub 2/-terminal amino acid sequence of LT. The gene spans 3 kb of DNA and is interrupted by three intervening sequences. The LT gene is located on human chromosome 6, as determined by Southern blot analysis of human-murine hybrid DNA. Putative transcriptional control regions and areas of homology with the promoters of interferon and other genes are identified

  7. Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.

    Science.gov (United States)

    Persani, Luca; Rossetti, Raffaella; Cacciatore, Chiara; Bonomi, Marco

    2009-08-01

    Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI.

  8. Chromosomal sensitivity to X-rays in lymphocytes from patients with Turner syndrome

    International Nuclear Information System (INIS)

    Heras, J.G.; Coco, R.

    1986-01-01

    Lymphocytes from patients with Turner syndrome were irradiated with X-rays to determine the chromosomal aberration frequency in first-division metaphases. Five patients with 45,X karyotype; three 45,X/46,Xi(X)q mosaics; one 45,X/47,XXX mosaic and 9 female controls were studied. Patients with a 45,X karyotype exhibited a radioinduced chromosomal aberration frequency similar to controls. In the mosaics, 45,X cells has a mean frequency of 38.75 +- 2.16; 46,Xi(X)q cells a mean of 38 +- 2.16 and the control group a rate of 36.25 +- 4.32. No differences were observed between 45,X and 46,Xi(X)q cells, 45,X and normal cells or 46,Xi(X)q and normal cells. Apparently neither the X monosomy nor the Xq isochromosome influences the 'in vitro' X-ray-induced chromosomal damage in Turner syndrome lymphocytes. (Auth.)

  9. MECP2 promoter methylation and X chromosome inactivation in autism.

    Science.gov (United States)

    Nagarajan, Raman P; Patzel, Katherine A; Martin, Michelle; Yasui, Dag H; Swanberg, Susan E; Hertz-Picciotto, Irva; Hansen, Robin L; Van de Water, Judy; Pessah, Isaac N; Jiang, Ruby; Robinson, Wendy P; LaSalle, Janine M

    2008-06-01

    Epigenetic mechanisms have been proposed to play a role in the etiology of autism. This hypothesis is supported by the discovery of increased MECP2 promoter methylation associated with decreased MeCP2 protein expression in autism male brain. To further understand the influence of female X chromosome inactivation (XCI) and neighboring methylation patterns on aberrant MECP2 promoter methylation in autism, multiple methylation analyses were peformed on brain and blood samples from individuals with autism. Bisulfite sequencing analyses of a region 0.6 kb upstream of MECP2 in brain DNA samples revealed an abrupt transition from a highly methylated region in both sexes to a region unmethylated in males and subject to XCI in females. Chromatin immunoprecipitation analysis demonstrated that the CCTC-binding factor (CTCF) bound to this transition region in neuronal cells, consistent with a chromatin boundary at the methylation transition. Male autism brain DNA samples displayed a slight increase in methylation in this transition region, suggesting a possible aberrant spreading of methylation into the MECP2 promoter in autism males across this boundary element. In addition, autistic female brain DNA samples showed evidence for aberrant MECP2 promoter methylation as an increase in the number of bisulfite sequenced clones with undefined XCI status for MECP2 but not androgen receptor (AR). To further investigate the specificity of MECP2 methylation alterations in autism, blood DNA samples from females and mothers of males with autism were also examined for XCI skewing at AR, but no significant increase in XCI skewing was observed compared to controls. These results suggest that the aberrant MECP2 methylation in autism brain DNA samples is due to locus-specific rather than global X chromosome methylation changes.

  10. Divergent actions of long noncoding RNAs on X-chromosome ...

    Indian Academy of Sciences (India)

    2015-10-20

    Oct 20, 2015 ... Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of ... could also get genetically inactive and late replicating when ... tial to achieve the chromosomal level modifications were.

  11. The analysis of distribution of the chromosome aberration breakpoints from medical diagnostic X-ray workers

    International Nuclear Information System (INIS)

    Wang Qin; Li Jin; Tang Weisheng; Wang Zhiquan

    2003-01-01

    Objective: To analyze the distribution of the chromosome aberration breakpoints from medical diagnostic x-ray workers. Methods: The breakpoints of lymphocyte chromosomes are analyzed using G-banding. Results: There are 146 breakpoints among 3545 metaphase in 37 cases of X-ray workers. There are statistically significant differences between observed values and expected values (χ 2 =42.82, df=23, P 0.05). Conclusion: The chromosome aberration breakpoints of medical diagnostic X-ray workers are non-random. The observed values of breakpoint numbers are higher than those of the expected values in 7 and 14 chromosomes (P<0.05)

  12. Primary vitreoretinal dysplasia resembling Norrie's disease in a female: association with X autosome chromosomal translocation.

    OpenAIRE

    Ohba, N.; Yamashita, T.

    1986-01-01

    A female infant with the typical clinical and histopathological features of vitreoretinal dysplasia is described. She had an apparently balanced reciprocal chromosomal translocation 46XX,t(X;10) with the X chromosome breakpoint being on the short arm. Since the parents' karyotypes were normal, it is most plausible that a de novo chromosomal translocation disrupted the vitreoretinal dysplasia gene itself. The severe clinical symptoms of this heterozygous female patient were explained by non-ra...

  13. The effect of 3-aminobenzamide on X-ray induction of chromosome aberrations in Down syndrome lymphocytes

    International Nuclear Information System (INIS)

    McLaren, R.A.; Au, W.W.; Legator, M.S.

    1989-01-01

    Human lymphocytes from normal and Down syndrome (DS) subjects were examined to determine the effect of 3-aminobenzamide (3AB) on X-ray-induced chromosome aberrations. Lymphocytes were treated with 150 or 300 rad of X-rays in the presence of 3 mM 3AB for various times after irradiation, and then the cells were analyzed for the presence of chromosome aberrations in mitotic cells. 3-Aminobenzamide had no effect on the frequency of chromosome aberrations as a result of treatment with X-rays in the presence of 3AB. These observations indicate that DS lymphocytes are more sensitive to the inhibition of poly(ADP)ribose synthetase than normal lymphocytes. (author). 44 refs.; 3 tabs

  14. Maternal XX/X chromosome mosaicism in donor oocyte in vitro fertilization (IVF

    Directory of Open Access Journals (Sweden)

    Paul R. Brezina

    2012-06-01

    Results: The rates of maternal X chromosome mosaicism noted in the cycles from women with miscarriages (3%, 4%, 4%, and 6% were not statistically different from cycles in TS-Mosaic women with normal deliveries (3% and 11%. These data suggest that the rate of maternal X chromosome mosaicism does not affect pregnancy loss rates in TS-Mosaic women undergoing donor oocyte IVF.

  15. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome

    International Nuclear Information System (INIS)

    Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.

    1987-01-01

    A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and α-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome

  16. X Chromosome Inactivation and Breast Cancer: Epigenetic Alteration in Tumor Initiation and Progression

    National Research Council Canada - National Science Library

    Panning, Barbara

    2007-01-01

    We tested whether reactivation of the inactive X chromosome in the mouse mammary gland contributes to tumorigenesis in vivo and whether that reactivation of the inactive X can cooperate with the MYC...

  17. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    Science.gov (United States)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  18. Centromere Destiny in Dicentric Chromosomes: New Insights from the Evolution of Human Chromosome 2 Ancestral Centromeric Region.

    Science.gov (United States)

    Chiatante, Giorgia; Giannuzzi, Giuliana; Calabrese, Francesco Maria; Eichler, Evan E; Ventura, Mario

    2017-07-01

    Dicentric chromosomes are products of genomic rearrangements that place two centromeres on the same chromosome. Due to the presence of two primary constrictions, they are inherently unstable and overcome their instability by epigenetically inactivating and/or deleting one of the two centromeres, thus resulting in functionally monocentric chromosomes that segregate normally during cell division. Our understanding to date of dicentric chromosome formation, behavior and fate has been largely inferred from observational studies in plants and humans as well as artificially produced de novo dicentrics in yeast and in human cells. We investigate the most recent product of a chromosome fusion event fixed in the human lineage, human chromosome 2, whose stability was acquired by the suppression of one centromere, resulting in a unique difference in chromosome number between humans (46 chromosomes) and our most closely related ape relatives (48 chromosomes). Using molecular cytogenetics, sequencing, and comparative sequence data, we deeply characterize the relicts of the chromosome 2q ancestral centromere and its flanking regions, gaining insight into the ancestral organization that can be easily broadened to all acrocentric chromosome centromeres. Moreover, our analyses offered the opportunity to trace the evolutionary history of rDNA and satellite III sequences among great apes, thus suggesting a new hypothesis for the preferential inactivation of some human centromeres, including IIq. Our results suggest two possible centromere inactivation models to explain the evolutionarily stabilization of human chromosome 2 over the last 5-6 million years. Our results strongly favor centromere excision through a one-step process. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Xist RNA is confined to the nuclear territory of the silenced X chromosome throughout the cell cycle

    NARCIS (Netherlands)

    I.H. Jonkers (Iris); K. Monkhorst (Kim); E. Rentmeester (Eveline); J.A. Grootegoed (Anton); F.G. Grosveld (Frank); J.H. Gribnau (Joost)

    2008-01-01

    textabstractIn mammalian female cells, one X chromosome is inactivated to prevent a dose difference in the expression of X-encoded proteins between males and females. Xist RNA, required for X chromosome inactivation, is transcribed from the future inactivated X chromosome (Xi), where it spreads in

  20. Chromosome painting reveals asynaptic full alignment of homologs and HIM-8-dependent remodeling of X chromosome territories during Caenorhabditis elegans meiosis.

    Science.gov (United States)

    Nabeshima, Kentaro; Mlynarczyk-Evans, Susanna; Villeneuve, Anne M

    2011-08-01

    During early meiotic prophase, a nucleus-wide reorganization leads to sorting of chromosomes into homologous pairs and to establishing associations between homologous chromosomes along their entire lengths. Here, we investigate global features of chromosome organization during this process, using a chromosome painting method in whole-mount Caenorhabditis elegans gonads that enables visualization of whole chromosomes along their entire lengths in the context of preserved 3D nuclear architecture. First, we show that neither spatial proximity of premeiotic chromosome territories nor chromosome-specific timing is a major factor driving homolog pairing. Second, we show that synaptonemal complex-independent associations can support full lengthwise juxtaposition of homologous chromosomes. Third, we reveal a prominent elongation of chromosome territories during meiotic prophase that initiates prior to homolog association and alignment. Mutant analysis indicates that chromosome movement mediated by association of chromosome pairing centers (PCs) with mobile patches of the nuclear envelope (NE)-spanning SUN-1/ZYG-12 protein complexes is not the primary driver of territory elongation. Moreover, we identify new roles for the X chromosome PC (X-PC) and X-PC binding protein HIM-8 in promoting elongation of X chromosome territories, separable from their role(s) in mediating local stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG-12 patches. Further, we present evidence that HIM-8 functions both at and outside of PCs to mediate chromosome territory elongation. These and other data support a model in which synapsis-independent elongation of chromosome territories, driven by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby facilitating assessment of their suitability as potential pairing partners.

  1. Chromosome Painting Reveals Asynaptic Full Alignment of Homologs and HIM-8–Dependent Remodeling of X Chromosome Territories during Caenorhabditis elegans Meiosis

    Science.gov (United States)

    Nabeshima, Kentaro; Mlynarczyk-Evans, Susanna; Villeneuve, Anne M.

    2011-01-01

    During early meiotic prophase, a nucleus-wide reorganization leads to sorting of chromosomes into homologous pairs and to establishing associations between homologous chromosomes along their entire lengths. Here, we investigate global features of chromosome organization during this process, using a chromosome painting method in whole-mount Caenorhabditis elegans gonads that enables visualization of whole chromosomes along their entire lengths in the context of preserved 3D nuclear architecture. First, we show that neither spatial proximity of premeiotic chromosome territories nor chromosome-specific timing is a major factor driving homolog pairing. Second, we show that synaptonemal complex-independent associations can support full lengthwise juxtaposition of homologous chromosomes. Third, we reveal a prominent elongation of chromosome territories during meiotic prophase that initiates prior to homolog association and alignment. Mutant analysis indicates that chromosome movement mediated by association of chromosome pairing centers (PCs) with mobile patches of the nuclear envelope (NE)–spanning SUN-1/ZYG-12 protein complexes is not the primary driver of territory elongation. Moreover, we identify new roles for the X chromosome PC (X-PC) and X-PC binding protein HIM-8 in promoting elongation of X chromosome territories, separable from their role(s) in mediating local stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG-12 patches. Further, we present evidence that HIM-8 functions both at and outside of PCs to mediate chromosome territory elongation. These and other data support a model in which synapsis-independent elongation of chromosome territories, driven by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby facilitating assessment of their suitability as potential pairing partners. PMID:21876678

  2. A high-resolution comparative map between pig chromosome 17 and human chromosomes 4, 8, and 20: Identification of synteny breakpoints

    DEFF Research Database (Denmark)

    Lahbib-Mansais, Yvette; Karlskov-Mortensen, Peter; Mompart, Florence

    2005-01-01

    We report on the construction of a high-resolution comparative map of porcine chromosome 17 (SSC17) focusing on evolutionary breakpoints with human chromosomes. The comparative map shows high homology with human chromosome 20 but suggests more limited homologies with other human chromosomes. SSC1...

  3. Mutational landscape of the human Y chromosome-linked genes ...

    Indian Academy of Sciences (India)

    Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism. Deepali Pathak, Sandeep Kumar Yadav, Leena Rawal and Sher Ali. J. Genet. 94, 677–687. Table 1. Details showing age, sex, karyotype, clinical features and diagnosis results of the patients with H. Hormone profile.

  4. The use of a mutationally unstable X-chromosome in Drosophila melanogaster for mutagenicity testing

    International Nuclear Information System (INIS)

    Rasmuson, B.; Svahlin, H.; Rasmuson, A.; Montell, I.; Olofsson, H.

    1978-01-01

    Somatic eye-colour mutations in an unstable genetic system, caused by a transposable element in the white locus of the X-chromosome in Drosophila melanogaster, is suggested as an assay system for mutagenicity testing. The system is evaluated by comparison with a corresponding system in a stable X-chromosome. Its sensitivity is confirmed with X-ray and EMS treatment, and it is found to be confined to the specific segment of the X-chromosome where the transposable element is localized. (Auth.)

  5. Report on the Second International Workshop on Human Chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowski, D.J. [Brigham and Women`s Hospital, Boston, MA (United States); Armour, J. [Univ. of Leicester (England). Dept. of Genetics; Bale, A.E. [Yale Univ., New Haven, CT (United States). Dept. of Genetics] [and others

    1993-12-31

    The Second International Workshop on Human Chromosome 9 was held in Chatham, Massachusetts on April 18--20, 1993. Fifty-three abstracts were received and the data presented on posters. The purpose of the meeting was to bring together all interested investigators working on the map of chromosome 9, many of whom had disease-specific interests. After a brief presentation of interests and highlighted results, the meeting broke up into the following subgroups for production of consensus maps: 9p; 9cen-q32; 9q32 ter. A global mapping group also met. Reports of each of these working groups is presented in the summary.

  6. Induction and rejoining of DNA double-strand breaks and interphase chromosome breaks after exposure to x-rays in one normal and two hypersensitive human fibroblast cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Badie, C.; Alsbeih, G.; Malaise, E.P. [Institute Gustave-Roussy, Villejuif (France)] [and others

    1995-10-01

    The aim of this work was to measure simultaneously and in a quantitative manner double-strand breaks (DSBs), interphase chromosome breaks and cell lethality either immediately after irradiation, or at various times thereafter (up to 24 h), in cells of three nontransformed human fibroblast cell lines of widely different intrinsic radiosensitivity. We wished to assess initial damage, repair kinetics and residual damage at the DNA and the chromosome level, and to correlate these parameters with cell killings. We employed HF19 cells, a normal fibroblast cell line, AT2 cells, a radiosensitive cell line from a patient suffering from ataxia telangiectasia (AT), and 180BR cells, a radiosensitive cell line from a patient with no clinical symptoms of AT. AT2 and 180BR cells, in addition to being radiosensitive, also display a reduced ability to repair potentially lethal damage compared to HF19 cells. The yield of DSBs, as measured by pulsed-field gel electrophoresis, is similar in all three cell lines (slopes correspond to 1.6-1.7% Gy{sup -1} of DNA-associated radioactivity released from the gel well into the lane). In contrast, residual DSBs measured 24 h after irradiation are almost zero for HF19 cells (0.1% confidence interval=0-1.4%), but are 12.5% ({plus_minus}2.3%) and 43.8% ({plus_minus}1.2%) of those measured immediately after irradiation in HF19, AT2 and 180BR cells, respectively. Neither the initial yield of DSBs nor that of excess interphase chromosomes breaks can explain the differences in radiosensitivity between the three cell lines; however, there is a correlation between residual DSBs, rate of DSB rejoining at 24 h, residual interphase chromosome breaks on the one hand and cell survival on the other hand. 74 refs., 6 figs., 4 tabs.

  7. The sequence and analysis of duplication rich human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-08-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  8. The Sequence and Analysis of Duplication Rich Human Chromosome 16

    Science.gov (United States)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-01-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  9. Condensin-driven remodelling of X chromosome topology during dosage compensation

    Science.gov (United States)

    Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

    2015-07-01

    The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using

  10. Chromosome aberrations in human lymphocytes for investigation of individual radiosensitivity

    International Nuclear Information System (INIS)

    Zitzelsberger, H.; Bauchinger, M.

    2000-01-01

    Stable translocations and insertions which are not selected against during cell proliferation can be reliably scored by use of fluorescence in situ hybridisation (FISH) which allows painting of selected chromosomes along their entire length. This temporal persistence makes them particulary valuable for quantifying post human radiation exposures ('biodosimetry'). A disadvantage of this approach is that for routine use only a partial genome analysis can be performed which is mostly based on triple combinations of DNA probes for particular chromosomes. Translocation frequencies from partial genome analysis are often scaled-up to equal the full genome. Basic assumptions for such scaling are, that double strand breaks leading to translocations must be distributed randomly throughout the genome and no preferential interaction between particular pairs of chromosomes occurs. Thus, the probability of a particular chromosome being involved in an exchange is proportional to its DNA content. However, this is not always supported by experimental findings and may thus indicate a differential radiosensitivity of particular chromosomes. Translocation measurements in peripheral blood of different healthy donors irradiated in vitro with the same dose revealed also some evidence for the existence of interindividual differences in radiosensitivity. Similar findings have been already demonstrated after therapeutic irradiation of tumour patients. Consequences thereof may result for long-term retrospective biodosimetry. In order to provide reliable estimates of an individual's exposure to ionising radiation, the extent, distribution and dose-dependence of the observed variability has to be carefully examined in larger groups of persons and larger sets of calibration data. (orig.) [de

  11. The DNA sequence and biology of human chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Grimwood, J; Gordon, L A; Olsen, A; Terry, A; Schmutz, J; Lamerdin, J; Hellsten, U; Goodstein, D; Couronne, O; Tran-Gyamfi, M

    2004-04-06

    Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high GC content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in Mendelian disorders, including familial hypercholesterolemia and insulin-resistant diabetes. Nearly one quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.

  12. Human interphase chromosomes: a review of available molecular cytogenetic technologies

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2010-01-01

    Full Text Available Abstract Human karyotype is usually studied by classical cytogenetic (banding techniques. To perform it, one has to obtain metaphase chromosomes of mitotic cells. This leads to the impossibility of analyzing all the cell types, to moderate cell scoring, and to the extrapolation of cytogenetic data retrieved from a couple of tens of mitotic cells to the whole organism, suggesting that all the remaining cells possess these genomes. However, this is far from being the case inasmuch as chromosome abnormalities can occur in any cell along ontogeny. Since somatic cells of eukaryotes are more likely to be in interphase, the solution of the problem concerning studying postmitotic cells and larger cell populations is interphase cytogenetics, which has become more or less applicable for specific biomedical tasks due to achievements in molecular cytogenetics (i.e. developments of fluorescence in situ hybridization -- FISH, and multicolor banding -- MCB. Numerous interphase molecular cytogenetic approaches are restricted to studying specific genomic loci (regions being, however, useful for identification of chromosome abnormalities (aneuploidy, polyploidy, deletions, inversions, duplications, translocations. Moreover, these techniques are the unique possibility to establish biological role and patterns of nuclear genome organization at suprachromosomal level in a given cell. Here, it is to note that this issue is incompletely worked out due to technical limitations. Nonetheless, a number of state-of-the-art molecular cytogenetic techniques (i.e multicolor interphase FISH or interpahase chromosome-specific MCB allow visualization of interphase chromosomes in their integrity at molecular resolutions. Thus, regardless numerous difficulties encountered during studying human interphase chromosomes, molecular cytogenetics does provide for high-resolution single-cell analysis of genome organization, structure and behavior at all stages of cell cycle.

  13. The mapping of novel genes to human chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Buenaventura, J.M. [Sarah Lawrence College, Bronxville, NY (United States)

    1994-12-01

    The principle goal of our laboratory is the discovery of new genes on human chromosome 19. One of the strategies to achieve this goal is through the use of cDNA clones known as {open_quotes}expressed sequence tags{close_quotes} (ESTs). ESTs, short segments of sequence from a cDNA clone that correspond to the mRNA, occur as unique regions in the genome and, therefore, can be used as markers for specific positions. In collaboration with researchers from Genethon in France, fifteen cDNA clones from a normalized human infant brain cDNA library were tested and determined to map to chromosome 19. A verification procedure is then followed to confirm assignment to chromosome 19. First, primers for each cDNA clone are developed and then amplified by polymerase chain reaction from genomic DNA. Next, a {sup 32}P-radiolabeled probe is made by polymerase chain reaction for each clone and then hybridized against filters containing an LLNL chromosome 19-specific cosmid library to find putative locations on the chromosome. The location is then verified by running a polymerase chain reactions from the positive cosmids. With the Browser database at LLNL, additional information about the positive cosmids can be found. Through use of the BLAST database at the National Library of Medicine, homologous sequences to the clones can be found. Among the fifteen cDNA clones received from Genethon, all have been amplified by polymerase chain reaction. Three have turned out as repetitive elements in the genome. Ten have been mapped to specific locations on chromosome 19. Putative locations have been found for the remaining two clones and thus verification testing will proceed.

  14. Statistical properties of nucleotides in human chromosomes 21 and 22

    International Nuclear Information System (INIS)

    Zhang Linxi; Sun Tingting

    2005-01-01

    In this paper the statistical properties of nucleotides in human chromosomes 21 and 22 are investigated. The n-tuple Zipf analysis with n = 3, 4, 5, 6, and 7 is used in our investigation. It is found that the most common n-tuples are those which consist only of adenine (A) and thymine (T), and the rarest n-tuples are those in which GC or CG pattern appears twice. With the n-tuples become more and more frequent, the double GC or CG pattern becomes a single GC or CG pattern. The percentage of four nucleotides in the rarest ten and the most common ten n-tuples are also considered in human chromosomes 21 and 22, and different behaviors are found in the percentage of four nucleotides. Frequency of appearance of n-tuple f(r) as a function of rank r is also examined. We find the n-tuple Zipf plot shows a power-law behavior for r n-1 and a rapid decrease for r > 4 n-1 . In order to explore the interior statistical properties of human chromosomes 21 and 22 in detail, we divide the chromosome sequence into some moving windows and we discuss the percentage of ξη (ξ, η = A, C, G, T) pair in those moving windows. In some particular regions, there are some obvious changes in the percentage of ξη pair, and there maybe exist functional differences. The normalized number of repeats N 0 (l) can be described by a power law: N 0 (l) ∼ l -μ . The distance distributions P 0 (S) between two nucleotides in human chromosomes 21 and 22 are also discussed. A two-order polynomial fit exists in those distance distributions: log P 0 (S) = a + bS + cS 2 , and it is quite different from the random sequence

  15. A role for Aurora C in the chromosomal passenger complex during human preimplantation embryo development

    NARCIS (Netherlands)

    Santos, Margarida Avo; van de Werken, Christine; de Vries, Marieke; Jahr, Holger; Vromans, Martijn J. M.; Laven, Joop S. E.; Fauser, Bart C.; Kops, Geert J.; Lens, Susanne M.; Baart, Esther B.

    BACKGROUND: Human embryos generated by IVF demonstrate a high incidence of chromosomal segregation errors during the cleavage divisions. To analyse underlying molecular mechanisms, we investigated the behaviour of the chromosomal passenger complex (CPC) in human oocytes and embryos. This important

  16. DNA amount of X and B chromosomes in the grasshoppers Eyprepocnemis plorans and Locusta migratoria.

    Science.gov (United States)

    Ruiz-Ruano, F J; Ruiz-Estévez, M; Rodríguez-Pérez, J; López-Pino, J L; Cabrero, J; Camacho, J P M

    2011-01-01

    We analyzed the DNA amount in X and B chromosomes of 2 XX/X0 grasshopper species (Eyprepocnemis plorans and Locusta migratoria), by means of Feulgen image analysis densitometry (FIAD), using previous estimates in L. migratoria as standard (5.89 pg). We first analyzed spermatids of 0B males and found a bimodal distribution of integrated optical densities (IODs), suggesting that one peak corresponded to +X and the other to -X spermatids. The difference between the 2 peaks corresponded to the X chromosome DNA amount, which was 1.28 pg in E. plorans and 0.80 pg in L. migratoria. In addition, the +X peak in E. plorans gave an estimate of the C-value in this species (10.39 pg). We next analyzed diplotene cells from 1B males in E. plorans and +B males in L. migratoria (a species where Bs are mitotically unstable and no integer B number can be defined for an individual) and measured B chromosome IOD relative to X chromosome IOD, within the same cell, taking advantage of the similar degree of condensation for both positively heteropycnotic chromosomes at this meiotic stage. From this proportion, we estimated the DNA amount for 3 different B chromosome variants found in individuals from 3 E. plorans Spanish populations (0.54 pg for B1 from Saladares, 0.51 pg for B2 from Salobreña and 0.64 for B24 from Torrox). Likewise, we estimated the DNA amount of the B chromosome in L. migratoria to be 0.15 pg. To automate measurements, we wrote a GPL3 licensed Python program (pyFIA). We discuss the utility of the present approach for estimating X and B chromosome DNA amount in a variety of situations, and the meaning of the DNA amount estimates for X and B chromosomes in these 2 species. Copyright © 2011 S. Karger AG, Basel.

  17. Social cognition and underlying cognitive mechanisms in children with an extra X chromosome : a comparison with autism spectrum disorder

    NARCIS (Netherlands)

    van Rijn, S.; Stockmann, L.; van Buggenhout, G.; van Ravenswaaij-Arts, C.; Swaab, H.

    Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with

  18. Distribution of X-ray-induced chromosome breakpoints in Down syndrome lymphocytes

    International Nuclear Information System (INIS)

    Shafik, H.M.; Au, W.W.; Whorton, E.B. Jr.; Legator, M.S.

    1990-01-01

    Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X-rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X-rays. Cells were harvested after 3 days in culture and 193 G-banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P less than 0.05). These 16 bands are also found to be locations of cancer breakpoints, oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be initiated in the transformation process. We propose that similar stable and site-specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia

  19. Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome.

    Science.gov (United States)

    Chauhan, Pooja; Jaiswal, Sushil Kumar; Lakhotia, Anjali Rani; Rai, Amit Kumar

    2016-09-01

    In the present study, we reported two cases of TS with mosaic ring X chromosome showing common clinical characteristics of TS like growth retardation and ovarian dysfunction. The purpose of the present study was to cytogenetically characterize both cases. Whole blood culture and G-banding were performed for karyotyping the cases following standard protocol. Origin of the ring chromosome and degree of mosaicism were further determined by fluorescence in situ hybridization (FISH). Breakpoints and loss of genetic material in formation of different ring X chromosomes r (X) in cases were determined with the help of cytogenetic microarray. Cases 1 and 2 with ring chromosome were cytogenetically characterized as 45, X [114]/46Xr (X) (p22.11q21.32) [116] and 45, X [170]/46, Xr (X) (p22.2q21.33) [92], respectively. Sizes of these ring X chromosomes were found to be ~75 and ~95 Mb in cases 1 and 2, respectively, using visual estimation as part of cytogenetic observation. In both cases, we observed breakpoints on Xq chromosome were within relatively narrow region between Xq21.33 and Xq22.1 compared to regions in previously reported cases associated with ovarian dysgenesis. Our observation agrees with the fact that despite of large heterogeneity, severity of the cases with intact X-inactive specific transcript (XIST) is dependent on degree of mosaicism and extent of Xq deletion having crucial genes involved directly or indirectly in various physiological involving ovarian cyclicity.

  20. NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively

    Energy Technology Data Exchange (ETDEWEB)

    Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)] [and others

    1997-03-01

    NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.

  1. Standard guidelines for the chromosome-centric human proteome project.

    Science.gov (United States)

    Paik, Young-Ki; Omenn, Gilbert S; Uhlen, Mathias; Hanash, Samir; Marko-Varga, György; Aebersold, Ruedi; Bairoch, Amos; Yamamoto, Tadashi; Legrain, Pierre; Lee, Hyoung-Joo; Na, Keun; Jeong, Seul-Ki; He, Fuchu; Binz, Pierre-Alain; Nishimura, Toshihide; Keown, Paul; Baker, Mark S; Yoo, Jong Shin; Garin, Jerome; Archakov, Alexander; Bergeron, John; Salekdeh, Ghasem Hosseini; Hancock, William S

    2012-04-06

    The objective of the international Chromosome-Centric Human Proteome Project (C-HPP) is to map and annotate all proteins encoded by the genes on each human chromosome. The C-HPP consortium was established to organize a collaborative network among the research teams responsible for protein mapping of individual chromosomes and to identify compelling biological and genetic mechanisms influencing colocated genes and their protein products. The C-HPP aims to foster the development of proteome analysis and integration of the findings from related molecular -omics technology platforms through collaborations among universities, industries, and private research groups. The C-HPP consortium leadership has elicited broad input for standard guidelines to manage these international efforts more efficiently by mobilizing existing resources and collaborative networks. The C-HPP guidelines set out the collaborative consensus of the C-HPP teams, introduce topics associated with experimental approaches, data production, quality control, treatment, and transparency of data, governance of the consortium, and collaborative benefits. A companion approach for the Biology and Disease-Driven HPP (B/D-HPP) component of the Human Proteome Project is currently being organized, building upon the Human Proteome Organization's organ-based and biofluid-based initiatives (www.hupo.org/research). The common application of these guidelines in the participating laboratories is expected to facilitate the goal of a comprehensive analysis of the human proteome.

  2. Termini of human chromosomes display elevated rates of mitotic recombination.

    Science.gov (United States)

    Cornforth, M N; Eberle, R L

    2001-01-01

    The strand-specific in situ hybridization technique of CO-FISH was used to probe telomeres of human mitotic cells in order to determine the spontaneous frequency of crossover. This approach allowed the detection of recombinational crossovers occurring anywhere along the length of individual chromosomes, including reciprocal events taking place between sister chromatids. Although the process of sister chromatid exchange (SCE) is the most prominent type of recombination in somatic mammalian cells, our results show that SCEs accounted for less than a third of the recombinational events revealed by CO-FISH. It is concluded that chromosomal regions near the termini of chromosome arms undergo extraordinarily high rates of spontaneous recombination, producing terminal crossovers whose small size precludes detection by standard cytogenetic methods. That similar results were observed for transformed epithelial cells, as well as primary fibroblasts, suggests that the phenomenon is a common characteristic of human cells. These findings are noteworthy because, although telomeric and subtelomeric DNA is known to be preferentially involved in certain types of recombination, the tips of somatic mammalian chromosomes have not previously been identified as preferred sites for crossover. Implications of these results are discussed in terms of limitations imposed on CO-FISH for its proposed use in directional hybridization mapping.

  3. Hexavalent chromium induces chromosome instability in human urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Sandra S. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Liou, Louis [Department of Pathology, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 (United States); Adam, Rosalyn M. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Wise, John Pierce Sr., E-mail: john.wise@louisville.edu [Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States)

    2016-04-01

    Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

  4. Different radiosensitization effects of the halogenated compounds on the human chromosome in vitro

    International Nuclear Information System (INIS)

    Kang, Y.S.

    1976-01-01

    Unscheduled DNA synthesis and chromosome aberrations were compared following X- or UV-irradiation or methyl methanesulfonate treatment in cultures of HeLa S 3 or KB cells or human and rabbit lymphocytes. The sensitization by incorporation of the halouridines BUdR and IUdR was also investigated. Unscheduled DNA synthesis occurred in two established cell lines after irradiation with 0 to 10 kR of X-rays. The rate of unscheduled synthesis was dose dependent and differed for the two cell lines. The unscheduled synthesis was not correlated with the modal chromosome number nor with the number of aberrations produced. UV-irradiated rabbit lymphocytes exhibited unscheduled DNA synthesis which saturated after a dose of 250 ergs/mm 2 . In contrast the incorporation of BUdR or IUdR eliminated this saturation and caused an increasing effect with increasing dose up to 1000 ergs/mm 2 . The degree of sensitization varied between the two halo-uridines, BUdR being more effective at high doses while IUdR was a more potent sensitizer at low doses. Chromosome aberrations were not directly related to unscheduled DNA synthesis but were sensitized by halo-uridine incorporation. In this case IUdR was more potent than BUdR at all doses studied. Methyl methanesulfonate was an effective producer of chromosome aberration in human lymphocytes of both the chromosome and chromatid type. Prior incorporation of BUdR or IUdR did not increase the total aberration produced but did increase the number of chromosome type aberration at the expense of the chromatid type

  5. A scale invariant clustering of genes on human chromosome 7

    Directory of Open Access Journals (Sweden)

    Kendal Wayne S

    2004-01-01

    Full Text Available Abstract Background Vertebrate genes often appear to cluster within the background of nontranscribed genomic DNA. Here an analysis of the physical distribution of gene structures on human chromosome 7 was performed to confirm the presence of clustering, and to elucidate possible underlying statistical and biological mechanisms. Results Clustering of genes was confirmed by virtue of a variance of the number of genes per unit physical length that exceeded the respective mean. Further evidence for clustering came from a power function relationship between the variance and mean that possessed an exponent of 1.51. This power function implied that the spatial distribution of genes on chromosome 7 was scale invariant, and that the underlying statistical distribution had a Poisson-gamma (PG form. A PG distribution for the spatial scattering of genes was validated by stringent comparisons of both the predicted variance to mean power function and its cumulative distribution function to data derived from chromosome 7. Conclusion The PG distribution was consistent with at least two different biological models: In the microrearrangement model, the number of genes per unit length of chromosome represented the contribution of a random number of smaller chromosomal segments that had originated by random breakage and reconstruction of more primitive chromosomes. Each of these smaller segments would have necessarily contained (on average a gamma distributed number of genes. In the gene cluster model, genes would be scattered randomly to begin with. Over evolutionary timescales, tandem duplication, mutation, insertion, deletion and rearrangement could act at these gene sites through a stochastic birth death and immigration process to yield a PG distribution. On the basis of the gene position data alone it was not possible to identify the biological model which best explained the observed clustering. However, the underlying PG statistical model implicated neutral

  6. Y chromosome diversity, human expansion, drift, and cultural evolution.

    Science.gov (United States)

    Chiaroni, Jacques; Underhill, Peter A; Cavalli-Sforza, Luca L

    2009-12-01

    The relative importance of the roles of adaptation and chance in determining genetic diversity and evolution has received attention in the last 50 years, but our understanding is still incomplete. All statements about the relative effects of evolutionary factors, especially drift, need confirmation by strong demographic observations, some of which are easier to obtain in a species like ours. Earlier quantitative studies on a variety of data have shown that the amount of genetic differentiation in living human populations indicates that the role of positive (or directional) selection is modest. We observe geographic peculiarities with some Y chromosome mutants, most probably due to a drift-related phenomenon called the surfing effect. We also compare the overall genetic diversity in Y chromosome DNA data with that of other chromosomes and their expectations under drift and natural selection, as well as the rate of fall of diversity within populations known as the serial founder effect during the recent "Out of Africa" expansion of modern humans to the whole world. All these observations are difficult to explain without accepting a major relative role for drift in the course of human expansions. The increasing role of human creativity and the fast diffusion of inventions seem to have favored cultural solutions for many of the problems encountered in the expansion. We suggest that cultural evolution has been subrogating biologic evolution in providing natural selection advantages and reducing our dependence on genetic mutations, especially in the last phase of transition from food collection to food production.

  7. Root length in the permanent teeth of women with an additional X chromosome (47,XXX females).

    Science.gov (United States)

    Lähdesmäki, Raija E; Alvesalo, Lassi J

    2010-07-01

    Previous studies have demonstrated differential effects of the X and Y chromosomes on dental development. The expression of sexual dimorphism in terms of tooth size, shape, number and developmental timing has been explained especially by Y chromosome influence. The Y chromosome promotes enamel, crown and root dentin development. The X chromosome has an effect on enamel deposition. The aim of this research is to study the influence of the extra X chromosome on the development of permanent tooth root length. The study subjects (all of whom were from the Kvantti Dental Research Project) were seven 47,XXX females, five female relatives and 51 and 52 population control men and women, respectively. Measurements were made from panoramic radiographs on available permanent teeth by a digital calliper according to established procedures. The results showed that the maxillary root lengths of the 47,XXX females were of the same magnitude as those in normal women, but the mandibular root lengths were longer in 47,XXX females than in normal men or women. Increased enamel thickness in the teeth of 47,XXX females is apparently caused by the active enamel gene in all X chromosomes having no increased influence on crown dentin formation. These results in 47,XXX females indicate an increase in root dentin development, at least in the mandible, which together with the data on crown formation reflects a continuous long-lasting effect of the X chromosome on dental development.

  8. Cell killing and chromosomal aberration induced by heavy-ion beams in cultured human tumor cells

    International Nuclear Information System (INIS)

    Takakura, K.; Funada, A.; Mohri, M.; Lee, R.; Aoki, M.; Furusawa, Y.; Gotoh, E.

    2003-01-01

    Full text: To clarify the relation between cell death and chromosomal aberration in cultured human tumor cells irradaited with heavy-ion beams. The analyses were carried out on the basis of the linear energy transfer (LET) values of heavy ion beams as radiation source. Exponentially growing human tumor cells, Human Salivary Gland Tumor cells (HSG cells), were irradiated with various high energy heavy ions, such as 13 keV/micrometer carbon (C) ions as low LET charged particle radiation source, 120 keV/ micrometer carbon (C) ions and 440 keV/micrometer iron (Fe) ions as high LET charged particle radiation sources.The cell death was analysed by the colony formation method, and the chromosomal aberration and its repairing kinetics was analysed by prematurely chromosome condensation method (PCC method) using calyculin A. Chromatid-type breaks, isochromatid breaks and exchanges were scored for the samples from the cells keeping with various incubation time after irradiation. The LET dependence of the cell death was similar to that of the chromosome exchange formation after 12 hours incubation. A maximum peak was around 120 keV/micrometer. However it was not similar to the LET dependence of isochromatid breaks or chromatid breaks after 12 hours incubation. These results suggest that the exchanges formed in chromosome after irradiation should be one of essential causes to lead the cell death. The different quality of induced chromosome damage between high-LET and low-LET radiation was also shown. About 89 % and 88 % chromatid breaks induced by X rays and 13 keV/micrometer C ions were rejoined within 12 hours of post-irradiation, though only 71% and 58 % of chromatid breaks induced by 120 keV/micrometer C ions and 440 keV/micrometer Fe ions were rejoined within 12 hours of post-irradiation

  9. Cytogenetic evaluation of Fansidar on human lymphocyte chromosomes in vitro.

    Science.gov (United States)

    Praveen, Nuzhat; Saifi, Muheet Alam; Shadab, G G H A

    2011-01-01

    Fansidar is a fixed combination of two antimalarial agents a diaminopyrimidine (Pyrimethamine) and a sulphonamide (Sulphadoxine) in the ratio 1:20- that have been used extensively worldwide for the treatment of Chloroquine resistant Plasmodium falciparum malaria, toxoplasmosis and Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. This study examined the effect of Fansidar on chromosomes in human lymphocyte culture. Fansidar was added to peripheral blood lymphocyte cultures in vitro at four different concentrations: 5,15, 25 and 50 microl in the ratio 1:20, 3:60, 5:100 and 10:200 microg ml(-1). Result shows that this drug induces moderate increase in the frequency of gaps, breaks and rearrangements. Therefore it can be concluded that Fansidar has moderate clastogenic effect on human chromosomes in vitro.

  10. Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Good

    2010-09-01

    Full Text Available The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

  11. Widespread Over-Expression of the X Chromosome in Sterile F1 Hybrid Mice

    Science.gov (United States)

    Good, Jeffrey M.; Giger, Thomas; Dean, Matthew D.; Nachman, Michael W.

    2010-01-01

    The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F1 males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F1 hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility. PMID:20941395

  12. Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

    Science.gov (United States)

    Good, Jeffrey M; Giger, Thomas; Dean, Matthew D; Nachman, Michael W

    2010-09-30

    The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

  13. New insights into human nondisjunction of chromosome 21 in oocytes.

    Directory of Open Access Journals (Sweden)

    Tiffany Renee Oliver

    2008-03-01

    Full Text Available Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1 a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2 a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.

  14. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes as a biomar......We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  15. An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

    Science.gov (United States)

    Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

    2016-01-01

    Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover

  16. Effect of x-rays on the somatic chromosomes of the exotic fish, Tilapia mossambica

    Energy Technology Data Exchange (ETDEWEB)

    Manna, G.K.; Som, R.C. (Kalyani Univ. (India). Dept. of Zoology)

    1982-03-01

    Male and female T. mossambica were x-rayed with 100 r and the metaphase chromosome aberrations in their gill epithelia were studied at 13 different intervals against suitable control. The chromosomes of males appeared more radio-sensitive than those of females. Among the diploid complement of 44 chromosomes, the individual type aberrations were non-random in both sexes. The longest pair of chromosomes, taken as the marker pair, was found very highly radio-sensitive, while the remaining 21 pairs as non-markers were somewhat resistant to x-radiation when the observed and the expected numbers were subjected to statistical analysis. The break in the marker chromosome was also non-randomly distributed as the distal half had a significantly large number of breaks.

  17. Human male infertility, the Y chromosome, and dinosaur extinction

    Directory of Open Access Journals (Sweden)

    Sherman J. Silber

    2011-06-01

    Our studies of the Y chromosome and male infertility suggest that the default mechanism for determining the sex of offspring is the temperature of egg incubation, and that genetic sex determination (based on sex chromosomes like X and Y has evolved many times over and over again in different ways, in different genera, as a more foolproof method than temperature variation of assuring a balanced sex ratio in offspring. The absence of such a genetic sex determining mechanism in dinosaurs may have led to a skewed sex ratio when global temperature dramatically changed 65,000,000 years ago, resulting in a preponderance of males, and consequentially a rapid decline in population.

  18. Chromosome segregation regulation in human zygotes : Altered mitotic histone phosphorylation dynamics underlying centromeric targeting of the chromosomal passenger complex

    NARCIS (Netherlands)

    Van De Werken, C.; Avo Santos, M.; Laven, J. S E; Eleveld, C.; Fauser, B. C J M; Lens, S. M A; Baart, E. B.

    2015-01-01

    STUDY QUESTION Are the kinase feedback loops that regulate activation and centromeric targeting of the chromosomal passenger complex (CPC), functional during mitosis in human embryos? SUMMARY ANSWER Investigation of the regulatory kinase pathways involved in centromeric CPC targeting revealed normal

  19. DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription.

    Directory of Open Access Journals (Sweden)

    Natasha M Zamudio

    Full Text Available Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L, have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an auto-regulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative non-coding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter's and Turner's syndromes.

  20. Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1996-04-15

    Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

  1. Identification of selection footprints on the X chromosome in pig.

    Directory of Open Access Journals (Sweden)

    Yunlong Ma

    Full Text Available Identifying footprints of selection can provide a straightforward insight into the mechanism of artificial selection and further dig out the causal genes related to important traits. In this study, three between-population and two within-population approaches, the Cross Population Extend Haplotype Homozygosity Test (XPEHH, the Cross Population Composite Likelihood Ratio (XPCLR, the F-statistics (Fst, the Integrated Haplotype Score (iHS and the Tajima's D, were implemented to detect the selection footprints on the X chromosome in three pig breeds using Illumina Porcine60K SNP chip. In the detection of selection footprints using between-population methods, 11, 11 and 7 potential selection regions with length of 15.62 Mb, 12.32 Mb and 9.38 Mb were identified in Landrace, Chinese Songliao and Yorkshire by XPEHH, respectively, and 16, 13 and 17 potential selection regions with length of 15.20 Mb, 13.00 Mb and 19.21 Mb by XPCLR, 4, 2 and 4 potential selection regions with length of 3.20 Mb, 1.60 Mb and 3.20 Mb by Fst. For within-population methods, 7, 10 and 9 potential selection regions with length of 8.12 Mb, 8.40 Mb and 9.99 Mb were identified in Landrace, Chinese Songliao and Yorkshire by iHS, and 4, 3 and 2 potential selection regions with length of 3.20 Mb, 2.40 Mb and 1.60 Mb by Tajima's D. Moreover, the selection regions from different methods were partly overlapped, especially the regions around 22∼25 Mb were detected under selection in Landrace and Yorkshire while no selection in Chinese Songliao by all three between-population methods. Only quite few overlap of selection regions identified by between-population and within-population methods were found. Bioinformatics analysis showed that the genes relevant with meat quality, reproduction and immune were found in potential selection regions. In addition, three out of five significant SNPs associated with hematological traits reported in our genome-wide association study were harbored in

  2. X-ray induction of autosomal translocations in spermatozoa of Drosophila melanogaster and maternal effects of X.Y-chromosomes

    International Nuclear Information System (INIS)

    Leigh, B.

    1979-01-01

    Wild-type ORK Drosophila melanogaster males were given an exposure of 3000 R X-radiation. Mature sperm were then sampled by mating to X.Y/X.Y, X.Y/X, or X/X females that carried markers on the second and third chromosomes for the detection of induced autosomal translocations. Two pairs of maternal stocks were used and heterozygous X.Y/X females were obtained by making both reciprocal crosses. The highest frequencies of induced translocations were obtained with X/X females. In one series these frequencies are higher than those obtained with either X.Y/X or X.Y/X.Y females. In the other series a uniform frequency of translocations was obtained with all types of female, except for one of the two types of heterozygous female, which gave lower frequencies. The experiments have provided data which show that the addition of Y-chromosomes to the maternal genome does not have a specific effect on the recovery of induced paternal autosomal translocations. Maternal Y-chromosomes increased the proportions of fertile F 1 males, this effect being consistent in direction but varying in degree. (Auth.)

  3. 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

  4. Chromosomal localization of the human vesicular amine transporter genes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, D.; Finn, P.; Liu, Y.; Roghani, A.; Edwards, R.H.; Klisak, I.; Kojis, T.; Heinzmann, C.; Sparkes, R.S. (UCLA School of Medicine, Los Angeles, CA (United States))

    1993-12-01

    The physiologic and behavioral effects of pharmacologic agents that interfere with the transport of monoamine neurotransmitters into vesicles suggest that vesicular amine transport may contribute to human neuropsychiatric disease. To determine whether an alteration in the genes that encode vesicular amine transport contributes to the inherited component of these disorders, the authors have isolated a human cDNA for the brain transporter and localized the human vesciular amine transporter genes. The human brain synaptic vesicle amine transporter (SVAT) shows unexpected conservation with rat SVAT in the regions that diverge extensively between rat SVAT and the rat adrenal chromaffin granule amine transporter (CGAT). Using the cloned sequences with a panel of mouse-human hybrids and in situ hybridization for regional localization, the adrenal CGAT gene (or VAT1) maps to human chromosome 8p21.3 and the brain SVAT gene (or VAT2) maps to chromosome 10q25. Both of these sites occur very close to if not within previously described deletions that produce severe but viable phenotypes. 26 refs., 3 figs., 1 tab.

  5. HACking the centromere chromatin code: insights from human artificial chromosomes.

    Science.gov (United States)

    Bergmann, Jan H; Martins, Nuno M C; Larionov, Vladimir; Masumoto, Hiroshi; Earnshaw, William C

    2012-07-01

    The centromere is a specialized chromosomal region that serves as the assembly site of the kinetochore. At the centromere, CENP-A nucleosomes form part of a chromatin landscape termed centrochromatin. This chromatin environment conveys epigenetic marks regulating kinetochore formation. Recent work sheds light on the intricate relationship between centrochromatin state, the CENP-A assembly pathway and the maintenance of centromere function. Here, we review the emerging picture of how chromatin affects mammalian kinetochore formation. We place particular emphasis on data obtained from Human Artificial Chromosome (HAC) biology and the targeted engineering of centrochromatin using synthetic HACs. We discuss implications of these findings, which indicate that a delicate balance of histone modifications and chromatin state dictates both de novo centromere formation and the maintenance of centromere identity in dividing cell populations.

  6. Low level dose induced chromosome aberrations in human blood lymphocytes

    International Nuclear Information System (INIS)

    Pohl-Rueling, J.

    1992-01-01

    Unstable structural aberrations in chromosomes of human blood lymphocytes cannot be used as biological dosemeters in the low dose range, when extrapolating from high doses using a linear dose response, as required by the original formula of the dual radiation action theory. A survey is given of experimental dose-response curves of chromosome aberrations, obtained in investigations not only by this institute, in cooperation with many other laboratories, but also by various authors in different areas of the world. The results are not compatible with the predicted linear dose relationships at in vivo dose ranges up to 30 mGy.y -1 . The aberration frequencies rise sharply with dose within the normal environmental exposure up to about twice that level. At higher doses, aberration frequencies increase less rapidly and reach a plateau. Some in vitro experiments of various authors with higher doses of low LET radiations, up to about 400 mGy have found dose responses with steps. (author)

  7. Chromosome surveys of human populations: between epidemiology and anthropology.

    Science.gov (United States)

    de Chadarevian, Soraya

    2014-09-01

    It is commonly held that after 1945 human genetics turned medical and focussed on the individual rather than on the study of human populations that had become discredited. However, a closer look at the research practices at the time quickly reveals that human population studies, using old and new tools, prospered in this period. The essay focuses on the rise of chromosome analysis as a new tool for the study of human populations. It reviews a broad array of population studies ranging from newborn screening programmes to studies of isolated or 'primitive' people. Throughout, it highlights the continuing role of concerns and opportunities raised by the propagation of atomic energy for civilian and military uses, the collection of large data bases and computers, and the role of international organisations like the World Health Organisation and the International Biological Programme in shaping research agendas and carving out a space for human heredity in the postwar era. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Unique Case Reports Associated with Ovarian Failure: Necessity of Two Intact X Chromosomes

    Directory of Open Access Journals (Sweden)

    Lakshmi Rao Kandukuri

    2012-01-01

    Full Text Available Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months with low level of oestrogen and raised level of Luteinizing Hormone (LH and Follicle Stimulating Hormone (FSH > 20 IU/l occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22 and q28 and (mos,45XO/46,X+ringX involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.

  9. A pericentric inversion of chromosome X disrupting F8 and resulting in haemophilia A.

    Science.gov (United States)

    Xin, Yu; Zhou, Jingyi; Ding, Qiulan; Chen, Changming; Wu, Xi; Wang, Xuefeng; Wang, Hongli; Jiang, Xiaofeng

    2017-08-01

    The frequency of X chromosome pericentric inversion is much less than that of autosome chromosome. We hereby characterise a pericentric inversion of X chromosome associated with severe factor VIII (FVIII) deficiency in a sporadic haemophilia A (HA) pedigree. PCR primer walking and genome walking strategies were adopted to identify the exact breakpoints of the inversion. Copy number variations (CNVs) of the F8 and the whole chromosomes were detected by AccuCopy and Affymetrix CytoScan High Definition (HD) assays, respectively. A karyotype analysis was performed by cytogenetic G banding technique. We identified a previously undescribed type of pericentric inversion of the X chromosome [inv(X)(p11.21q28)] in the proband with FVIII:C inversion segment was approximately 64.4% of the total chromosomal length. The karyotype analysis of the X chromosome confirmed the pericentric inversion of the X chromosome in the proband and his mother. A haplotype analysis traced the inversion to his maternal grandfather, who was not a somatic mosaic of the inversion. This finding indicated that the causative mutation may originate from his germ cells or a rare possibility of germ-cell mosaicism. The characterisation of pericentric inversion involving F8 extended the molecular mechanisms causing HA. The pericentric inversion rearrangement involves F8 by non-homologous end joining is responsible for pathogensis of severe HA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

    Science.gov (United States)

    Inda, María del Mar; Fan, Xing; Muñoz, Jorge; Perot, Christine; Fauvet, Didier; Danglot, Giselle; Palacio, Ana; Madero, Pilar; Zazpe, Idoya; Portillo, Eduardo; Tuñón, Teresa; Martínez-Peñuela, José María; Alfaro, Jorge; Eiras, José; Bernheim, Alain; Castresana, Javier S

    2003-01-01

    Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss. Copyright 2002 Wiley-Liss, Inc.

  11. Human Chromosome 21: Mapping of the chromosomes and cloning of cDNAs

    Energy Technology Data Exchange (ETDEWEB)

    Antonarakis, S.E.

    1991-09-01

    The objective of the research funded by DOE grant DE-FG02-89ER60857 from 6/15/89 to 8/31/91 was to contribute to the physical mapping of human chromosome 21 (HC21) by cloning large fragments of DNA into Yeast Artificial Chromosomes (YACs) and identify YACs that map on HC21. A total of 54 sequence tagged sites (STS) have been developed and mapped in our laboratory to HC21 and can be used as initial reference points for YAC identification and construction of overlapping clones. A small YAC library was constructed which is HC21 specific. DNA from somatic cell hybrid WAV17 or from flow-sorted HC21 was partially digested with EcoRI, ligated into vectors PJS97, PJS98, and YACs have been obtained with average size insert of more than 300 kb. This library has been deposited in D. Patterson's lab for the Joint YAC screening effort. Additional YAC libraries from ICI Pharmaceuticals or from Los Alamos National Laboratories have been screened with several STS and positive YACs have been identified. Work in progress includes screening of YAC libraries in order to construct overlapping clones, characterization of the cloning ends of YACs, characterization of additional STS and cloning of HC21 specific cDNAs. 15 refs., 2 figs., 5 tabs.

  12. Chromosomal sensitivity to X-rays in lymphocytes from patients with Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Heras, J G; Coco, R

    1986-03-01

    Lymphocytes from patients with Turner syndrome were irradiated with X-rays to determine the chromosomal aberration frequency in first-division metaphases. Five patients with 45,X karyotype; three 45,X/46,Xi(X)q mosaics; one 45,X/47,XXX mosaic and 9 female controls were studied. Patients with a 45,X karyotype exhibited a radioinduced chromosomal aberration frequency similar to controls. In the mosaics, 45,X cells has a mean frequency of 38.75 +- 2.16; 46,Xi(X)q cells a mean of 38 +- 2.16 and the control group a rate of 36.25 +- 4.32. No differences were observed between 45,X and 46,Xi(X)q cells, 45,X and normal cells or 46,Xi(X)q and normal cells. Apparently neither the X monosomy nor the Xq isochromosome influences the in vitro X-ray-induced chromosomal damage in Turner syndrome lymphocytes. (Auth.). 29 references, 4 tables.

  13. Sequence and expression analysis of gaps in human chromosome 20

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Seemann, Stefan; Mang, Yuan

    2012-01-01

    /or overlap disease-associated loci, including the DLGAP4 locus. In this study, we sequenced ~99% of all three unfinished gaps on human chr 20, determined their complete genomic sizes and assessed epigenetic profiles using a combination of Sanger sequencing, mate pair paired-end high-throughput sequencing......The finished human genome-assemblies comprise several hundred un-sequenced euchromatic gaps, which may be rich in long polypurine/polypyrimidine stretches. Human chromosome 20 (chr 20) currently has three unfinished gaps remaining on its q-arm. All three gaps are within gene-dense regions and...... and chromatin, methylation and expression analyses. We found histone 3 trimethylated at Lysine 27 to be distributed across all three gaps in immortalized B-lymphocytes. In one gap, five novel CpG islands were predominantly hypermethylated in genomic DNA from peripheral blood lymphocytes and human cerebellum...

  14. Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kraft, Daniela, E-mail: d.kraft@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Ritter, Sylvia, E-mail: s.ritter@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Durante, Marco, E-mail: m.durante@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Institute for Condensed Matter Physics, Physics Department, Technical University Darmstadt, Hochschulstraße 6-8, 64289 Darmstadt (Germany); Seifried, Erhard, E-mail: e.seifried@blutspende.de [Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Fournier, Claudia, E-mail: c.fournier@gsi.de [GSI Helmholtz Center for Heavy Ion Research, Department of Biophysics, Planckstr. 1, 64291 Darmstadt (Germany); Tonn, Torsten, E-mail: t.tonn@blutspende.de [Institute for Transfusion Medicine und Immunohematology, DRK-Blutspendedienst Baden-Wuerttemberg—Hessen, Johann Wolfgang Goethe-University Hospital, Sandhofstrasse 1, 60528 Frankfurt (Germany); Technische Universität Dresden, Med. Fakultät Carl Gustav Carus, Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Blasewitzer Straße 68/70, 01307 Dresden (Germany)

    2015-07-15

    Highlights: • Radiation induced formation and transmission of chromosomal aberrations were assessed. • Cytogenetic analysis was performed in human CD34+ HSPC by mFISH. • We report transmission of stable aberrations in irradiated, clonally expanded HSPC. • Unstable aberrations in clonally expanded HSPC occur independently of irradiation. • Carbon ions and X-rays bear a similar risk for propagation of cytogenetic changes. - Abstract: In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34{sup +} cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60–85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼30–35% apoptotic cells for 2 Gy carbon ions compared to ∼25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼70% and

  15. A new species of Endecous Saussure, 1878 (Orthoptera, Gryllidae) from northeast Brazil with the first X1X20 chromosomal sex system in Gryllidae.

    Science.gov (United States)

    Zefa, Edison; Redü, Darlan Rutz; Da Costa, Maria Kátia Matiotti; Fontanetti, Carmem S; Gottschalk, Marco Silva; Padilha, Giovanna Boff; Fernandes e Silva, Anelise; Martins, Luciano De P

    2014-08-06

    In this paper we describe a new species of Luzarinae cricket collected from the cave "Gruta de Ubajara, municipality of Ubajara, State of Ceará, Brazil, highlighting phallic sclerites morphology and chromosome complement as diagnostic characters. We presented meiotic and mitotic characterization in order to define the karyotype with 2n = 12 + X1X2♂/12 + X1X1X2X2♀. This represents the first record of X1X20 chromosomal sex system in Gryllidae.

  16. Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Chiurazzi, P.; Genuardi, M.; Kozak, L.; Neri, G. [Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy)] [and others

    1996-07-12

    A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10{sup -6/-7}) CGG repeat slippage events and/or loss of a stabilizing AGG via A-to-C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10{sup -4/-5}) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.

  17. X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids

    Czech Academy of Sciences Publication Activity Database

    Bhattacharyya, Tanmoy; Reifová, R.; Gregorová, Soňa; Šimeček, Petr; Gergelits, Václav; Mistrik, M.; Martincová, Iva; Piálek, Jaroslav; Forejt, Jiří

    2014-01-01

    Roč. 10, č. 2 (2014), e1004088 ISSN 1553-7404 R&D Projects: GA AV ČR Premium Academiae of the Academy of Sciences of the Czech Republic; GA MŠk(CZ) LD11079; GA ČR GA206/08/0640; GA MŠk ED1.1.00/02.0109 Institutional support: RVO:68081766 ; RVO:68378050 Keywords : hybrid sterility * meiotic asynapsis * chromosome substitution strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.167, year: 2013

  18. Screening human populations for chromosome damage. Progress report, March 1982-November 1982

    International Nuclear Information System (INIS)

    Norman, A.

    1982-01-01

    The micronuclear counts in 73 relatively young and healthy patients obtained in previous studies were examined. The natural logarithm of the micronuclear counts (LMNC) was approximately normally distributed so we have tested the effects of age, sex, and medical x-ray exposure on the counts. The results show a clear dependence of micronuclear counts on age, and demonstrate that studies of chromosome damage in radiation workers or in other populations exposed to radiation may be misinterpreted if the effects of age and medical x-ray examinations are not controlled. The results also show that the variability in LNMC among the individuals examined cannot be accounted for totally by the factors of age, sex, or medical x-rays. There are at least two other important sources of variation: counting statistics and degree of lymphocyte proliferation. A single set of harlequin stained cells may be sufficient for estimating micronuclear yields, the degree of lymphocyte proliferation, and possibly the frequency of chromosome aberrations. These results point to the usefulness of the micronucleus assay for screening human populations for chromosome damage

  19. The effects of severe mixed environmental pollution on human chromosomes.

    Science.gov (United States)

    Katsantoni, A; Nakou, S; Antoniadou-Koumatou, I; Côté, G B

    1986-01-01

    Cytogenetic studies were conducted on healthy young mothers, shortly after child birth, in two residential areas each with an approximate population of 20,000, situated about 25 km from Athens, Greece. One of the areas, Elefsis, is subject to severe mixed industrial pollution, and the other, Koropi, is relatively free of pollution. Chromosomal aberrations were investigated in 16 women from each area in 72 hour lymphocyte cultures treated with gentian violet to enhance any chromosomal instability induced by the pollution. The women were of a comparable socioeconomic level, aged between 20 and 31 years, and with no history of factors associated with mutagenesis. Venous blood samples were taken from the two groups and processed concurrently. The slides were coded and examined independently by two observers, who were unaware of the source of the samples. A total of 100 cells was examined on each sample. The two observers obtained highly comparable results. Women from Elefsis had an average of 0.42 anomalies per cell and those from Koropi had 0.39. The absence of a statistically significant difference between the two groups clearly shows that the severe mixed environmental pollution of Elefsis has no significant visible effect on human chromosomes in most residents. However, two Elefsis women had abnormal results and could be at risk. Their presence is not sufficient to raise significantly their group's average, but the induction by pollution of an increased rate of chromosomal anomalies in only a few people at risk could account for the known association between urban residence and cancer mortality. PMID:3783622

  20. Cloning and chromosomal localization of the three human syntrophin genes

    Energy Technology Data Exchange (ETDEWEB)

    Feener, C.A.; Anderson, M.D.S.; Selig, S. [Children`s Hospital, Boston, MA (United States)] [and others

    1994-09-01

    Dystrophin, the protein product the Duchenne muscular dystrophy locus, is normally found to be associated with a complex of proteins. Among these dystrophin-associated proteins are the syntrophins, a group of 59 kDa membrane-associated proteins. When the syntrophins are purified based upon their association with dystrophin, they have been shown previously to form two distinct groups, the acidic ({alpha}) and basic ({beta}) forms. Based on peptide and rodent cDNA sequences, three separate syntrophin genes have been cloned and characterized from human tissues. The predicted amino acid sequences from these cDNA reveal that these proteins are related but are distinct with respect to charge, as predicted from their biochemistry. The family consists of one acidic ({alpha}-syntrophin, analogous to mouse syntrophin-1) and two basic ({beta}{sub 1}-syntrophin; and {beta}{sub 2}-syntrophin, analogous to mouse syntrophin-2) genes. Each of the three genes are widely expressed in a variety of human tissues, but the relative abundance of the three are unique with respect to each other. {alpha}-syntrophin is expressed primarily in skeletal muscle and heart as a single transcript. {beta}{sub 1}-syntrophin is expressed widely in up to five distinct transcript sizes, and is most abundant in brain. The human chromosomal locations of the three syntrophins are currently being mapped. {beta}{sub 1}-syntrophin maps to chromosome 8q23-24 and {beta}{sub 2}-syntrophin to chromosome 16. The {alpha}-syntrophin gene will be mapped accordingly. Although all three genes are candidates for neuromuscular diseases, the predominant expression of {alpha}-syntrophin in skeletal muscle and heart makes it a strong candidate to be involved in a neuromuscular disease.

  1. Tissue-specific features of the X chromosome and nucleolus spatial dynamics in a malaria mosquito, Anopheles atroparvus.

    Science.gov (United States)

    Bondarenko, Semen M; Artemov, Gleb N; Sharakhov, Igor V; Stegniy, Vladimir N

    2017-01-01

    Spatial organization of chromosome territories is important for maintenance of genomic stability and regulation of gene expression. Recent studies have shown tissue-specific features of chromosome attachments to the nuclear envelope in various organisms including malaria mosquitoes. However, other spatial characteristics of nucleus organization, like volume and shape of chromosome territories, have not been studied in Anopheles. We conducted a thorough analysis of tissue-specific features of the X chromosome and nucleolus volume and shape in follicular epithelium and nurse cells of the Anopheles atroparvus ovaries using a modern open-source software. DNA of the polytene X chromosome from ovarian nurse cells was obtained by microdissection and was used as a template for amplification with degenerate oligo primers. A fluorescently labeled X chromosome painting probe was hybridized with formaldehyde-fixed ovaries of mosquitoes using a 3D-FISH method. The nucleolus was stained by immunostaining with an anti-fibrillarin antibody. The analysis was conducted with TANGO-a software for a chromosome spatial organization analysis. We show that the volume and position of the X chromosome have tissue-specific characteristics. Unlike nurse cell nuclei, the growth of follicular epithelium nuclei is not accompanied with the proportional growth of the X chromosome. However, the shape of the X chromosome does not differ between the tissues. The dynamics of the X chromosome attachment regions location is tissue-specific and it is correlated with the process of nucleus growth in follicular epithelium and nurse cells.

  2. Structural rearrangements of chromosomes in the domestic chicken: experimental production by X-irradiation of spermatozoa

    International Nuclear Information System (INIS)

    Wooster, W.E.; Fechheimer, N.S.; Jaap, R.G.

    1977-01-01

    In order to produce chicks heterozygous for structural aberrations of chromosomes, 67 hens were inseminated with semen that had been exposed to 1200 R of X-rays. A sample of 204 chicks was hatched and survived. Among these, 18 (8.9%) contained rearrangements comprising 19 translocations and one pericentric inversion. All 10 males and eight females heterozygous for rearrangements were fertile and transmitted these rearrangements to approximately half their hatched progeny. Each of the major chromosomes of the chicken karyotype, except number 6, was involved in one or more of the translocations. The pericentric inversion was of a segment of chromosome number 2. (author)

  3. A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

    Science.gov (United States)

    Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

    2012-01-01

    The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

  4. Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease.

    Science.gov (United States)

    Gal, A; Wieringa, B; Smeets, D F; Bleeker-Wagemakers, L; Ropers, H H

    1986-01-01

    Norrie disease (ND), an X-linked recessive disorder, is characterized by congenital blindness followed by bulbar atrophy. We have examined a three-generation family in which ND is part of a complex X-linked syndrome with severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections as additional features. This syndrome is apparently due to an interstitial deletion, as evidenced by the failure of the L1.28 DNA probe (DXS7 locus, Xp11.3) to detect complementary DNA sequences on the defective X chromosome of an affected male and of several obligatory heterozygotes. Attempts to further define this deletion with other DNA probes from the proximal short arm of the X chromosome or by prometaphase chromosome analysis were unsuccessful.

  5. Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.

    Directory of Open Access Journals (Sweden)

    Diana Chang

    Full Text Available Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, the X chromosome has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS. We present tailored analytical methods and software that facilitate X-wide association studies (XWAS, which we further applied to reanalyze data from 16 GWAS of different autoimmune and related diseases (AID. We associated several X-linked genes with disease risk, among which (1 ARHGEF6 is associated with Crohn's disease and replicated in a study of ulcerative colitis, another inflammatory bowel disease (IBD. Indeed, ARHGEF6 interacts with a gastric bacterium that has been implicated in IBD. (2 CENPI is associated with three different AID, which is compelling in light of known associations with AID of autosomal genes encoding centromere proteins, as well as established autosomal evidence of pleiotropy between autoimmune diseases. (3 We replicated a previous association of FOXP3, a transcription factor that regulates T-cell development and function, with vitiligo; and (4 we discovered that C1GALT1C1 exhibits sex-specific effect on disease risk in both IBDs. These and other X-linked genes that we associated with AID tend to be highly expressed in tissues related to immune response, participate in major immune pathways, and display differential gene expression between males and females. Combined, the results demonstrate the importance of the X chromosome in autoimmunity, reveal the potential of extensive XWAS, even based on existing data, and provide the tools and incentive to properly include the X chromosome in future studies.

  6. Radioprotective effect of penicillin on the x-ray induced chromosome aberrations in the Syrian hamster

    International Nuclear Information System (INIS)

    Dey, S.K.; Manna, G.K.

    1981-01-01

    The frequency of chromosome aberrations in the bone marrow cells of Syrian hamsters treated with penicillin and X-rays separately and conjointly was found to be 27% in X-irradiated series, 6.3% in penicillin treated series while it was 7.6%, 8% and 6.3% respectively for the treatment of penicillin prior to, almost simultaneously with and after X-irradiation. The results indicated the protective action of penicillin on the frequency of radiation-induced chromosome damages. (author)

  7. High-speed AFM of human chromosomes in liquid

    Energy Technology Data Exchange (ETDEWEB)

    Picco, L M; Dunton, P G; Ulcinas, A; Engledew, D J; Miles, M J [H H Wills Physics Laboratory and IRC in Nanotechnology, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Hoshi, O; Ushiki, T [Division of Microscopic Anatomy and Bio-Imaging, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori 1, Niigata, 951-8150 (Japan)], E-mail: m.j.miles@bristol.ac.uk

    2008-09-24

    Further developments of the previously reported high-speed contact-mode AFM are described. The technique is applied to the imaging of human chromosomes at video rate both in air and in water. These are the largest structures to have been imaged with high-speed AFM and the first imaging in liquid to be reported. A possible mechanism that allows such high-speed contact-mode imaging without significant damage to the sample is discussed in the context of the velocity dependence of the measured lateral force on the AFM tip.

  8. +2.71 LOD score at zero recombination is not sufficient for establishing linkage between X-linked mental retardation and X-chromosome markers

    Energy Technology Data Exchange (ETDEWEB)

    Robledo, R.; Melis, P.; Siniscalco, M. [and others

    1996-07-12

    Nonspecific X-linked mental retardation (MRX) is the denomination attributed to the familial type of mental retardation compatible with X-linked inheritance but lacking specific phenotypic manifestations. It is thus to be expected that families falling under such broad definition are genetically heterogeneous in the sense that they may be due to different types of mutations occurring, most probably, at distinct X-chromosome loci. To facilitate a genetic classification of these conditions, the Nomenclature Committee of the Eleventh Human Gene Mapping Workshop proposed to assign a unique MRX-serial number to each family where evidence of linkage with one or more X-chromosome markers had been established with a LOD score of at least +2 at zero recombination. This letter is meant to emphasize the inadequacy of this criterion for a large pedigree where the segregation of the disease has been evaluated against the haplotype constitution of the entire X-chromosome carrying the mutation in question. 12 refs., 2 figs., 1 tab.

  9. Progress towards construction of a total restriction fragment map of a human chromosome.

    NARCIS (Netherlands)

    H. Vissing; F.G. Grosveld (Frank); E. Solomon; G. Moore; N. Lench; N. Shennan; R. Williamson

    1987-01-01

    textabstractWe present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human

  10. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

    KAUST Repository

    Hurst, Laurence D.; Ghanbarian, Avazeh T.; Forrest, Alistair R. R.; Huminiecki, Lukasz

    2015-01-01

    to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia

  11. Investigating the role of X chromosome breakpoints in premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Baronchelli Simona

    2012-07-01

    Full Text Available Abstract The importance of the genetic factor in the aetiology of premature ovarian failure (POF is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF that were detected during a screening of 269 affected women. Conventional and molecular cytogenetics were valuable tools for locating the breakpoint regions and thus the following karyotypes were defined: 46,X,der(Xt(X;19(p21.1;q13.42mat, 46,X,t(X;2(q21.33;q14.3dn, 46,X,der(Xt(X;Y(q26.2;q11.223mat and 46,X,t(X;13(q13.3;q31dn. A bioinformatic analysis of the breakpoint regions identified putative candidate genes for ovarian failure near the breakpoint regions on the X chromosome or on autosomes that were involved in the translocation event. HS6ST1, HS6ST2 and MATER genes were identified and their functions and a literature review revealed an interesting connection to the POF phenotype. Moreover, the 19q13.32 locus is associated with the age of onset of the natural menopause. These results support the position effect of the breakpoint on flanking genes, and cytogenetic techniques, in combination with bioinformatic analysis, may help to improve what is known about this puzzling disorder and its diagnostic potential.

  12. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Venken, Koen J. T.; Popodi, Ellen; Holtzman, Stacy L.; Schulze, Karen L.; Park, Soo; Carlson, Joseph W.; Hoskins, Roger A.; Bellen, Hugo J.; Kaufman, Thomas C.

    2010-07-22

    We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using C31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

  13. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster.

    Science.gov (United States)

    Venken, Koen J T; Popodi, Ellen; Holtzman, Stacy L; Schulze, Karen L; Park, Soo; Carlson, Joseph W; Hoskins, Roger A; Bellen, Hugo J; Kaufman, Thomas C

    2010-12-01

    We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using ΦC31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

  14. An integrated physical map of 210 markers assigned to the short arm of human chromosome 11

    NARCIS (Netherlands)

    Redeker, E.; Hoovers, J. M.; Alders, M.; van Moorsel, C. J.; Ivens, A. C.; Gregory, S.; Kalikin, L.; Bliek, J.; de Galan, L.; van den Bogaard, R.; Visser, J.; van der Voort, R.; Feinberg, A. P.; Little, P. F. R.; Westerveld, A.; Mannens, M.

    1994-01-01

    Using a panel of patient cell lines with chromosomal breakpoints, we constructed a physical map for the short arm of human chromosome 11. We focused on 11p15, a chromosome band harboring at least 25 known genes and associated with the Beckwith-Wiedemann syndrome, several childhood tumors, and

  15. Molecular characterization of X chromosome fragility in idiopathic ...

    African Journals Online (AJOL)

    Heba Alla Hosny Omar

    2015-11-23

    Nov 23, 2015 ... Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients ... hence the wide clinical spectrum of disorders caused by this ... fragile X syndrome, autism and other less well-characterized.

  16. Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

    International Nuclear Information System (INIS)

    Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

    1990-01-01

    A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

  17. Y Chromosome analysis of prehistoric human populations in the West Liao River Valley, Northeast China.

    Science.gov (United States)

    Cui, Yinqiu; Li, Hongjie; Ning, Chao; Zhang, Ye; Chen, Lu; Zhao, Xin; Hagelberg, Erika; Zhou, Hui

    2013-09-30

    The West Liao River valley in Northeast China is an ecologically diverse region, populated in prehistory by human populations with a wide range of cultures and modes of subsistence. To help understand the human evolutionary history of this region, we performed Y chromosome analyses on ancient human remains from archaeological sites ranging in age from 6500 to 2700 BP. 47 of the 70 individuals provided reproducible results. They were assigned into five different Y sub-haplogroups using diagnostic single nucleotide polymorphisms, namely N1 (xN1a, N1c), N1c, C/C3e, O3a (O3a3) and O3a3c. We also used 17 Y short tandem repeat loci in the non-recombining portion of the Y chromosome. There appears to be significant genetic differences between populations of the West Liao River valley and adjacent cultural complexes in the prehistoric period, and these prehistoric populations were shown to carry similar haplotypes as present-day Northeast Asians, but at markedly different frequencies. Our results suggest that the prehistoric cultural transitions were associated with immigration from the Yellow River valley and the northern steppe into the West Liao River valley. They reveal the temporal continuity of Y chromosome lineages in populations of the West Liao River valley over 5000 years, with a concurrent increase in lineage diversity caused by an influx of immigrants from other populations.

  18. Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.

    Science.gov (United States)

    Zhang, Qiang; Guo, Xiaohong; Tian, Tian; Wang, Teng; Li, Qiaoli; Wang, Lei; Liu, Yun; Xing, Qinghe; He, Lin; Zhao, Xinzhi

    2017-05-01

    Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi

    2013-12-03

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ∼0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (∼0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ∼1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

  20. A study of some problems in chromosome cultivation after ionization radiation of human blood in vitro

    International Nuclear Information System (INIS)

    Jiang Benrong; Yao Bo; Chen Zhijian

    1992-01-01

    The effects of Cytochalasin B (Cyt-B) and cultural time on mitotic index (MI) during chromosome culture of human peripheral blood irradiated by 6 MV X-ray in vitro were studied. The results showed: (1) a successful cultivation with enough mitotic figures could be carried out in order to estimate the irradiation dose with chromosome aberrations and when the predicted dose was above 6 Gy in a radiation accident, when the predicted dose was up to 15 Gy the cultural time should be prolonged and Cyt-B should be added to the cultural medium; (2) it was possible to establish a dose effect calibration curve for doses above 5 Gy by adding Cyt-B and prolonging the cultural time; so that its value as a biological dosimeter for clinical application might be increased than before

  1. The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer.

    Science.gov (United States)

    Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette; Gronemeyer, Hinrich; Vincent-Salomon, Anne; Stern, Marc-Henri; Heard, Edith

    2015-04-01

    Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear. Here we show that breast tumors and cell lines frequently display major epigenetic instability of the inactive X chromosome, with highly abnormal 3D nuclear organization and global perturbations of heterochromatin, including gain of euchromatic marks and aberrant distributions of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells and a significant degree of aberrant gene activity from the inactive X chromosome, including several genes involved in cancer promotion. We demonstrate that many of these genes are aberrantly reactivated in primary breast tumors, and we further demonstrate that epigenetic instability of the inactive X can lead to perturbed dosage of X-linked factors. Taken together, our study provides the first integrated analysis of the inactive X chromosome in the context of breast cancer and establishes that epigenetic erosion of the inactive X can lead to the disappearance of the Barr body in breast cancer cells. This work offers new insights and opens up the possibility of exploiting the inactive X chromosome as an epigenetic biomarker at the molecular and cytological levels in cancer. © 2015 Chaligné et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Accelerated pseudogenization on the neo-X chromosome in Drosophila miranda

    KAUST Repository

    Nozawa, Masafumi

    2016-11-29

    Y chromosomes often degenerate via the accumulation of pseudogenes and transposable elements. By contrast, little is known about X-chromosome degeneration. Here we compare the pseudogenization process between genes on the neo-sex chromosomes in Drosophila miranda and their autosomal orthologues in closely related species. The pseudogenization rate on the neo-X is much lower than the rate on the neo-Y, but appears to be higher than the rate on the orthologous autosome in D. pseudoobscura. Genes under less functional constraint and/or genes with male-biased expression tend to become pseudogenes on the neo-X, indicating the accumulation of slightly deleterious mutations and the feminization of the neo-X. We also find a weak trend that the genes with female-benefit/male-detriment effects identified in D. melanogaster are pseudogenized on the neo-X, implying the masculinization of the neo-X. These observations suggest that both X and Y chromosomes can degenerate due to a complex suite of evolutionary forces.

  3. A Female Patient with FMR1 Premutation and Mosaic X Chromosome Aneuploidy and Two Sons with Intellectual Disability.

    Science.gov (United States)

    Galanina, Ekaterina M; Tulupov, Andrey A; Lemskaya, Natalya A; Korostyshevskaya, Aleksandra M; Maksimova, Yuliya V; Shorina, Asia R; Savelov, Andrey A; Sergeeva, Irina G; Isanova, Evgeniya R; Grishchenko, Irina V; Yudkin, Dmitry V

    2017-03-01

    In this report, we describe a molecular cytogenetic study of a family burdened with intellectual disability (ID) and suicide. Our study revealed that the mother has a heterozygous premutation in the FMR1 gene and supernumerary X chromosomes as well as X-derived marker chromosomes. Both of her sons have ID and a normal chromosome number. One of the sons has fragile X syndrome, and the other has ID of an unclear nature.

  4. Chromosomal location of the human gene for DNA polymerase β

    International Nuclear Information System (INIS)

    McBride, O.W.; Zmudzka, B.Z.; Wilson, S.H.

    1987-01-01

    Inhibition studies indicate that DNA polymerase β has a synthetic role in DNA repair after exposure of mammalian cells to some types of DNA-damaging agents. The primary structure of the enzyme is highly conserved in vertebrates, and nearly full-length cDNAs for the enzyme were recently cloned from mammalian cDNA libraries. Southern blot analysis of DNA from a panel of human-rodent somatic cell hybrids, using portions of the cDNA as probe, indicates that the gene for human DNA polymerase β is single copy and located on the short arm or proximal long arm of chromosome 8 (8pter-8q22). A restriction fragment length polymorphism (RFLP) was detected in normal individuals by using a probe from the 5' end of the cDNA, and this RFLP probably is due to an insertion or duplication of DNA in 20-25% of the population. This restriction site can be used as one marker for chromosome 8 genetic linkage studies and for family studies of traits potentially involving this DNA repair gene

  5. Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. II. Results obtained after induction of breaks in chromosome 1 by X-irradiation.

    Science.gov (United States)

    Burgerhout, W G; Smit, S L; Jongsma, A P

    1977-01-01

    The position of genes coding for PGD, PPH1, UGPP, GuK1, PGM1, Pep-C, and FH on human chromosome 1 was investigated by analysis of karyotype and enzyme phenotypes in man-Chinese hamster somatic cell hybrids carrying aberrations involving chromosome 1. Suitable hybrid cell lines were obtained by X-irradiation of hybrid cells carrying an intact chromosome 1 and by fusion of human cells from a clonal population carrying a translocation involving chromosome 1 with Chinese hamster cells. The latter human cell population had been isolated following X-irradiation of primary Lesch-Nyhan fibroblasts. In addition, products of de novo chromosome breakage in the investigated hybrid lines were utilized. By integrating the results of these analyses with earlier findings in our laboratory, the following positions of genes are deduced: PGD and PPH1 in 1p36 leads to 1p34; PGM1 in 1p32; UGPP in 1q21 leads to 1q23; GuK1 in 1q31 leads to 1q42; Pep-C in 1q42; and FH in 1qter leads to 1q42.

  6. Human nucleolus organizers on nonhomologous chromosomes can share the same ribosomal gene variants.

    Science.gov (United States)

    Krystal, M; D'Eustachio, P; Ruddle, F H; Arnheim, N

    1981-01-01

    The distributions of three human ribosomal gene polymorphisms among individual chromosomes containing nucleolus organizers were analyzed by using mouse--human hybrid cells. Different nucleolus organizers can contain the same variant, suggesting the occurrence of genetic exchanges among ribosomal gene clusters on nonhomologous chromosomes. Such exchanges appear to occur less frequently in mice. This difference is discussed in terms of the nucleolar organization and chromosomal location of ribosomal gene clusters in humans and mice. Images PMID:6272316

  7. Structure and chromosomal localization of the human renal kallikrein gene

    International Nuclear Information System (INIS)

    Evans, B.A.; Yun, Z.X.; Close, J.A.

    1988-01-01

    Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7

  8. Computational simulation of chromosome breaks in human liver

    International Nuclear Information System (INIS)

    Yang Jianshe; Li Wenjian; Jin Xiaodong

    2006-01-01

    An easy method was established for computing chromosome breaks in cells exposed to heavily charged particles. The cell chromosome break value by 12 C +6 ions was theoretically calculated, and was tested with experimental data of chromosome breaks by using a premature chromosome condensation technique. The theoretical chromosome break value agreed well with the experimental data. The higher relative biological effectiveness of the heavy ions was closely correlated to its physical characteristics. In addition, the chromosome break value can be predicted off line. (authors)

  9. Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, G. (Orvostudomanyi Egyetem, Szeged (Hungary). Orvosbiologiai Intezet)

    1982-01-01

    Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners.

  10. Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

    International Nuclear Information System (INIS)

    Szemere, G.

    1982-01-01

    Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners. (author)

  11. Reduced polymorphism associated with X chromosome meiotic drive in the stalk-eyed fly Teleopsis dalmanni.

    Directory of Open Access Journals (Sweden)

    Sarah J Christianson

    Full Text Available Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp approximately 50 cM apart and one autosomal region (comprising 921 bp for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies.

  12. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    International Nuclear Information System (INIS)

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray--induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosomes aberrations, and hence higher aberration frequencies in Down than normal cells

  13. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    International Nuclear Information System (INIS)

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray-induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosome aberrations, and hence higher aberration frequencies in Down than normal cells

  14. Chromosomes

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  15. Molecular characterization of X chromosome fragility in idiopathic ...

    African Journals Online (AJOL)

    Background: Fragile X syndrome (FXS) is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or ...

  16. High resistance of fibroblasts from Mongolian gerbil embryos to cell killing and chromosome aberrations by X-irradiation

    International Nuclear Information System (INIS)

    Suzuki, F.; Nakao, N.; Nikaido, O.; Kondo, S.

    1992-01-01

    Mongolian gerbil (Meriones unguiculatus) is known to be one of the most radioresistant animal species. In order to determine whether there is any correlation between mortality of mammals exposed to γ- or X-rays and radiation sensitivity of culture cells derived from different mammalian species, we have examined the X-ray survival curves of normal diploid fibroblasts from Mongolian gerbil embryos and compared with those of other cultured embryo cells from various laboratory animals and normal human. There was a big difference in cell survival to X-rays among different mammalian species. The D 0 values of Mongolian gerbil cells ranged from 2.3 to 2.6 Gy which are twice as high as those of human cells. The mean D 0 value of human cells was 1.1 Gy. Mouse, rat, Chinese hamster and Syrian/golden hamster cells showed similar D 0 values ranging from 1.7 to 2.0 Gy. When cells were irradiated with 2 Gy of X-rays, three times longer mitotic delay was observed in human cells than in Mongolian gerbil cells. At this X-ray dose, furthermore, ten times more chromosome aberrations were detected in human cells than in Mongolian gerbil cells, and the frequencies of other rodent cells lay between the values for the two cell strains. These data indicate that the Mongolian gerbil cells are resistant to X-ray-induced cell killing and chromosome aberrations, and that radiation sensitivity of primarily cultured mammalian cells may be reflected by their radioresistance in vivo. (author)

  17. Effect of estradiol on radiation-induced chromosome aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    Kanda, Reiko; Hayata, Isamu

    1999-01-01

    As a part of studies on physiological factors that affect radiosensitivity, we examined the in vitro effect of estradiol (E2) on the yield of radiation-induced chromosome aberrations in human peripheral lymphocytes. Lymphocytes were cultured for 3 days in the medium containing E2 at 0-100000 ng/ml. On the second day, they were irradiated by X-rays at 3 Gy, and then 2% phytohemagglutinin and 0.05 μg/ml colcemid were added to the medium. After further 48 h, mitotic indices and the yields of chromosome aberrations were examined at various E2 concentrations. E2 treatment at concentrations above 1000 ng/ml resulted in dose-related inhibition of mitosis. Repeated experiments showed that the yield of dicentrics plus centric rings in the culture containing E2 at 100 ng/ml was significantly higher than the yields at 0 ng/ml. Similarly, the yield of total chromosome breaks in the culture containing E2 at 100 ng/ml was significantly higher than that at 1 ng/ml. This study provides the direct evidence in human that radiosensitivity may vary in relation to hormonal conditions. (author)

  18. Gene expression, nucleotide composition and codon usage bias of genes associated with human Y chromosome.

    Science.gov (United States)

    Choudhury, Monisha Nath; Uddin, Arif; Chakraborty, Supriyo

    2017-06-01

    Analysis of codon usage pattern is important to understand the genetic and evolutionary characteristics of genomes. We have used bioinformatic approaches to analyze the codon usage bias (CUB) of the genes located in human Y chromosome. Codon bias index (CBI) indicated that the overall extent of codon usage bias was low. The relative synonymous codon usage (RSCU) analysis suggested that approximately half of the codons out of 59 synonymous codons were most frequently used, and possessed a T or G at the third codon position. The codon usage pattern was different in different genes as revealed from correspondence analysis (COA). A significant correlation between effective number of codons (ENC) and various GC contents suggests that both mutation pressure and natural selection affect the codon usage pattern of genes located in human Y chromosome. In addition, Y-linked genes have significant difference in GC contents at the second and third codon positions, expression level, and codon usage pattern of some codons like the SPANX genes in X chromosome.

  19. Molecular mechanism in the formation of a human ring chromosome 21

    International Nuclear Information System (INIS)

    Wong, C.; Kazazian, H.H. Jr.; Stetten, G.; Earnshaw, W.C.; Antonarakis, S.E.; Van Keuren, M.L.

    1989-01-01

    The authors have characterized the structural rearrangements of a chromosome 21 that led to the de novo formation of a human ring chromosome 21 [r(21)]. Molecular cloning and chromosomal localization of the DNA regions flanking the ring junction provide evidence for a long arm to long arm fusion in formation of the r(21). In addition, the centromere and proximal long arm region of a maternal chromosome 21 are duplicated in the r(21). Therefore, the mechanism in formation of the r(21) was complex involving two sequential chromosomal rearrangements. (i) Duplication of the centromere and long arm of one maternal chromosome 21 occurred forming a rearranged intermediate. (ii) Chromosomal breaks in both the proximal and telomeric long arm regions on opposite arms of this rearranged chromosome occurred with subsequent reunion producing the r(21)

  20. Chromosome aberrations in human lymphocytes after irradiation with NIRS-cyclotron fast neutrons in vitro

    International Nuclear Information System (INIS)

    Muramatsu, Susumu; Maruyama, Takashi

    1977-01-01

    The dose-response relationships for inducing chromosome aberrations (dicentrics) in human lymphocytes were studied by whole-blood microculture following in vitro exposures at various doses either 200 kVp x-rays or NIRS-cyclotron fast neutrons. The yields of dicentrics induced were dependent on the exposure dose of two types of radiations between 48 to 384 rad and 25 to 400 rad by x-rays and fast neutrons, respectively. The dicentrics yields gave the best fit to the linear quadratic function Y=αD + βD 2 ; namely Y sub(X)=3.66 x 10 -4 D + 8.01 x 10 -6 D 2 for x-rays and Y sub(N)=28.90 x 10 -4 D + 4.04 x 10 -6 D 2 for fast neutrons. The RBE value of NIRS-cyclotron fast neutrons versus 200 kVP x-rays decreased with increasing neutron doses, for example from 2.3 at 50 rad to 1.2 at doses up to 300 rad. (auth.)

  1. The Social Behavioral Phenotype in Boys and Girls with an Extra X Chromosome (Klinefelter Syndrome and Trisomy X): A Comparison with Autism Spectrum Disorder

    Science.gov (United States)

    van Rijn, Sophie; Stockmann, Lex; Borghgraef, Martine; Bruining, Hilgo; van Ravenswaaij-Arts, Conny; Govaerts, Lutgarde; Hansson, Kerstin; Swaab, Hanna

    2014-01-01

    The present study aimed to gain more insight in the social behavioral phenotype, and related autistic symptomatology, of children with an extra X chromosome in comparison to children with ASD. Participants included 60 children with an extra X chromosome (34 boys with Klinefelter syndrome and 26 girls with Trisomy X), 58 children with ASD and 106…

  2. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

    DEFF Research Database (Denmark)

    McGinniss, M J; Kazazian, H H; Stetten, G

    1992-01-01

    We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

  3. Genealogical and evolutionary inference with the human Y chromosome.

    Science.gov (United States)

    Stumpf, M P; Goldstein, D B

    2001-03-02

    Population genetics has emerged as a powerful tool for unraveling human history. In addition to the study of mitochondrial and autosomal DNA, attention has recently focused on Y-chromosome variation. Ambiguities and inaccuracies in data analysis, however, pose an important obstacle to further development of the field. Here we review the methods available for genealogical inference using Y-chromosome data. Approaches can be divided into those that do and those that do not use an explicit population model in genealogical inference. We describe the strengths and weaknesses of these model-based and model-free approaches, as well as difficulties associated with the mutation process that affect both methods. In the case of genealogical inference using microsatellite loci, we use coalescent simulations to show that relatively simple generalizations of the mutation process can greatly increase the accuracy of genealogical inference. Because model-free and model-based approaches have different biases and limitations, we conclude that there is considerable benefit in the continued use of both types of approaches.

  4. The Human Proteome Organization Chromosome 6 Consortium: integrating chromosome-centric and biology/disease driven strategies.

    Science.gov (United States)

    Borchers, C H; Kast, J; Foster, L J; Siu, K W M; Overall, C M; Binkowski, T A; Hildebrand, W H; Scherer, A; Mansoor, M; Keown, P A

    2014-04-04

    The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent

  5. Human sperm sex chromosome disomy and sperm DNA damage assessed by the neutral comet assay.

    Science.gov (United States)

    McAuliffe, M E; Williams, P L; Korrick, S A; Dadd, R; Marchetti, F; Martenies, S E; Perry, M J

    2014-10-10

    Is there an association between human sperm sex chromosome disomy and sperm DNA damage? An increase in human sperm XY disomy was associated with higher comet extent; however, there was no other consistent association of sex chromosome disomies with DNA damage. There is limited published research on the association between sex chromosome disomy and sperm DNA damage and the findings are not consistent across studies. We conducted a cross-sectional study of 190 men (25% ever smoker, 75% never smoker) from subfertile couples presenting at the Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003. Multiprobe fluorescence in situ hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and total sex chromosome disomy in sperm nuclei using an automated scoring method. The neutral comet assay was used to measure sperm DNA damage, as reflected by comet extent, percentage DNA in the comet tail, and tail distributed moment. Univariate and multiple linear regression models were constructed with sex chromosome disomy (separate models for each of the four disomic conditions) as the independent variable, and DNA damage parameters (separate models for each measure of DNA damage) as the dependent variable. Men with current or past smoking history had significantly greater comet extent (µm: regression coefficients with 95% CI) [XX18: 15.17 (1.98, 28.36); YY18: 14.68 (1.50, 27.86); XY18: 15.41 (2.37, 28.45); Total Sex Chromosome Disomy: 15.23 (2.09, 28.38)], and tail distributed moment [XX18: 3.01 (0.30, 5.72); YY18: 2.95 (0.24, 5.67); XY18: 3.04 (0.36, 5.72); Total Sex Chromosome Disomy: 3.10 (0.31, 5.71)] than men who had never smoked. In regression models adjusted for age and smoking, there was a positive association between XY disomy and comet extent. For an increase in XY disomy from 0.56 to 1.47% (representing the 25th to 75th percentile), there was a mean increase of 5.08 µm in comet extent. No other statistically significant

  6. Cloning and comparative mapping of a human chromosome 4-specific alpha satellite DNA sequence

    Energy Technology Data Exchange (ETDEWEB)

    D' Aiuto, L.; Marzella, R.; Archidiacono, N.; Rocchi, M. (Universita di Bari (Italy)); Antonacci, R. (Instituto Anatomia Umana Normale, Modena (Italy))

    1993-11-01

    The authors have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed. 33 refs., 4 figs.

  7. X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

    Science.gov (United States)

    Dumont, Beth L

    2017-04-01

    Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

  8. Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

    Science.gov (United States)

    Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

    2014-03-01

    Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

  9. May anomalous X chromosome methylation be responsible for the ...

    Indian Academy of Sciences (India)

    performed, in a woman who carried a fragile X full muta- tion. DNA extracted ... women's health (Christiansen 2006). .... However, the same productivity was observed from the ... This work was supported by a grant from Ministerio de Sanidad y.

  10. Meiotic chromosomal translocations in male mice induced by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

    1983-01-01

    The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

  11. Report of the Fourth international workshop on human chromosome 18 mapping 1996

    International Nuclear Information System (INIS)

    Silverman, G.A.; Overhauser, J.; Gerken, S.; Aburomia, R.; O'Connell, P.; Krauter, K.S.; Detera-Wadleigh, S.D.; Yoshikawa, T.; Collins, A.R.; Geurts van Kessel, A.

    1996-01-01

    The fourth international workshop on human chromosome 18 mapping was held in Boston, Massachusetts, USA on October 7-9, 1996. The workshop was attended by 34 participants from 7 countries. The goals of the workshop were to (1) generate integrated genetic and physical maps, (2) update the transcriptional map, (3) assess the syntenic relationships between human chromosome 18 and the mouse genome, and (4) establish a chromosome 18 web site

  12. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))

    1994-04-01

    The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.

  13. 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

    2016-01-01

    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 of Rnf12 to up-regulate Xist significantly 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-regulated Rnf12/Xist expression, 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

  14. Cloning, expression, and chromosome mapping of human galectin-7

    DEFF Research Database (Denmark)

    Madsen, Peder; Rasmussen, H H; Flint, T

    1995-01-01

    The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. Here we report the cloning and expression of a novel member of this family (galectin-7) that correspond to IEF (isoelectric focusing) 17 (12,700 Da; pI, 7.6) in the human...... keratinocyte protein data base, and that is strikingly down-regulated in SV40 transformed keratinocytes (K14). The cDNA was cloned from a lambda gt11 cDNA expression library using degenerated oligodeoxyribonucleotides back-translated from an IEF 17 peptide sequence. The protein encoded by the galectin-7 clone......14 keratinocytes imply a role in cell-cell and/or cell-matrix interactions necessary for normal growth control. The galectin-7 gene was mapped to chromosome 19. Udgivelsesdato: 1995-Mar-17...

  15. Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9

    International Nuclear Information System (INIS)

    Kaur, G.P.; Athwal, R.S.

    1989-01-01

    Complementation of the repair defect in xeroderma pigmentosum cells of complementation group A was achieved by the transfer of human chromosome 9. A set of mouse-human hybrid cell lines, each containing a single Ecogpt-marked human chromosome, was used as a source of donor chromosomes. Chromosome transfer to XPTG-1 cells, a hypoxanthine/guanine phosphoribosyltransferase-deficient mutant of simian virus 40-transformed complementation group A cells, was achieved by microcell fusion and selection for Ecogpt. Chromosome-transfer clones of XPTG-1 cells, each containing a different human donor chromosome, were analyzed for complementation of sensitivity to UV irradiation. Among all the clones, increased levels of resistance to UV was observed only in clones containing chromosome 9. Since our recipient cell line XPTG-1 is hypoxanthine/guanine phosphoribosyltransferase deficient, cultivation of Ecogpt+ clones in medium containing 6-thioguanine permits selection of cells for loss of the marker and, by inference, transferred chromosome 9. Clones isolated for growth in 6-thioguanine, which have lost the Ecogpt-marked chromosome, exhibited a UV-sensitive phenotype, confirming the presence of the repair gene(s) for complementation group A on chromosome 9

  16. Genetic analysis of tumorigenesis: XXXII. Localization of constitutionally amplified KRAS sequences to Chinese hamster chromosomes X and Y by in situ hybridization.

    Science.gov (United States)

    Stenman, G; Anisowicz, A; Sager, R

    1988-11-01

    The KRAS gene is constitutionally amplified in the Chinese hamster. We have mapped the amplified sequences by in situ hybridization to two major sites on the X and Y chromosomes, Xq4 and Yp2. No autosomal site was detected despite a search under relaxed hybridization conditions. KRAS DNA is amplified about 50-fold compared to a human cell line known to have a diploid number of KRAS sequences, whereas mRNA expression is 5- to 10-fold lower than in normal human cells. While mRNA expression levels do not necessarily parallel gene copy number, the low expression level strongly suggests that the amplified sequences are transcriptionally silent. It is suggested that the amplified sequences arose from the original KRAS gene on chromosome 8 and that the KRAS sequences on the Y chromosome arose by X-Y recombination.

  17. Genetic analysis of eight x-chromosomal short tandem repeat loci in ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-07-29

    Jul 29, 2015 ... programs to perform population genetics analyses under Linux and. Windows. Mol. Ecol. Resour. 10: 564-567. Ferreira da Silva IH, Barbosa AG, Azevedo DA, Sanchez-Diz P,. Gusmao L, Tavares CC (2010). An X-chromosome pentaplex in two linkage groups: haplotype data in Alagoas and Rio de Janeiro.

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

    DEFF Research Database (Denmark)

    Pereira, Vania; Gusmão, Leonor; Valente, Cristina

    2012-01-01

    Due to differences in transmission between X-chromosomal and autosomal DNA, the comparison of data derived from both markers allows deeper insight into the forces that shape the patterns of genetic diversity in populations. In this study, we applied this comparative approach to a sample of Portug...

  19. Exploring the power of rice (O. sativa x O. rufipogon) chromosome segment substitution line libraries

    Science.gov (United States)

    Transgressive variation was reported as an increase in grain yield for several rice (Oryza sativa x O. rufipogon) advanced backcross mapping populations. The objective of this study was to develop chromosome segment substitution line (CSSL) libraries to further dissect the reported transgressive var...

  20. Chromosome translocations in chinese medical X-ray workers analyzed by fluorescence in situ hybridization

    International Nuclear Information System (INIS)

    Sun Yuanming; Li Jin; Wang Qin; Tang Weisheng; Wang Zhiquan

    2002-01-01

    Objective: To study long-term radiation effect in occupational workers exposed to low dose X-rays using the method of fluorescence in situ hybridization (FISH). Method: Chromosome translocations of 25 medical X-ray workers were analyzed by FISH with chromosome No. 4 and No. 7 probes according to PAINT (The Protocol for Aberration Identification and Nomenclature Terminology) system. Results: The frequency of genome translocation in X-ray workers was (13.14 ± 1.23)/1000 cells. The rate of complete and incomplete translocation was 1:1.7. According to the calendar year of entry before/after the year of 1965 as the border, the data showed that the incomplete translocation of the after 1965 group was obviously higher than those of the controls (P < 0.01 and P < 0.05, respectively). Conclusion: The chromosome translocation in early Chinese medical X-ray workers is mainly the incomplete one, the frequency of translocation does not dependent on chromosomal DNA content, and incomplete and complete ones increase along with prolongation of working years in their position

  1. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

    NARCIS (Netherlands)

    Hurst, Laurence D; Ghanbarian, Avazeh T; Forrest, Alistair R R; Huminiecki, Lukasz; Clevers, J.C.; van de Wetering, M.L.

    2015-01-01

    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally

  2. The guanine-rich fragile X chromosome repeats are reluctant to form tetraplexes

    Czech Academy of Sciences Publication Activity Database

    Fojtík, Petr; Kejnovská, Iva; Vorlíčková, Michaela

    2004-01-01

    Roč. 32, č. 1 (2004), s. 298-306 ISSN 0305-1048 R&D Projects: GA ČR GA204/01/0561; GA AV ČR IAA4004201 Institutional research plan: CEZ:AV0Z5004920 Keywords : fragile X chromosome syndrom * trinucleotide repeats * DNA polymorphism Subject RIV: BO - Biophysics Impact factor: 7.260, year: 2004

  3. Chromosomal clustering of a human transcriptome reveals regulatory background

    Directory of Open Access Journals (Sweden)

    Purmann Antje

    2005-09-01

    Full Text Available Abstract Background There has been much evidence recently for a link between transcriptional regulation and chromosomal gene order, but the relationship between genomic organization, regulation and gene function in higher eukaryotes remains to be precisely defined. Results Here, we present evidence for organization of a large proportion of a human transcriptome into gene clusters throughout the genome, which are partly regulated by the same transcription factors, share biological functions and are characterized by non-housekeeping genes. This analysis was based on the cardiac transcriptome identified by our genome-wide array analysis of 55 human heart samples. We found 37% of these genes to be arranged mainly in adjacent pairs or triplets. A significant number of pairs of adjacent genes are putatively regulated by common transcription factors (p = 0.02. Furthermore, these gene pairs share a significant number of GO functional classification terms. We show that the human cardiac transcriptome is organized into many small clusters across the whole genome, rather than being concentrated in a few larger clusters. Conclusion Our findings suggest that genes expressed in concert are organized in a linear arrangement for coordinated regulation. Determining the relationship between gene arrangement, regulation and nuclear organization as well as gene function will have broad biological implications.

  4. Comparison of initial DNA (Chromosome) damage/repair in cells exposed to heavy ion particles and X-rays

    International Nuclear Information System (INIS)

    Okayasu, Ryuichi; Okada, Maki; Noguchi, Mitsuho; Saito, Shiori; Okabe, Atsushi; Takakura, Kahoru

    2005-01-01

    We have studied cell survival and chromosome damage/repair in normal and non homologous end-joining (NHEJ) deficient human cells exposed to carbon ions (290 MeV/u, ∼70 keV/um), iron ions (500 MeV/u, ∼200 keV/um) and X-rays. In order to examine the effect of heavy ion on double strand break (DSB) repair machinery, the auto-phosphorylation of DNA-PKcs was also investigated. The important discoveries made during this period are: 200 keV/um iron irradiation induced additional molecular damage beyond that 70 keV/um carbon did. Iron irradiation not only caused an inefficient G1 chromosome repair, but also induced non-repairable DSB/chromosome damage. The auto-phosphorylation of DNA-PKcs was significantly affected by high linear energy transfer (LET) irradiation when compared to X-rays. These results indicate NHEJ machinery was markedly disturbed by high LET radiation when compared to low LET radiation. (author)

  5. Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro

    International Nuclear Information System (INIS)

    Bocian, E.; Ziemba-zak, B.; Rosiek, O.; Sablinski, J.

    1978-01-01

    The induction of chromosome aberrations in human peripheral blood lymphocytes by tritiated water or 180 kV X-rays in vitro was studied. Lymphocytes were exposed to various concentrations of HTO for 2 h or for 53 h. Chromosome and chromatid type aberrations were scored during the first mitotic division after stimulation with phytohaemagglutinin. For the analysis of the dose-response relationship the data were fitted by the method of least-squares to different models. After acute exposure to tritium β-rays and X-rays, the dicentrics + centric rings and terminal + interstitial deletions gave the best fit to the linear-quadratic function. However, data for these types of aberrations after 53 h exposure to HTO gave equally good fit to the linear and linear-quadratic functions. The best description of the dose-response relationship for chromatid aberrations is given by the linear model. In the system studied the RBE of tritium β-rays as compared to 180 KV X-rays was 1.17+-0.02. (Auth.)

  6. Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes.

    Directory of Open Access Journals (Sweden)

    Kaitlin M Stimpson

    2010-08-01

    Full Text Available Genome rearrangement often produces chromosomes with two centromeres (dicentrics that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extra-chromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.

  7. Influence of DMSO on Carbon K ultrasoft X-rays induced chromosome aberrations in V79 Chinese hamster cells

    Energy Technology Data Exchange (ETDEWEB)

    Natarajan, Adayapalam T., E-mail: natarajan@live.nl [University of Tuscia, Viterbo (Italy); Palitti, Fabrizio [University of Tuscia, Viterbo (Italy); Hill, Mark A. [CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Stevens, David L. [MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Ahnstroem, Gunnar [Department of Microbiology and Genetic Toxicology, Stockholm University, Stockholm (Sweden)

    2010-09-10

    Ultrasoft X-rays have been shown to be very efficient in inducing chromosomal aberrations in mammalian cells. The present study was aimed to evaluate the modifying effects of DMSO (a potent scavenger of free radicals) on the frequencies of chromosome aberrations induced by soft X-rays. Confluent held G1 Chinese hamster cells (V79) were irradiated with Carbon K ultrasoft X-rays in the presence and absence of 1 M DMSO and frequencies of chromosome aberrations in the first division cells were determined. DMSO reduced the frequencies of exchange types of aberrations (dicentrics and centric rings) by a factor of 2.1-3.5. The results indicate that free radicals induced by ultrasoft X-rays contribute to a great extent to the induction of chromosome aberrations. The possible implications of these results in interpreting the mechanisms involved in the high efficiency of ultrasoft X-rays in the induction of chromosome aberrations are discussed.

  8. Conserved chromosomal positions of dual domains of the ets protooncogene in cats, mice, and humans

    International Nuclear Information System (INIS)

    Watson, D.K.; McWilliams-Smith, M.J.; Kozak, C.

    1986-01-01

    The mammalian protooncogene homologue of the avian v-ets sequence from the E26 retrovirus consists of two sequentially distinct domains located on different chromosomes. Using somatic cell hybrid panels, the authors have mapped the mammalian homologue of the 5' v-ets-domain to chromosome 11 (ETS1) in man, to chromosome 9 (ets-1) in mouse, and to chromosome D1 (ETS1) in the domestic cat. The mammalian homologue of the 3' v-ets domain was similarly mapped to human chromosome 21 (ETS2), to mouse chromosome 16 (Ets-2), and to feline chromosome C2 (ETS2). Both protooncogenes fell in syntenic groups of homologous linked loci that were conserved among the three species. The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals

  9. Techniques for imaging human metaphase chromosomes in liquid conditions by atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ushiki, Tatsuo; Hoshi, Osamu [Division of Microscopic Anatomy and Bio-imaging, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510 (Japan); Shigeno, Masatsugu [SII NanoTechnology Incorporated, RBM Tsukiji Building, Shintomi 2-15-5, Chuo-ku, Tokyo 104-0041 (Japan)], E-mail: t-ushiki@med.niigata-u.ac.jp

    2008-09-24

    The purpose of this study was to obtain three-dimensional images of wet chromosomes by atomic force microscopy (AFM) in liquid conditions. Human metaphase chromosomes-obtained either by chromosome spreads or by an isolation technique-were observed in a dynamic mode by AFM in a buffer solution. Under suitable operating conditions with a soft triangular cantilever (with the spring constant of 0.08-0.4 N m{sup -1}), clear images of fixed chromosomes in the chromosome spread were obtained by AFM. For imaging isolated chromosomes with the height of more than 400 nm, a cantilever with a high aspect ratio probing tip was required. The combination of a Q-control system and the sampling intelligent scan (SIS) system in dynamic force mode AFM was useful for obtaining high-quality images of the isolated chromosomes, in which globular or cord-like structures about 50 nm thick were clearly observed on the surface of each chromatid.

  10. Phospho-Bcl-xL(Ser62) influences spindle assembly and chromosome segregation during mitosis.

    Science.gov (United States)

    Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

    2014-01-01

    Functional analysis of a series of phosphorylation mutants reveals that Bcl-xL(Ser62Ala) influences cell entry into anaphase and mitotic exit in taxol-exposed cells compared with cells expressing wild-type Bcl-xL or a series of other phosphorylation mutants, an effect that appears to be independent of its anti-apoptotic activity. During normal mitosis progression, Bcl-xL(Ser62) is strongly phosphorylated by PLK1 and MAPK14/SAPKp38α at the prometaphase, metaphase, and the anaphase boundaries, while it is de-phosphorylated at telophase and cytokinesis. Phospho-Bcl-xL(Ser62) localizes in centrosomes with γ-tubulin and in the mitotic cytosol with some spindle-assembly checkpoint signaling components, including PLK1, BubR1, and Mad2. In taxol- and nocodazole-exposed cells, phospho-Bcl-xL(Ser62) also binds to Cdc20- Mad2-, BubR1-, and Bub3-bound complexes, while Bcl-xL(Ser62Ala) does not. Silencing Bcl-xL expression and expressing the phosphorylation mutant Bcl-xL(Ser62Ala) lead to an increased number of cells harboring mitotic spindle defects including multipolar spindle, chromosome lagging and bridging, aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h. Together, the data indicate that during mitosis, Bcl-xL(Ser62) phosphorylation impacts on spindle assembly and chromosome segregation, influencing chromosome stability. Observations of mitotic cells harboring aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h were also made with cells expressing the phosphorylation mutant Bcl-xL(Ser49Ala) and dual mutant Bcl-xL(Ser49/62Ala).

  11. Chromosome microdissection and cloning in human genome and genetic disease analysis

    International Nuclear Information System (INIS)

    Kao, Faten; Yu, Jingwei

    1991-01-01

    A procedure has been described for microdissection and microcloning of human chromosomal DNA sequences in which universal amplification of the dissected fragments by Mbo I linker adaptor and polymerase chain reaction is used. A very large library comprising 700,000 recombinant plasmid microclones from 30 dissected chromosomes of human chromosome 21 was constructed. Colony hybridization showed that 42% of the clones contained repetitive sequences and 58% contained single or low-copy sequences. The insert sizes generated by complete Mbo I cleavage ranged from 50 to 1,100 base pairs with a mean of 416 base pairs. Southern blot analysis of microclones from the library confirmed their human origin and chromosome 21 specificity. Some of these clones have also been regionally mapped to specific sites of chromosome 21 by using a regional mapping panel of cell hybrids. This chromosome microtechnology can generate large numbers of microclones with unique sequences from defined chromosomal regions and can be used for processes such as (i) isolating corresponding yeast artificial chromosome clones with large inserts, (ii) screening various cDNA libraries for isolating expressed sequences, and (iii) constructing region-specific libraries of the entire human genome. The studies described here demonstrate the power of this technology for high-resolution genome analysis and explicate their use in an efficient search for disease-associated genes localized to specific chromosomal regions

  12. The parental origin of the extra X chromosome in 47,XXX females.

    Science.gov (United States)

    May, K M; Jacobs, P A; Lee, M; Ratcliffe, S; Robinson, A; Nielsen, J; Hassold, T J

    1990-01-01

    We used X-linked DNA polymorphisms to study the parental origin of X chromosome nondisjunction in 28 47,XXX live-born females. Errors in oogenesis accounted for 26 of the cases, with the majority of these being attributable to an error at meiosis I. We observed an association between advanced parental age and meiosis I nondisjunction--but not meiosis II nondisjunction--in the maternally derived cases. In studies of recombination we found little evidence for an association between pairing failure and X chromosome nondisjunction, but our results suggest that increased recombination near the centromere may play a role in the etiology of the 47,XXX condition. Images Figure 1 Figure 2 PMID:2316522

  13. Retrospective Dose Reconstruction for Medical Diagnostic X Ray Workers in China using Stable Chromosome Aberrations

    International Nuclear Information System (INIS)

    Wang, Q.; Liu, P.; Li, J.; Wang, Q.; Tang, S.; Sun, M.; Wang, L.; Aoyama, T.; Sugahara, T.

    1998-01-01

    The chromosome rearrangements in medical diagnostic X ray workers were analysed using the G-banding technique and evaluated collectively in accumulated doses. A total of 9102 metaphase spreads from 84 medical diagnostic X ray workers and 17 controls were scored. The results showed that: (1) the frequencies of translocation, stable chromosome aberration and total aberration in X ray workers were significantly higher than those of controls (P < 0.05 γ 0.005), unstable chromosome aberrations (including dicentric and acentric aberration) tended upwards; (2) the main aberration in stable aberrations was reciprocal translocation; (3) the stable aberration predominated strikingly in total aberrations. The medical diagnostic X ray workers were divided into three groups according to calendar year of entry. The data showed that the frequencies of translocation, stable aberration and total aberration increased with earlier year of entry, especially in two groups who started working before 1970. According to the equation recommended by Straume et al, linear coefficient (α) in the linear quadratic model provided by Fernandez's experiment, their collective accumulation doses calculated were 0.53, 0.26 and 0.06 Gy for calendar year of entry before 1960, 1960-1969, and after 1970, in X ray workers, respectively. (author)

  14. Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells.

    Science.gov (United States)

    Sato, Hiroshi; Kato, Hiroki; Yamaza, Haruyoshi; Masuda, Keiji; Nguyen, Huong Thi Nguyen; Pham, Thanh Thi Mai; Han, Xu; Hirofuji, Yuta; Nonaka, Kazuaki

    2017-01-01

    Embryonic trisomy leads to abortion or congenital genetic disorders in humans. The most common autosomal chromosome abnormalities are trisomy of chromosomes 13, 18, and 21. Although alteration of gene dosage is thought to contribute to disorders caused by extra copies of chromosomes, genes associated with specific disease phenotypes remain unclear. To generate a normal cell from a trisomic cell as a means of etiological analysis or candidate therapy for trisomy syndromes, we developed a system to eliminate a targeted chromosome from human cells. Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that harbored three copies of chromosome 21. The DNA cassette included two inverted loxP sites and a herpes simplex virus thymidine kinase (HSV-tk) gene. This system causes missegregation of chromosome 21 after expression of Cre recombinase and subsequently enables the selection of cells lacking the chromosome by culturing in a medium that includes ganciclovir (GCV). Cells harboring only two copies of chromosome 21 were efficiently induced by transfection of a Cre expression vector, indicating that this approach is useful for eliminating a targeted chromosome.

  15. Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Sato

    2017-01-01

    Full Text Available Embryonic trisomy leads to abortion or congenital genetic disorders in humans. The most common autosomal chromosome abnormalities are trisomy of chromosomes 13, 18, and 21. Although alteration of gene dosage is thought to contribute to disorders caused by extra copies of chromosomes, genes associated with specific disease phenotypes remain unclear. To generate a normal cell from a trisomic cell as a means of etiological analysis or candidate therapy for trisomy syndromes, we developed a system to eliminate a targeted chromosome from human cells. Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that harbored three copies of chromosome 21. The DNA cassette included two inverted loxP sites and a herpes simplex virus thymidine kinase (HSV-tk gene. This system causes missegregation of chromosome 21 after expression of Cre recombinase and subsequently enables the selection of cells lacking the chromosome by culturing in a medium that includes ganciclovir (GCV. Cells harboring only two copies of chromosome 21 were efficiently induced by transfection of a Cre expression vector, indicating that this approach is useful for eliminating a targeted chromosome.

  16. Homologous subfamilies of human alphoid repetitive DNA on different nucleolus organizing chromosomes

    International Nuclear Information System (INIS)

    Joergensen, A.L.; Bostock, C.J.; Bak, A.L.

    1987-01-01

    The organization of alphoid repeated sequences on human nucleolus-organizing (NOR) chromosomes 13, 21, and 22 has been investigated. Analysis of hybridization of alphoid DNA probes to Southern transfers of restriction enzyme-digested DNA fragments from hybrid cells containing single human chromosomes shows that chromosomes 13 and 21 share one subfamily of alphoid repeats, whereas a different subfamily may be held in common by chromosomes 13 and 22. The sequences of cloned 680-base-pair EcoRI fragments of the alphoid DNA from chromosomes 13 and 21 show that the basic unit of this subfamily is indistinguishable on each chromosome. The sequence of cloned 1020-base-pair Xba I fragments from chromosome 22 is related to, but distinguishable from, that of the 680-base-pair EcoRI alphoid subfamily of chromosomes 13 and 21. These results suggest that, at some point after they originated and were homogenized, different subfamilies of alphoid sequences must have exchanged between chromosomes 13 and 21 and separately between chromosomes 13 and 22

  17. Utility of X-chromosome SNPs in relationship testing

    DEFF Research Database (Denmark)

    Tomas, Carmen; Sanchez, Juan Jose; Castro, J.A.

    2008-01-01

    of the SBE primers varied between 18 and 85 nucleotides. We analyzed the allele and haplotype frequencies in 1078 unrelated males. All the SNPs were polymorphic and the lowest minor allele frequency was 0.103. All the haplotypes were unique. The forensic parameters were calculated in the Danish and Somali...... populations. In the Danish population (Ná=á93), the power of discrimination (PD) in females was one in 4.4áÎá109 individuals and the PD in males was one in 2.6áÎá106. The PD in Somalis (Ná=á91) was one in 2.7áÎá109 in females and one in 1.7áÎá106 in males. Finally, we present an example of how the 25 X...

  18. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

    Directory of Open Access Journals (Sweden)

    Maria Balcova

    2016-04-01

    Full Text Available Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm and Mus m. domesticus (Mmd, it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2 genomic locus on Chromosome X (Chr X by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s responsible for variation in the global recombination rate between closely related mouse subspecies.

  19. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

    Science.gov (United States)

    Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri

    2016-04-01

    Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.

  20. Repair of x-ray induced chromosomal damage in trisomy 2- and normal diploid lymphocytes

    International Nuclear Information System (INIS)

    Countryman, P.I.; Heddle, J.A.; Crawford, E.

    1977-01-01

    The frequency of chromosomal aberrations produced by x-rays is greater in lymphocytes cultured from trisomy 21 patients (Down's syndrome) than from normal diploid donors. This increase, which can be detected by a micronucleus assay for chromosomal damage, was postulated by us to result from a defect in the rejoining system which repairs chromosomal breaks. The postulated defect would result in a longer rejoining time, therapy permitting more movement of broken ends and thus enhancing the frequency of exchanges. To test this possibility, the time required for the rejoining (repair) of chromosome breaks was measured in lymphocytes from five Down's syndrome (four trisomy 21 and one D/G translocation partial trisomy 21) donors, from a monosomy 21 donor, and from five diploid donors. The rejoining time was reduced in the Down's syndrome lymphocytes in comparison to the normal diploid and monosomy 21 lymphocytes. Thus the repair of chromosome breaks, far from being defective as evidenced by a longer rejoining time in Down's syndrome cells, occurred more rapidly than in normal cells

  1. DNA Catenation Maintains Structure of Human Metaphase Chromosomes

    DEFF Research Database (Denmark)

    L. V. Bauer, David; Marie, Rodolphe; Rasmussen, Kristian Hagsted

    2012-01-01

    Mitotic chromosome structure is pivotal to cell division but difficult to observe in fine detail using conventional methods. DNA catenation has been implicated in both sister chromatid cohesion and chromosome condensation, but has never been observed directly. We have used a lab-on-a-chip microfl...

  2. Filipino DNA variation at 12 X-chromosome short tandem repeat markers.

    Science.gov (United States)

    Salvador, Jazelyn M; Apaga, Dame Loveliness T; Delfin, Frederick C; Calacal, Gayvelline C; Dennis, Sheila Estacio; De Ungria, Maria Corazon A

    2018-06-08

    Demands for solving complex kinship scenarios where only distant relatives are available for testing have risen in the past years. In these instances, other genetic markers such as X-chromosome short tandem repeat (X-STR) markers are employed to supplement autosomal and Y-chromosomal STR DNA typing. However, prior to use, the degree of STR polymorphism in the population requires evaluation through generation of an allele or haplotype frequency population database. This population database is also used for statistical evaluation of DNA typing results. Here, we report X-STR data from 143 unrelated Filipino male individuals who were genotyped via conventional polymerase chain reaction-capillary electrophoresis (PCR-CE) using the 12 X-STR loci included in the Investigator ® Argus X-12 kit (Qiagen) and via massively parallel sequencing (MPS) of seven X-STR loci included in the ForenSeq ™ DNA Signature Prep kit of the MiSeq ® FGx ™ Forensic Genomics System (Illumina). Allele calls between PCR-CE and MPS systems were consistent (100% concordance) across seven overlapping X-STRs. Allele and haplotype frequencies and other parameters of forensic interest were calculated based on length (PCR-CE, 12 X-STRs) and sequence (MPS, seven X-STRs) variations observed in the population. Results of our study indicate that the 12 X-STRs in the PCR-CE system are highly informative for the Filipino population. MPS of seven X-STR loci identified 73 X-STR alleles compared with 55 X-STR alleles that were identified solely by length via PCR-CE. Of the 73 sequence-based alleles observed, six alleles have not been reported in the literature. The population data presented here may serve as a reference Philippine frequency database of X-STRs for forensic casework applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Sexy gene conversions: locating gene conversions on the X-chromosome.

    Science.gov (United States)

    Lawson, Mark J; Zhang, Liqing

    2009-08-01

    Gene conversion can have a profound impact on both the short- and long-term evolution of genes and genomes. Here, we examined the gene families that are located on the X-chromosomes of human (Homo sapiens), chimpanzee (Pan troglodytes), mouse (Mus musculus) and rat (Rattus norvegicus) for evidence of gene conversion. We identified seven gene families (WD repeat protein family, Ferritin Heavy Chain family, RAS-related Protein RAB-40 family, Diphosphoinositol polyphosphate phosphohydrolase family, Transcription Elongation Factor A family, LDOC1-related family, Zinc Finger Protein ZIC, and GLI family) that show evidence of gene conversion. Through phylogenetic analyses and synteny evidence, we show that gene conversion has played an important role in the evolution of these gene families and that gene conversion has occurred independently in both primates and rodents. Comparing the results with those of two gene conversion prediction programs (GENECONV and Partimatrix), we found that both GENECONV and Partimatrix have very high false negative rates (i.e. failed to predict gene conversions), which leads to many undetected gene conversions. The combination of phylogenetic analyses with physical synteny evidence exhibits high resolution in the detection of gene conversions.

  4. The constrained maximal expression level owing to haploidy shapes gene content on the mammalian X chromosome

    DEFF Research Database (Denmark)

    Hurst, Laurence D.; Ghanbarian, Avazeh T.; Forrest, Alistair R R

    2015-01-01

    that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues...... abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed...

  5. Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic drive.

    Directory of Open Access Journals (Sweden)

    Urban Friberg

    Full Text Available Diploid organisms have two copies of all genes, but only one is carried by each haploid gamete and diploid offspring. This causes a fundamental genetic conflict over transmission rate between alternative alleles. Single genes, or gene clusters, only rarely code for the complex phenotypes needed to give them a transmission advantage (drive phenotype. However, all genes on a male's X and Y chromosomes co-segregate, allowing different sex-linked genes to code for different parts of the drive phenotype. Correspondingly, the well-characterized phenomenon of male gametic drive, occurring during haploid gametogenesis, is especially common on sex chromosomes. The new theory of sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive extends the logic of gametic drive into the diploid phase of the lifecycle, whenever there is competition among siblings or harmful sib-sib mating. The X and Y are predicted to gain a transmission advantage by harming offspring of the sex that does not carry them.Here we analyzed a mutant X-chromosome in Drosophila simulans that produced an excess of daughters when transmitted from males. We developed a series of tests to differentiate between gametic and SA-zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is responsible for the sex ratio bias. Driving sires produce about 50% more surviving daughters than sons.Sex-ratio distortion due to genetic conflict has evolved via gametic drive and maternally transmitted endosymbionts. Our data indicate that sex chromosomes can also drive by harming the non-carrier sex of offspring.

  6. Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic drive.

    Science.gov (United States)

    Friberg, Urban; Stewart, Andrew D; Rice, William R

    2011-01-01

    Diploid organisms have two copies of all genes, but only one is carried by each haploid gamete and diploid offspring. This causes a fundamental genetic conflict over transmission rate between alternative alleles. Single genes, or gene clusters, only rarely code for the complex phenotypes needed to give them a transmission advantage (drive phenotype). However, all genes on a male's X and Y chromosomes co-segregate, allowing different sex-linked genes to code for different parts of the drive phenotype. Correspondingly, the well-characterized phenomenon of male gametic drive, occurring during haploid gametogenesis, is especially common on sex chromosomes. The new theory of sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive) extends the logic of gametic drive into the diploid phase of the lifecycle, whenever there is competition among siblings or harmful sib-sib mating. The X and Y are predicted to gain a transmission advantage by harming offspring of the sex that does not carry them. Here we analyzed a mutant X-chromosome in Drosophila simulans that produced an excess of daughters when transmitted from males. We developed a series of tests to differentiate between gametic and SA-zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is responsible for the sex ratio bias. Driving sires produce about 50% more surviving daughters than sons. Sex-ratio distortion due to genetic conflict has evolved via gametic drive and maternally transmitted endosymbionts. Our data indicate that sex chromosomes can also drive by harming the non-carrier sex of offspring.

  7. Characterization of cDNAs encoding human leukosialin and localization of the leukosialin gene to chromosome 16

    International Nuclear Information System (INIS)

    Pallant, A.; Eskenazi, A.; Frelinger, J.G.; Mattei, M.G.; Fournier, R.E.K.; Carlsson, S.R.; Fukuda, M.

    1989-01-01

    The authors describe the isolation and characterization of cDNA clones encoding human leukosialin, a major sialoglycoprotein of human leukocytes. Leukosialin is very closely related or identical to the sialophorin molecule, which is involved in T-cell proliferation and whose expression is altered in Wiskott-Aldrich syndrome (WAS), an X-chromosome-linked immunodeficiency disease. Using a rabbit antiserum to leukosialin, a cDNA clone was isolated from a λgt11 cDNA library constructed from human peripheral blood cells. The λgt11 clone was used to isolate longer cDNA clones that correspond to the entire coding sequence of leukosialin. DNA sequence analysis reveals three domains in the predicted mature protein. The extracellular domain is enriched for Ser, Thr, and Pro and contains four contiguous 18-amino acid repeats. The transmembrane and intracellular domains of the human leukosialin molecule are highly homologous to the rat W3/13 molecule. RNA gel blot analysis reveals two polyadenylylated species of 2.3 and 8 kilobases. Southern blot analysis suggests that human leukosialin is a single-copy gene. Analysis of monochromosomal cell hybrids indicates that the leukosialin gene is not X chromosome linked and in situ hybridization shows leukosialin is located on chromosome 16. These findings demonstrate that the primary mutation in WAS is not a defect in the structural gene for leukosialin

  8. Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    Monobe, Manami

    2002-01-01

    We here investigated and reported the effects of beer drinking on radiation-induced chromosome aberrations in blood lymphocytes. Human blood that was collected either before or after drinking a 700 ml beer was in vitro irradiated with 200 kVp X rays or 50 keV/μm carbon ions. The relation between the radiation dose and the aberration frequencies (fragments and dicentrics) was significantly (P<0.05) lower for lymphocytes collected 3 h after beer drinking than those before drinking. Fitting the dose response to a linear quadratic model showed that the alpha term of carbon ions was significantly (P<0.05) decreased by beer drinking. A decrease of dicentric formation was detected as early as 0.5 h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of lymphocytes was higher after beer drinking than before, indicating that a division delay would not be responsible for the low aberrations induced by beer drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which corresponded to a concentration of 6-times higher than the maximum ethanol concentration in the blood after beer drinking, reduced the dicentric formation caused by X-ray irradiation, but not by carbon-ion irradiation. The beer-induced reduction of dicentric formation was not affected by serum. It is concluded that beer could contain non-ethanol elements that reduce the chromosome damage of lymphocytes induced by high-LET radiation. (author)

  9. Kinetics of human lymphocyte division and chromosomal radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, N O; Bianchi, M S; Larramendy, M [Instituto Multidisciplinario de Biologia Celular, La Plata (Argentinia)

    1979-12-01

    Human blood from normal donors was irradiated with 200 R during the G/sub 0/ phase, and the X-ray sensitivity of early and late dividing lymphocytes in culture was expressed as percentage of induced dicentrics. Cells in first or subsequent divisions were individualized by BrdU-Giemsa techniques. Lymphocytes in the first division at 40, 44 and 72 h after the start of culture had a lower sensitivity to radiation than lymphocytes making their first division at 48, 52 and 56 h. It was observed that: (a) the combination of radiation followed by BrdU did not increase the clastoyenic action of X-rays, (b)X-rays in the dose and duration used in our cultures did not increase the frequency of SCEs, and (c) minor changes in culture conditions probably influenced the frequency of SCEs.

  10. Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion

    Energy Technology Data Exchange (ETDEWEB)

    Shashi, V.; Golden, W.L.; Allinson, P.S. [Univ. of Virginia Health Sciences Center, Charlottesville, VA (United States)] [and others

    1996-06-01

    It has been demonstrated in animal studies that, in animals heterozygous for pericentric chromosomal inversions, loop formation is greatly reduced during meiosis. This results in absence of recombination within the inverted segment, with recombination seen only outside the inversion. A recent study in yeast has shown that telomeres, rather than centromeres, lead in chromosome movement just prior to meiosis and may be involved in promoting recombination. We studied by cytogenetic analysis and DNA polymorphisms the nature of meiotic recombination in a three-generation family with a large pericentric X chromosome inversion, inv(X)(p21.1q26), in which Duchenne muscular dystrophy (DMD) was cosegregating with the inversion. On DNA analysis there was no evidence of meiotic recombination between the inverted and normal X chromosomes in the inverted segment. Recombination was seen at the telomeric regions, Xp22 and Xq27-28. No deletion or point mutation was found on analysis of the DMD gene. On the basis of the FISH results, we believe that the X inversion is the mutation responsible for DMD in this family. Our results indicate that (1) pericentric X chromosome inversions result in reduction of recombination between the normal and inverted X chromosomes; (2) meiotic X chromosome pairing in these individuals is likely initiated at the telomeres; and (3) in this family DMD is caused by the pericentric inversion. 50 refs., 7 figs., 1 tab.

  11. Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability

    OpenAIRE

    Fukawatase, Yoshihiro; Toyoda, Masashi; Okamura, Kohji; Nakamura, Ken-ichi; Nakabayashi, Kazuhiko; Takada, Shuji; Yamazaki-Inoue, Mayu; Masuda, Akira; Nasu, Michiyo; Hata, Kenichiro; Hanaoka, Kazunori; Higuchi, Akon; Takubo, Kaiyo; Umezawa, Akihiro

    2014-01-01

    Ataxia telangiectasia is a neurodegenerative inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. iPS cells lacking ATM (AT-iPS cells) exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. While parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro for at least 80 passages (560 days). Whole exome analysis also showed a compa...

  12. Molecular analysis of the distribution of chromosomal breakpoints: characterization of a 'hot' region for breaks in human chromosome 11

    International Nuclear Information System (INIS)

    Vannais, D.B.; Hirai, Y.; Cologne, J.B.; Waldren, C.A.; Ueno, A.

    2003-01-01

    Full text: Ionizing radiation randomly damages DNA and chromosomes whereas subsequent chromosome breaks are non-random. Assuming, as an ideal and naive but useful proposition, that breaks are equally likely anywhere in the chromosome and that a deletion always occurs between two breaks, the frequency of fragments would decrease linearly with increasing fragment size. This simple distribution is not, however, observed. To shed light on the 'real' situation of break formation we mapped breakpoints in the human chromosome no. 11 of 353 independent CD59- mutants isolated from human/hamster hybrid AL cells exposed to radiations (high and low dose-rate gamma rays, high LET carbon or nitrogen ions, protons) or chemicals (arsenic or irradiated, mutagenic histidine) or unexposed. The number of breaks per unit length of DNA differed significantly in different regions of chromosome 11.The highest level of breaks (140/mbp) were in the 0.8 mbp segment between CD59 and Catalase (CAT). Finer mapping of break points was carried out using 26 PCR primer pairs spread across this interval in 15 independent mutants. In two mutants, the break point was in a 107 bp fragment; in the other 13 the breaks were in a single 35 mbp fragment, but not all were at exactly the same site; 4 of 13 occurred in 3 different 3 mbp sub-segments. We are sequencing these fragments to look for such features as repeats: 'colder' regions like that between CD59 and WT will also be analyzed. But, since at least some breaks occurred at different sites and the frequency and distribution of breaks was about the same for all treatments, our we postulate that hot (and cold spots) may be due more to structural features or specific repair than to sequence or type of damage

  13. Yleaf: Software for Human Y-Chromosomal Haplogroup Inference from Next-Generation Sequencing Data.

    Science.gov (United States)

    Ralf, Arwin; Montiel González, Diego; Zhong, Kaiyin; Kayser, Manfred

    2018-05-01

    Next-generation sequencing (NGS) technologies offer immense possibilities given the large genomic data they simultaneously deliver. The human Y-chromosome serves as good example how NGS benefits various applications in evolution, anthropology, genealogy, and forensics. Prior to NGS, the Y-chromosome phylogenetic tree consisted of a few hundred branches, based on NGS data, it now contains many thousands. The complexity of both, Y tree and NGS data provide challenges for haplogroup assignment. For effective analysis and interpretation of Y-chromosome NGS data, we present Yleaf, a publically available, automated, user-friendly software for high-resolution Y-chromosome haplogroup inference independently of library and sequencing methods.

  14. Effect of aspirin on chromosome aberration and DNA damage induced by X-rays in mice

    Science.gov (United States)

    Niikawa, M.; Chuuriki, K.; Shibuya, K.; Seo, M.; Nagase, H.

    In order to reveal the anticlastogenic potency of aspirin, we evaluated the suppressive ability of aspirin on chromosome aberrations induced by X-ray. Aspirin at doses of 0.5, 5 and 50 mg/kg was administrated intraperitoneally or orally at 0.5 h after or before the X-ray irradiation. The anticlastogenic activity of aspirin on chromosome aberrations induced by X-ray was determined in the mouse micronucleus test and alkaline single cell gel electrophoresis (SCG) assay in vivo. The frequency by polychromatic erythrocytes with micronuclei (MNPCEs) was decreased by about 19-61% at 0.5 h after and about 23-62% at 0.5 h before the X-ray irradiation. DNA damage by X-ray was significantly decreased by oral administration of aspirin at 0.5 h after or before the X-ray irradiation for the SCG assay. We consider aspirin can be used as preventive agents against exposure of X-ray.

  15. 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.

  16. Search for linkage to schizophrenia on the X and Y chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Devoto, M.; Ott, J. [Columbia Univ., New York, NY (United States); Vita, A. [Univ. of Milan (Italy)] [and others

    1994-06-15

    Markers for X chromosome loci were used in linkage studies of a large group of small families (n = 126) with at least two schizophrenic members in one sibship. Based on the hypothesis that a gene for schizophrenia could be X-Y linked, with homologous loci on both X and Y, our analyses included all families regardless of the pattern of familial inheritance. Lod scores were computed with both standard X-linked and a novel X-Y model, and sib-pair analyses were performed for all markers examining the sharing of maternal alleles. Small positive lod scores were obtained for loci pericentromeric, from Xp11.4 to Xq12. Lod scores were also computed separately in families selected for evidence of maternal inheritance and absence of male to male transmission of psychosis. The lod scores for linkage to the locus DXS7 reached a maximum of 1.83 at 0.08% recombination, assuming dominant inheritance on the X chromosome in these families (n = 34). Further investigation of the X-Y homologous gene hypothesis focussing on this region is warranted. 39 refs. 1 fig., 6 tabs.

  17. Replication Banding Patterns in Human Chromosomes Detected Using 5-ethynyl-2'-deoxyuridine Incorporation

    International Nuclear Information System (INIS)

    Hoshi, Osamu; Ushiki, Tatsuo

    2011-01-01

    A novel technique using the incorporation of 5-ethynyl-2'-deoxyuridine (EdU) into replicating DNA is described for the analysis of replicating banding patterns of human metaphase chromosomes. Human lymphocytes were synchronized with excess thymidine and treated with EdU during the late S phase of the cell cycle. The incorporated EdU was then detected in metaphase chromosomes using Alexa Fluor® 488 azides, through the 1,3-dipolar cycloaddition reaction of organic azides with the terminal acetylene group of EdU. Chromosomes with incorporated EdU showed a banding pattern similar to G-banding of normal human chromosomes. Imaging by atomic force microscopy (AFM) in liquid conditions showed that the structure of the chromosomes was well preserved even after EdU treatment. Comparison between fluorescence microscopy and AFM images of the same chromosome 1 indicated the presence of ridges and grooves in the chromatid arm, features that have been previously reported in relation to G-banding. These results suggest an intimate relationship between EdU-induced replication bands and G- or R-bands in human chromosomes. This technique is thus useful for analyzing the structure of chromosomes in relation to their banding patterns following DNA replication in the S phase

  18. Construction of an Unstable Ring-X Chromosome Bearing the Autosomal Dopa Decarboxylase Gene in Drosophila melanogaster and Analysis of Ddc Mosaics

    OpenAIRE

    Gailey, Donald A.; Bordne, Deborah L.; Vallés, Ana Maria; Hall, Jeffrey C.; White, Kalpana

    1987-01-01

    An unstable Ring-X chromosome, Ddc+- Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)wvC and a Rod-X chromosome which contained a P-element mediated Ddc + insert. The resulting Ddc+-Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc+-Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics reveal...

  19. No interaction between X-ray induced lesions in maternal and paternal chromosomes in inseminated eggs of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Wuergler, F.E.; Graf, U.; Jeanneret, P.

    1978-01-01

    X-ray induced premutational lesions persist in mature gametes of drosophila until fertilization. Repairable lesions in sperm and oocyte chromosomes are repaired exclusively by maternal repair systems in the inseminated egg. Interactions between irradiated genomes in inseminated eggs might result in additional lethality if breaks induced in separate nuclei, which would normally be repaired, could interact to form dicentric chromosomes. Adult drosophila flies were X-irradiated (up to 5 kR), individual females crossed to three or four males, and the dose-response curves for dominant lethals (embryonic lethality) compared. The results indicate thet the potentially lethal damage present in irradiated sperm chromosomes was expressed independently of whether or not the oocyte was also irradiated. There were no (or only very few) interactions between maternal and paternal chromosome complements, and the maternal repair systems acting on radiation-induced chromosome breaks in sperm were resistant to X-rays. (U.K.)

  20. 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

  1. Cytogenetic analysis of X-ray induced chromosome aberrations in spontaneous leukaemic AKR mice

    International Nuclear Information System (INIS)

    Szollar, J.

    1975-01-01

    The increased frequency of numerical and structural chromosomal aberrations in spontaneously leukaemic AKR mice, compared with the values of healthy control CBA/H-T 6 T 6 mice, induced by X-irradiation, might be connected with the predisposition to malignant growth, probably indirectly helping the virus activation, or acting together with the immune deficiency, by creating a weaker system that is more sensitive to carcinogenic agents

  2. The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer

    OpenAIRE

    Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M.; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette; Gronemeyer, Hinrich; Vincent-Salomon, Anne; Stern, Marc-Henri; Heard, Edith

    2015-01-01

    Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear. Here we show that breast tumors and cell lines frequently display major epigenetic instability of the inactive X chromosome, with highly abnormal 3D nuclear organization and global perturbations of heterochromatin, including gain of euchromatic marks and aberrant distributions of repressive marks such as ...

  3. CGG repeats associated with fragile X chromosome form left-handed Z-DNA structure

    Czech Academy of Sciences Publication Activity Database

    Renčiuk, Daniel; Kypr, Jaroslav; Vorlíčková, Michaela

    2011-01-01

    Roč. 95, č. 3 (2011), s. 174-181 ISSN 0006-3525 R&D Projects: GA ČR(CZ) GA202/07/0094; GA AV ČR(CZ) IAA100040701 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : fragile X chromosome syndrome * Z-DNA * trinucleotide repeats Subject RIV: BO - Biophysics Impact factor: 2.870, year: 2011

  4. Resolution and evolution of the duck-billed platypus karyotype with an X1Y1X2Y2X3Y3X4Y4X5Y5 male sex chromosome constitution.

    Science.gov (United States)

    Rens, Willem; Grützner, Frank; O'brien, Patricia C M; Fairclough, Helen; Graves, Jennifer A M; Ferguson-Smith, Malcolm A

    2004-11-16

    The platypus (2n = 52) has a complex karyotype that has been controversial over the last three decades. The presence of unpaired chromosomes and an unknown sex-determining system especially has defied attempts at conventional analysis. This article reports on the preparation of chromosome-specific probes from flow-sorted chromosomes and their application in the identification and classification of all platypus chromosomes. This work reveals that the male karyotype has 21 pairs of chromosomes and 10 unpaired chromosomes (E1-E10), which are linked by short regions of homology to form a multivalent chain in meiosis. The female karyotype differs in that five of these unpaired elements (E1, E3, E5, E7, and E9) are each present in duplicate, whereas the remaining five unpaired elements (E2, E4, E6, E8, and E10) are absent. This finding indicates that sex is determined by the alternate segregation of the chain of 10 during spermatogenesis so that equal numbers of sperm bear either one of the two groups of five elements, i.e., five X and five Y chromosomes. Chromosome painting reveals that these X and Y chromosomes contain pairing (XY shared) and differential (X- or Y-specific) segments. Y differential regions must contain male-determining genes, and X differential regions should be dosage-compensated in the female. Two models for the evolution of the sex-determining system are presented. The resolution of the longstanding debate over the platypus karyotype is an important step toward the understanding of mechanisms of sex determination, dosage compensation, and karyotype evolution.

  5. A Role for the X Chromosome in Sex Differences in Variability in General Intelligence?

    Science.gov (United States)

    Johnson, Wendy; Carothers, Andrew; Deary, Ian J

    2009-11-01

    There is substantial evidence that males are more variable than females in general intelligence. In recent years, researchers have presented this as a reason that, although there is little, if any, mean sex difference in general intelligence, males tend to be overrepresented at both ends of its overall distribution. Part of the explanation could be the presence of genes on the X chromosome related both to syndromal disorders involving mental retardation and to population variation in general intelligence occurring normally. Genes on the X chromosome appear overrepresented among genes with known involvement in mental retardation, which is consistent with a model we developed of the population distribution of general intelligence as a mixture of two normal distributions. Using this model, we explored the expected ratios of males to females at various points in the distribution and estimated the proportion of variance in general intelligence potentially due to genes on the X chromosome. These estimates provide clues to the extent to which biologically based sex differences could be manifested in the environment as sex differences in displayed intellectual abilities. We discuss these observations in the context of sex differences in specific cognitive abilities and evolutionary theories of sexual selection. © 2009 Association for Psychological Science.

  6. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    International Nuclear Information System (INIS)

    Burkhardt, W.C.; Jackson, J.F.; Songcharoen, S.; Meydrech, E.F.

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05). (author)

  7. Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

    Science.gov (United States)

    Bateman, J B; Kojis, T L; Cantor, R M; Heinzmann, C; Ngo, J T; Spence, M A; Inana, G; Kivlin, J D; Curtis, D; Sparkes, R S

    1993-01-01

    Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

  8. Variation of autosomes and X chromosome STR in breast cancer and gynecological cancer tissues

    Directory of Open Access Journals (Sweden)

    Hou Youxiang

    2017-04-01

    Full Text Available This study analyses 1000 cases of patients with breast cancer and 2000 cases of patients with gynecological cancer (1000 cases of malignant tumor, 1000 cases of benign tumors, where breast cancer and malignant tumor patients comprise the observation group, while patients with benign tumors comprise the control group. Through DNA extraction, STR genotyping and variation verification, microdissection, individual STR mutation rate and loci STR mutation rate of the two groups of patients were calculated. Results show that there are no significant (P > 0.05 differences in the STR variation of autosomes and X chromosome between patients in the observation group and those in the reference group. However, significant (P < 0.05 intergroup differences were found for STR variation typing between patients with malignant and benign tumors. Using STR genotyping for autosomes and X chromosomes, gynecological cancer patients were found to be more likely to mutate, with a clear relationship between STR variation and tumor differentiation degrees. The study on the variation analysis of autosomes and X chromosome STR in breast and gynecological cancer tissues is expected to have a high application value when applied to medical research and identification processes.

  9. Chromosome alterations in the X-ray-induced transformants of cultured mouse cell line

    International Nuclear Information System (INIS)

    Kodama, Seiji; Komatsu, Kenshi; Okumura, Yutaka; Sasaki, M.S.

    1989-01-01

    Mouse m5S cells were subjected to soft X-ray irradiation. Twenty-four transformants were separated as indicators of focus formation. Two clones, cl.4103 and cl.6310, were chosen for the analysis of chromosome alterations in transformants. A parent strain, m5S/1M, served as the control. Anchorage independence (AG) was not detected in the control strain, irrespective of culture conditions and population doubling number (PDN). In the case of transformants, the frequency of AG was increased with increasing PDN for cl.4103, and was constant for cl.6310, irrespective of PDN. Karyotype of m5S/1M was 42, X, -Y, +der (6) t(6;13), t(8;8), +8, +15. In addition, -13, der(10) and -der(6)t(6;13), der(5), +mar occurred as karyotype alterations for cl.4103 and cl. 6310, respectively. The present experiment indicated that chromosome alterations secondary to primary alterations occur in a high frequency in the transforming process of X-ray irradiated cells, and that the secondary chromosome alterations result in selective proliferation of transformed clones. (Namekawa, K)

  10. Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Burkhardt, W C; Jackson, J F; Songcharoen, S; Meydrech, E F [Mississippi Univ., Jackson (USA). Medical Center

    1980-01-01

    Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P=0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P<0.05).

  11. An X chromosome effect responsible for asymmetric reproductive isolation between male Drosophila virilis and heterospecific females.

    Science.gov (United States)

    Nickel, Desirée; Civetta, Alberto

    2009-01-01

    Reproductive isolation between closely related species is expressed through uncoordinated courtship, failed fertilization, and (or) postzygotic barriers. Behavioural components of mating often form an initial barrier to hybridization between species. In many animals, females are responsible for mating discrimination in both intra- and interspecific crosses; males of Drosophila virilis group represent an exception to this trend. Using overall productivity tests, we show that a lower proportion of D. virilis males sire progeny when paired with a heterospecific female (Drosophila novamexicana or Drosophila americana texana) for 2 weeks. This suggests male mate discrimination or some other kind of asymmetrical incompatibility in courtship and mating or early zygote mortality. We used males from D. virilis-D. novamexicana and from D. virilis-D. a. texana backcross populations to map chromosome effects responsible for male reproductive isolation. Results from the analysis of both backcross male populations indicate a major X chromosome effect. Further, we conduct a male behavioural analysis to show that D. virilis males significantly fail to continue courtship after the first step of courtship, when they tap heterospecific females. The combined results of a major X chromosome effect and the observation that D. virilis males walk away from females after tapping suggest that future studies should concentrate on the identification of X-linked genes affecting the ability of males to recognize conspecific females.

  12. Transfer of unstable chromosomal aberrations in human peripheral lymphocytes at cell division and their significance for the aberration frequency

    International Nuclear Information System (INIS)

    Stephan, G.; Chang Tsangpi.

    1986-04-01

    In 48 h cultures, the fraction of human lymphocytes in 2nd mitosis was found to be between 0 and 42.5% (mean value 8.7%). The X-ray exposure from irradiating with 2 Gy resulted in a cell cycle delay which varied from donor to donor. A loss of nearly 50% of dicentric chromosomes and acentric fragments from unstable chromosomes occurred at cell division, while centric rings were not impeded. When dicentric chromosomes, or acentric fragments are found in 2nd mitosis, they show a characteristic differential staining, which means that chromatides at cell division fall free and are replicated in daughter cells. When plotting dose effect curves of dicentric chromosomes, up to 20% of 2nd mitosis fractions have little influence on the aberration rate. This may be additionally verified as part of the 'biological dosimetry' in a person with 24% of 2nd mitosis. When the rates of dicentric chromosomes exclusively evaluated from 1st mitosis after irradiation with 2.0 Gy were related to the donors age, no age-dependent sensitivity to radiation could be observed. Aberration rates which deviate from person to person are comparable to the results achieved by conventional staining methods. (orig./MG) [de

  13. Social cognition and underlying cognitive mechanisms in children with an extra X chromosome: a comparison with autism spectrum disorder.

    Science.gov (United States)

    van Rijn, S; Stockmann, L; van Buggenhout, G; van Ravenswaaij-Arts, C; Swaab, H

    2014-06-01

    Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Trisomy X), 56 children with autism spectrum disorder (ASD) and 88 non-clinical controls, aged 9-18 years, were included. Similar to children with ASD, children with an extra X chromosome showed significant impairments in social cognition. Regression analyses showed that different cognitive functions predicted social cognitive skills in the extra X and ASD groups. The social cognitive deficits were similar for boys and girls with an extra X chromosome, and not specific for a subgroup with high Autism Diagnostic Interview Revised autism scores. Thus, children with an extra X chromosome show social cognitive deficits, which may contribute to social dysfunction, not only in children showing a developmental pattern that is 'typical' for autism but also in those showing mild or late presenting autism symptoms. Our findings may also help explain variance in type of social deficit: children may show similar social difficulties, but these may arise as a consequence of different underlying information processing deficits. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  14. Recombinant chromosome 7 in a mosaic 45,X/47,XXX patient.

    Science.gov (United States)

    Tirado, Carlos A; Gotway, Garrett; Torgbe, Emmanuel; Iyer, Santha; Dallaire, Stephanie; Appleberry, Taylor; Suterwala, Mohamed; Garcia, Rolando; Valdez, Federico; Patel, Sangeeta; Koduru, Prasad

    2012-01-01

    Individuals with pericentric inversions are at risk for producing offspring with chromosomal gains and losses, while those carrying paracentric inversions usually produce unviable gametes [Madan, 1995]. In this current study, we present a newborn with dysmorphic features and malformations, whose karyotype showed an abnormal copy of chromomosome 7 described at first as add(7)(q32) as well as mos 45,X/47,XXX. Array comparative genomic hybridization (CGH) revealed an interstitial deletion in the long arm of chromosome 7 involving bands q35 to q36.3 but retaining the 7q subtelomere. The patient's deletion is believed to be due to meiotic recombination in the inversion loop in the phenotypically normal father who seems to carry two paracentric inversions in the long arm of chromosome 7, which was described as rec(7)(7pter- > q35::q36.3- > 7qter)pat. The abnormal copy of chromosome 7 in the father has been described as: der(7)(7pter- > q22.1::q36.3- > q35::q22.1- > q35::q36.3- > 7qter). This is a unique karyotype that to our knowledge has not been previously reported in the literature and predisposes to meiotic recombination that can result in deletions or duplications of 7q35-36. Copyright © 2011 Wiley Periodicals, Inc.

  15. Cosmic radiation induced chromosomal aberrations in human lymphocytes

    International Nuclear Information System (INIS)

    De Angelis, G.; Facius, R.; Reitz, G.

    2003-01-01

    Since decades, elevated frequencies of dicentric chromosomes (DIC) in human lymphocytes have successfully been used as a biological dosimeter in cases of acute, often accidental exposures to ionizing radiation. As long as duration and time lags after exposure are small compared to the lifetime of DIC, their frequencies can also be used to assess doses from protracted, chronic irradiation. E.g., within the substantial range of uncertainties, the frequencies of DIC observed in cosmonauts are compatible with the frequencies expected from doses of low and high LET radiation to which they were exposed in low earth orbit (LEO). On the other hand, frequencies of DIC detected in lymphocytes of civilian aviation crewmembers rarely correlate with the doses accumulated all along their professional career. For such long duration exposures with relatively low induction rates, the concomitant decay of DIC frequencies due to the removal during exposure of lymphocytes carrying DIC has to be taken into account. We present temporal profiles of frequencies of DIC during the exposure calculated with a model of exponential decay of DIC for some scenarios of chronic exposure to cosmic radiation. E.g., even after a 'heavily' shielded Mars mission, the expected frequencies of DIC in lymphocytes of astronauts will be 10 to 40 times higher than the terrestrial control levels. For air flight personnel we calculated the time profiles of frequencies of DIC in lymphocytes of a 'typical' pilot, a male cabin attendant and a female cabin attendant whose professional radiation exposures were recalculated for the actual flight routes flown during their entire flight career as recorded in detailed duty logs. These results demonstrate that experimental (epidemiological) studies concerning DIC in air or space flight personnel must explicitly take into consideration the temporal exposure profiles in the prospective study population and that the point in time at which blood samples are to be drawn must

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia

    International Nuclear Information System (INIS)

    Rithidech, K.; Bond, V.P.; Cronkite, E.P.; Thompson, M.H.; Bullis, J.E.

    1995-01-01

    In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hyper mutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer. 15 refs., 1 fig., 2 tabs

  18. Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity for chromosomes 13, 14, and 21: implications for recombination between nonhomologues and Robertsonian translocations

    Energy Technology Data Exchange (ETDEWEB)

    Choo, K H; Vissel, B; Brown, R; Filby, R G; Earle, E

    1988-02-25

    The authors report a new subfamily of alpha satellite DNA (pTRA-2) which is found on all the human acrocentric chromosomes. The alphoid nature of the cloned DNA was established by partial sequencing. Southern analysis of restriction enzyme-digested DNA fragments from mouse/human hybrid cells containing only human chromosome 21 showed that the predominant higher-order repeating unit for pTRA-2 is a 3.9 kb structure. Analysis of a consensus in situ hybridization profile derived from 13 normal individuals revealed the localization of 73% of all centromeric autoradiographic grains over the five acrocentric chromosomes, with the following distribution: 20.4%, 21.5%, 17.1%, 7.3% and 6.5% on chromosomes 13, 14, 21, 15 and 22 respectively. An average of 1.4% of grains was found on the centromere of each of the remaining 19 nonacrocentric chromosomes. These results indicate the presence of a common subfamily of alpha satellite DNA on the five acrocentric chromosomes and suggest an evolutionary process consistent with recombination exchange of sequences between the nonhomologues. The results further suggests that such exchanges are more selective for chromosomes 13, 14 and 21 than for chromosomes 15 and 22. The possible role of centromeric alpha satellite DNA in the aetiology of 13q14q and 14q21q Robertsonian translocation involving the common and nonrandom association of chromosomes 13 and 14, and 14 and 21 is discussed.

  19. Chromosome segregation regulation in human zygotes: altered mitotic histone phosphorylation dynamics underlying centromeric targeting of the chromosomal passenger complex.

    Science.gov (United States)

    van de Werken, C; Avo Santos, M; Laven, J S E; Eleveld, C; Fauser, B C J M; Lens, S M A; Baart, E B

    2015-10-01

    Are the kinase feedback loops that regulate activation and centromeric targeting of the chromosomal passenger complex (CPC), functional during mitosis in human embryos? Investigation of the regulatory kinase pathways involved in centromeric CPC targeting revealed normal phosphorylation dynamics of histone H2A at T120 (H2ApT120) by Bub1 kinase and subsequent recruitment of Shugoshin, but phosphorylation of histone H3 at threonine 3 (H3pT3) by Haspin failed to show the expected centromeric enrichment on metaphase chromosomes in the zygote. Human cleavage stage embryos show high levels of chromosomal instability. What causes this high error rate is unknown, as mechanisms used to ensure proper chromosome segregation in mammalian embryos are poorly described. In this study, we investigated the pathways regulating CPC targeting to the inner centromere in human embryos. We characterized the distribution of the CPC in relation to activity of its two main centromeric targeting pathways: the Bub1-H2ApT120-Sgo-CPC and Haspin-H3pT3-CPC pathways. The study was conducted between May 2012 and March 2014 on human surplus embryos resulting from in vitro fertilization treatment and donated for research. In zygotes, nuclear envelope breakdown was monitored by time-lapse imaging to allow timed incubations with specific inhibitors to arrest at prometaphase and metaphase, and to interfere with Haspin and Aurora B/C kinase activity. Functionality of the targeting pathways was assessed through characterization of histone phosphorylation dynamics by immunofluorescent analysis, combined with gene expression by RT-qPCR and immunofluorescent localization of key pathway proteins. Immunofluorescent analysis of the CPC subunit Inner Centromere Protein revealed the pool of stably bound CPC proteins was not strictly confined to the inner centromere of prometaphase chromosomes in human zygotes, as observed in later stages of preimplantation development and somatic cells. Investigation of the

  20. A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker

    Directory of Open Access Journals (Sweden)

    Roberto L. P. Mazzaschi

    2014-01-01

    Full Text Available A skin sample from a 17-year-old female was received for routine karyotyping with a set of clinical features including clonic seizures, cardiomyopathy, hepatic adenomas, and skeletal dysplasia. Conventional karyotyping revealed a mosaic Turner syndrome karyotype with a cell line containing a small marker of X chromosome origin. This was later confirmed on peripheral blood cultures by conventional G-banding, fluorescence in situ hybridisation and microarray analysis. Similar Turner mosaic marker chromosome cases have been previously reported in the literature, with a variable phenotype ranging from the mild “classic” Turner syndrome to anencephaly, agenesis of the corpus callosum, complex heart malformation, and syndactyly of the fingers and toes. This case report has a phenotype that is largely discordant with previously published cases as it lies at the severe end of the Turner variant phenotype scale. The observed cytogenetic abnormalities in this study may represent a coincidental finding, but we cannot exclude the possibility that the marker has a nonfunctioning X chromosome inactivation locus, leading to functional disomy of those genes carried by the marker.

  1. X-Chromosome Effects on Attention Networks: Insights from Imaging Resting-State Networks in Turner Syndrome.

    Science.gov (United States)

    Green, Tamar; Saggar, Manish; Ishak, Alexandra; Hong, David S; Reiss, Allan L

    2017-07-18

    Attention deficit hyperactivity disorder (ADHD) is strongly affected by sex, but sex chromosomes' effect on brain attention networks and cognition are difficult to examine in humans. This is due to significant etiologic heterogeneity among diagnosed individuals. In contrast, individuals with Turner syndrome (TS), who have substantially increased risk for ADHD symptoms, share a common genetic risk factor related to the absence of the X-chromosome, thus serving as a more homogeneous genetic model. Resting-state functional MRI was employed to examine differences in attention networks between girls with TS (n = 40) and age- sex- and Tanner-matched controls (n = 33). We compared groups on resting-state functional connectivity measures from data-driven independent components analysis (ICA) and hypothesis-based seed analysis. Using ICA, reduced connectivity was observed in both frontoparietal and dorsal attention networks. Similarly, using seeds in the bilateral intraparietal sulcus (IPS), reduced connectivity was observed between IPS and frontal and cerebellar regions. Finally, we observed a brain-behavior correlation between IPS-cerebellar connectivity and cognitive attention measures. These findings indicate that X-monosomy contributes affects to attention networks and cognitive dysfunction that might increase risk for ADHD. Our findings not only have clinical relevance for girls with TS, but might also serve as a biological marker in future research examining the effects of the intervention that targets attention skills. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Initial damage in human interphase chromosomes from alpha particles with linear energy transfers relevant to radon exposure

    International Nuclear Information System (INIS)

    Loucas, B.D.; Geard, C.R.

    1994-01-01

    To determine the efficiency at which α particles at LETs chosen to simulate exposure to radon progeny break chromosomes, the premature chromosome condensation technique was used to measure breaks soon after irradiation. Noncycling human fibroblasts were irradiated with graded doses of monoenergetic α particles accelerated to produce LETs of 90, 120, 150, 180 and 200 keV/pm at the midpoint of the cell nuclei. Premature chromosome condensation was initiated immediately after irradiation and cells were scored for the total number of prematurely condensed chromosomes and fragments per cell. Similar experiments were conducted with 250 kVp X rays for comparison. Irradiation with α particles produced 8.6 to 13.1 excess fragments per gray, while X rays produced 5.8 excess fragments, resulting in RBEs around 2. Calculations of the number of breaks produced on average by a single particle traversal of a cell nucleus indicated that at the LETs tested more than one break was produced by each traversal, the maximum being that produced by 180 keV/μm α particles. When chromosome aberrations are scored at metaphase after high-LET irradiation, RBEs considerably greater than those recorded here have been reported. These results showing relatively small differences in initial break levels for α particles in the LET range of the radon progeny relative to X rays indicate that the great aberration frequencies are not due principally to an increase in breakage efficiency, but interactions between breaks along the same particle track are important. 16 refs., 4 figs

  3. Chromosome Aberrations in Human Lymphocytes Irradiated with Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The purpose of the present experiment was to provide data on the dose-dependent production of chromosome aberrations such as dicentrics, centric rings, and excess acentrics. Radiation is one of the more dangerous clastogens in the environment. Ionizing radiation causes chromosome breakages and various cytogenetic aberrations in exposed cells. In an investigation into radiation emergencies, it is important to estimate the dose to exposed persons for several reasons. Physical dosimeters (e. g., film badges) may misrepresent the actual radiation dose and may not be available in a radiological accident or terrorism incident. Biological dosimetry is suitable for estimating the radiation dose during such accidents. The dicentric chromosome assay is very sensitive and a reliable bio-indicator in cases of accidental overexposure.

  4. Nuclear organization in human sperm: preliminary evidence for altered sex chromosome centromere position in infertile males.

    Science.gov (United States)

    Finch, K A; Fonseka, K G L; Abogrein, A; Ioannou, D; Handyside, A H; Thornhill, A R; Hickson, N; Griffin, D K

    2008-06-01

    Many genetic defects with a chromosomal basis affect male reproduction via a range of different mechanisms. Chromosome position is a well-known marker of nuclear organization, and alterations in standard patterns can lead to disease phenotypes such as cancer, laminopathies and epilepsy. It has been demonstrated that normal mammalian sperm adopt a pattern with the centromeres aligning towards the nuclear centre. The purpose of this study was to test the hypothesis that altered chromosome position in the sperm head is associated with male infertility. The average nuclear positions of fluorescence in-situ hybridization signals for three centromeric probes (for chromosomes X, Y and 18) were compared in normoozoospermic men and in men with compromised semen parameters. In controls, the centromeres of chromosomes X, Y and 18 all occupied a central nuclear location. In infertile men the sex chromosomes appeared more likely to be distributed in a pattern not distinguishable from a random model. Our findings cast doubt on the reliability of centromeric probes for aneuploidy screening. The analysis of chromosome position in sperm heads should be further investigated for the screening of infertile men.

  5. A 2-megabase physical contig incorporating 43 DNA markers on the human X chromosome at p11.23-p11.22 from ZNF21 to DXS255

    Energy Technology Data Exchange (ETDEWEB)

    Boycott, K.M.; Bech-Hansen, N.T. [Univ. of Calgary, Alberta (Canada); Halley, G.R.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1996-05-01

    A comprehensive physical contig of yeast artificial chromosomes (YACs) and cosmid clones between ZNF21 and DXS255 has been constructed, spanning 2 Mb within the region Xp11.23-p11.22. As a portion of the region was found to be particularly unstable in yeast, the integrity of the contig is dependent on additional information provided by the sequence-tagged site (STS) content of cosmid clones and DNA marker retention in conventional and radiation hybrids. The contig was formatted with 43 DNA markers, including 19 new STSs from YAC insert ends and an internal Alu-PCR product. The density of STSs across the contig ranges from one marker every 20 kb to one every 60 kb, with an average density of one marker every 50 kb. The relative order of previously known gene and expressed sequence tags in this region is predicted to be Xpter-ZNF21-DXS7465E (MG66)-DXS7927E (MG81)-WASP, DXS1011E, DXS7467E (MG21)-DXS-7466E (MG44)-GATA1-DXS7469E (Xp664)-TFE3-SYP (DXS1007E)-Xcen. This contig extends the coverage in Xp11 and provides a framework for the future identification and mapping of new genes, as well as the resources for developing DNA sequencing templates. 47 refs., 1 fig., 4 tabs.

  6. Synaptonemal complex aberrations in the pseudoautosomal region of X, Y chromosomes in irradiated hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Allen, J.W.; Collins, B.W. [Environmental Protection Agency, Research Triangle Park, NC (United States); Poorman-Allen, P. [Wellcome Research Lab., Research Triangle Park, N.C. (United States); Sontag, M.R. [Duke Univ., Durham, NC (United States). Medical Center

    1994-05-01

    The effects of X-radiation, bleomycin and amsacrine (m-AMSA) on the meiotic chromosomes of male Armenian hamsters were determined by electron microscopic analysis of synaptonemal complex (SC) damage. Pachytene stage cells were analyzed 5 or 6 days following their treatment at putative preleptotene-leptotene stages of meiosis. Of the multiple types of SC aberrations observed to be significantly increased over control levels, lateral element breakage and synaptic anomalies were most prevalent. The focus of these studies was on the sex chromosomes which, in the Armenian hamster, reveal an unusally well-defined pseudoautosomal region. In the XY pair, radiation and chemical treatments caused certain forms of structural and synaptic anomalies which appeared to be preferentially localized to telomeric and/or crossover regions. The nature of these specific aberrations, involving breakage, bridge formation and asynapsis, is not well understood; however, their distributions are suggestive of possible relationships with sites and processes of crossing over. (author).

  7. Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

    Science.gov (United States)

    Murphy, D L; Sims, K B; Karoum, F; Garrick, N A; de la Chapelle, A; Sankila, E M; Norio, R; Breakefield, X O

    1991-01-01

    Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

  8. A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

    Science.gov (United States)

    Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

    2010-12-01

    Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

  9. Microarray Analysis of Copy Number Variants on the Human Y Chromosome Reveals Novel and Frequent Duplications Overrepresented in Specific Haplogroups.

    Directory of Open Access Journals (Sweden)

    Martin M Johansson

    Full Text Available The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175 individuals presented the highest percentage (95% of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9% and deletions (2.8% was even larger.Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in

  10. 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 c...

  11. Computer graphics of SEM images facilitate recognition of chromosome position in isolated human metaphase plates.

    Science.gov (United States)

    Hodge, L D; Barrett, J M; Welter, D A

    1995-04-01

    There is general agreement that at the time of mitosis chromosomes occupy precise positions and that these positions likely affect subsequent nuclear function in interphase. However, before such ideas can be investigated in human cells, it is necessary to determine first the precise position of each chromosome with regard to its neighbors. It has occurred to us that stereo images, produced by scanning electron microscopy, of isolated metaphase plates could form the basis whereby these positions could be ascertained. In this paper we describe a computer graphic technique that permits us to keep track of individual chromosomes in a metaphase plate and to compare chromosome positions in different metaphase plates. Moreover, the computer graphics provide permanent, easily manipulated, rapid recall of stored chromosome profiles. These advantages are demonstrated by a comparison of the relative position of group A-specific and groups D- and G-specific chromosomes to the full complement of chromosomes in metaphase plates isolated from a nearly triploid human-derived cell (HeLa S3) to a hypo-diploid human fetal lung cell.

  12. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. (Harvard Medical School, Boston, MA (USA))

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

  13. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    International Nuclear Information System (INIS)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F.

    1988-01-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid β precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS

  14. Human chromosome 9 can complement UV sensitivity of xeroderma pigmentosum group A cells

    International Nuclear Information System (INIS)

    Ishizaki, Kanji; Sasaki, Masao S.; Ikenaga, Mituo; Nakamura, Yusuke

    1990-01-01

    A single human chromosome derived from normal human fibroblasts and tagged with the G418 resistance gene was transferred into SV40-transformed xeroderma pigmentosum group A (XP-A) cells via microcell fusion. When chromosome 1 or 12 was transferred, UV sensitivity of microcell hybrid cells was not changed. By contrast, after transferring chromosome 9,7 of 11 reipient clones were as UV-resistant as normal human cells. Four other clones were still as UV-sensitive as the parental XP-A cells. Southern hybridization analysis using a polymorphic probe, pEKZ19.3, which is homologous to a sequence of the D9S17 locus on chromosome 9, has confirmed that at least a part of normal human chromosome 9 was transferred into the recipient clones. However, amounts iof UV-induced unscheduled DNA synthesis in the UV-resistant clones were only one-third of those in normal human cells. These results indicate that a gene on chromosome 9 can confer complementation of high UV sensitivity of XP-A cells although it is still possible that 2 or more genes might be involved in the defective-repair phenotypes of XP-A. (author). 20 refs.; 3 figs.; 1 tab

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  16. Genome association study of human chromosome 13 and ...

    Indian Academy of Sciences (India)

    Ministry of Health, Department of Cardiology, Qilu Hospital of Shandong University,. Jinan, Shandong ... chromosome 13 and susceptibility to coronary artery disease in a Chinese population. J. Genet. .... of the 164 bp allele in cases was significantly lower than .... 5-lipoxygenase activating protein (FLAP), is associated with.

  17. Hypertensive Cerebral Hemorrhage in a Patient with Turner Syndrome Caused by Deletion in the Short Arm of the X Chromosome.

    Science.gov (United States)

    Hori, Yusuke S; Ohkura, Takahiro; Ebisudani, Yuki; Umakoshi, Michiari; Ishi, Masato; Oda, Kazunori; Aoi, Mizuho; Inoue, Takushi; Furujo, Mahoko; Tanaka, Hiroyuki; Fukuhara, Toru

    2018-01-01

    Turner syndrome is a chromosomal disorder usually caused by complete deletion of an X chromosome, with deletion in the short arm of the X chromosome being a rare cause of the condition. Patients with Turner syndrome commonly develop hypertension, and associated vascular complications such as aortic dissection or cerebral hemorrhage have been reported. Cerebral hemorrhage in Turner syndrome is a rare complication, and only a few reports have been published. In these reports, all patients have XO karyotypes or a mosaic type as the cause of Turner syndrome, while no other Turner syndrome types have been documented. In this report, we present for the first time a patient with Turner syndrome caused by deletion in the short arm of the X chromosome who experienced hypertensive hemorrhage as a late complication. © 2017 S. Karger AG, Basel.

  18. Human active X-specific DNA methylation events showing stability across time and tissues

    Science.gov (United States)

    Joo, Jihoon Eric; Novakovic, Boris; Cruickshank, Mark; Doyle, Lex W; Craig, Jeffrey M; Saffery, Richard

    2014-01-01

    The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression. The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a ‘patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping. Such genes are therefore potentially subject to sex-specific imbalance between males and females. Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa). Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin. Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans. Further work is needed to investigate these phenomena. PMID:24713664

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

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Xue

    2010-01-01

    Full Text Available 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. However, four out of the eight HDF lines at high passage numbers (≥P10 exhibited duplicated hallmarks of inactive X chromosome including two punctuate signals of histone H3 lysine 27 trimethylation (H3K27me3 and X inactive-specific transcript (XIST RNA signals in approximately 8.5–18.5% of the cells. Our data suggest that the copy number of inactive X chromosomes in a subset of female HDF is increased by a two-fold. Consistently, DNA fluorescent in situ hybridization (FISH identified 3-4 copies of X chromosomes in one nucleus in this subset of cells with two inactive Xs. We conclude that female HDF cultures exhibit a higher risk of genetic anomalies such as carrying an increased number of X chromosomes including both active and inactive X chromosomes at a high passage (≥P10.

  20. A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2013-01-01

    Full Text Available Disorders of sex development (DSD, formerly termed “intersex” conditions, arise from numerous causes. CAH secondary to 21-hydroxylase deficiency is the most common cause of DSD. Sex chromosome disorders, including sex chromosome mosaicism, are the second most common cause of DSD. We discuss a medically complex neonate with DSD presenting with ambiguous genitalia. Hormone levels suggested 21-hydroxylase deficiency. Molecular analysis revealed compound heterozygous mutations in the 21-hydroxylase gene (CYP21A2, confirming the diagnosis of CAH. Chromosome analysis revealed sex chromosome mosaicism with three cell lines: 45,X[8]/45,X,tas(Y;16(p11.32;p13.3[8]/45,X,t(Y;8(p11.32;p23.3[4] with the Y chromosome in telomere association with chromosomes 8p and 16p in different cell lines, a “jumping translocation.” Histologically, the right gonad had irregular, distended seminiferous tubules with hyperplastic germ cells contiguous with ovarian stroma and primordial follicles. The left gonad had scant ovarian stroma and embryonic remnants. Chromosome analyses showed mosaicism in both gonads: 45,X[17]/45,X,tas(Y;8(p11.32;p23.3[3]. This is the first case of coexisting CAH and 45,X/46,XY mosaicism reported in the English literature and the third case of a constitutional chromosome Y “jumping translocation.” Our report documents the medical and genetic complexity of children such as this one with ambiguous genitalia and discusses the need for a multidisciplinary team approach.

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

    Directory of Open Access Journals (Sweden)

    Jesse M Engreitz

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

  2. Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

    Science.gov (United States)

    Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

    2018-03-01

    Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  3. Repressive but not activating epigenetic modifications are aberrant on the inactive X chromosome in live cloned cattle.

    Science.gov (United States)

    Geng-Sheng, Cao; Yu, Gao; Kun, Wang; Fang-Rong, Ding; Ning, Li

    2009-08-01

    X inactivation is the process of a chromosome-wide silencing of the majority of genes on the X chromosome during early mammalian development. This process may be aberrant in cloned animals. Here we show that repressive modifications, such as methylation of DNA, and the presence of methylated histones, H3K9me2 and H3K27me3, exhibit distinct aberrance on the inactive X chromosome in live clones. In contrast, H3K4me3, an active gene marker, is obviously missing from the inactive X chromosome in all cattle studied. This suggests that the disappearance of active histone modifications (H3K4me3) seems to be more important for X inactivation than deposition of marks associated with heterochromatin (DNA methylation, H3K27me3 and H3K9me2). It also implies that even apparently normal clones may have subtle abnormalities in repressive, but not activating epigenetic modifications on the inactive X when they survive to term. We also found that the histone H3 methylations were enriched and co-localized at q21-31 of the active X chromosome, which may be associated with an abundance of LINE1 repeat elements. © 2009 The Authors. Journal compilation © 2009 Japanese Society of Developmental Biologists.

  4. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    International Nuclear Information System (INIS)

    Sasaki, H.; Nishimoto, T.

    1989-01-01

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD

  5. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, H.; Nishimoto, T. (Kyushu Univ., Fukuoka (Japan))

    1989-10-01

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD.

  6. Investigation of X-ray-induced chromosome aberrations in 'preleukaemic' mammalian cells

    International Nuclear Information System (INIS)

    Szollar, J.

    1977-01-01

    A study was done on the frequency of numerical and structural aberrations induced by different doses of X-ray irradiation in spontaneously leukaemic AKR mice, compared with the values of healthy control CBA/H-T 6 T 6 mice. Both were irradiated under the same conditions, but their chromosomes were affected in a different way. The number of cells containing aneuploid sets, rings, fragments, or metacentric chromosomes was significantly higher in the 2-month-old AKR mice than in the control CBA group. The increased chromosomal fragility found in AKR bone marrow cells 5-7 months before the manifestation of lymphoid leukaemia might be an important factor in the development of malignant condition. This genetic imbalance could provide a possible reason for an increase of spontaneous malfunction of the cellular system, as well as for an increased sensitivity to external factors. Thus it might be connected directly with the predisposition to malignant growth, or it has an indirect role helping virus activation, or acting together with the immune deficiency, by creating a weaker system that is more sensitive to carcinogenic agents

  7. Effects of arsenic upon the no-disyuntion and X chromosome loss mechanisms in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Gomez C, M.T.

    1994-01-01

    In the present investigation we make the analysis of the effect of the sodium arsenite chemistry in concentration 0.2 m M over the events of no-disyuntion and chromosome loss X in germinal cells of Drosophila melanogaster. The Drosophila lineages used for this assay were: females (y 2 w a / y 2 w a ; e/e) and males (X C2 yf bb- / B s Y y+). Those lineages were propagated and isolated for to be used after in the assays. Subsequently these, we make some links types with these individuals with the object to observed the effects of the oral administration of sodium arsenite in the adult individuals, in each one, we induce a damage in the sperm of the male with gamma radiation (25 Gy) and was observed immediately the results of the different assay applied in the first generation (F 1 ). Finally, we analyze and compare the results in contrast with and other investigation we find that the chemistry cause a significant increment in the chromosome loss X either the No-disyuntion was not significative. Also, the arsenite sodium increment the male descendant productivity, so, we deduced that the sodium arsenite do not cause an inhibition of the reparation mechanisms present in the Drosophila melanogaster female ovocites, but the chemistry operated like a modulator of this mechanisms, and prevent an increment of the damage provoked for the gamma radiation over the Drosophila melanogaster male sperm. (Author)

  8. Use of chromosome translocations for measuring prior environment exposures in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  9. Interspecific comparisons of the sensitivity to chromosome aberration production by x rays

    International Nuclear Information System (INIS)

    Brewen, J.G.

    1978-01-01

    It is concluded that arm number probably plays a minor role, if any, in the relative radiosensitivity of a species. Instead the reported differences are probably a reflection of inherent basic biological mechanisms of repair that vary from one order of mammals to the next. It should be added, however, that the ultimate goal of all of these studies is to make a reasonable risk estimate for man. In that context the best approach is that of conservatism and the current data on mouse and man suggest that man has 1.5 to 2.0 times the risk of mice for chromosome rearrangement induction by x rays

  10. Location of the handedness gene on the X and Y chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Corballis, M.C.; Lee, K. [Univ. of Auckland (New Zealand); McManus, I.C. [Univ. College London (United Kingdom); Crow, T.J. [Warneford Hospital, Oxford (United Kingdom)

    1996-02-16

    Accumulated data from five handedness surveys show that concordance for sex is slightly but reliably higher among siblings of the same handedness than among those of opposite handedness. This is consistent with Crow`s theory that the genetic locus for handedness is in an X-Y homologous region of the sex chromosomes. The small size of the effect is predicted from genetic models in which there is a substantial random component underlying phenotypic left handedness. The findings are relevant to the putative role of cerebral asymmetry in the aetiology of psychosis. 15 refs., 3 tabs.

  11. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

    Science.gov (United States)

    Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

    2016-01-01

    Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal’s sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID:27356611

  12. Population genetic study of 34 X-Chromosome markers in 5 main ethnic groups of China.

    Science.gov (United States)

    Zhang, Suhua; Bian, Yingnan; Li, Li; Sun, Kuan; Wang, Zheng; Zhao, Qi; Zha, Lagabaiyila; Cai, Jifeng; Gao, Yuzhen; Ji, Chaoneng; Li, Chengtao

    2015-12-04

    As a multi-ethnic country, China has some indigenous population groups which vary in culture and social customs, perhaps as a result of geographic isolation and different traditions. However, upon close interactions and intermarriage, admixture of different gene pools among these ethnic groups may occur. In order to gain more insight on the genetic background of X-Chromosome from these ethnic groups, a set of X-markers (18 X-STRs and 16 X-Indels) was genotyped in 5 main ethnic groups of China (HAN, HUI, Uygur, Mongolian, Tibetan). Twenty-three private alleles were detected in HAN, Uygur, Tibetan and Mongolian. Significant differences (p population differentiation of HUI and Uygur. However, the HAN, Tibetan and Mongolian ethnic groups were closely clustered. Eighteen X-Indels exhibited in general congruent phylogenetic signal and similar cluster among the 5 ethnic groups compared with 16 X-STRs. Aforementioned results proved the genetic polymorphism and potential of the 34 X-markers in the 5 ethnic groups.

  13. Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte.

    Science.gov (United States)

    Bao, Siqin; Miyoshi, Naoki; Okamoto, Ikuhiro; Jenuwein, Thomas; Heard, Edith; Azim Surani, M

    2005-08-01

    The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 trimethylation of lysine 27 (H3-3meK27), without the expected colocalization with Eed/Ezh2. Subsequently, Xist re-appears on the original inactive X, and the silent Xist on the active X undergoes re-activation, resulting in unusual biallelic Xist RNA domains. Despite this abnormal Xist expression pattern, colocalization of H3-3meK27 and Eed is thereafter confined to a single Xist domain, which is presumably on the original inactive X. These epigenetic events differ markedly from the kinetics of preferential paternal X inactivation in normal embryos. All the epigenetic marks on the X are apparently erased in the epiblast, suggesting that the oocyte and epiblast may have distinct properties for stepwise programming of the genome.

  14. An X-linked Myh11-CreERT2 mouse line resulting from Y to X chromosome-translocation of the Cre allele.

    Science.gov (United States)

    Liao, Mingmei; Zhou, Junmei; Wang, Fen; Ali, Yasmin H; Chan, Kelvin L; Zou, Fei; Offermanns, Stefan; Jiang, Zhisheng; Jiang, Zhihua

    2017-09-01

    The Myh11-CreER T2 mouse line (Cre + ) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y Cre+ ), which excluded its application in female mice. Our group established a Cre + colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X-linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y Cre+ mice. This mosaicism, however, diminished in homozygous X Cre+ /X Cre+ mice. In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous X Cre+ /X Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X-inactivation. The homozygous X Cre+ /X Cre+ mice produce uniform Cre activity in arterial SMCs. © 2017 Wiley Periodicals, Inc.

  15. Human tissue factor: cDNA sequence and chromosome localization of the gene

    International Nuclear Information System (INIS)

    Scarpati, E.M.; Wen, D.; Broze, G.J. Jr.; Miletich, J.P.; Flandermeyer, R.R.; Siegel, N.R.; Sadler, J.E.

    1987-01-01

    A human placenta cDNA library in λgt11 was screened for the expression of tissue factor antigens with rabbit polyclonal anti-human tissue factor immunoglobulin G. Among 4 million recombinant clones screened, one positive, λHTF8, expressed a protein that shared epitopes with authentic human brain tissue factor. The 1.1-kilobase cDNA insert of λHTF8 encoded a peptide that contained the amino-terminal protein sequence of human brain tissue factor. Northern blotting identified a major mRNA species of 2.2 kilobases and a minor species of ∼ 3.2 kilobases in poly(A) + RNA of placenta. Only 2.2-kilobase mRNA was detected in human brain and in the human monocytic U937 cell line. In U937 cells, the quantity of tissue factor mRNA was increased several fold by exposure of the cells to phorbol 12-myristate 13-acetate. Additional cDNA clones were selected by hybridization with the cDNA insert of λHTF8. These overlapping isolates span 2177 base pairs of the tissue factor cDNA sequence that includes a 5'-noncoding region of 75 base pairs, an open reading frame of 885 base pairs, a stop codon, a 3'-noncoding region of 1141 base pairs, and a poly(a) tail. The open reading frame encodes a 33-kilodalton protein of 295 amino acids. The predicted sequence includes a signal peptide of 32 or 34 amino acids, a probable extracellular factor VII binding domain of 217 or 219 amino acids, a transmembrane segment of 23 acids, and a cytoplasmic tail of 21 amino acids. There are three potential glycosylation sites with the sequence Asn-X-Thr/Ser. The 3'-noncoding region contains an inverted Alu family repetitive sequence. The tissue factor gene was localized to chromosome 1 by hybridization of the cDNA insert of λHTF8 to flow-sorted human chromosomes

  16. Development, Beam characterization and chromosomal effectiveness of X-rays of RBC characteristic X-ray generator

    International Nuclear Information System (INIS)

    Endo, Satoru; Hoshi, Masaharu; Takada, Jun; Takatsuji, Toshihiro; Ejima, Yosuke; Saigusa, Shin; Tachibana, Akira; Sasaki, Masao S.

    2006-01-01

    A characteristic hot-filament type X-ray generator was constructed for irradiation of cultured cells. The source provides copper K, iron K, chromium K, molybdenum L, aluminium K and carbon K shell characteristic X-rays. When cultured mouse m5S cells were irradiated and frequencies of dicentrics were fitted to a linear-quadratic model, Y=αD+βD 2 , the chromosomal effectiveness was not a simple function of photon energy. The α-terms increased with the decrease of the photon energy and then decreased with further decrease of the energy with an inflection point at around 10 keV. The β-terms stayed constant for the photon energy down to 10 keV and then increased with further decrease of energy. Below 10 keV, the relative biological effectiveness (RBE) at low doses was proportional to the photon energy, which contrasted to that for high energy X- or γ-rays where the RBE was inversely related with the photon energy. The reversion of the energy dependency occurred at around 1-2 Gy, where the RBE of soft X-rays was insensitive to X-ray energy. The reversion of energy-RBE relation at a moderate dose may shed light on the controversy on energy dependency of RBE of ultrasoft X-rays in cell survival experiments. (author)

  17. Extensive fragmentation of the X chromosome in the bed bug Cimex lectularius Linnaeus, 1758 (Heteroptera, Cimicidae: a survey across Europe

    Directory of Open Access Journals (Sweden)

    David Sadílek

    2013-10-01

    Full Text Available Variation in the number of chromosomes was revealed in 61 samples of Cimex lectularius Linnaeus, 1758 from the Czech Republic and other European countries, hosted on Myotis Kaup, 1829 (4 and Homo sapiens Linnaeus, 1758 (57. The karyotype of all the specimens of C. lectularius analysed contained 26 autosomes and a varying number of the sex chromosomes. The number of sex chromosomes showed extensive variation, and up to 20 fragments were recorded. Altogether, 12 distinct karyotypes were distinguished. The male karyotypes consisted of 29, 30, 31, 32, 33, 34, 35, 36, 37, 40, 42 and 47 chromosomes. The females usually exhibited the number of chromosomes which was complementary to the number established in the males from the same sample. However, 11 polymorphic samples were revealed in which the karyotypes of females and males were not complementary each other. The complement with 2n = 26+X1X2Y was found in 44% of the specimens and 57,4% samples of bed bugs studied. The karyotypes with higher chromosome numbers as well as individuals with chromosomal mosaics were usually found within the samples exhibiting particularly extensive variation between individuals, and such complements were not found within samples contaning a few or single specimen. The occurrence of chromosomal mosaics with the karyotype constitution varying between cells of single individual was observed in five specimens (4.3% from five samples. We assume that polymorphism caused by fragmentation of the X chromosome may result in meiotic problems and non-disjunction can produce unbalanced gametes and result in lowered fitness of individuals carrying higher numbers of the X chromosome fragments. This effect should be apparently enhanced with the increasing number of the fragments and this may be the reason for the observed distribution pattern of individual karyotypes in the studied samples and the rarity of individuals with extremely high chromosome numbers. The assumed lowering of the

  18. International study of factors affecting human chromosome translocations

    Czech Academy of Sciences Publication Activity Database

    Sigurdson, A.J.; Ha, M.; Hauptmann, M.; Bhatti, P.; Šrám, Radim; Beskid, Olena; Tawn, E.J.; Whitehouse, C.A.; Lindholm, C.; Nakano, M.; Kodama, Y.; Nakamura, N.; Vorobtsova, I.; Oestreicher, U.; Stephan, G.; Yong, L.C.; Bauchinger, M.; Schmid, E.; Chung, H.W.; Darroudi, F.; Roy, L.; Voisin, P.; Barquinero, J.F.; Livingston, G.; Blakey, D.; Hayata, I.; Zhang, W.; Wang, Ch.; Benett, L.M.; Littlefield, L.G.; Edwards, A.A.; Kleinerman, R.A.; Tucker, J.D.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 112-121 ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SI/340/2/00; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosome translocations * FISH * Background frequency Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.363, year: 2008

  19. Loss of heterozygosity of chromosome 15 in human lung carcinomas

    International Nuclear Information System (INIS)

    Mitchell, C.E.; Palmisano, W.A.; Lechner, J.F.

    1994-01-01

    Loss of heterozygosity (LOH) in tumors may be associated with the inactivation of tumor suppressor genes. A tumor suppressor gene for lung cancer may reside on chromosome 15, because deletions in this chromosome are frequently observed. Recently, it was reported that a newly discovered gene, GTPase-activating protein-3 (GAP3) maps to chromosome 15. GAP3 is a member of a family of GAP-related genes. Although the precise function of GAP3 is not known, it is thought that GAP3 is involved in the regulation of ras-like GTPase activities. Ras proteins have a low intrinsic activity, and their inactivation is dependent on GAPS in vivo. Oncogenic mutants of ras proteins, for example, at codons 12, 13, or 61, are resistant to GAP-mediated GTPase stimulation and are constituitively locked in their active, GTP-bound states. The purpose of this investigation was to determine the frequency and extent of LOH of GAP3 in a group of patients with lung cancer

  20. Hoechst 33342: the dye that enabled differentiation of living X-and Y-chromosome bearing mammalian sperm.

    Science.gov (United States)

    Garner, D L

    2009-01-01

    Hoechst 33342 is the fluorophore used routinely to measure DNA in X- and Y-chromosome-bearing mammalian sperm so they can be separated by flow sorting. A difference of artificial insemination of somewhere around a million female mammals. Offspring with obvious abnormalities are no more frequent than after insemination of unsorted sperm into cows, horses, humans, pigs, sheep, rabbits, dolphins and other mammals. There is no apparent genotoxic effect from exposure of sperm to Hoechst 33342, although information on cellular toxicity or development of embryos resulting from Hoechst 33342-stained sperm is less reassuring. Little is known about the fate of sperm-delivered Hoechst dye in the female reproductive tract or on progeny of resultant offspring.

  1. Culture of human oocytes with granulocyte-macrophage colony-stimulating factor has no effect on embryonic chromosomal constitution

    DEFF Research Database (Denmark)

    Agerholm, Inge; Loft, Anne; Hald, Finn

    2010-01-01

    -vitro culture of human embryos in the presence of 2 ng/ml GM-CSF resulted in 34.8% (8/23) uniformly normal embryos. Culture without 2 ng/ml GM-CSF resulted in 33.3% (9/27) uniformly normal embryos. A trend towards a higher number of TQE in the test group was observed; however, due to lack of TQE in the control...... women donating 86 oocytes. The primary endpoint was to investigate the chromosomal constitution of human embryos (fluorescence in-situ hybridization analysis for chromosomes 13, 16, 18, 21, 22, X and Y) cultured with or without GM-CSF. The secondary endpoints were number of top-quality embryos (TQE......) and number of normally developed embryos evaluated morphologically on day 3. The cytogenetic analyses demonstrated non-inferiority and therefore the chromosomal constitution of human embryos cultured in vitro in the presence of 2 ng/ml GM-CSF was no worse than the control group cultured without GM-CSF. In...

  2. Culture of human oocytes with granulocyte-macrophage colony-stimulating factor has no effect on embryonic chromosomal constitution

    DEFF Research Database (Denmark)

    Agerholm, Inge; Loft, Anne; Hald, Finn

    2010-01-01

    women donating 86 oocytes. The primary endpoint was to investigate the chromosomal constitution of human embryos (fluorescence in-situ hybridization analysis for chromosomes 13, 16, 18, 21, 22, X and Y) cultured with or without GM-CSF. The secondary endpoints were number of top-quality embryos (TQE......) and number of normally developed embryos evaluated morphologically on day 3. The cytogenetic analyses demonstrated non-inferiority and therefore the chromosomal constitution of human embryos cultured in vitro in the presence of 2 ng/ml GM-CSF was no worse than the control group cultured without GM-CSF. In......-vitro culture of human embryos in the presence of 2 ng/ml GM-CSF resulted in 34.8% (8/23) uniformly normal embryos. Culture without 2 ng/ml GM-CSF resulted in 33.3% (9/27) uniformly normal embryos. A trend towards a higher number of TQE in the test group was observed; however, due to lack of TQE in the control...

  3. A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.

    Directory of Open Access Journals (Sweden)

    Julie Cocquet

    2012-09-01

    Full Text Available Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked multicopy genes has long been suggested but never demonstrated. The Y-encoded multicopy gene Sly has been shown to have a predominant role in the epigenetic repression of post meiotic sex chromatin (PMSC and, as such, represses X and Y genes, among which are its X-linked homologs Slx and Slxl1. Here, we produced mice that are deficient for both Sly and Slx/Slxl1 and observed that Slx/Slxl1 has an opposite role to that of Sly, in that it stimulates XY gene expression in spermatids. Slx/Slxl1 deficiency rescues the sperm differentiation defects and near sterility caused by Sly deficiency and vice versa. Slx/Slxl1 deficiency also causes a sex ratio distortion towards the production of male offspring that is corrected by Sly deficiency. All in all, our data show that Slx/Slxl1 and Sly have antagonistic effects during sperm differentiation and are involved in a postmeiotic intragenomic conflict that causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouse X and Y chromosomes. It may also be at the basis of cases of F1 male hybrid sterility where the balance between Slx/Slxl1 and Sly copy number, and therefore expression, is disrupted. To the best of our knowledge, our work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the concept that intragenomic conflict is an important evolutionary force which impacts on gene expression, genome structure, and speciation.

  4. Analysis of chromosomal abnormalities: a study of partial exposure to X-rays

    International Nuclear Information System (INIS)

    Andrade, Aida M.G. de; Mendes, Mariana E.; Mendonça, Julyanne C.G.; Melo, Laís; Hwang, Suy; Santos, Neide; Lima, Fabiana F. de; Centro Regional de Ciências Nucleares; Universidade Federal de Pernambuco

    2017-01-01

    Biological dosimetry is used in case of supposed accidental overexposure. The most commonly used biomarkers for assessing the absorbed dose are unstable chromosomal abnormalities. In a case of a partial body exposure, the frequencies of those abnormalities varies according to the area of the exposed body and may be substantially different from a total exposure of the body with an identical dose. The present study aimed to evaluate the frequency of chromosomal changes simulating, with blood samples, partial (25%, 50%) and full body irradiation (100%) in X-ray beam. The irradiation was performed at Metrology Service (CRCN-NE / CNEN) with a bundle of 250kVp X-rays, resulting in the absorbed dose of 1.0 Gy. Prior to obtain the metaphases, irradiated blood was mixed with non-irradiated blood, and then the mitotic metaphases for the chromosomal analyzes were obtained by culturing lymphocytes and the slides were stained with 5% Giemsa. It was observed that there was an increase in dicentric frequency when the dose percentage increases in both subjects (0.024 and 0.049 in subject 1 and 0.016 and 0.038 in subject 2) after irradiation. The cellular distribution was 'contaminated' only at dose 25% of the first individual who had a prolongation of the distribution. The Qdr and Dolphin methods were used to estimate partial absorbed dose, but the Qdr method was not efficient and whereas the Dolphin method was efficient when the individual had a prolonged cell distribution. It is necessary to increase the number of observations to be sure of the observed behaviors. (author)

  5. Analysis of chromosomal abnormalities: a study of partial exposure to X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Aida M.G. de; Mendes, Mariana E.; Mendonça, Julyanne C.G.; Melo, Laís; Hwang, Suy; Santos, Neide; Lima, Fabiana F. de, E-mail: aidamgandrade@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil); Centro Regional de Ciências Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Universidade Federal de Pernambuco (UFPE),Recife (Brazil). Centro de Biociências. Departamento de Genética

    2017-11-01

    Biological dosimetry is used in case of supposed accidental overexposure. The most commonly used biomarkers for assessing the absorbed dose are unstable chromosomal abnormalities. In a case of a partial body exposure, the frequencies of those abnormalities varies according to the area of the exposed body and may be substantially different from a total exposure of the body with an identical dose. The present study aimed to evaluate the frequency of chromosomal changes simulating, with blood samples, partial (25%, 50%) and full body irradiation (100%) in X-ray beam. The irradiation was performed at Metrology Service (CRCN-NE / CNEN) with a bundle of 250kVp X-rays, resulting in the absorbed dose of 1.0 Gy. Prior to obtain the metaphases, irradiated blood was mixed with non-irradiated blood, and then the mitotic metaphases for the chromosomal analyzes were obtained by culturing lymphocytes and the slides were stained with 5% Giemsa. It was observed that there was an increase in dicentric frequency when the dose percentage increases in both subjects (0.024 and 0.049 in subject 1 and 0.016 and 0.038 in subject 2) after irradiation. The cellular distribution was 'contaminated' only at dose 25% of the first individual who had a prolongation of the distribution. The Qdr and Dolphin methods were used to estimate partial absorbed dose, but the Qdr method was not efficient and whereas the Dolphin method was efficient when the individual had a prolonged cell distribution. It is necessary to increase the number of observations to be sure of the observed behaviors. (author)

  6. Overexpression of the heterochromatinization factor BAHD1 in HEK293 cells differentially reshapes the DNA methylome on autosomes and X chromosome.

    Directory of Open Access Journals (Sweden)

    Emanuele eLibertini

    2015-12-01

    Full Text Available BAH domain-containing protein 1 (BAHD1 is involved in heterochromatin formation and gene repression in human cells. BAHD1 also localizes to the inactive X chromosome (Xi, but the functional significance of this targeting is unknown. So far, research on this protein has been hampered by its low endogenous abundance and its role in epigenetic regulation remains poorly explored. In this work, we used whole-genome bisulfite sequencing (BS-seq to compare the DNA methylation profile of HEK293 cells expressing low levels of BAHD1 (HEK-CT to that of isogenic cells stably overexpressing BAHD1 (HEK-BAHD1. We show that increasing BAHD1 levels induces de novo DNA methylation on autosomes and a marked hypomethylation on the X chromosome (chrX. We identified 91,358 regions that have different methylation patterns in HEK-BAHD1 compared to HEK-CT cells (termed BAHD1-DMRs, of which 83,850 mapped on autosomes and 7,508 on the X chromosome (chrX. Autosomal BAHD1-DMRs were predominantly hypermethylated and located to satellites, interspersed repeats and intergenic regions. In contrast, BAHD1-DMRs on chrX were mainly hypomethylated and located to gene bodies and enhancers. We further found that BAHD1-DMRs display a higher-order organization by being clustered within large chromosomal domains. Half of these BAHD1-Associated differentially methylated Domains (BADs overlapped with lamina-associated domains (LADs. Based on these results, we propose that BAHD1-mediated heterochromatin formation is linked to DNA methylation and may play a role in the spatial architecture of the genome.

  7. Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

    Science.gov (United States)

    Rego, Eduardo M; Pandolfi, Pier Paolo

    2002-08-01

    Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene lead to the formation of two fusion genes: X-RARalpha and RARalpha-X (where X is the alternative RARalpha fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X-RARalpha fusion protein is indeed oncogenic. However, recent data indicate that the RARalpha-X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.

  8. Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

    International Nuclear Information System (INIS)

    AbuBakar, S.; Au, W.W.; Legator, M.S.; Albrecht, T.

    1988-01-01

    Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed

  9. The contribution of color to visual memory in X-chromosome-linked dichromats.

    Science.gov (United States)

    Gegenfurtner, K R; Wichmann, F A; Sharpe, L T

    1998-04-01

    We used a recognition memory paradigm to assess the visual memory of X-chromosome-linked dichromats for color images of natural scenes. The performance of 17 protanopes and 14 deuteranopes, who lack the second (red-green opponent) subsystem of color vision, but retain the primordial (yellow-blue opponent) subsystem, was compared with that of 36 color normal observers. During the presentation phase, 48 images of natural scenes were displayed on a CRT for durations between 50 and 1000 msec. Each image was followed by a random noise mask. Half of the images were presented in color and half in black and white. In the subsequent query phase, the same 48 images were intermixed with 48 new images and the subjects had to indicate which of the images they had already seen during the presentation phase. We find that the performance of the color normal observers increases with exposure duration. However, they perform 5-10% better for colored than for black and white images, even at exposure durations as short as 50 msec. Surprisingly, performance is not impaired for the dichromats, whose recognition performance is also better for colored than for black and white images. We conclude either that X-chromosome-linked dichromats may be able to compensate for their reduced chromatic information range when viewing complex natural scenes or that the chromatic information in most natural scenes, for the durations tested, is sufficiently represented by the surviving primordial color subsystem.

  10. Family-based multi-SNP X chromosome analysis using parental information

    Directory of Open Access Journals (Sweden)

    Alison S. Wise

    2016-02-01

    Full Text Available We propose a method for association analysis of haplotypes on the X chromosome that offers both improved power and robustness to population stratification in studies of affected offspring and their parents if all three have been genotyped. The method makes use of assumed parental haplotype exchangeability, a weaker assumption than Hardy-Weinberg equilibrium. Parental haplotype exchangeability requires that in the source population, of the three X chromosome haplotypes carried by the two parents, each is equally likely to be carried by the father. We propose a pseudo-sibling approach that exploits that exchangeability assumption. Our method extends the single-SNP PIX-LRT method to multiple SNPs in a high linkage block. We describe methods for testing the parental haplotype exchangeability assumption and also for determining how apparent violations can be distinguished from true fetal effects or maternally-mediated effects. We show results of simulations that demonstrate nominal type I error rate and good power. The methods are then applied to dbGaP data on the birth defect oral cleft, using both Asian and Caucasian families with cleft.

  11. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes

    NARCIS (Netherlands)

    Skaletsky, Helen; Kuroda-Kawaguchi, Tomoko; Minx, Patrick J.; Cordum, Holland S.; Hillier, LaDeana; Brown, Laura G.; Repping, Sjoerd; Pyntikova, Tatyana; Ali, Johar; Bieri, Tamberlyn; Chinwalla, Asif; Delehaunty, Andrew; Delehaunty, Kim; Du, Hui; Fewell, Ginger; Fulton, Lucinda; Fulton, Robert; Graves, Tina; Hou, Shun-Fang; Latrielle, Philip; Leonard, Shawn; Mardis, Elaine; Maupin, Rachel; McPherson, John; Miner, Tracie; Nash, William; Nguyen, Christine; Ozersky, Philip; Pepin, Kymberlie; Rock, Susan; Rohlfing, Tracy; Scott, Kelsi; Schultz, Brian; Strong, Cindy; Tin-Wollam, Aye; Yang, Shiaw-Pyng; Waterston, Robert H.; Wilson, Richard K.; Rozen, Steve; Page, David C.

    2003-01-01

    The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate and ampliconic. These classes

  12. Dose response relationships and analysis of primary processes of radiation-induced chromosomal aberrations in human peripheral lymphocytes

    International Nuclear Information System (INIS)

    Schmid, E.

    1977-02-01

    Human peripheral lymphocytes were irradiated with 220 kV X-rays, 3 MeV electrons and 15 MeV neutrons. The frequency of dicentric, acentric and atypical chromosomes and the exhange aberrations were measured and dose effect curves were constructed. The aim is to prepare the chromosome analysis to a biological dosimetry. The aberration findings could be adapted to the linear-quadrativ model y = c+ αD + βD 2 . With increasing LET the quantity lambda increased which is a measure for the share of the linear and quadratical components of the dose effect obtained. In case of electrons the RBE-values increased with increasing doses. In the case of neutrons they had their maximum in the low dose range. The feed back distances which lead to formation of primary lesions are for X-rays and electrons approximately 1 μm, for neutrons 1.7 μm. In a fractionation experiment with X-rays, the time of formation of exchange aberrations in radiation-induced primary breaks was measured. The number of dicentric chromosomes decreased with increasing time, while the intercellular distribution was not changed. The number of primary breaks decreasing per temporal interval is proportional to the number of the existing primary breaks. The average feed back time during which the primary breaks lead to induction of dicentric chromosomes, is 110 min. In order to determine the correspondence of the results of in-vivo and in-vitro experiments 15 patients and their blood were irradiated with 60 C-γ-rays. No significant differences were measured. (AJ) [de

  13. Human Artificial Chromosomes with Alpha Satellite-Based De Novo Centromeres Show Increased Frequency of Nondisjunction and Anaphase Lag

    OpenAIRE

    Rudd, M. Katharine; Mays, Robert W.; Schwartz, Stuart; Willard, Huntington F.

    2003-01-01

    Human artificial chromosomes have been used to model requirements for human chromosome segregation and to explore the nature of sequences competent for centromere function. Normal human centromeres require specialized chromatin that consists of alpha satellite DNA complexed with epigenetically modified histones and centromere-specific proteins. While several types of alpha satellite DNA have been used to assemble de novo centromeres in artificial chromosome assays, the extent to which they fu...

  14. No influence of parental origin of intact X chromosome and/or Y chromosome sequences on three-year height response to growth hormone therapy in Turner syndrome

    Directory of Open Access Journals (Sweden)

    Hye Jin Lee

    2014-09-01

    Full Text Available PurposeWhether parental origin of the intact X chromosome and/or the presence of Y chromosome sequences (Yseq play a role in three-year height response to growth hormone (GH were investigated.MethodsPaternal (Xp or maternal (Xm origin of X chromosome was assessed by microsatellite marker analysis and the presence of hidden Yseq was analyzed. The first-, second-, and third-year GH response was measured as a change in height z-score (Z_Ht in Turner syndrome (TS patients with 45,Xp (n=10, 45,Xm (n=15, and 45,X/46,X,+mar(Y (Xm_Yseq (n=8.ResultsThe mean baseline Z_Ht did not differ according to Xp or Xm origin, however the mean baseline Z_Ht was higher in the Xm_Yseq group than in Xm group, after adjusting for bone age delay and midparental Z_Ht (P=0.04. There was no difference in the height response to GH between the 3 groups. The height response to GH decreased progressively each year (P<0.001, such that the third-year increase in Z_Ht was not significant. This third-year decrease in treatment response was unaffected by Xp, Xm, and Xm_Yseq groups. Increasing GH dosage from the second to third-year of treatment positively correlated with the increase in Z_Ht (P=0.017.ConclusionThere was no evidence of X-linked imprinted genes and/or Yseq affecting height response to 3 years of GH therapy. Increasing GH dosages may help attenuate the decrease in third-year GH response in TS patients with 45,X and/or 46,X/+mar(Y.

  15. Three-Dimensional Organization of Chromosome Territories and the Human Interphase Cell Nucleus

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); C. Münkel (Christian); J. Langowski (Jörg)

    1998-01-01

    textabstractTo study the three-dimensional organization of chromosome territories and the human interphase cell nucleus we developed models which could be compared to experiments. Despite the successful linear sequencing of the human genome its 3D-organization is widely unknown. Using Monte

  16. Three-Dimensional Organization of Chromosome Territories and the Human Cell Nucleus

    NARCIS (Netherlands)

    T.A. Knoch (Tobias)

    1999-01-01

    textabstractTo study the three-dimensional organization of chromosome territories and the human interphase cell nucleus we developed models, which could be compared to experiments. Despite the successful linear sequencing of the human genome its 3D-organization is widely unknown. Using Monte

  17. Incompatibility between X chromosome factor and pericentric heterochromatic region causes lethality in hybrids between Drosophila melanogaster and its sibling species.

    Science.gov (United States)

    Cattani, M Victoria; Presgraves, Daven C

    2012-06-01

    The Dobzhansky-Muller model posits that postzygotic reproductive isolation results from the evolution of incompatible epistatic interactions between species: alleles that function in the genetic background of one species can cause sterility or lethality in the genetic background of another species. Progress in identifying and characterizing factors involved in postzygotic isolation in Drosophila has remained slow, mainly because Drosophila melanogaster, with all of its genetic tools, forms dead or sterile hybrids when crossed to its sister species, D. simulans, D. sechellia, and D. mauritiana. To circumvent this problem, we used chromosome deletions and duplications from D. melanogaster to map two hybrid incompatibility loci in F(1) hybrids with its sister species. We mapped a recessive factor to the pericentromeric heterochromatin of the X chromosome in D. simulans and D. mauritiana, which we call heterochromatin hybrid lethal (hhl), which causes lethality in F(1) hybrid females with D. melanogaster. As F(1) hybrid males hemizygous for a D. mauritiana (or D. simulans) X chromosome are viable, the lethality of deficiency hybrid females implies that a dominant incompatible partner locus exists on the D. melanogaster X. Using small segments of the D. melanogaster X chromosome duplicated onto the Y chromosome, we mapped a dominant factor that causes hybrid lethality to a small 24-gene region of the D. melanogaster X. We provide evidence suggesting that it interacts with hhl(mau). The location of hhl is consistent with the emerging theme that hybrid incompatibilities in Drosophila involve heterochromatic regions and factors that interact with the heterochromatin.

  18. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    International Nuclear Information System (INIS)

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-01-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system

  19. Radiobiological application of atomic force microscopy. Analysis on human chromosomes in culture medium

    International Nuclear Information System (INIS)

    Watanabe, Makoto; Kinjo, Yasuhito

    1995-01-01

    We have proposed a 'Heterogeneous Chromatin Target Model' on the regulating mechanisms involved in chromosome mutation due to ionizing radiations. The heterogeneity of chromatin is derived from the highly condensed organization of chromatin segments that consist of hypersensitive and fragile sites in the fluctuating assembly of nucleosome clusters (superbeads). The above consideration is going to be subjected to a new experimental approach applying the atomic force microscope (AFM), one of the most promising members of a family of scanning probe microscope (SPM). The AFM can be operated in liquid as well as in air. A living specimen can be examined without any preparative procedures (for instance, fixation, staining, vecuum evaporation and so on). Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. In the present report, the mitotic metaphase chromosomes released from living cells (human lymphocytes RPMI) were spread on the clean surface of distilled water filled in a trough. The spread surface film, in which the chromosomes were embedded, was picked up and adhered tightly on a specimen substrate made of silicon. The whole-mounted chromosome were submerged in a solution of culture medium and observed within a liquid immersion cell for AFM. We used an AFM system, SPA-300 made by Seiko Instruments. The particulate chromatin segments of nucleosome clusters (superbeads) were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (author)

  20. Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    International Nuclear Information System (INIS)

    AlSuhaibani, E.S

    2008-01-01

    The present work is aimed at evaluating the radioprotective effect of curcumin on γ radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 γg/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against γ-radiation induced chromosome aberration at certain doses. (author)

  1. Biodosimetry for medical diagnostic X-ray workers using stable chromosome aberration

    International Nuclear Information System (INIS)

    Wang Zhiquan; Liu Xuping; Li Jin

    1996-01-01

    The stable chromosome aberrations of medical diagnostic X-ray workers were analyzed using G-banding and their accumulative doses were evaluated. The results showed that the frequencies of reciprocal translocation, stable aberration and total aberration among the 4417 metaphase spread from 44 cases of medical diagnostic X-ray workers were distinctly higher than control values (P<0.05∼0.005). The stable aberration predominated strikingly in total aberration and reciprocal translocation was 57% in the stable aberrations. The medical diagnostic X-ray workers were divided into 3 groups according to calendar year of entry. The data showed that the frequencies of total aberration, stable aberration and reciprocal translocation increased with working years, especially in two groups who started working before 1970, there are statistically significant differences between the calendar year of entry before 1960 and 1960∼1969 in X-ray workers and control group. According to the equation recommended by Straume, linear coefficient (α) in linear quadratic model recommended by Schmid and the transformation coefficient by Lucas, the accumulative doses calculated are 0.58, 0.37 and 0.07 Gy for calendar year of entry before 1960, 1960∼1969 and after 1970 in X-ray workers, respectively

  2. Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

    Energy Technology Data Exchange (ETDEWEB)

    Prager, D.; Braunstein, G.D. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-04-01

    Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linked form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.

  3. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes.

    Directory of Open Access Journals (Sweden)

    Andreas Bolzer

    2005-05-01

    Full Text Available Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs in nuclei of quiescent (G0 and cycling (early S-phase human diploid fibroblasts (46, XY. Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes-independently of their gene density-were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding.

  4. Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology.

    Science.gov (United States)

    Moralli, Daniela; Monaco, Zoia L

    2015-02-01

    De novo artificial chromosomes expressing genes have been generated in human embryonic stem cells (hESc) and are maintained following differentiation into other cell types. Human artificial chromosomes (HAC) are small, functional, extrachromosomal elements, which behave as normal chromosomes in human cells. De novo HAC are generated following delivery of alpha satellite DNA into target cells. HAC are characterized by high levels of mitotic stability and are used as models to study centromere formation and chromosome organisation. They are successful and effective as gene expression vectors since they remain autonomous and can accommodate larger genes and regulatory regions for long-term expression studies in cells unlike other viral gene delivery vectors currently used. Transferring the essential DNA sequences for HAC formation intact across the cell membrane has been challenging for a number of years. A highly efficient delivery system based on HSV-1 amplicons has been used to target DNA directly to the ES cell nucleus and HAC stably generated in human embryonic stem cells (hESc) at high frequency. HAC were detected using an improved protocol for hESc chromosome harvesting, which consistently produced high-quality metaphase spreads that could routinely detect HAC in hESc. In tumour cells, the input DNA often integrated in the host chromosomes, but in the host ES genome, it remained intact. The hESc containing the HAC formed embryoid bodies, generated teratoma in mice, and differentiated into neuronal cells where the HAC were maintained. The HAC structure and chromatin composition was similar to the endogenous hESc chromosomes. This review will discuss the technological advances in HAC vector delivery using HSV-1 amplicons and the improvements in the identification of de novo HAC in hESc.

  5. Clonal chromosomal and genomic instability during human multipotent mesenchymal stromal cells long-term culture.

    Directory of Open Access Journals (Sweden)

    Victoria Nikitina

    Full Text Available Spontaneous mutagenesis often leads to appearance of genetic changes in cells. Although human multipotent mesenchymal stromal cells (hMSC are considered as genetically stable, there is a risk of genomic and structural chromosome instability and, therefore, side effects of cell therapy associated with long-term effects. In this study, the karyotype, genetic variability and clone formation analyses have been carried out in the long-term culture MSC from human gingival mucosa.The immunophenotype of MSC has been examined using flow cytofluorometry and short tandem repeat (STR analysis has been carried out for authentication. The karyotype has been examined using GTG staining and mFISH, while the assessment of the aneuploidy 8 frequency has been performed using centromere specific chromosome FISH probes in interphase cells.The immunophenotype and STR loci combination did not change during the process of cultivation. From passage 23 the proliferative activity of cultured MSCs was significantly reduced. From passage 12 of cultivation, clones of cells with stable chromosome aberrations have been identified and the biggest of these (12% are tetrasomy of chromosome 8. The random genetic and structural chromosomal aberrations and the spontaneous level of chromosomal aberrations in the hMSC long-term cultures were also described.The spectrum of spontaneous chromosomal aberrations in MSC long-term cultivation has been described. Clonal chromosomal aberrations have been identified. A clone of cells with tetrasomy 8 has been detected in passage 12 and has reached the maximum size by passage 18 before and decreased along with the reduction of proliferative activity of cell line by passage 26. At later passages, the MSC line exhibited a set of cells with structural variants of the karyotype with a preponderance of normal diploid cells. The results of our study strongly suggest a need for rigorous genetic analyses of the clone formation in cultured MSCs before

  6. Active role of a human genomic insert in replication of a yeast artificial chromosome.

    Science.gov (United States)

    van Brabant, A J; Fangman, W L; Brewer, B J

    1999-06-01

    Yeast artificial chromosomes (YACs) are a common tool for cloning eukaryotic DNA. The manner by which large pieces of foreign DNA are assimilated by yeast cells into a functional chromosome is poorly understood, as is the reason why some of them are stably maintained and some are not. We examined the replication of a stable YAC containing a 240-kb insert of DNA from the human T-cell receptor beta locus. The human insert contains multiple sites that serve as origins of replication. The activity of these origins appears to require the yeast ARS consensus sequence and, as with yeast origins, additional flanking sequences. In addition, the origins in the human insert exhibit a spacing, a range of activation efficiencies, and a variation in times of activation during S phase similar to those found for normal yeast chromosomes. We propose that an appropriate combination of replication origin density, activation times, and initiation efficiencies is necessary for the successful maintenance of YAC inserts.

  7. Protannotator: a semiautomated pipeline for chromosome-wise functional annotation of the "missing" human proteome.

    Science.gov (United States)

    Islam, Mohammad T; Garg, Gagan; Hancock, William S; Risk, Brian A; Baker, Mark S; Ranganathan, Shoba

    2014-01-03

    The chromosome-centric human proteome project (C-HPP) aims to define the complete set of proteins encoded in each human chromosome. The neXtProt database (September 2013) lists 20,128 proteins for the human proteome, of which 3831 human proteins (∼19%) are considered "missing" according to the standard metrics table (released September 27, 2013). In support of the C-HPP initiative, we have extended the annotation strategy developed for human chromosome 7 "missing" proteins into a semiautomated pipeline to functionally annotate the "missing" human proteome. This pipeline integrates a suite of bioinformatics analysis and annotation software tools to identify homologues and map putative functional signatures, gene ontology, and biochemical pathways. From sequential BLAST searches, we have primarily identified homologues from reviewed nonhuman mammalian proteins with protein evidence for 1271 (33.2%) "missing" proteins, followed by 703 (18.4%) homologues from reviewed nonhuman mammalian proteins and subsequently 564 (14.7%) homologues from reviewed human proteins. Functional annotations for 1945 (50.8%) "missing" proteins were also determined. To accelerate the identification of "missing" proteins from proteomics studies, we generated proteotypic peptides in silico. Matching these proteotypic peptides to ENCODE proteogenomic data resulted in proteomic evidence for 107 (2.8%) of the 3831 "missing proteins, while evidence from a recent membrane proteomic study supported the existence for another 15 "missing" proteins. The chromosome-wise functional annotation of all "missing" proteins is freely available to the scientific community through our web server (http://biolinfo.org/protannotator).

  8. Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome

    International Nuclear Information System (INIS)

    Goodfellow, P.J.; Mondello, C.; Darling, S.M.; Pym, B.; Little, P.; Goodfellow, P.N.

    1988-01-01

    The authors have identified and characterized a Hpa II tiny fragment (HTF) island associated with the promoter region of the pseudoautosomal gene MIC2. The MIC2 HTF island is unmethylated on both the active and inactive X chromosome and is similarly unmethylated on the Y chromosome. Unlike the majority of genes borne on the X chromosome, MIC2 fails to undergo X chromosome inactivation. HTF islands associated with X chromosome-liked genes that are inactivated are highly methylated on the inactive or transcriptionally silent homologue. The failure of MIC2 to undergo X chromosome inactivation correlates with the lack of methylation of HTF island at the 5' end of the gene. These results provide further evidence that DNA methylation plays an important role in the phenomenon of X chromosome inactivation

  9. 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

    complex, unlike at other parts of the genome, such as CG-rich regions, where Jarid2 and PRC2 binding are interdependent. Conversely, we show that Jarid2 loss prevents efficient PRC2 and H3K27me3 enrichment to Xist-coated chromatin. Jarid2 thus represents an important intermediate between PRC2 and Xist RNA......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...... for the initial targeting of the PRC2 complex to the X chromosome during onset of XCI....

  10. Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

    International Nuclear Information System (INIS)

    Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

  11. Evidence for X-chromosomal schizophrenia associated with microRNA alterations.

    Directory of Open Access Journals (Sweden)

    Jinong Feng

    2009-07-01

    Full Text Available Schizophrenia is a severe disabling brain disease affecting about 1% of the population. Individual microRNAs (miRNAs affect moderate downregulation of gene expression. In addition, components required for miRNA processing and/or function have also been implicated in X-linked mental retardation, neurological and neoplastic diseases, pointing to the wide ranging involvement of miRNAs in disease.To explore the role of miRNAs in schizophrenia, 59 microRNA genes on the X-chromosome were amplified and sequenced in males with (193 and without (191 schizophrenia spectrum disorders to test the hypothesis that ultra-rare mutations in microRNA collectively contribute to the risk of schizophrenia. Here we provide the first association of microRNA gene dysfunction with schizophrenia. Eight ultra-rare variants in the precursor or mature miRNA were identified in eight distinct miRNA genes in 4% of analyzed males with schizophrenia. One ultra-rare variant was identified in a control sample (with a history of depression (8/193 versus 1/191, p = 0.02 by one-sided Fisher's exact test, odds ratio = 8.2. These variants were not found in an additional 7,197 control X-chromosomes.Functional analyses of ectopically expressed copies of the variant miRNA precursors demonstrate loss of function, gain of function or altered expression levels. While confirmation is required, this study suggests that microRNA mutations can contribute to schizophrenia.

  12. Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags

    Science.gov (United States)

    de Souza, Sandro J.; Camargo, Anamaria A.; Briones, Marcelo R. S.; Costa, Fernando F.; Nagai, Maria Aparecida; Verjovski-Almeida, Sergio; Zago, Marco A.; Andrade, Luis Eduardo C.; Carrer, Helaine; El-Dorry, Hamza F. A.; Espreafico, Enilza M.; Habr-Gama, Angelita; Giannella-Neto, Daniel; Goldman, Gustavo H.; Gruber, Arthur; Hackel, Christine; Kimura, Edna T.; Maciel, Rui M. B.; Marie, Suely K. N.; Martins, Elizabeth A. L.; Nóbrega, Marina P.; Paçó-Larson, Maria Luisa; Pardini, Maria Inês M. C.; Pereira, Gonçalo G.; Pesquero, João Bosco; Rodrigues, Vanderlei; Rogatto, Silvia R.; da Silva, Ismael D. C. G.; Sogayar, Mari C.; de Fátima Sonati, Maria; Tajara, Eloiza H.; Valentini, Sandro R.; Acencio, Marcio; Alberto, Fernando L.; Amaral, Maria Elisabete J.; Aneas, Ivy; Bengtson, Mário Henrique; Carraro, Dirce M.; Carvalho, Alex F.; Carvalho, Lúcia Helena; Cerutti, Janete M.; Corrêa, Maria Lucia C.; Costa, Maria Cristina R.; Curcio, Cyntia; Gushiken, Tsieko; Ho, Paulo L.; Kimura, Elza; Leite, Luciana C. C.; Maia, Gustavo; Majumder, Paromita; Marins, Mozart; Matsukuma, Adriana; Melo, Analy S. A.; Mestriner, Carlos Alberto; Miracca, Elisabete C.; Miranda, Daniela C.; Nascimento, Ana Lucia T. O.; Nóbrega, Francisco G.; Ojopi, Élida P. B.; Pandolfi, José Rodrigo C.; Pessoa, Luciana Gilbert; Rahal, Paula; Rainho, Claudia A.; da Ro's, Nancy; de Sá, Renata G.; Sales, Magaly M.; da Silva, Neusa P.; Silva, Tereza C.; da Silva, Wilson; Simão, Daniel F.; Sousa, Josane F.; Stecconi, Daniella; Tsukumo, Fernando; Valente, Valéria; Zalcberg, Heloisa; Brentani, Ricardo R.; Reis, Luis F. L.; Dias-Neto, Emmanuel; Simpson, Andrew J. G.

    2000-01-01

    Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1,181 (1.45%) were found to match sequences in chromosome 22 with at least one ORESTES contig for 162 (65.6%) of the 247 known genes, for 67 (44.6%) of the 150 related genes, and for 45 of the 148 (30.4%) EST-predicted genes on this chromosome. Using a set of stringent criteria to validate our sequences, we identified a further 219 previously unannotated transcribed sequences on chromosome 22. Of these, 171 were in fact also defined by EST or full length cDNA sequences available in GenBank but not utilized in the initial annotation of the first human chromosome sequence. Thus despite representing less than 15% of all expressed human sequences in the public databases at the time of the present analysis, ORESTES sequences defined 48 transcribed sequences on chromosome 22 not defined by other sequences. All of the transcribed sequences defined by ORESTES coincided with DNA regions predicted as encoding exons by genscan. (http://genes.mit.edu/GENSCAN.html). PMID:11070084

  13. Higher incidence of spontaneous sister-chromatid exchanges (SCEs) and X-ray-induced chromosome aberrations in peripheral blood lymphocytes during pregnancy

    International Nuclear Information System (INIS)

    Sharma, T.; Das, B.C.

    1986-01-01

    In vitro cultures of peripheral blood lymphocytes from human and muntjac (barking deer) females who were at an advanced stage of pregnancy (32-37 weeks pregnant women and 20-24 weeks pregnant muntjacs) showed an enhanced frequency of SCEs and X-ray-induced chromosome aberrations when compared with those of nonpregnant females. Lymphocyte cultures of nonpregnant females to which sex hormones progesterone, oestrogen and human chorionic gonadotropin (HCG) were added together exogenously also showed higher frequency of SCEs. The plausible reason(s) for such high incidence of SCEs during pregnancy is discussed. (orig.)

  14. A powerful parent-of-origin effects test for qualitative traits on X chromosome in general pedigrees.

    Science.gov (United States)

    Zou, Qi-Lei; You, Xiao-Ping; Li, Jian-Long; Fung, Wing Kam; Zhou, Ji-Yuan

    2018-01-05

    Genomic imprinting is one of the well-known epigenetic factors causing the association between traits and genes, and has generally been examined by detecting parent-of-origin effects of alleles. A lot of methods have been proposed to test for parent-of-origin effects on autosomes based on nuclear families and general pedigrees. Although these parent-of-origin effects tests on autosomes have been available for more than 15 years, there has been no statistical test developed to test for parent-of-origin effects on X chromosome, until the parental-asymmetry test on X chromosome (XPAT) and its extensions were recently proposed. However, these methods on X chromosome are only applicable to nuclear families and thus are not suitable for general pedigrees. In this article, we propose the pedigree parental-asymmetry test on X chromosome (XPPAT) statistic to test for parent-of-origin effects in the presence of association, which can accommodate general pedigrees. When there are missing genotypes in some pedigrees, we further develop the Monte Carlo pedigree parental-asymmetry test on X chromosome (XMCPPAT) to test for parent-of-origin effects, by inferring the missing genotypes given the observed genotypes based on a Monte Carlo estimation. An extensive simulation study has been carried out to investigate the type I error rates and the powers of the proposed tests. Our simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects. Moreover, XMCPPAT substantially outperforms the existing tests and has a much higher power than XPPAT which only uses complete nuclear families (with both parents) from pedigrees. We also apply the proposed methods to analyze rheumatoid arthritis data for their practical use. The proposed XPPAT and XMCPPAT test statistics are valid and powerful in detecting parent-of-origin effects on X chromosome for qualitative traits based on general pedigrees and thus are recommended.

  15. Damage of chromosoms under irradiation of human blood lymphocytes and development of bystander effect.

    Science.gov (United States)

    Shemetun, O V

    2016-12-01

    the research the distribution of radiation induced damages among chromosomes and their bands in irra diated in vitro human blood lymphocytes and in unirradiated bystander cells.Material and methods of research: cultivation of human peripheral blood lymphocytes by semi micromethod D.A. Hungerford, modeling of radiation induced bystander effect in mixed cultures consisting of irradiated in vitro and non irradiated blood lymphocytes from persons of different gender, GTG staining of metaphase chromosomes and their cytogenetic analysis. Break points in chromosomes under the formation of aberrations were identified in exposed in vitro human peripheral blood lymphocytes in doses 0.25 Gy (95 breaks in 1248 cells) and 1.0 Gy (227 breaks in 726 cells) and in non irradiated bystander cells under their joint cultivation with irradiated in vitro human lymphocytes (51 breaks in 1137 cells at irradiation of adjacent populations of lymphocytes in dose 0.25 Gy and 75 breaks in 1321 cells at irradiation of adjacent population of lymphocytes in a dose 1.0 Gy). The distribution of injuries among the chromo somes and their bands was investigated. in radiation exposed in vitro human peripheral blood lymphocytes as well as in bystander cells the fre quency of damaged bands and number of breaks which localized in them exceeded the control value (p chromosomes were damaged according to their relative length. Location of bands with increasing number of breaks coincided with the «hot spots» of chromosome damage following irradiation and fragile sites. More sensitive to damage were G negative euchromatin chromosome bands, in which were localized 82 88 % breaks. Damageability of telomeric regions in the irradiated cells had no significant difference from the control, while in bystander cells was lower than control value (p < 0.05). O. V. Shemetun.

  16. Radiation-induced chromosome aberrations and cell killing in normal human fibroblasts and ataxia telangiectasia fibroblasts

    International Nuclear Information System (INIS)

    Kawata, T.; Saito, M.; Uno, T.; Ito, H.; Shigematsu, N.

    2003-01-01

    Full text: When cells are held in a non-dividing state (G0) after irradiation, an enhanced survival can be observed compared to that of immediate plating. A change of survival depending on post irradiation condition is known to be repair of potentially lethal damage (RPLD). The effects of confluent holding recovery (24-h incubation following irradiation) on chromosome aberrations in normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052C) were examined. A chemical-induced premature chromosome condensation (PCC) technique with fluorescent in situ hybridization (FISH) was applied to study chromosome aberrations in G2 and M-phase. Results from cell survival showed that the capacity for potentially lethal damage repair was normal in AG1522 cells but very little in GM02052C cells. The frequency of chromosome aberrations in AG1522 cells decreased when cells were allowed to repair for 24-h. Especially complex type exchanges were found to decrease markedly at high doses (4Gy and 6Gy). However, the frequency of chromosome aberrations including complex type exchanges showed little decrease in GM02052C cells. Confluent holding can effectively reduce chromosome aberrations, especially complex type exchanges in normal cells

  17. Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19.

    Directory of Open Access Journals (Sweden)

    Marco Di Stefano

    Full Text Available The connection between chromatin nuclear organization and gene activity is vividly illustrated by the observation that transcriptional coregulation of certain genes appears to be directly influenced by their spatial proximity. This fact poses the more general question of whether it is at all feasible that the numerous genes that are coregulated on a given chromosome, especially those at large genomic distances, might become proximate inside the nucleus. This problem is studied here using steered molecular dynamics simulations in order to enforce the colocalization of thousands of knowledge-based gene sequences on a model for the gene-rich human chromosome 19. Remarkably, it is found that most (≈ 88% gene pairs can be brought simultaneously into contact. This is made possible by the low degree of intra-chromosome entanglement and the large number of cliques in the gene coregulatory network. A clique is a set of genes coregulated all together as a group. The constrained conformations for the model chromosome 19 are further shown to be organized in spatial macrodomains that are similar to those inferred from recent HiC measurements. The findings indicate that gene coregulation and colocalization are largely compatible and that this relationship can be exploited to draft the overall spatial organization of the chromosome in vivo. The more general validity and implications of these findings could be investigated by applying to other eukaryotic chromosomes the general and transferable computational strategy introduced here.

  18. Linear dose-response of acentric chromosome fragments down to 1 R of x-rays in grasshopper neuroblasts, a potential mutagen-test system

    International Nuclear Information System (INIS)

    Gaulden, M.E.; Read, C.B.

    1978-01-01

    Grasshopper-embryo neuroblasts have no spontaneous chromosome breakage; therefore they permit easy detection of agents that break chromosomes. An X-ray exposure of 1 R induces in them a detectable number of chromosome fragments. The dose-response of acentric fragment frequency fits a linear model between 0 and 128 R. Thus another cell type is added to those previously demonstrated to have no threshold dose for the induction of chromosome or gene mutations

  19. Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

    Energy Technology Data Exchange (ETDEWEB)

    Trask, B.J.; Friedman, C. [Univ. of Washington, Seattle, WA (United States); Giorgi, D. [CNRS, Montpelier (France)] [and others

    1994-09-01

    We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

  20. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  1. Epigenetics with special reference to the human X chromosome ...

    Indian Academy of Sciences (India)

    Deepti Deobagkar

    Received 30 October 2017; revised 5 April 2018; accepted 10 April 2018; published online 5 June 2018. Abstract. Epigenetics ..... the locations of consistently methylated genes were exam- .... innovation grant and UGC CAS for the work.

  2. Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome.

    Science.gov (United States)

    Stambolian, D; Favor, J; Silvers, W; Avner, P; Chapman, V; Zhou, E

    1994-07-15

    The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized by the congenital onset of cataracts. The cataracts have morphologies similar to those of cataracts found in the human Nance Horan (X-linked cataract dental) syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the localization of the Xcat mutation with respect to known molecular markers on the mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained from an interspecific cross. Genomic DNA from each mouse was subjected to Southern and PCR analysis to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Xcat to a 2-cM region, eliminate several genes from consideration as the Xcat mutation, identify molecular probes tightly linked with Xcat, and suggest candidate genes responsible for the Xcat phenotype.

  3. Characterization of A-11, a newly discovered X-chromosomal gene that is under both single-active-X control and tissue-specific control

    International Nuclear Information System (INIS)

    Nadon, N.L.

    1987-01-01

    The A-11 transcript is present in fibroblasts, but is not normally expressed in B- or T-lymphoblastoid cells. The regulation of the A-11 loci on both the active and inactive X chromosomes is very easily perturbed. The A-11 locus on the fibroblast-derived inactive X in a hybrid cell is reactivated at a very high rate by 5-azacytidine, an inhibitor of DNA methylation, while the A-11 locus on the active X in B-lymphoblastoid cells is derepressed at a very high rate after gamma irradiation. The A-11 gene codes for a mature transcript of about 1.9 kb. The A-11 cDNA clone is incomplete, and contains 753 bases from the 3' end of the gene. A genomic clone that contains about 17 kb of human DNA and hybridizes to the A-11 cDNA was isolated. This clone contains at least the last exon of the A-11 gene, as determined by Northern blotting, nuclease protection experiments, and DNA sequencing. When the genomic clone is transferred into mouse cells. A-11 transcripts of both normal and abnormal sizes are produced, indicating that it is possible that the genomic clone contains the entire locus. However, at this time, the 5' end of the gene has not been located

  4. High-Throughput Screening of a Luciferase Reporter of Gene Silencing on the Inactive X Chromosome.

    Science.gov (United States)

    Keegan, Alissa; Plath, Kathrin; Damoiseaux, Robert

    2018-01-01

    Assays of luciferase gene activity are a sensitive and quantitative reporter system suited to high-throughput screening. We adapted a luciferase assay to a screening strategy for identifying factors that reactivate epigenetically silenced genes. This epigenetic luciferase reporter is subject to endogenous gene silencing mechanisms on the inactive X chromosome (Xi) in primary mouse cells and thus captures the multilayered nature of chromatin silencing in development. Here, we describe the optimization of an Xi-linked luciferase reactivation assay in 384-well format and adaptation of the assay for high-throughput siRNA and chemical screening. Xi-luciferase reactivation screening has applications in stem cell biology and cancer therapy. We have used the approach described here to identify chromatin-modifying proteins and to identify drug combinations that enhance the gene reactivation activity of the DNA demethylating drug 5-aza-2'-deoxycytidine.

  5. X-chromosome STR markers data in a Cabo Verde immigrant population of Lisboa.

    Science.gov (United States)

    Afonso Costa, Heloísa; Morais, Paulo; Vieira da Silva, Cláudia; Matos, Sara; Marques Santos, Rodolfo; Espinheira, Rosa; Costa Santos, Jorge; Amorim, António

    2014-01-01

    Population genetic data of 12 X chromosomal short tandem repeats markers (DXS10074, DXS10079, DXS10101, DXS10103, DXS10134, DXS10135, DXS10146, DXS10148, DXS7132, DXS7423, DXS8378 and HPRTB) were analysed in 54 females and 95 males of an immigrant population from Cabo Verde living in Lisboa. The obtained results for forensic statistical parameters such as observed heterozigosity, polymorphism information content, power of discrimination and mean exclusion chance, based on single allele frequencies, reveal that this multiplex system is highly informative and can represent an important tool for genetic identification purposes in the immigrant population of Cabo Verde. Since the studied short tandem repeats genetic markers are distributed on four linkage groups, that can provide independent genotype information, we studied those groups as haploytes. The forensic efficiency parameters for the linked groups were all higher than 0.97, with linkage group I being the most polymorphic and linkage group III the less informative.

  6. Unique signatures of natural background radiation on human Y chromosomes from Kerala, India.

    Directory of Open Access Journals (Sweden)

    Sanjay Premi

    Full Text Available The most frequently observed major consequences of ionizing radiation are chromosomal lesions and cancers, although the entire genome may be affected. Owing to its haploid status and absence of recombination, the human Y chromosome is an ideal candidate to be assessed for possible genetic alterations induced by ionizing radiation. We studied the human Y chromosome in 390 males from the South Indian state of Kerala, where the level of natural background radiation (NBR is ten-fold higher than the worldwide average, and that from 790 unexposed males as control.We observed random microdeletions in the Azoospermia factor (AZF a, b and c regions in >90%, and tandem duplication and copy number polymorphism (CNP of 11 different Y-linked genes in about 80% of males exposed to NBR. The autosomal homologues of Y-linked CDY genes largely remained unaffected. Multiple polymorphic copies of the Y-linked genes showing single Y-specific signals suggested their tandem duplication. Some exposed males showed unilocus duplication of DAZ genes resulting in six copies. Notably, in the AZFa region, approximately 25% of exposed males showed deletion of the DBY gene, whereas flanking genes USP9Y and UTY remained unaffected. All these alterations were detected in blood samples but not in the germline (sperm samples.Exposure to high levels of NBR correlated with several interstitial polymorphisms of the human Y chromosome. CNPs and enhanced transcription of the SRY gene after duplication are envisaged to compensate for the loss of Y chromosome in some cells. The aforesaid changes, confined to peripheral blood lymphocytes, suggest a possible innate mechanism protecting the germline DNA from the NBR. Genome analysis of a larger population focusing on greater numbers of genes may provide new insights into the mechanisms and risks of the resultant genetic damages. The present work demonstrates unique signatures of NBR on human Y chromosomes from Kerala, India.

  7. Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, C.M.; Frankel, W.N. [Jackson Lab., Bar Harbor, ME (United States); Richards, J.E. [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others

    1997-05-01

    Npy1r and Npy2r, the genes encoding mouse type 1 and type 2 neuropeptide Y receptors, have been mapped by interspecific backcross analysis. Previous studies have localized the human genes encoding these receptors to chromosome 4q31-q32. We have now assigned Npy1r and Npy2r to conserved linkage groups on mouse Chr 8 and Chr 3, respectively, which correspond to the distal region of human chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance between the human genes to be approximately 6 cM. Although ancient tandem duplication events may account for some closely spaced G-protein-coupled receptor genes, the large genetic distance between the human type 1 and type 2 neuropeptide Y receptor genes raises questions about whether this mechanism accounts for their proximity. 20 refs., 1 fig.

  8. Finding genes on the X chromosome by which homo may have become sapiens

    Energy Technology Data Exchange (ETDEWEB)

    Turner, G. [Univ. of Newcastle, Waratah, New South Wales (Australia)

    1996-06-01

    The map of the X chromosome is now littered, from one telomere to the other, with genes for mental handicap, alone or in combination with other features. In this issue of the journal, report such an entity from the Scottish Highlands, which they give the catchy title of {open_quotes}PPM-X syndrome,{close_quotes} denoting the association of pyramidal tract signs, psychosis, and macroorchidism with mental handicap (XLMR). They have localized this to Xq28 and discuss other genes in the same area, which include L1CAM (associated with MASA [mental retardation, aphasia, shuffling gait, and adducted thumbs] and X-linked hydrocephalus) and two genes for nonspecific XLMR-MRX3 and MRX25. It is also the localization of the gene for G6PD deficiency, which, in earlier studies, had demonstrated linkage to bipolar affective disorders, although this has been questioned in more recent studies. There may well be other families with this pattern of abnormalities who have remained undescribed because depression is so often not diagnosed in those with moderate mental handicap. The occurrence, in this family, of mental handicap with a bipolar disorder may be the chance association of two common disorders, or it may a significant association; at this stage, one cannot judge. 8 refs.

  9. Relationship between X-ray irradiation and chromosomal damage in bone marrow tissue of mice

    International Nuclear Information System (INIS)

    Chaubey, R.C.; George, K.P.; Sundaram, K.

    1976-01-01

    X-ray induced chromosomal damage in bone-marrow tissue of male mice was studied using micronucleus technique. Dose response relationship was evaluated. Male Swiss mice received whole body x-ray irradiation at different doses from 25-1000 rads. Animals were sacrificed at the end of 24 hours, bone-marrow smears were made and stained in May-Grunwald-Giemsa. The preparatians were scored for the following types of aberrations: micronuclei in young erythocytes-polychromatic cells and in the mature erythrocytes-normechromatic cells. A dose dependent increase in the frequency of micronuclei in polychromatic cells up to a dose of 100 rads was observed. In addition the effect of post-irradiation duration on the frequency of micronuclei in polychromatic and normochromatic cells were studied. Male Swiss mice were exposed to 200 rads x-rays and were then sacrificed at different time intervals after irradiation and bone-marrow preparations were made and scored. Maximum polychromatic cells with micronuclei were observed in 24 hours post-irradiated animals, thereafter a decrease in the frequency of polychromatic cells with micronuclei was observed in 40 hours post irradiated animals. (author

  10. Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

    Science.gov (United States)

    Hittelman, W N; Broussard, L C; McCredie, K

    1979-11-01

    The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

  11. A Quest for Missing Proteins : update 2015 on Chromosome-Centric Human Proteome Project

    NARCIS (Netherlands)

    Horvatovich, Péter; Lundberg, Emma K; Chen, Yu-Ju; Sung, Ting-Yi; He, Fuchu; Nice, Edouard C; Goode, Robert J A; Yu, Simon; Ranganathan, Shoba; Baker, Mark S; Domont, Gilberto B; Velasquez, Erika; Li, Dong; Liu, Siqi; Wang, Quanhui; He, Qing-Yu; Menon, Rajasree; Guan, Yuanfang; Corrales, Fernando Jose; Segura, Victor; Casal, José Ignacio; Pascual-Montano, Alberto; Albar, Juan Pablo; Fuentes, Manuel; Gonzalez-Gonzalez, Maria; Diez, Paula; Ibarrola, Nieves; Degano, Rosa M; Mohammed, Yassene; Borchers, Christoph H; Urbani, Andrea; Soggiu, Alessio; Yamamoto, Tadashi; Archakov, Alexander I; Ponomarenko, Elena; Lisitsa, Andrey V; Lichti, Cheryl F; Mostovenko, Ekaterina; Kroes, Roger A; Rezeli, Melinda; Vegvari, Akos; Fehniger, Thomas E; Bischoff, Rainer; Vizcaíno, Juan Antonio; Deutsch, Eric W; Lane, Lydie; Nilsson, Carol L; Marko-Varga, György; Omenn, Gilbert S; Jeong, Seul-Ki; Cho, Jin-Young; Paik, Young-Ki; Hancock, William S

    2015-01-01

    This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level

  12. Fluorescence in situ hybridization on human metaphase chromosomes detected by near-field scanning optical microscopy

    NARCIS (Netherlands)

    Moers, M.H.P.; Moers, M.H.P.; Kalle, W.H.J.; Kalle, W.H.J.; Ruiter, A.G.T.; Wiegant, J.C.A.G.; Raap, A.K.; Greve, Jan; de Grooth, B.G.; van Hulst, N.F.

    1996-01-01

    Fluorescence in situ hybridization o­n human metaphase chromosomes is detected by near-field scanning optical microscopy. This combination of cytochemical and scanning probe techniques enables the localization and identification of several fluorescently labelled genomic DNA fragments o­n a single

  13. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans

    Science.gov (United States)

    York, Dan; Higgins, Robert J.; LeCouteur, Richard A.; Joshi, Nikhil; Bannasch, Danika

    2016-01-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID:27251041

  14. Students as "Humans Chromosomes" in Role-Playing Mitosis and Meiosis

    Science.gov (United States)

    Chinnici, Joseph P.; Yue, Joyce W.; Torres, Kieron M.

    2004-01-01

    Students often find it challenging to understand mitosis and meiosis and determine their processes. To develop an easier way to understand these terms, students are asked to role-play mitosis and meiosis and students themselves act as human chromosomes, which help students to learn differences between mitosis and meiosis.

  15. Cloning, chromosome localization and features of a novel human ...

    Indian Academy of Sciences (India)

    Unknown

    Math2 may have the same functions in the nervous system. [Guo L., Jiang M., Ma Y., Cheng ... from a human foetal brain cDNA library, and its localiza- tion in the human ... using the BLASTN,. BLASTP and BLASTX algorithms on the NCBI web.

  16. A First Generation Comparative Chromosome Map between Guinea Pig (Cavia porcellus) and Humans.

    Science.gov (United States)

    Romanenko, Svetlana A; Perelman, Polina L; Trifonov, Vladimir A; Serdyukova, Natalia A; Li, Tangliang; Fu, Beiyuan; O'Brien, Patricia C M; Ng, Bee L; Nie, Wenhui; Liehr, Thomas; Stanyon, Roscoe; Graphodatsky, Alexander S; Yang, Fengtang

    2015-01-01

    The domesticated guinea pig, Cavia porcellus (Hystricomorpha, Rodentia), is an important laboratory species and a model for a number of human diseases. Nevertheless, genomic tools for this species are lacking; even its karyotype is poorly characterized. The guinea pig belongs to Hystricomorpha, a widespread and important group of rodents; so far the chromosomes of guinea pigs have not been compared with that of other hystricomorph species or with any other mammals. We generated full sets of chromosome-specific painting probes for the guinea pig by flow sorting and microdissection, and for the first time, mapped the chromosomal homologies between guinea pig and human by reciprocal chromosome painting. Our data demonstrate that the guinea pig karyotype has undergone extensive rearrangements: 78 synteny-conserved human autosomal segments were delimited in the guinea pig genome. The high rate of genome evolution in the guinea pig may explain why the HSA7/16 and HSA16/19 associations presumed ancestral for eutherians and the three syntenic associations (HSA1/10, 3/19, and 9/11) considered ancestral for rodents were not found in C. porcellus. The comparative chromosome map presented here is a starting point for further development of physical and genetic maps of the guinea pig as well as an aid for genome assembly assignment to specific chromosomes. Furthermore, the comparative mapping will allow a transfer of gene map data from other species. The probes developed here provide a genomic toolkit, which will make the guinea pig a key species to unravel the evolutionary biology of the Hystricomorph rodents.

  17. Chromosomal Conditions

    Science.gov (United States)

    ... and more. Stony Point, NY 10980 Close X Home > Complications & Loss > Birth defects & other health conditions > Chromosomal conditions Chromosomal conditions ... Disorders See also: Genetic counseling , Your family health history Last reviewed: February, 2013 ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & ...

  18. Generation of meiomaps of genome-wide recombination and chromosome segregation in human oocytes

    DEFF Research Database (Denmark)

    Ottolini, Christian S; Capalbo, Antonio; Newnham, Louise

    2016-01-01

    We have developed a protocol for the generation of genome-wide maps (meiomaps) of recombination and chromosome segregation for the three products of human female meiosis: the first and second polar bodies (PB1 and PB2) and the corresponding oocyte. PB1 is biopsied and the oocyte is artificially......-nucleotide polymorphisms (SNPs) genome-wide by microarray. Informative maternal heterozygous SNPs are phased using a haploid PB2 or oocyte as a reference. A simple algorithm is then used to identify the maternal haplotypes for each chromosome, in all of the products of meiosis for each oocyte. This allows mapping...

  19. 5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.

    Science.gov (United States)

    Machado, Filipe Brum; Machado, Fabricio Brum; Faria, Milena Amendro; Lovatel, Viviane Lamim; Alves da Silva, Antonio Francisco; Radic, Claudia Pamela; De Brasi, Carlos Daniel; Rios, Álvaro Fabricio Lopes; de Sousa Lopes, Susana Marina Chuva; da Silveira, Leonardo Serafim; Ruiz-Miranda, Carlos Ramon; Ramos, Ester Silveira; Medina-Acosta, Enrique

    2014-01-01

    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

  20. 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

  1. Establishment of a molecular genetic map of distal mouse chromosome 1: further definition of a conserved linkage group syntenic with human chromosome 1q.

    Science.gov (United States)

    Seldin, M F; Morse, H C; LeBoeuf, R C; Steinberg, A D

    1988-01-01

    A linkage map of distal mouse chromosome 1 was constructed by restriction fragment length polymorphism analysis of DNAs from seven sets of recombinant inbred (RI) strains. The data obtained with seven probes on Southern hybridization combined with data from previous studies suggest the gene order Cfh, Pep-3/Ren-1,2, Ly-5, Lamb-2, At-3, Apoa-2/Ly-17,Spna-1. These results confirm and extend analyses of a large linkage group which includes genes present on a 20-30 cM span of mouse chromosome 1 and those localized to human chromosome 1q21-32. Moreover, the data indicate similar relative positions of human and mouse complement receptor-related genes REN, CD45, LAMB2, AT3, APOA2, and SPTA. These results suggest that mouse gene analyses may help in detailed mapping of human genes within such a syntenic group.

  2. [Familial febrile convulsions is supposed to link to human chromosome 19p13.3].

    Science.gov (United States)

    Qi, Y; Lü, J; Wu, X

    2001-01-10

    To localize the familial febrile convulsion (FC) genes on human chromosomes. For 63 FC pedigrees, tetranucleotide repeat markers D19S253 D19S395 and D19S591 on the short arm of chromosome 19, as well as dinucleotide repeat markers D8S84 and D8S85 on the long arm of chromosome 8 were genotyped. Transmission disequilibrium test (TDT) and Lod score calculation were carried out. The data were processed by PPAP software package. All the alleles in every locus of FC probands and normal controls were in Hardy-Weinburg balance. Transmission disequilibrium was found on D8S84, D19S395 and D19S591 in FC families. chi(2) values were 4.0, 5.124 and 7.364 separately. Each P value was < 0.05, and significantly meaningful. The two-point Lod scores between D8S84 and FC, D8S85 and FC, D19S253 and FC, D19S395 and FC, D19S591 and FC are 0.00002, 0.000017, 0.58, 1.53 and 1.42 respectively. The multi-point Lod score among markers on chromosome 8q and FC was 0.88, while Lod score among markers on chromosome 19p and FC reached 2.78. The results by both the non-parameter (TDT) and parameter (Lod score) methods were consistant on a whole. FC is linked with chromosome region 19p13.3, but not with chromosome 8q.

  3. Analysis of the frequency of unstable chromosome aberrations in human lymphocytes irradiated with 60Co

    International Nuclear Information System (INIS)

    Mendonca, Julyanne C.G.; Mendes, Mariana E.; Lima, Fabiana F.; Santos, Neide

    2013-01-01

    The aim of this study was to analyze the frequency of unstable chromosomal aberrations induced by gamma radiation from a 60 Co source at two different doses. Samples were obtained from a healthy donor and exposed to 60 Co source (Gammacel 220 ) located in the Department of Nuclear Energy of Pernambuco Federal University (DEN/UFPe/Brazil) with a rate of air Kerma to 3,277 Gy/h. Exposures resulted in absorbed dose 0.51 Gy and 0.77 Gy. Mitotic metaphases were obtained by culturing lymphocytes for chromosome analysis and the slides were stained with 5% Giemsa. Among the unstable chromosomal aberrations the dicentric chromosomes, ring chromosomes and acentric fragments were analyzed. To calculate the significance level the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. To calculate the significance level of the chi - square test was used, considering relevant differences between the frequencies when the value of p < 0.05. The results showed that there was significant difference of the frequencies of dicentric chromosomes (from 0.18 to 0.51 to 0.37 Gy to 0.77 Gy), however there was no statistically significant difference between the frequencies of acentric fragments ( 0.054 to 0, 51 Gy to 0.063 to 0.77 Gy) and ring chromosomes (0.001 to 0.51 Gy to 0.003 to 0.77 Gy). The low number of rings is found justified, considering that in irradiated human lymphocytes, its appearance is rare relative to dicentrics. The results confirm that dicentrics are the most reliable biomarkers in estimating dose after exposure to gamma radiation. These two points will make the calibration curve dose-response being built for Biological Dosimetry Laboratory of CRCN-NE/CNEN

  4. Cytogenetic analysis of CpG-oligonucleotide DSP30 plus Interleukin-2-Stimulated canine B-Cell lymphoma cells reveals the loss of one X Chromosome as the sole abnormality.

    Science.gov (United States)

    Reimann-Berg, N; Murua Escobar, H; Kiefer, Y; Mischke, R; Willenbrock, S; Eberle, N; Nolte, I; Bullerdiek, J

    2011-01-01

    Human and canine lymphoid neoplasms are characterized by non-random cytogenetic abnormalities. However, due to the low mitotic activity of the B cells, cytogenetic analyses of B-cell lymphoid proliferations are difficult to perform. In the present study we stimulated canine B-cell lymphoma cells with the immunostimulatory CpG-oligonucleotide DSP30 in combination with interleukin-2 (IL-2) and obtained an adequate number of metaphases. Cytogenetic analyses revealed the loss of one X chromosome as the sole cytogenetic aberration. Chromosome analysis of the corresponding blood showed a normal female karyotype. Monosomy X as the sole clonal chromosomal abnormality is found in human hematopoietic malignancies as well, thus the dog may serve as a promising animal model. Copyright © 2011 S. Karger AG, Basel.

  5. Linkage and RH mapping of 10 genes to a QTL region for fatness and muscling traits on pig chromosome X

    Czech Academy of Sciences Publication Activity Database

    Čepica, Stanislav; Masopust, Martin; Knoll, Aleš; Bartenschlager, H.; Yerle, M.; Rohrer, G. A.; Geldermann, H.

    2006-01-01

    Roč. 37, 6 (2006), s. 603-604 ISSN 0268-9146 R&D Projects: GA ČR GA523/04/0106 Institutional research plan: CEZ:AV0Z50450515 Keywords : pig chromosome X Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.520, year: 2006

  6. Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome.

    Science.gov (United States)

    Rydzewski, W T; Carioscia, S A; Liévano, G; Lynch, V D; Patten, M M

    2016-06-01

    Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  7. Fine-structure analysis and gentic organization at the base of the x chromosome in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Lifschytz, E.

    1978-01-01

    Genetic organization at the base of the X chromosome was studied through the analysis of x-ray-induced deficiencies. Deficiencies were recovered so as to have a preselected right end anchored in the centric heterochromatin to the right of the su(f) locus. Free ends of deficiencies occurred at any of 22 intervals in Section 20 and in the proximal portion of Section 19 of Bridges' (1938) polytene chromosome map. The distribution of 130 such free ends of deficiencies induced in normal, In(1)sc 8 , and In(1)w/sup m4/ chromosomes suggests that on the single section level, genes are flanked by hot or cold sites for x-ray-induced breaks, and that occurrence of the hot spots is dependent on their interaction with the fixed-end sites in the centric heterochromatin. In the light of these results, it is argued that long heterochromatic sequences separate the relatively few genes in Section 20, and thus endow it with several characteristics typical of heterochromatic regions. Section 20 is considered to be a transition region between the mostly heterochromatic and mostly euchromatic regions of the X chromosome; the differences between them are suggested as being merely quantitative

  8. Chromosomal damages and mutagenesis in mammalian and human cells induced by ionizing radiations with different LET

    International Nuclear Information System (INIS)

    Govorun, R.D.

    1997-01-01

    On the basis of literature and proper data the inference was made about essential role of structural chromosomal (and gene) damages in spontaneous and radiation-induced mutagenesis of mammalian and human cells on HPRT-loci. The evidences of increasing role of these damages in the mutagenesis after the influence of ionizing radiations with high LET are adduced. The consequences of HPRT-gene damages have been examined hypothetically. The geterogeneity of mutant subclones on their cytogenetical properties were revealed experimentally. The data reflect a phenomenon of the reproductive chromosomal instability in many generations of mutant cell. The mutagenesis of mammalian cells is also accompanied by the impairment of chromosome integrity with high probability as a stage of appropriate genome reorganization because of changed vital conditions

  9. Cytogenetic biological dosimetry in radiological protection: chromosome aberration analysis in human lymphocyties

    International Nuclear Information System (INIS)

    Campos, I.M.A. de.

    1988-01-01

    The effects of ionizing radiation on chromosomes have been know for several decades and dose effect relationships are also fairly well established for several doses and dose rates. Apart from its biological significance, the interpretation of chromosome aberration frequency associated with human exposure to radiation plays an important role in dose assessment, particularly in cases where exposure is though to have occurred but no physical dose monitoring system was present. Based on the cytogenetic data obtained from seven cases of exposure to radiation the aberration frequency have been fitted to the quadratic function Y= αD + βD 2 as the dose response curves from literature. The dose equivalent estimate by frequency of chromosomic aberration found here was compared with 60 Co and 192 Ir already published curves obtained at almost similar dose rate together with some hematological data. (author) [pt

  10. Effects of radiation and porphyrin on mitosis and chromosomes in human hematopoietic cell lines

    International Nuclear Information System (INIS)

    Tan, J.C.; Huang, C.C.; Fiel, R.J.

    1976-01-01

    The effect on mitosis of a human hematopoietic cell line RPMI-1788 treated with a metal chelate (Zn ++ ) of meso-tetra (p-carboxyphenyl) porphine (Zn-TCPP) alone at various concentrations or in combination with gamma-irradiation at various doses were studied. The results showed that both Zn-TCPP and radiation were effective in interfering with normal mitosis and that the effect of radiation was relatively more effective. Data also suggest interacting effects between Zn-TCPP and gamma-irradiation. At low doses of radiation, Zn-TCPP potentiated the effect of radiation. The reverse seemed to be true at a high dose of radiation. The effects of two porphyrins (Zn-TCPP and hematoporphyrin) and radiation on chromosomes were also studied. Chromosomal aberrations characteristic of radiation were observed. The porphyrins were found not to be effective chromosome-breaking agents under the experimental conditions tested

  11. Interspecific comparisons of the sensitivity to chromosome aberration production by x rays. [Comparative in vitro radiosensitivity of leukocyte chromosomes from mice to man

    Energy Technology Data Exchange (ETDEWEB)

    Brewen, J.G.

    1978-01-01

    It is concluded that arm number probably plays a minor role, if any, in the relative radiosensitivity of a species. Instead the reported differences are probably a reflection of inherent basic biological mechanisms of repair that vary from one order of mammals to the next. It should be added, however, that the ultimate goal of all of these studies is to make a reasonable risk estimate for man. In that context the best approach is that of conservatism and the current data on mouse and man suggest that man has 1.5 to 2.0 times the risk of mice for chromosome rearrangement induction by x rays.

  12. Reactivation of chromosomally integrated human herpesvirus-6 by telomeric circle formation.

    Directory of Open Access Journals (Sweden)

    Bhupesh K Prusty

    Full Text Available More than 95% of the human population is infected with human herpesvirus-6 (HHV-6 during early childhood and maintains latent HHV-6 genomes either in an extra-chromosomal form or as a chromosomally integrated HHV-6 (ciHHV-6. In addition, approximately 1% of humans are born with an inheritable form of ciHHV-6 integrated into the telomeres of chromosomes. Immunosuppression and stress conditions can reactivate latent HHV-6 replication, which is associated with clinical complications and even death. We have previously shown that Chlamydia trachomatis infection reactivates ciHHV-6 and induces the formation of extra-chromosomal viral DNA in ciHHV-6 cells. Here, we propose a model and provide experimental evidence for the mechanism of ciHHV-6 reactivation. Infection with Chlamydia induced a transient shortening of telomeric ends, which subsequently led to increased telomeric circle (t-circle formation and incomplete reconstitution of circular viral genomes containing single viral direct repeat (DR. Correspondingly, short t-circles containing parts of the HHV-6 DR were detected in cells from individuals with genetically inherited ciHHV-6. Furthermore, telomere shortening induced in the absence of Chlamydia infection also caused circularization of ciHHV-6, supporting a t-circle based mechanism for ciHHV-6 reactivation.

  13. Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose-effect curve)

    International Nuclear Information System (INIS)

    Al-Achkar, W.

    2001-09-01

    In order to draw a dose-effect curve, experimentally gamma ray induced chromosomal aberrations in human peripheral lymphocytes from eight healthy people were studied. Samples from 4 males and 4 females were irradiated in tubes with 0.15, 0.25, 0.5, 1, 1.5, 2, 2.5 gray of gamma ray (Co 60 at dose rate 0.3 Gy/min). Irradiated and control samples were incubated in 37 centigrade for 48 hours cell cultures. Cell cultures then were stopped and metaphases spread, Giemsa stained to score the induced chromosomal aberrations. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics + rings and total numbers of breaks in cell for each individual or for all people were drawn. An increase of all chromosomal aberrations types with the elevation of the doses was observed. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

  14. Dose Assessment using Chromosome Aberration Analyses in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin-Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The healthy five donors were recruited to establish the dose-response calibration curve for chromosomal aberrations by ionizing radiation exposure. Our cytogenetic results revealed that the mean frequency of chromosome aberration increased with increasing radiation dose. In this study, dicentric assay and CBMN assay were compared considering the sensitivity and accuracy of dose estimation. Therefore, these chromosome aberration analyses will be the foundation for biological dosimetric analysis with additional research methods such as translocation and PCC assay. The conventional analysis of dicentric chromosomes in HPBL was suggested by Bender and Gooch in 1962. This assay has been for many years, the golden standard and the most specific method for ionizing radiation damage. The dicentric assay technique in HPBL has been shown as the most sensitive biological method and reliable bio-indicator of quantifying the radiation dose. In contrast, the micronucleus assay has advantages over the dicentric assay since it is rapid and requires less specialized expertise, and accordingly it can be applied to monitor a big population. The cytokinesis-block micronucleus (CBMN) assay is a suitable method for micronuceli measurement in cultured human as well as mammalian cells. The aim of our study was to establish the dose response curve of radiation-induced chromosome aberrations in HPBL by analyzing the frequency of dicentrics and micronuclei.

  15. Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes

    Science.gov (United States)

    Durante, M.; George, K.; Yang, T. C.

    1997-01-01

    Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

  16. Towards single particle imaging of human chromosomes at SACLA

    International Nuclear Information System (INIS)

    Robinson, Ian; Schwenke, Joerg; Yusuf, Mohammed; Estandarte, Ana; Zhang, Fucai; Chen, Bo; Clark, Jesse; Song, Changyong; Nam, Daewoong; Joti, Yasumasa; Tono, Kensuke; Yabashi, Makina; Ratnasari, Gina; Kaneyoshi, Kohei; Takata, Hideaki; Fukui, Kiichi

    2015-01-01

    Single particle imaging (SPI) is one of the front-page opportunities which were used to motivate the construction of the first x-ray free electron lasers (XFELs). SPI’s big advantage is that it avoids radiation damage to biological samples because the diffraction takes place in femtosecond single shots before any atomic motion can take place in the sample, hence before the onset of radiation damage. This is the ‘diffract before destruction’ theme, destruction being assured from the high x-ray doses used. This article reports our collaboration’s first attempt at SPI using the SACLA XFEL facility in June 2015. The report is limited to experience with the instrumentation and examples of data because we have not yet had time to invert them to images. (paper)

  17. Efficient identification of Y chromosome sequences in the human and Drosophila genomes

    Science.gov (United States)

    Carvalho, Antonio Bernardo; Clark, Andrew G.

    2013-01-01

    Notwithstanding their biological importance, Y chromosomes remain poorly known in most species. A major obstacle to their study is the identification of Y chromosome sequences; due to its high content of repetitive DNA, in most genome projects, the Y chromosome sequence is fragmented into a large number of small, unmapped scaffolds. Identification of Y-linked genes among these fragments has yielded important insights about the origin and evolution of Y chromosomes, but the process is labor intensive, restricting studies to a small number of species. Apart from these fragmentary assemblies, in a few mammalian species, the euchromatic sequence of the Y is essentially complete, owing to painstaking BAC mapping and sequencing. Here we use female short-read sequencing and k-mer comparison to identify Y-linked sequences in two very different genomes, Drosophila virilis and human. Using this method, essentially all D. virilis scaffolds were unambiguously classified as Y-linked or not Y-linked. We found 800 new scaffolds (totaling 8.5 Mbp), and four new genes in the Y chromosome of D. virilis, including JYalpha, a gene involved in hybrid male sterility. Our results also strongly support the preponderance of gene gains over gene losses in the evolution of the Drosophila Y. In the intensively studied human genome, used here as a positive control, we recovered all previously known genes or gene families, plus a small amount (283 kb) of new, unfinished sequence. Hence, this method works in large and complex genomes and can be applied to any species with sex chromosomes. PMID:23921660

  18. Efficient identification of Y chromosome sequences in the human and Drosophila genomes.

    Science.gov (United States)

    Carvalho, Antonio Bernardo; Clark, Andrew G

    2013-11-01

    Notwithstanding their biological importance, Y chromosomes remain poorly known in most species. A major obstacle to their study is the identification of Y chromosome sequences; due to its high content of repetitive DNA, in most genome projects, the Y chromosome sequence is fragmented into a large number of small, unmapped scaffolds. Identification of Y-linked genes among these fragments has yielded important insights about the origin and evolution of Y chromosomes, but the process is labor intensive, restricting studies to a small number of species. Apart from these fragmentary assemblies, in a few mammalian species, the euchromatic sequence of the Y is essentially complete, owing to painstaking BAC mapping and sequencing. Here we use female short-read sequencing and k-mer comparison to identify Y-linked sequences in two very different genomes, Drosophila virilis and human. Using this method, essentially all D. virilis scaffolds were unambiguously classified as Y-linked or not Y-linked. We found 800 new scaffolds (totaling 8.5 Mbp), and four new genes in the Y chromosome of D. virilis, including JYalpha, a gene involved in hybrid male sterility. Our results also strongly support the preponderance of gene gains over gene losses in the evolution of the Drosophila Y. In the intensively studied human genome, used here as a positive control, we recovered all previously known genes or gene families, plus a small amount (283 kb) of new, unfinished sequence. Hence, this method works in large and complex genomes and can be applied to any species with sex chromosomes.

  19. Poor socio-economic status in 47,XXX --an unexpected effect of an extra X chromosome.

    Science.gov (United States)

    Stochholm, Kirstine; Juul, Svend; Gravholt, Claus H

    2013-06-01

    One of the most common sex chromosomal abnormalities in females is 47,XXX syndrome, which is characterized by tall stature and reduced IQ, but with a variable phenotype. In order to elaborate on the characteristics of this syndrome, we undertook an investigation in all diagnosed 47,XXX females at risk in Denmark and compared their socio-economic status with an age-matched cohort of the female background population as well as with all Danes diagnosed with Turner syndrome. We focused on cohabitation, motherhoods, income, education, retirement and convictions. Furthermore, we investigated whether some of these parameters influenced the increased mortality identified previously. Thus, socio-economic data were retrieved in 108 47,XXX persons, 10,297 controls, and 831 with Turner syndrome. Comparing the 47,XXX persons with their controls, we identified significantly decreased numbers of first partnership, number of mothers, and number of persons with an education in 47,XXX persons. Significantly more 47,XXX persons retired. In the younger age groups an increased number had income below the median among controls. The increased mortality identified previously was not explained by the reduced number of partnerships or the reduced number of persons with an education. Comparing the 47,XXX persons with Turner syndrome persons, we identified increased number of first partnership, number of mothers, and reduced level of education. We hypothesize that the significantly decreased number of 47,XXX persons becoming mothers could be due to hypogonadism in some. The affected socio-economic status suggests that the presence of an extra X chromosome has more detrimental effects than previously appreciated. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome.

    Science.gov (United States)

    Zhu, D; Alcorn, D M; Antonarakis, S E; Levin, L S; Huang, P C; Mitchell, T N; Warren, A C; Maumenee, I H

    1990-11-01

    There are three types of X-linked cataracts recorded in Mendelian Inheritance in Man (McKusick 1988): congenital total, with posterior sutural opacities in heterozygotes; congenital, with microcornea or slight microphthalmia; and the cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker close to the gene responsible for the NH syndrome, linkage analysis on 36 members in a three-generation pedigree including seven affected males and nine carrier females was performed using 31 DNA markers. A LOD score of 1.662 at theta = 0.16 was obtained with probe 782 from locus DXS85 on Xp22.2-p22.3. Negative LOD scores were found at six loci on the short arm, one distal to DXS85, five proximal, and six probes spanning the long arm were highly negative. These results make the assignment of the locus for NH to the distal end of the short arm of the X chromosome likely.

  1. Premature chromosome condensation following x irradiation of mammalian cells: expression time and dose-response

    International Nuclear Information System (INIS)

    Griffiths, T.D.; Carpenter, J.G.

    1979-01-01

    Premature chromosome condensation (PCC) in Chinese hamster ovary (CHO) cells following exposure to 300-kVp x rays was first detected in the mitosis that followed the second postirradiation S phase. Thus, cells irradiated in G1 first expressed PCC at the second postirradiation mitosis while cells irradiated in G2 did not express PCC until the third postirradiation mitosis. Cells irradiated in the S phase expressed PCC at the second postirradiation mitosis with a frequency that was related to the position of the cells in the S phase at the time of exposure, cells in the first half of the S phase (at the time of exposure) showing a higher frequency than cells positioned in the second half. Thus, DNA replication during the first postirradiation S phase may be involved in the processing of lesions that eventually give rise to PCC. For cells in G1 at the time of exposure, the D/sub o/ for PCC expression at the second postirradiation mitosis was around 825 rad, indicating that PCC may play only a minor role in x-ray-induced cell killing. Autoradiographic analysis indicated approximately 50% of the PCC patches scored were replicating DNA at the time condensation was attempted. Daughter cells derived from such cells would suffer loss of genetic material

  2. Aneuploidy in immortalized human mesenchymal stem cells with non-random loss of chromosome 13 in culture.

    Science.gov (United States)

    Takeuchi, Masao; Takeuchi, Kikuko; Ozawa, Yutaka; Kohara, Akihiro; Mizusawa, Hiroshi

    2009-01-01

    Aneuploidy (an abnormal number of chromosomes) is commonly observed in most human cancer cells, highlighting the need to examine chromosomal instability in tumorigenesis. Previously, the immortalized human mesenchymal stem cell line UE6E7T-3 was shown to undergo a preferential loss of one copy of chromosome 13 after prolonged culture. Here, the loss of chromosome 13 was found to be caused by chromosome missegregation during mitosis, which involved unequal segregation, exclusion of the misaligned chromosome 13 on the metaphase plate, and trapping of chromosome 13 in the midbody region, as observed by fluorescence in situ hybridization. Near-diploid aneuploidy, not tetraploidy, was the direct result. The loss of chromosome 13 was non-random, and was detected by analysis of microsatellites and single nucleotide polymorphism-based loss of heterozygosity (LOH). Of the five microsatellite loci on chromosome 13, four loci showed microsatellite instability at an early stage in culture, and LOH was apparent at a late stage in culture. These results suggest that the microsatellite mutations cause changes in centromere integrity provoking loss of this chromosome in the UE6E7T-3 cell line. Thus, these results support the use of this cell line as a useful model for understanding the mechanism of aneuploid formation in cell cultures.

  3. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    International Nuclear Information System (INIS)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

    1986-01-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

  4. The effects of X-ray energy and an iodine-based contrast agent on chromosome aberrations

    International Nuclear Information System (INIS)

    Matsubara, Sho; Kubota, Nobuo; Katoh, Tsuguhisa; Yoshino, Norio; Sasaki, Takehito; Sasaki, Masao S.

    1994-01-01

    A study was undertaken to evaluate the effect of combining irradiation with X rays of various energies and an iodine-based contrast agent on the induction of chromosome aberrations in the peripheral lymphocytes of blood samples taken from healthy young donors. Although no enhancement of the effect of radiation was induced when blood samples with the iodine-based contrast agent were given 35 kV X irradiation, an 80 kV X-ray exposure induced an enhanced level of chromosome aberrations, and a 250 kV X irradiation, an enhancement of the frequencies of chromosome aberrations was seen in blood samples with the iodine-based contrast agent, especially when a Lucite phantom was employed in studies to increase the scattered rays. It was thus shown by microdosimetric analysis that X irradiation combined with an iodine-based contrast agent causes an enhancement of the absorbed radiation dose, which is dependent on the X-ray energies employed. This phenomenon may have clinical use in the radiotherapeutic management of tumors, although further extensive studies of tumor vascularity must be pursued before this can be applied clinically. 21 refs., 8 figs., 3 tabs

  5. Cloning, chromosome localization and features of a novel human ...

    Indian Academy of Sciences (India)

    We report cloning and some features of a novel human gene, MATH2, which encodes a protein of 337 amino acid residues with a basic helix–loop–helix domain ... State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China ...

  6. The DNA sequence, annotation and analysis of human chromosome 3

    DEFF Research Database (Denmark)

    Muzny, D.M.; Bolund, Lars; As part of the Chinese Human Genome Sequencing Consortium, E.T.A.L.

    2006-01-01

    as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion...

  7. Chromosomal locations of members of a family of novel endogenous human retroviral genomes

    International Nuclear Information System (INIS)

    Horn, T.M.; Huebner, K.; Croce, C.; Callahan, R.

    1986-01-01

    Human cellular DNA contains two distinguishable families of retroviral related sequences. One family shares extensive nucleotide sequence homology with infectious mammalian type C retroviral genomes. The other family contains major regions of homology with the pol genes of infectious type A and B and avian type C and D retroviral genomes. Analysis of the human recombinant clone HLM-2 has shown that the pol gene in the latter family is located within an endogenous proviral genome. The authors show that the proviral genome in HLM-2 and the related recombinant clone HLM-25 are located, respectively, on human chromosomes 1 and 5. Other related proviral genomes are located on chromosomes 7, 8, 11, 14, and 17

  8. Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation

    DEFF Research Database (Denmark)

    Durkin, M E; Loechel, F; Mattei, M G

    1997-01-01

    , heart, lung, skeletal muscle, kidney, and pancreas. The human laminin alpha5-chain gene (LAMA5) was assigned to chromosome 20q13.2-q13.3 by in situ hybridization, and the mouse gene (Lama5) was mapped by linkage analysis to a syntonic region of distal chromosome 2, close to the locus for the ragged (Ra...

  9. Induction of lethal mutations in the x-chromosome of unirradiated Drosophila oocytes after fertilization by irradiated spermatozoa

    International Nuclear Information System (INIS)

    Shaposhnikov, M.V.; Zainullin, V.G.

    2003-01-01

    Full text: In primary study on Drosophila it was found that irradiated male X-chromosomes induce recessive lethals in unirradiated female homologues (Abeleva et al., 1961, Radiobiologya. 1:123-126). The same effects were obtained in Drosophila in some recent investigations. The mechanisms of these effects is unknown. However it may be responsible for low-dose radiation effects as it induce mutations in unirradiated DNA. We assume that this effect may be a result of activation of error prone repair in response to preliminary DNA lesions in irradiated chromosome. In this research we analyse the frequencies of the recessive lethal mutations in the X-chromosome of Drosophila females mated with irradiated Basc males. We used acute irradiation with a dose rate of 10 Gy. For testing our hypothesis we use the mus209 and mei-41 mutant females. Mus209 is a PCNA gene homologue and mei-41 is a homologue of ATM gene. These genes are involved in post-replication DNA repair which may be error prone repair in Drosophila. It was obtained the tendency to decreasing the mutation rate at the mei-41[D5] background and decreasing mutation rate in mus209[B1] background in comparison with wild type strains CS (p<0.05). The obtained results demonstrate the possible role of mus209[B1] and mei-41[D5] genes in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue

  10. Stage specificity and dose-response relationships for chromosome aberrations induced in mouse primary spermatocytes following X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Y.; Tobari, I.; Utsugi, T.

    1986-05-01

    In this study, dose-response relationships were examined for chromosome aberrations observed at diakinesis-metaphase I of spermatocytes with X-irradiation at various stages of meiosis (diplotene, mid-pachytene, zygotene and leptotene). The frequencies of cells with X-ray-induced chromosome aberrations increased with dose at all stages in the applied range of 0.5-3.0 Gy and tended to increase as the irradiated stages descended after leptotene stage. In three stages, the frequencies increased exponentially with dose, but the rates of induction of chromosome breaks were markedly different depending on the stages at which spermatocytes were irradiated with X-rays. The rate of induction was the highest at diplotene and the lowest at leptotene, suggesting that diplotene spermatocytes had the highest radiosensitivity to the induction of chromosome breaks, followed by pachytene, zygotene and leptotene spermatocytes in that order. The dose-response relationships fitted well to linear equations for deletion-type aberrations at each stage, and to linear-quadratic equations for exchange-type aberrations at all stages except for leptotene. At leptotene, the chromatid exchanges were hardly observed, the aberrations being mainly consisted of iso-chromatid fragments. On the contrary, chromatid exchanges and iso-chromatide deletions were mainly observed at later stages (zygotene-diplotene).

  11. Studies on chromosomal aberrations and dominant lethal mutations induced by x irradiation in germ cells of male mice

    International Nuclear Information System (INIS)

    Wang Xianli; Wang Mingdong; Wang Bin; Sun Shuqing

    1992-01-01

    After male mice irradiated by 2 Gy X rays mated to normal virginal females superovulated with PMSG and HCG, pronuclei chromosome spreading of first-cleavage embryos were prepared and chromosomal aberrations of paternal pronuclei were observed. The results showed that the frequen