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Sample records for human chromosomal region

  1. 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.

  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. 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

  4. Identification of a herpes simplex labialis susceptibility region on human chromosome 21.

    Science.gov (United States)

    Hobbs, Maurine R; Jones, Brandt B; Otterud, Brith E; Leppert, Mark; Kriesel, John D

    2008-02-01

    Most of the United States population is infected with either herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, or both. Reactivations of HSV-1 infection cause herpes simplex labialis (HSL; cold sores or fever blisters), which is the most common recurring viral infection in humans. To investigate the possibility of a human genetic component conferring resistance or susceptibility to cold sores (i.e., a HSL susceptibility gene), we conducted a genetic linkage analysis that included serotyping and phenotyping 421 individuals from 39 families enrolled in the Utah Genetic Reference Project. Linkage analysis identified a 2.5-Mb nonrecombinant region of interest on the long arm of human chromosome 21, with a multipoint logarithm of odds score of 3.9 noted near marker abmc65 (D21S409). Nonparametric linkage analysis of the data also provided strong evidence for linkage (P = .0005). This region of human chromosome 21 contains 6 candidate genes for herpes susceptibility. The development of frequent cold sores is associated with a region on the long arm of human chromosome 21. This region contains several candidate genes that could influence the frequency of outbreaks of HSL.

  5. Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli

    OpenAIRE

    Sullivan, Gareth J.; Bridger, Joanna M.; Cuthbert, Andrew P.; Newbold, Robert F.; Bickmore, Wendy A.; McStay, Brian

    2001-01-01

    Human ribosomal gene repeats are distributed among five nucleolar organizer regions (NORs) on the p arms of acrocentric chromosomes. On exit from mitosis, nucleoli form around individual active NORs. As cells progress through the cycle, these mini-nucleoli fuse to form large nucleoli incorporating multiple NORs. It is generally assumed that nucleolar incorporation of individual NORs is dependent on ribosomal gene transcription. To test this assumption, we determined the nuclear location of in...

  6. 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.

  7. 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

  8. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing.

    Directory of Open Access Journals (Sweden)

    Irene Tiemann-Boege

    2006-05-01

    Full Text Available For decades, classical crossover studies and linkage disequilibrium (LD analysis of genomic regions suggested that human meiotic crossovers may not be randomly distributed along chromosomes but are focused instead in "hot spots." Recent sperm typing studies provided data at very high resolution and accuracy that defined the physical limits of a number of hot spots. The data were also used to test whether patterns of LD can predict hot spot locations. These sperm typing studies focused on several small regions of the genome already known or suspected of containing a hot spot based on the presence of LD breakdown or previous experimental evidence of hot spot activity. Comparable data on target regions not specifically chosen using these two criteria is lacking but is needed to make an unbiased test of whether LD data alone can accurately predict active hot spots. We used sperm typing to estimate recombination in 17 almost contiguous ~5 kb intervals spanning 103 kb of human Chromosome 21. We found two intervals that contained new hot spots. The comparison of our data with recombination rates predicted by statistical analyses of LD showed that, overall, the two datasets corresponded well, except for one predicted hot spot that showed little crossing over. This study doubles the experimental data on recombination in men at the highest resolution and accuracy and supports the emerging genome-wide picture that recombination is localized in small regions separated by cold areas. Detailed study of one of the new hot spots revealed a sperm donor with a decrease in recombination intensity at the canonical recombination site but an increase in crossover activity nearby. This unique finding suggests that the position and intensity of hot spots may evolve by means of a concerted mechanism that maintains the overall recombination intensity in the region.

  9. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Lennon, G.G.; Giorgi, D.; Martin, J.R. [Lawrence Livermore National Lab., CA (United States)] [and others

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  10. Utilization of a cloned alphoid repeating sequence of human DNA in the study of polymorphism of chromosomal heterochromatin regions

    International Nuclear Information System (INIS)

    Kruminya, A.R.; Kroshkina, V.G.; Yurov, Yu.B.; Aleksandrov, I.A.; Mitkevich, S.P.; Gindilis, V.M.

    1988-01-01

    The chromosomal distribution of the cloned PHS05 fragment of human alphoid DNA was studied by in situ hybridization in 38 individuals. It was shown that this DNA fraction is primarily localized in the pericentric regions of practically all chromosomes of the set. Significant interchromosomal differences and a weakly expressed interindividual polymorphism were discovered in the copying ability of this class of repeating DNA sequences; associations were not found between the results of hybridization and the pattern of Q-polymorphism

  11. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  12. Isolation of probes specific to human chromosomal region 6p21 from immunoselected irradiation-fusion gene transfer hybrids

    International Nuclear Information System (INIS)

    Ragoussis, J.; Jones, T.A.; Sheer, D.; Shrimpton, A.E.; Goodfellow, P.N.; Trowsdale, J.; Ziegler, A.

    1991-01-01

    A hybrid cell line (R21/B1) containing a truncated human chromosome 6 (6pter-6q21) and a human Y chromosome on a hamster background was irradiated and fused to A23 (TK-) or W3GH (HPRT-) hamster cells. Clones containing expressed HLA class I genes (4/40) were selected using monoclonal antibodies. These clones were recloned and analyzed with a panel of probes from the HLA region. One hybrid (4G6) contained the entire HLA complex. Two other hybrids (4J4 and 4H2) contained only the HLA class I region, while the fourth hybrid (5P9) contained HLA class I and III genes in addition to other genes located in the 6p21 chromosomal region. In situ hybridization showed that the hybrid cells contained more than one fragment of human DNA. Alu and LINE PCR products were derived from these cells and compared to each other as well as to products from two somatic cell hybrids having the 6p21 region in common. The PCR fragments were then screened on conventional Southern blots of the somatic cell hybrids to select a panel of novel probes encompassing the 6p21 region. In addition, the origin of the human DNA fragments in hybrid 4J4 was determined by regional mapping of PCR products

  13. Physical and transcription map of a 25 Mb region on human chromosome 7 (region q21-q22)

    Energy Technology Data Exchange (ETDEWEB)

    Scherer, S. [Univ. of Toronto (Canada)]|[Hosptial for Sick Children, Toronto (Canada); Little, S.; Vandenberg, A. [Hospital for Sick Children, Toronto (Canada)] [and others

    1994-09-01

    We are interested in the q21-q22 region of chromosome 7 because of its implication in a number of diseases. This region of about 25 Mb appears to be involved in ectrodactyly/ectodermal dysplasia/cleft plate (EEC) and split hand/split foot deformity (SHFD1), as well as myelodysplastic syndrome and acute non-lymphocyte leukemia. In order to identify the genes responsible for these and other diseases, we have constructed a physical map of this region. The proximal and distal boundaries of the region were operationally defined by the microsatellite markers D7S660 and D7S692, which are about 35 cM apart. This region between these two markers could be divided into 13 intervals on the basis of chromosome breakpoints contained in somatic cell hybrids. The map positions for 43 additional microsatellite markers and 25 cloned genes were determined with respect to these intervals. A physical map based on contigs of over 250 YACs has also been assembled. While the contigs encompass all of the known genetic markers mapped to the region and almost cover the entire 25-Mb region, there are 3 gaps on the map. One of these gaps spans a set of DNA markers for which no corresponding YAC clones could be identified. To connect the two adjacent contigs we have initiated cosmid walking with a chromosome 7-specific library (Lawrence Livermore Laboratory). A tiling path of 60 contiguous YAC clones has been assembled and used for direct cDNA selection. Over 300 cDNA clones have been isolated and characterized. They are being grouped into transcription units by Northern blot analysis and screening of full-length cDNA libraries. Further, exon amplification and direct cDNA library screening with evolutionarily conserved sequences are being performed for a 1-Mb region spanning the SHFD1 locus to ensure detection of all transcribed sequences.

  14. 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

  15. Comparative mapping of DNA probes derived from the V{sub k} immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, N.; Wienberg, J.; Ermert, K. [Universitaet Muenchen (Germany)] [and others

    1995-03-01

    Fluorescence in situ hybridization (FISH) of cosmid clones of human V{sub K} gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the K locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo Pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V{sub K}I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V{sub K} region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. 18 refs., 2 figs.

  16. 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

  17. Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1.

    Science.gov (United States)

    Jongsma, A P; Burgerhout, W G

    1977-01-01

    Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42.

  18. Isolation of a cosmid sublibrary for a region of chromosome 12 frequently amplified in human cancers using a complex chromosome microdissection probe

    Energy Technology Data Exchange (ETDEWEB)

    Elkahloun, A.G.; Meltzer, P.S.; Guan, Xin-Yuan [National Institutes of Health, Bethesda, MD (United States)] [and others

    1996-02-01

    Chromosome-specific cosmid libraries are in extremely useful resource for positional cloning projects. Once a particular region of interest has been identified, it would be of value to have an approach for isolating chromosome band-specific cosmids that could be assembled into a sublibrary for rapid screening. We constructed a region-specific sublibrary of 700 cosmids by screening a chromosome 12-specific cosmid library with a complex probe generated by degenerate oligonucleotide-primed PCR of a microdissected homogeneously staining region containing sequences amplified from chromosome 12q13-q15. Based on fluorescence in situ hybridization, approximately 60% of the cosmids in the sublibrary were derived from the microdissected region. To demonstrate further the utility of the sublibrary, a 150-kb contig containing the SAS and CDK4 genes was constructed, as well as several additional contigs between CDK4 and MDM2. This study demonstrates the possibility of utilizing probes generated by microdissection for assembling band-specific libraries that are amendable to rapid screening with multiple markers.

  19. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  20. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1

    DEFF Research Database (Denmark)

    Shaposhnikov, Sergey A.; Akopov, Sergey B.; Chernov, Igor P.

    2007-01-01

    There is abundant evidence that the DNA in eukaryotic cells is organized into loop domains that represent basic structural and functional units of chromatin packaging. To explore the DNA domain organization of the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1, we have...... in the region are regulated and of how the structural architecture and functional organization of the DNA are related....... identified a significant portion of the scaffold/matrix attachment regions (S/MARs) within this region. Forty independent putative S/MAR elements were assigned within the 16q22.1 locus. More than 90% of these S/MARs are AT rich, with GC contents as low as 27% in 2 cases. Thirty-nine (98%) of the S...

  1. A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors

    International Nuclear Information System (INIS)

    Sastre-Garau, X.; Couturier, J.; Favre, M.; Orth, G.

    1995-01-01

    The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors. (authors). 29 refs., 2 figs

  2. 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).

  3. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  4. 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.

  5. Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array CGH

    Science.gov (United States)

    Ichimura, Koichi; Mungall, Andrew J; Fiegler, Heike; Pearson, Danita M.; Dunham, Ian; Carter, Nigel P; Collins, V. Peter

    2009-01-01

    Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1780 clones (778 PACs and 1002 BACs) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs. PMID:16205629

  6. 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.

  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. Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia

    NARCIS (Netherlands)

    Mannens, M.; Hoovers, J. M.; Redeker, E.; Verjaal, M.; Feinberg, A. P.; Little, P.; Boavida, M.; Coad, N.; Steenman, M.; Bliek, J.

    1994-01-01

    Cytogenetic and DNA analyses of patients with the Beckwith-Wiedemann syndrome (BWS) enabled us to refine the localization of the syndrome at 11p15.3-pter to two distinct regions. One chromosome region (BWSCR1) is near the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. The other region

  9. 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).

  10. 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

  11. Physical mapping of the Bloom syndrome region by the identification of YAC and P1 clones from human chromosome 15 band q26.1

    Energy Technology Data Exchange (ETDEWEB)

    Straughen, J.; Groden, J. [Univ. of Cincinnati College of Medicine, OH (United States); Ciocci, S. [New York Blood Center, NY (United States)] [and others

    1996-07-01

    The gene for Bloom syndrome (BLM) has been mapped to human chromosome 15 band q26.1 by homozygosity mapping. Further refinement of the location of BLM has relied upon linkage-disequilibrium mapping and somatic intragenic recombination. In combination with these mapping approaches and to identify novel DNA markers and probes for the BLM candidate region, a contiguous representation of the 2-Mb region that contains the BLM gene was generated and is presented here. YAC and P1 clones from the region have been identified and ordered by using previously available genetic markers in the region along with newly developed sequence-tagged sites from radiation-restriction map of the 2-Mb region that allowed estimation of the distance between polymorphic microsatellite loci is also reported. This map and the DNA markers derived from it were instrumental in the recent identification of the BLM gene. 25 refs., 3 figs., 3 tabs.

  12. 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

  13. Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea

    International Nuclear Information System (INIS)

    Hank, Nicole C; Shapiro, Joan Rankin; Scheck, Adrienne C

    2006-01-01

    Glioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented. We have analyzed cells from primary and recurrent tumors from the same patient before and after in vitro selection for resistance to clinically relevant doses of BCNU. Karyotypic analyses were done to demonstrate the genetic makeup of these cells, and fluorescent in situ hybridization analyses have defined the region(s) of chromosome 22 retained in these BCNU-resistant cells. Karyotypic analyses demonstrated that cells selected for BCNU resistance were near-diploid with over-representation of chromosomes 7 and 22. In cells where whole copies of chromosome 22 were not identified, numerous fragments of this chromosome were retained and inserted into several marker and derivative chromosomes. Fluorescent in situ hybridization analyses using whole chromosome paints confirmed this finding. Additional FISH analysis using bacterial artificial chromosome probes spanning the length of chromosome 22 have allowed us to map the over-represented region to 22q12.3–13.32. Cells selected for BCNU resistance either in vivo or in vitro retain sequences mapped to chromosome 22. The specific over-representation of sequences mapped to 22q12.3–13.32 suggest the presence of a DNA sequence important to BCNU survival and/or resistance located in this region of chromosome 22

  14. Analysis of DNA restriction fragments greater than 5.7 Mb in size from the centromeric region of human chromosomes.

    Science.gov (United States)

    Arn, P H; Li, X; Smith, C; Hsu, M; Schwartz, D C; Jabs, E W

    1991-01-01

    Pulsed electrophoresis was used to study the organization of the human centromeric region. Genomic DNA was digested with rare-cutting enzymes. DNA fragments from 0.2 to greater than 5.7 Mb were separated by electrophoresis and hybridized with alphoid and simple DNA repeats. Rare-cutting enzymes (Mlu I, Nar I, Not I, Nru I, Sal I, Sfi I, Sst II) demonstrated fewer restriction sites at centromeric regions than elsewhere in the genome. The enzyme Not I had the fewest restriction sites at centromeric regions. As much as 70% of these sequences from the centromeric region are present in Not I DNA fragments greater than 5.7 and estimated to be as large as 10 Mb in size. Other repetitive sequences such as short interspersed repeated segments (SINEs), long interspersed repeated segments (LINEs), ribosomal DNA, and mini-satellite DNA that are not enriched at the centromeric region, are not enriched in Not I fragments of greater than 5.7 Mb in size.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22

    International Nuclear Information System (INIS)

    Tsai-Pflugfelder, M.; Liu, L.F.; Liu, A.A.; Tewey, K.M.; Whang-Peng, J.; Knutsen, T.; Huebner, K.; Croce, C.M.; Wang, J.C.

    1988-01-01

    Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage λ was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a λgt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the gene was mapped to chromosome 17q21-22 by in situ hybridization of a cloned fragment to metaphase chromosomes and by hybridization analysis with a panel of mouse-human hybrid cell lines, each retaining a subset of human chromosomes

  1. 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

  2. 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...

  3. 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

  4. 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

  5. A Gene Catalogue of the Euchromatic Male-Specific Region of the Horse Y Chromosome: Comparison with Human and Other Mammals

    OpenAIRE

    Paria, Nandina; Raudsepp, Terje; Pearks Wilkerson, Alison J.; O'Brien, Patricia C. M.; Ferguson-Smith, Malcom A.; Love, Charles C.; Arnold, Carolyn; Rakestraw, Peter; Murphy, William J.; Chowdhary, Bhanu P.

    2011-01-01

    Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY) contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY g...

  6. 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

  7. 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)

  8. Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Kere, J. [Washington Univ. School of Medicine, St. Louis, MO (United States)]|[Univ. of Helsinki (Finland); Grzeschik, K.H. [Univ. of Marburg (Germany); Limon, J. [Medical Academy, Gdansk (Poland); Gremaud, M.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States); De La Chapelle, A. [Univ. of Helsinki (Finland)

    1993-05-01

    Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

  9. 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...

  10. A gene catalogue of the euchromatic male-specific region of the horse Y chromosome: comparison with human and other mammals.

    Directory of Open Access Journals (Sweden)

    Nandina Paria

    Full Text Available Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse--an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages.

  11. A gene catalogue of the euchromatic male-specific region of the horse Y chromosome: comparison with human and other mammals.

    Science.gov (United States)

    Paria, Nandina; Raudsepp, Terje; Pearks Wilkerson, Alison J; O'Brien, Patricia C M; Ferguson-Smith, Malcom A; Love, Charles C; Arnold, Carolyn; Rakestraw, Peter; Murphy, William J; Chowdhary, Bhanu P

    2011-01-01

    Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY) contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse--an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages.

  12. Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.

    Directory of Open Access Journals (Sweden)

    Stephanie Kuhn

    Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A

    1998-01-01

    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  2. 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.

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2008-01-01

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

  6. 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.

  7. 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

  8. 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.

  9. 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....

  10. Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes

    International Nuclear Information System (INIS)

    Kelley-Clarke, Brenna; Ballestas, Mary E.; Komatsu, Takashi; Kaye, Kenneth M.

    2007-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes

  11. 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...

  12. 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)

  13. Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): comparisons with human and mouse

    DEFF Research Database (Denmark)

    Khlebodarova, TM; Malchenko, Sergey; Matveeva, NM

    1995-01-01

    Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of mink-rodent hybrid cells. Analysis of segregation...

  14. LINKAGE ANALYSIS OF KERATOSIS FOLLICULARIS SPINULOSA DECALVANS, AND REGIONAL ASSIGNMENT TO HUMAN-CHROMOSOME XP21.2-P22.2

    NARCIS (Netherlands)

    Oosterwijk, JC; NELEN, M; VANZANDVOORT, PM; VANOSCH, LDM; ORANJE, AP; WITTEBOPOST, D; VANOOST, BA

    Keratosis follicularis spinulosa decalvans (KFSD) is a rare X-chromosomal disorder. It consists of follicular hyperkeratosis of the skin, scarring alopecia of the scalp, absence of the eyebrows, and corneal degeneration. There is photophobia in childhood, but the symptoms tend to diminish after

  15. 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

  16. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms.

    Directory of Open Access Journals (Sweden)

    James A Fraser

    2004-12-01

    Full Text Available Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen Cryptococcus revealed sequential evolutionary events that fashioned this large, highly unusual region. We hypothesize that MAT evolved via four main steps, beginning with acquisition of genes into two unlinked sex-determining regions, forming independent gene clusters that then fused via chromosomal translocation. A transitional tripolar intermediate state then converted to a bipolar system via gene conversion or recombination between the linked and unlinked sex-determining regions. MAT was subsequently subjected to intra- and interallelic gene conversion and inversions that suppress recombination. These events resemble those that shaped mammalian sex chromosomes, illustrating convergent evolution in sex-determining structures in the animal and fungal kingdoms.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Delineation and analysis of chromosomal regions specifying Yersinia pestis.

    Science.gov (United States)

    Derbise, Anne; Chenal-Francisque, Viviane; Huon, Christèle; Fayolle, Corinne; Demeure, Christian E; Chane-Woon-Ming, Béatrice; Médigue, Claudine; Hinnebusch, B Joseph; Carniel, Elisabeth

    2010-09-01

    Yersinia pestis, the causative agent of plague, has recently diverged from the less virulent enteropathogen Yersinia pseudotuberculosis. Its emergence has been characterized by massive genetic loss and inactivation and limited gene acquisition. The acquired genes include two plasmids, a filamentous phage, and a few chromosomal loci. The aim of this study was to characterize the chromosomal regions acquired by Y. pestis. Following in silico comparative analysis and PCR screening of 98 strains of Y. pseudotuberculosis and Y. pestis, we found that eight chromosomal loci (six regions [R1pe to R6pe] and two coding sequences [CDS1pe and CDS2pe]) specified Y. pestis. Signatures of integration by site specific or homologous recombination were identified for most of them. These acquisitions and the loss of ancestral DNA sequences were concentrated in a chromosomal region opposite to the origin of replication. The specific regions were acquired very early during Y. pestis evolution and were retained during its microevolution, suggesting that they might bring some selective advantages. Only one region (R3pe), predicted to carry a lambdoid prophage, is most likely no longer functional because of mutations. With the exception of R1pe and R2pe, which have the potential to encode a restriction/modification and a sugar transport system, respectively, no functions could be predicted for the other Y. pestis-specific loci. To determine the role of the eight chromosomal loci in the physiology and pathogenicity of the plague bacillus, each of them was individually deleted from the bacterial chromosome. None of the deletants exhibited defects during growth in vitro. Using the Xenopsylla cheopis flea model, all deletants retained the capacity to produce a stable and persistent infection and to block fleas. Similarly, none of the deletants caused any acute flea toxicity. In the mouse model of infection, all deletants were fully virulent upon subcutaneous or aerosol infections. Therefore

  3. 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)

  4. 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...

  5. 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

  6. 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.

  7. Comparative mapping in the beige-satin region of mouse chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Perou, C.M.; Pryor, R.; Kaplan, J. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)] [and others

    1997-01-15

    The proximal end of mouse chromosome (Chr) 13 contains regions conserved on human chromosomes 1q42-q44, 6p23-p21, and 7p22-p13. This region also contains mutations that may be models for human disease, including beige (human Chediak-Higashi syndrome). An interspecific backcross of SB/Le and Mus spretus mice was used to generate a molecular genetic linkage map of mouse chromosome 13 with an emphasis on the proximal region including beige (bg) and satin (sa). This map provides the gene order of the two phenotypic markers bg and sa relative to restriction fragment length polymorphisms and simple sequence length polymorphisms in 131 backcross animals. In parallel, we have created a physical map of the region using Nidogen (Nid) as a molecular starting point for cloning a YAC contig that was used to identify the beige gene. The physical map provides the fine-structure order of genes and anonymous DNA fragments that was not resolved by the genetic linkage mapping. The results show that the bg region of mouse Chr 13 is highly conserved on human Chr 1q42-q44 and provide a starting point for a complete functional analysis of the entire bg-sa interval. 37 refs., 4 figs., 1 tab.

  8. 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.

  9. Evolution of the DAZ gene and the AZFc region on primate Y chromosomes

    Directory of Open Access Journals (Sweden)

    Yu Jane-Fang

    2008-03-01

    Full Text Available Abstract Background The Azoospermia Factor c (AZFc region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates. Results The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution. Conclusion The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.

  10. 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)

  11. 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.

  12. 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

  13. 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

  14. B chromosomes are associated with redistribution of genetic recombination towards lower recombination chromosomal regions in perennial ryegrass.

    Science.gov (United States)

    Harper, John; Phillips, Dylan; Thomas, Ann; Gasior, Dagmara; Evans, Caron; Powell, Wayne; King, Julie; King, Ian; Jenkins, Glyn; Armstead, Ian

    2018-04-09

    Supernumerary 'B' chromosomes are non-essential components of the genome present in a range of plant and animal species-including many grasses. Within diploid and polyploid ryegrass and fescue species, including the forage grass perennial ryegrass (Lolium perenne L.), the presence of B chromosomes has been reported as influencing both chromosome pairing and chiasma frequencies. In this study, the effects of the presence/absence of B chromosomes on genetic recombination has been investigated through generating DArT (Diversity Arrays Technology) marker genetic maps for six perennial ryegrass diploid populations, the pollen parents of which contained either two B or zero B chromosomes. Through genetic and cytological analyses of these progeny and their parents, we have identified that, while overall cytological estimates of chiasma frequencies were significantly lower in pollen mother cells with two B chromosomes as compared with zero B chromosomes, the recombination frequencies within some marker intervals were actually increased, particularly for marker intervals in lower recombination regions of chromosomes, namely pericentromeric regions. Thus, in perennial ryegrass, the presence of two B chromosomes redistributed patterns of meiotic recombination in pollen mother cells in ways which could increase the range of allelic variation available to plant breeders.

  15. 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...

  16. 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.

  17. 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.

  18. [Chromosomal variation in Chironomus plumosus L. (Diptera, Chironomidae) from populations of Bryansk region, Saratov region (Russia), and Gomel region (Belarus)].

    Science.gov (United States)

    Belyanina, S I

    2015-02-01

    Cytogenetic analysis was performed on samples of Chironomus plumosus L. (Diptera, Chironomidae) taken from waterbodies of various types in Bryansk region (Russia) and Gomel region (Belarus). Karyotypes of specimens taken from stream pools of the Volga were used as reference samples. The populations of Bryansk and Gomel regions (except for a population of Lake Strativa in Starodubskii district, Bryansk region) exhibit broad structural variation, including somatic mosaicism for morphotypes of the salivary gland chromosome set, decondensation of telomeric sites, and the presence of small structural changes, as opposed to populations of Saratov region. As compared with Saratov and Bryansk regions, the Balbiani ring in the B-arm of chromosome I is repressed in populations of Gomel region. It is concluded that the chromosome set of Ch. plumosus in a range of waterbodies of Bryansk and Gomel regions is unstable.

  19. 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

  20. Small chromosomal regions position themselves autonomously according to their chromatin class.

    Science.gov (United States)

    van de Werken, Harmen J G; Haan, Josien C; Feodorova, Yana; Bijos, Dominika; Weuts, An; Theunis, Koen; Holwerda, Sjoerd J B; Meuleman, Wouter; Pagie, Ludo; Thanisch, Katharina; Kumar, Parveen; Leonhardt, Heinrich; Marynen, Peter; van Steensel, Bas; Voet, Thierry; de Laat, Wouter; Solovei, Irina; Joffe, Boris

    2017-06-01

    The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes. © 2017 van de Werken et al.; Published by Cold Spring Harbor Laboratory Press.

  1. 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

  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. 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.

  4. Replication pattern of the pericentromeric region of chromosome 10q and expression of the RET protooncogene.

    Science.gov (United States)

    Cinti, R; Schena, F; Passalacqua, M; Ceccherini, I; Ravazzolo, R

    2004-08-15

    Regulation of the RET gene is highly specific during embryo development and is strictly tissue-specific. Control of transcription depends on mechanisms influenced by epigenetic processes, in particular, histone acetylation at regions flanking the 5' end of the gene. Since the RET gene is mapped in the pericentromeric region of the human chromosome 10, the implication of epigenetic processes is even more striking and worth to be investigated in an extended chromosomal tract. One experimental approach to study the chromatin status in relationship with gene transcription is to assess the replication timing, which we did by using fluorescent in situ hybridization in cells expressing or not expressing the RET gene. By using probes spanning a 700-kb genomic region from the RET locus toward the centromere, we found a relationship between RET expression and early replication. Different patterns were observed between cells naturally expressing RET and cells induced to expression of RET by treatment with sodium butyrate, an inhibitor of histone deacetylases. Three-dimensional analysis of the nuclear localization of fluorescent signals by confocal microscopy showed difference of localization between the RET probe and a probe for a housekeeping gene, G3PDH, located at 12p13.3, in cells that do not express RET, in accordance with previous data for other genes and chromosomal regions. However, RET-expressing cells showed a localization of signals which was not consistent with that expected for expressed genes.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Novel transcripts discovered by mining genomic DNA from defined regions of bovine chromosome 6

    Directory of Open Access Journals (Sweden)

    Eberlein Annett

    2009-04-01

    Full Text Available Abstract Background Linkage analyses strongly suggest a number of QTL for production, health and conformation traits in the middle part of bovine chromosome 6 (BTA6. The identification of the molecular background underlying the genetic variation at the QTL and subsequent functional studies require a well-annotated gene sequence map of the critical QTL intervals. To complete the sequence map of the defined subchromosomal regions on BTA6 poorly covered with comparative gene information, we focused on targeted isolation of transcribed sequences from bovine bacterial artificial chromosome (BAC clones mapped to the QTL intervals. Results Using the method of exon trapping, 92 unique exon trapping sequences (ETS were discovered in a chromosomal region of poor gene coverage. Sequence identity to the current NCBI sequence assembly for BTA6 was detected for 91% of unique ETS. Comparative sequence similarity search revealed that 11% of the isolated ETS displayed high similarity to genomic sequences located on the syntenic chromosomes of the human and mouse reference genome assemblies. Nearly a third of the ETS identified similar equivalent sequences in genomic sequence scaffolds from the alternative Celera-based sequence assembly of the human genome. Screening gene, EST, and protein databases detected 17% of ETS with identity to known transcribed sequences. Expression analysis of a subset of the ETS showed that most ETS (84% displayed a distinctive expression pattern in a multi-tissue panel of a lactating cow verifying their existence in the bovine transcriptome. Conclusion The results of our study demonstrate that the exon trapping method based on region-specific BAC clones is very useful for targeted screening for novel transcripts located within a defined chromosomal region being deficiently endowed with annotated gene information. The majority of identified ETS represents unknown noncoding sequences in intergenic regions on BTA6 displaying a

  14. 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.

  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. 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.

  17. 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.

  18. 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)

  19. Isolation of anonymous, polymorphic DNA fragments from human chromosome 22q12-qter

    NARCIS (Netherlands)

    J.P. Dumanski (Jan); A.H.M. Geurts van Kessel (Ad); M. Ruttledge (Martin); A. Wladis (Andreas); N. Sugawa (Noriaki); V.P. Collins (Peter); M. Nordenskjöld

    1990-01-01

    textabstractA series of 195 random chromosome 22-specific probes, equivalent to approximately 1% of the size of this chromosome, have been isolated from a chromosome 22-specific bacteriophage lambda genomic library. These probes were mapped to four different regions of chromosome 22 on a panel of

  20. 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.

  1. 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.

  2. 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.

  3. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1...... using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways....

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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....

  9. 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

  10. 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

  11. 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.

  12. A revised root for the human Y chromosomal phylogenetic tree: the origin of patrilineal diversity in Africa.

    Science.gov (United States)

    Cruciani, Fulvio; Trombetta, Beniamino; Massaia, Andrea; Destro-Bisol, Giovanni; Sellitto, Daniele; Scozzari, Rosaria

    2011-06-10

    To shed light on the structure of the basal backbone of the human Y chromosome phylogeny, we sequenced about 200 kb of the male-specific region of the human Y chromosome (MSY) from each of seven Y chromosomes belonging to clades A1, A2, A3, and BT. We detected 146 biallelic variant sites through this analysis. We used these variants to construct a patrilineal tree, without taking into account any previously reported information regarding the phylogenetic relationships among the seven Y chromosomes here analyzed. There are several key changes at the basal nodes as compared with the most recent reference Y chromosome tree. A different position of the root was determined, with important implications for the origin of human Y chromosome diversity. An estimate of 142 KY was obtained for the coalescence time of the revised MSY tree, which is earlier than that obtained in previous studies and easier to reconcile with plausible scenarios of modern human origin. The number of deep branchings leading to African-specific clades has doubled, further strengthening the MSY-based evidence for a modern human origin in the African continent. An analysis of 2204 African DNA samples showed that the deepest clades of the revised MSY phylogeny are currently found in central and northwest Africa, opening new perspectives on early human presence in the continent. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. 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)

  14. 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

  15. 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.

  16. [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.

  17. 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

  18. Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints

    International Nuclear Information System (INIS)

    Croce, C.M.; Huebner, K.; Isobe, M.; Fainstain, E.; Lifshitz, B.; Shtivelman, E.; Canaani, E.

    1987-01-01

    A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the other contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kikobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin λ light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph 1 ). Similarly, in mouse-human hybrids retaining a Ph 1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q + and 22, only BCR2 and BCR4 loci are retained. Thus, the order of loci on chromosome 22 is centromere → BCR2, BCR4, and IGL → BCR1 → BCR3 → SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph 1 chromosome

  19. The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24

    NARCIS (Netherlands)

    Baas, F.; Bikker, H.; Geurts van Kessel, A.; Melsert, R.; Pearson, P. L.; de Vijlder, J. J.; van Ommen, G. J.

    1985-01-01

    The human thyroglobulin (Tg) gene is localized to chromosome 8 and regionally to band q24 as shown independently by both in situ hybridization techniques and Southern blot analysis of human-rodent somatic cell hybrids. Analysis of hybrids derived from a Burkitt lymphoma, with a translocation

  20. Interphase Chromosome Conformation and Chromatin-Chromatin Interactions in Human Epithelial Cells Cultured Under Different Gravity Conditions

    Science.gov (United States)

    Zhang, Ye; Wong, Michael; Hada, Megumi; Wu, Honglu

    2015-01-01

    Microgravity has been shown to alter global gene expression patterns and protein levels both in cultured cells and animal models. It has been suggested that the packaging of chromatin fibers in the interphase nucleus is closely related to genome function, and the changes in transcriptional activity are tightly correlated with changes in chromatin folding. This study explores the changes of chromatin conformation and chromatin-chromatin interactions in the simulated microgravity environment, and investigates their correlation to the expression of genes located at different regions of the chromosome. To investigate the folding of chromatin in interphase under various culture conditions, human epithelial cells, fibroblasts, and lymphocytes were fixed in the G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome as separate colors. After images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multi-mega base pair scale. In order to determine the effects of microgravity on chromosome conformation and orientation, measures such as distance between homologous pairs, relative orientation of chromosome arms about a shared midpoint, and orientation of arms within individual chromosomes were all considered as potentially impacted by simulated microgravity conditions. The studies revealed non-random folding of chromatin in interphase, and suggested an association of interphase chromatin folding with radiation-induced chromosome aberration hotspots. Interestingly, the distributions of genes with expression changes over chromosome 3 in cells cultured under microgravity environment are apparently clustered on specific loci and chromosomes. This data provides important insights into how mammalian cells respond to microgravity at molecular level.

  1. Chromosomal location and gene paucity of the male specific region on papaya Y chromosome

    Czech Academy of Sciences Publication Activity Database

    Yu, Q.; Hou, S.; Hobza, Roman; Feltus, F.A.; Wang, X.; Jin, W.; Skelton, R.L.; Blas, A.; Lemke, C.; Saw, J.H.; Moore, P.H.; Alam, M.; Jiang, J.; Paterson, A.H.; Vyskot, Boris; Ming, R.

    2007-01-01

    Roč. 278, č. 2 (2007), s. 177-185 ISSN 1617-4615 R&D Projects: GA ČR(CZ) GA521/06/0056 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Carica papaya * repetitive sequences * sex chromosome Subject RIV: BO - Biophysics Impact factor: 2.978, year: 2007

  2. 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.

  3. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

    Directory of Open Access Journals (Sweden)

    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  4. Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered

    International Nuclear Information System (INIS)

    Finver, S.N.; Nishikura, K.; Finger, L.R.; Haluska, F.G.; Finan, J.; Nowell, P.C.; Croce, C.M.

    1988-01-01

    The authors cloned the translocation-associated and homologous normal MYC alleles from SKW-3, a leukemia T-cell line with the t(8; 14)(q24; q11) translocation, and determined the sequence of the MYC oncogene first exon and flanking 5' putative regulatory regions. S1 nuclease protection experiments utilizing a MYC first exon probe demonstrated transcriptional deregulation of the MYC gene associated with the T-cell receptor α locus on the 8q + chromosome of SKW-3 cells. Nucleotide sequence analysis of the translocation-associated (8q +) MYC allele identified a single base substitution within the upstream flanking region; the homologous nontranslocated allele contained an additional substitution and a two-base deletion. None of the deletions or substitutions localized to putative 5' regulatory regions. The MYC first exon sequence was germ line in both alleles. These results demonstrate that alterations within the putative 5' MYC regulatory regions are not necessarily involved in MYC deregulation in T-cell leukemias, and they show that juxtaposition of the T-cell receptor α locus to a germ-line MYC oncogene results in MYC deregulation

  5. The terminal region of the E. coli chromosome localises at the periphery of the nucleoid

    Directory of Open Access Journals (Sweden)

    Stouf Mathieu

    2011-02-01

    Full Text Available Abstract Background Bacterial chromosomes are organised into a compact and dynamic structures termed nucleoids. Cytological studies in model rod-shaped bacteria show that the different regions of the chromosome display distinct and specific sub-cellular positioning and choreographies during the course of the cell cycle. The localisation of chromosome loci along the length of the cell has been described. However, positioning of loci across the width of the cell has not been determined. Results Here, we show that it is possible to assess the mean positioning of chromosomal loci across the width of the cell using two-dimension images from wide-field fluorescence microscopy. Observed apparent distributions of fluorescent-tagged loci of the E. coli chromosome along the cell diameter were compared with simulated distributions calculated using a range of cell width positioning models. Using this method, we detected the migration of chromosome loci towards the cell periphery induced by production of the bacteriophage T4 Ndd protein. In the absence of Ndd production, loci outside the replication terminus were located either randomly along the nucleoid width or towards the cell centre whereas loci inside the replication terminus were located at the periphery of the nucleoid in contrast to other loci. Conclusions Our approach allows to reliably observing the positioning of chromosome loci along the width of E. coli cells. The terminal region of the chromosome is preferentially located at the periphery of the nucleoid consistent with its specific roles in chromosome organisation and dynamics.

  6. 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

  7. 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

  8. Analysis of the conservation of synteny between Fugu and human chromosome 12

    Directory of Open Access Journals (Sweden)

    Koop Ben F

    2003-07-01

    Full Text Available Abstract Background The pufferfish Fugu rubripes (Fugu with its compact genome is increasingly recognized as an important vertebrate model for comparative genomic studies. In particular, large regions of conserved synteny between human and Fugu genomes indicate its utility to identify disease-causing genes. The human chromosome 12p12 is frequently deleted in various hematological malignancies and solid tumors, but the actual tumor suppressor gene remains unidentified. Results We investigated approximately 200 kb of the genomic region surrounding the ETV6 locus in Fugu (fETV6 in order to find conserved functional features, such as genes or regulatory regions, that could give insight into the nature of the genes targeted by deletions in human cancer cells. Seven genes were identified near the fETV6 locus. We found that the synteny with human chromosome 12 was conserved, but extensive genomic rearrangements occurred between the Fugu and human ETV6 loci. Conclusion This comparative analysis led to the identification of previously uncharacterized genes in the human genome and some potentially important regulatory sequences as well. This is a good indication that the analysis of the compact Fugu genome will be valuable to identify functional features that have been conserved throughout the evolution of vertebrates.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

    DEFF Research Database (Denmark)

    Ebert, Grit; Steininger, Anne; Weißmann, Robert

    2014-01-01

    of the Williams-Beuren syndrome locus we demonstrate by cross-species comparison that these SDs have inserted at the borders of a topological domain and that they flank regions with distinct DNA conformation. CONCLUSIONS: Our study suggests a link of nuclear architecture and the propagation of SDs across......BACKGROUND: Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which can lead to structural variants and genomic disorders...... chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome....

  14. 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

  15. 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

  16. 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

  17. Genetic integrity of the human Y chromosome exposed to groundwater arsenic

    Directory of Open Access Journals (Sweden)

    Ali Sher

    2010-08-01

    Full Text Available Abstract Background Arsenic is a known human carcinogen reported to cause chromosomal deletions and genetic anomalies in cultured cells. The vast human population inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to critical levels of arsenic present in the groundwater. The genetic and physiological mechanism of arsenic toxicity in the human body is yet to be fully established. In addition, lack of animal models has made work on this line even more challenging. Methods Human male blood samples were collected with their informed consent from 5 districts in West Bengal having groundwater arsenic level more than 50 μg/L. Isolation of genomic DNA and preparation of metaphase chromosomes was done using standard protocols. End point PCR was performed for established sequence tagged sites to ascertain the status of recombination events. Single nucleotide variants of candidate genes and amplicons were carried out using appropriate restriction enzymes. The copy number of DYZ1 array per haploid genome was calculated using real time PCR and its chromosomal localization was done by fluorescence in-situ hybridization (FISH. Results We studied effects of arsenic exposure on the human Y chromosome in males from different areas of West Bengal focusing on known recombination events (P5-P1 proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3, single nucleotide variants (SNVs of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY and the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1 repeat arrays was analyzed. Barring a few microdeletions, no major changes were detected in blood DNA samples. SNV analysis showed a difference in some alleles. Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some males. Conclusions Our Y chromosome analysis suggests that the same is protected from the effects of arsenic by some unknown mechanisms maintaining its structural and functional

  18. 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

  19. [Late-replicating regions in salivary gland polytene chromosomes of Drosophila melanogaster].

    Science.gov (United States)

    Kolesnikov, T D; Andreenkova, N G; Beliaeva, E S; Goncharov, F P; Zykova, T Iu; Boldyreva, L V; Pokholkova, g V; Zhimulev, I F

    2013-01-01

    About 240 specific regions that are replicated at the very end of the S-phase have been identified in D. melanogaster polytene chromosomes. These regions have a repressive chromatine state, low gene density, long intergenic distances and are enriched in tissue specific genes. In polytene chromosomes, about a quarter of these regions have no enough time to complete replication. As a result, underreplication zones represented by fewer DNA copy number, appear. We studied 60 chromosome regions that demonstrated the most pronounced under-replication. By comparing the location of these regions on a molecular map with syntenic blocks found earlier for Drosophila species by von Grotthuss et al., 2010, we have shown that across the genus Drosophila, these regions tend to have conserved gene order. This forces us to assume the existence of evolutionary mechanisms aimed at maintaining the integrity of these regions.

  20. 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)

  1. 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 ...

  2. Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

    Science.gov (United States)

    Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

    2009-10-01

    Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

  3. 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....

  4. The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3.

    Science.gov (United States)

    Sims, K B; Lebo, R V; Benson, G; Shalish, C; Schuback, D; Chen, Z Y; Bruns, G; Craig, I W; Golbus, M S; Breakefield, X O

    1992-05-01

    Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.

  5. 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.

  6. Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells

    Science.gov (United States)

    Jia, Pingping; Chastain, Megan; Zou, Ying; Her, Chengtao

    2017-01-01

    Abstract Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI. Moreover, TSI requires telomerase activity but is independent of the functional status of p53 and Rb. Lastly, we show that TSI is associated with chromosome instabilities including chromosome loss, micronuclei formation and chromosome breakage that are further elevated by replication stress. Our studies uncover a novel link between MLH1, telomerase, telomere and genome stability. PMID:28180301

  7. Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B

    International Nuclear Information System (INIS)

    Brown-Shimer, S.; Johnson, K.A.; Bruskin, A.; Green, N.R.; Hill, D.E.; Lawrence, J.B.; Johnson, C.

    1990-01-01

    The inactivation of growth suppressor genes appears to play a major role in the malignant process. To assess whether protein phosphotyrosyl phosphatases function as growth suppressors, the authors have isolated a cDNA clone encoding human protein phosphotyrosyl phosphatase 1B for structural and functional characterization. The translation product deduced from the 1,305-nucleotide open reading frame predicts a protein containing 435 amino acids and having a molecular mass of 49,966 Da. The amino-terminal 321 amino acids deduced from the cDNA sequence are identical to the empirically determined sequence of protein phosphotyrosyl phosphatase 1B. A genomic clone has been isolated and used in an in situ hybridization to banded metaphase chromosomes to determine that the gene encoding protein phosphotyrosyl phosphatase 1B maps as a single-copy gene to the long arm of chromosome 20 in the region q13.1-q13.2

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

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

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

  10. 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

  11. 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...

  12. 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

  13. Geographic stratification of linkage disequilibrium: a worldwide population study in a region of chromosome 22

    Directory of Open Access Journals (Sweden)

    González-Neira Anna

    2004-11-01

    Full Text Available Abstract Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America. The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD.

  14. Genetic analysis of autoimmune sialadenitis in nonobese diabetic mice: a major susceptibility region on chromosome 1.

    Science.gov (United States)

    Boulard, Olivier; Fluteau, Guy; Eloy, Laure; Damotte, Diane; Bedossa, Pierre; Garchon, Henri-Jean

    2002-04-15

    The nonobese diabetic (NOD) mouse strain provides a good study model for Sjögren's syndrome (SS). The genetic control of SS was investigated in this model using different matings, including a (NOD x C57BL/6 (B6))F(2) cross, a (NOD x NZW)F(2) cross, and ((NOD x B6) x NOD) backcross. Multiple and different loci were detected depending on parent strain combination and sex. Despite significant complexity, two main features were prominent. First, the middle region of chromosome 1 (chr.1) was detected in all crosses. Its effect was most visible in the (NOD x B6)F(2) cross and dominated over that of other loci, including those mapping on chr.8, 9, 10, and 16; the effect of these minor loci was observed only in the absence of the NOD haplotype on chr.1. Most critically, the chr.1 region was sufficient to trigger an SS-like inflammatory infiltrate of salivary glands as shown by the study of a new C57BL/6 congenic strain carrying a restricted segment derived from NOD chr.1. Second, several chromosomal regions were previously associated with NOD autoimmune phenotypes, including Iddm (chr.1, 2, 3, 9, and 17, corresponding to Idd5, Idd13, Idd3, Idd2, and Idd1, respectively), accounting for the strong linkage previously reported between insulitis and sialitis, and autoantibody production (chr.10 and 16, corresponding to Bana2 and Bah2, respectively). Interestingly, only two loci were detected in the (NOD x NZW)F(2) cross, on chr.1 in females and on chr.7 in males, probably because of the latent autoimmune predisposition of the NZW strain. Altogether these findings reflect the complexity and heterogeneity of human SS.

  15. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular...

  16. Human Y chromosome copy number variation in the next generation sequencing era and beyond.

    Science.gov (United States)

    Massaia, Andrea; Xue, Yali

    2017-05-01

    The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

  17. Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion.

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    Laurits Skov

    2017-08-01

    Full Text Available The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP and indel variation on the Y chromosome tree is called very accurately. This includes variation called in a 0.9 Mb centromeric heterochromatic region, which is by far the most variable in the Y chromosome. Among the variation is also longer sequence-stretches not present in the reference genome but shared with the chimpanzee Y chromosome. We analyzed 2.7 Mb of large inverted repeats (palindromes for variation patterns among the two palindrome arms and identified 603 mutation and 416 gene conversions events. We find clear evidence for GC-biased gene conversion in the palindromes (and a balancing AT mutation bias, but irrespective of this, also a strong bias towards gene conversion towards the ancestral state, suggesting that palindromic gene conversion may alleviate Muller's ratchet. Finally, we also find a large number of large-scale gene duplications and deletions in the palindromic regions (at least 24 and find that such events can consist of complex combinations of simultaneous insertions and deletions of long stretches of the Y chromosome.

  18. Chromosomal clustering of a human transcriptome reveals regulatory background

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    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.

  19. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health.

    Science.gov (United States)

    Wood, Michael L; Royle, Nicola J

    2017-07-12

    Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease.

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

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    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.

  1. 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

  2. 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.

  3. Cytogenetic and molecular genetic characterization of immortalized human ovarian surface epithelial cell lines: consistent loss of chromosome 13 and amplification of chromosome 20.

    Science.gov (United States)

    Jin, Yuesheng; Zhang, Hao; Tsao, Sai Wah; Jin, Charlotte; Lv, Mei; Strömbeck, Bodil; Wiegant, Joop; Wan, Thomas Shek Kong; Yuen, Po Wing; Kwong, Yok-Lam

    2004-01-01

    This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the hsrs were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis.

  4. Whole Genome Scan to Detect Chromosomal Regions Affecting Multiple Traits in Dairy Cattle

    NARCIS (Netherlands)

    Schrooten, C.; Bink, M.C.A.M.; Bovenhuis, H.

    2004-01-01

    Chromosomal regions affecting multiple traits ( multiple trait quantitative trait regions or MQR) in dairy cattle were detected using a method based on results from single trait analyses to detect quantitative trait loci (QTL). The covariance between contrasts for different traits in single trait

  5. Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Lidsky, A.S.; Law, M.L.; Morse, H.G.; Kao, F.T.; Rabin, M.; Ruddle, F.H.; Woo, S.L.C.

    1985-09-01

    Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. To define the regional map position of the disease locus and the PAH gene on human chromosome 12, DNA was isolated from human-hamster somatic cell hybrids with various deletions of human chromosome 12 and was analyzed by Southern blot analysis using the human cDNA PAH clone as a hybridization probe. From these results, together with detailed biochemical and cytogenetic characterization of the hybrid cells, the region on chromosome 12 containing the human PAH gene has been defined as 12q14.3..-->..qter. The PAH map position on chromosome 12 was further localized by in situ hybridization of /sup 125/I-labeled human PAH cDNA to chromosomes prepared from a human lymphoblastoid cell line. Results of these experiments demonstrated that the region on chromosome 12 containing the PAH gene and the PKU locus in man is 12q22..-->..12q24.1. These results not only provide a regionalized map position for a major human disease locus but also can serve as a reference point for linkage analysis with other DNA markers on human chromosome 12.

  6. Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome

    International Nuclear Information System (INIS)

    Lidsky, A.S.; Law, M.L.; Morse, H.G.; Kao, F.T.; Rabin, M.; Ruddle, F.H.; Woo, S.L.C.

    1985-01-01

    Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. To define the regional map position of the disease locus and the PAH gene on human chromosome 12, DNA was isolated from human-hamster somatic cell hybrids with various deletions of human chromosome 12 and was analyzed by Southern blot analysis using the human cDNA PAH clone as a hybridization probe. From these results, together with detailed biochemical and cytogenetic characterization of the hybrid cells, the region on chromosome 12 containing the human PAH gene has been defined as 12q14.3→qter. The PAH map position on chromosome 12 was further localized by in situ hybridization of 125 I-labeled human PAH cDNA to chromosomes prepared from a human lymphoblastoid cell line. Results of these experiments demonstrated that the region on chromosome 12 containing the PAH gene and the PKU locus in man is 12q22→12q24.1. These results not only provide a regionalized map position for a major human disease locus but also can serve as a reference point for linkage analysis with other DNA markers on human chromosome 12

  7. Construction of physical maps for the sex-specific regions of papaya sex chromosomes

    Directory of Open Access Journals (Sweden)

    Na Jong-Kuk

    2012-05-01

    Full Text Available Abstract Background Papaya is a major fruit crop in tropical and subtropical regions worldwide. It is trioecious with three sex forms: male, female, and hermaphrodite. Sex determination is controlled by a pair of nascent sex chromosomes with two slightly different Y chromosomes, Y for male and Yh for hermaphrodite. The sex chromosome genotypes are XY (male, XYh (hermaphrodite, and XX (female. The papaya hermaphrodite-specific Yh chromosome region (HSY is pericentromeric and heterochromatic. Physical mapping of HSY and its X counterpart is essential for sequencing these regions and uncovering the early events of sex chromosome evolution and to identify the sex determination genes for crop improvement. Results A reiterate chromosome walking strategy was applied to construct the two physical maps with three bacterial artificial chromosome (BAC libraries. The HSY physical map consists of 68 overlapped BACs on the minimum tiling path, and covers all four HSY-specific Knobs. One gap remained in the region of Knob 1, the only knob structure shared between HSY and X, due to the lack of HSY-specific sequences. This gap was filled on the physical map of the HSY corresponding region in the X chromosome. The X physical map consists of 44 BACs on the minimum tiling path with one gap remaining in the middle, due to the nature of highly repetitive sequences. This gap was filled on the HSY physical map. The borders of the non-recombining HSY were defined genetically by fine mapping using 1460 F2 individuals. The genetically defined HSY spanned approximately 8.5 Mb, whereas its X counterpart extended about 5.4 Mb including a 900 Kb region containing the Knob 1 shared by the HSY and X. The 8.5 Mb HSY corresponds to 4.5 Mb of its X counterpart, showing 4 Mb (89% DNA sequence expansion. Conclusion The 89% increase of DNA sequence in HSY indicates rapid expansion of the Yh chromosome after genetic recombination was suppressed 2–3 million years ago. The

  8. Chromosomal mutations and chromosome loss measured in a new human-hamster hybrid cell line, ALC: studies with colcemid, ultraviolet irradiation, and 137Cs gamma-rays

    Science.gov (United States)

    Kraemer, S. M.; Waldren, C. A.; Chatterjee, A. (Principal Investigator)

    1997-01-01

    Small mutations, megabase deletions, and aneuploidy are involved in carcinogenesis and genetic defects, so it is important to be able to quantify these mutations and understand mechanisms of their creation. We have previously quantified a spectrum of mutations, including megabase deletions, in human chromosome 11, the sole human chromosome in a hamster-human hybrid cell line AL. S1- mutants have lost expression of a human cell surface antigen, S1, which is encoded by the M1C1 gene at 11p13 so that mutants can be detected via a complement-mediated cytotoxicity assay in which S1+ cells are killed and S1- cells survive. But loss of genes located on the tip of the short arm of 11 (11p15.5) is lethal to the AL hybrid, so that mutants that have lost the entire chromosome 11 die and escape detection. To circumvent this, we fused AL with Chinese hamster ovary (CHO) cells to produce a new hybrid, ALC, in which the requirement for maintaining 11p15.5 is relieved, allowing us to detect mutations events involving loss of 11p15.5. We evaluated the usefulness of this hybrid by conducting mutagenesis studies with colcemid, 137Cs gamma-radiation and UV 254 nm light. Colcemid induced 1000 more S1- mutants per unit dose in ALC than in AL; the increase for UV 254 nm light was only two-fold; and the increase for 137Cs gamma-rays was 12-fold. The increase in S1- mutant fraction in ALC cells treated with colcemid and 137Cs gamma-rays were largely due to chromosome loss and 11p deletions often containing a breakpoint within the centromeric region.

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

    Directory of Open Access Journals (Sweden)

    Eichler Evan E

    2008-08-01

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

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase

    International Nuclear Information System (INIS)

    Finocchiaro, G.; Taroni, F.; Martin, A.L.; Colombo, I.; Tarelli, G.T.; DiDonato, S.; Rocchi, M.

    1991-01-01

    The authors have cloned and sequenced a cDNA encoding human liver carnitine palmitoyltransferase an inner mitochondrial membrane enzyme that plays a major role in the fatty acid oxidation pathway. Mixed oligonucleotide primers whose sequences were deduced from one tryptic peptide obtained from purified CPTase were used in a polymerase chain reaction, allowing the amplification of a 0.12-kilobase fragment of human genomic DNA encoding such a peptide. A 60-base-pair (bp) oligonucleotide synthesized on the basis of the sequence from this fragment was used for the screening of a cDNA library from human liver and hybridized to a cDNA insert of 2255 bp. This cDNA contains an open reading frame of 1974 bp that encodes a protein of 658 amino acid residues including 25 residues of an NH 2 -terminal leader peptide. The assignment of this open reading frame to human liver CPTase is confirmed by matches to seven different amino acid sequences of tryptic peptides derived from pure human CPTase and by the 82.2% homology with the amino acid sequence of rat CPTase. The NH 2 -terminal region of CPTase contains a leucine-proline motif that is shared by carnitine acetyl- and octanoyltransferases and by choline acetyltransferase. The gene encoding CPTase was assigned to human chromosome 1, region 1q12-1pter, by hybridization of CPTase cDNA with a DNA panel of 19 human-hanster somatic cell hybrids

  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. 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.

  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. 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

  19. Convergence and divergence of tumor-suppressor and proto-oncogenes in chimpanzee from human chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Verma, R.S.; Ramesh, K.H. [Long Island College Hospital, Brooklyn, NY (United States)

    1994-09-01

    Due to the emergence of molecular technology, the phylogenetic evolution of the human genome via apes has become a saltatory even. In the present investigation, cosmid probes for P53, Charcot-Marie-Tooth [CMTIA], HER-2/NEU and myeloperoxidase [MPO] were used. Probes mapping to these genetic loci are well-defined on human chromosome 17 [HSA 17]. We localized these genes on chimpanzee [Pan troglodyte] chromosomes by FISH technique employing two different cell lines. Our results indicate that chimpanzee chromosome 19 [PTR 19] differs from HSA 17 by a pericentric inversion. The P53 gene assigned to HSA 17p13.1 is localized on PTR 19p15 and the MPO sequence of HSA 17q21.3-23 hybridized to PTR 19q23. Perplexing enough, HER-2/NEU assigned to HSA 17q11.2 localized to PTR 19p12. Obviously, there is convergence of P53 and MPO regions and distinctive divergence of HER-2/NEU and CMT1A regions of human and chimpanzee. This investigation has demonstrated the pronounced genetic shuffling which occurred during the origin of HSA 17. Molecular markers should serve as evolutionary punctuations in defining the precise sequence of genetic events that led to the evolution of other chromosomes whose genomic synteny, although similar, have surprisingly evolved through different mechanisms.

  20. 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.)

  1. Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9

    International Nuclear Information System (INIS)

    Wetsel, R.A.; Lemons, R.S.; Le Beau, M.M.; Barnum, S.R.; Noack, D.; Tack, B.F.

    1988-01-01

    A human C5 clone (pC5HG2) was isolated from a cDNA library constructed from Hep G2 mRNA. he DNA sequence showed that the pC5HG2 insert was comprised of 3309 base pairs of pro-C5 coding sequence and 404 base pairs of 3'-untranslated sequence. The derived amino acid sequence contained the entire coding sequence of the C5 α-chain, the β-α-chain junction region, and 100 amino acids (approximately 50%) of the β-chain. Protein sequences of four C5 tryptic peptides were aligned exactly to this sequence and demonstrated that C5 synthesized and secreted by Hep G2 cells is probably identical with plasma-derived C5. Coding sequence alignment of the human C5 sequences with those of murine C5 indicated that 80% of the nucleotides and 79% of the amino acids were placed identically in the two species. Amino acid sequence alignment of the homologous family members C3, C4, and α 2 -macroglobulin with that of C5 demonstrated 27%, 25%, and 19% identity, respectively. As was found in murine C5, the corresponding thiol ester region of human C5 contained several conserved amino acids, but the critical cysteine and glutamine residues which give rise to the intramolecular thiol ester bond in C3, C4, and α 2 -macroglobulin were absent in C5, having been replaced by serine and alanine, respectively. With the use of a panel of hamster-human somatic cell hybrids, the C5 gene was mapped to human chromosome 9. In situ chromosomal hybridization studies employing metaphase cells further localized the gene to bands 9q32-34, with the largest cluster of grains at 9q34.1

  2. Ring Chromosome 17 Not Involving the Miller-Dieker Region: A Case with Drug-Resistant Epilepsy.

    Science.gov (United States)

    Coppola, Antonietta; Morrogh, Deborah; Farrell, Fiona; Balestrini, Simona; Hernandez-Hernandez, Laura; Krithika, S; Sander, Josemir W; Waters, Jonathan J; Sisodiya, Sanjay M

    2017-12-01

    Chromosomal abnormalities are often identified in people with neurodevelopmental disorders including intellectual disability, autism, and epilepsy. Ring chromosomes, which usually involve gene copy number loss, are formed by fusion of subtelomeric or telomeric chromosomal regions. Some ring chromosomes, including ring 14, 17, and 20, are strongly associated with seizure disorders. We report an individual with a ring chromosome 17, r(17)(p13.3q25.3), with a terminal 17q25.3 deletion and no short arm copy number loss, and with a phenotype characterized by intellectual disability and drug-resistant epilepsy, including a propensity for nonconvulsive status epilepticus.

  3. Fine mapping analysis confirms and strengthens linkage of four chromosomal regions in familial hypospadias

    NARCIS (Netherlands)

    Soderhall, C.; Korberg, I.B.; Thai, H.T.; Cao, J.; Chen, Y; Zhang, X.; Shulu, Z.; Zanden, L.F.M. van der; Rooij, I.A.L.M. van; Frisen, L.; Roeleveld, N.; Markljung, E.; Kockum, I.; Nordenskjold, A.

    2015-01-01

    Hypospadias is a common male genital malformation and is regarded as a complex disease affected by multiple genetic as well as environmental factors. In a previous genome-wide scan for familial hypospadias, we reported suggestive linkage in nine chromosomal regions. We have extended this analysis by

  4. 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

  5. Analysis of 62 hybrid assembled human Y chromosomes exposes rapid structural changes and high rates of gene conversion

    DEFF Research Database (Denmark)

    Gonzalez-Izarzugaza, Jose Maria; Skov, Laurits; Maretty, Lasse

    2017-01-01

    The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the po......The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats...... and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we...... use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp) in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP...

  6. Mapping of the gene encoding the. beta. -amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, D.; Gardiner, K.; Kao, F.T.; Tanzi, R.; Watkins, P.; Gusella, J.F. (Eleanor Roosevelt Institute for Cancer Research, Denver, CO (USA))

    1988-11-01

    The gene encoding the {beta}-amyloid precursor protein has been assigned to human chromosome 21, as has a gene responsible for at least some cases of familial Alzheimer disease. Linkage studies strongly suggest that the {beta}-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers. The precise location of the {beta}-amyloid precursor protein gene on chromosome 21 has not yet been determined. Here the authors show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the {beta}-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q/22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.

  7. In situ hybridization of bat chromosomes with human (TTAGGGn probe, after previous digestion with Alu I

    Directory of Open Access Journals (Sweden)

    Karina de Cassia Faria

    2002-01-01

    Full Text Available The purpose of this work was to verify the ability of the enzyme Alu I to cleave and/or remove satellite DNA sequences from heterochromatic regions in chromosomes of bats, by identifying the occurrence of modifications in the pattern of fluorescence in situ hybridization with telomeric DNA. The localization and fluorescence intensity of the telomeric DNA sites of the Alu-digested and undigested chromosomes of species Eumops glaucinus, Carollia perspicillata, and Platyrrhinus lineatus were analyzed. Telomeric sequences were detected at the termini of chromosomes of all three species, although, in C. perspicillata, the signals were very faint or absent in most chromosomes. This finding was interpreted as being due to a reduced number of copies of the telomeric repeat, resulting from extensive telomeric association and/or rearrangements undergone by the chromosomes of Carollia. Fluorescent signals were also observed in centromeric and pericentromeric regions in several two-arm chromosomes of E. glaucinus and C. perspicillata. In E. glaucinus and P. lineatus, some interstitial and terminal telomeric sites were observed to be in association with regions of constitutive heterochromatin and ribosomal DNA (NORs. After digestion, these telomeric sites showed a significant decrease in signal intensity, indicating that enzyme Alu I cleaves and/or removes part of the satellite DNA present in these regions. These results suggest that the telomeric sequence is a component of the heterochromatin, and that the C-band- positive regions of bat chromosomes have a different DNA composition.

  8. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

    International Nuclear Information System (INIS)

    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S.

    1988-01-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease

  9. Styl RFLP recognized by a human IRBP cDNA localized to chromosome 10

    Energy Technology Data Exchange (ETDEWEB)

    Chin, K S; Mathew, C G.P.; Fong, S L; Bridges, C D; Ponder, B A.J.

    1988-02-25

    A 2184 bp cDNA (H.4 IRBP) encoding human interstitial retinol-biding protein isolated from a human retina cDNA library in lambdagt10 by screening with a bovine IRBP cDNA probe. Styl identifies a 2-allele polymorphism with bands at 2.3 kb (Cl) and 1.95 kb (C2) and invariant bands at 1.1, 1.0 and 0.8kb. Codominant segregation was observed in two informative families. The RFLP was mapped to chromosome 10 using somatic cell hybrids. In situ hybridization suggests regional assignments near p11.2 -q11.2 with a secondary site of hybridization at q24-25.

  10. 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

  11. An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

    Science.gov (United States)

    Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

    2008-10-01

    Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

  12. Early embryonic failure: Expression and imprinted status of candidate genes on human chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Sherman, L.S.; Bennett, P.R.; Moore, G.E. [Queen Charlotte`s and Chelsea Hospital, London (United Kingdom)

    1994-09-01

    Two cases of maternal uniparental (hetero)disomy for human chromosome 21 (mUPD21) have been identified in a systematic search for UPD in 23 cases of early embryonic failure (EEF). Bi-parental origin of the other chromosome pairs was confirmed using specific VNTR probes or dinucleotide repeat analysis. Both maternally and paternally derived isochromosomes 21q have previously been identified in two individuals with normal phenotypes. Full UPD21 has a different mechanism of origin than uniparental isochromosome 21q and its effect on imprinted genes and phenotypic outcome will therefore not necessarily be the same. EEF associated with mUPD21 suggests that developmentally important genes on HSA 21 may be imprinted such that they are only expressed from either the maternally or paternally derived alleles. We have searched for monoallelic expression of candidate genes on HSA 21 in human pregnancy (CBS, IFNAR, COL6A1) using intragenic DNA polymorphisms. These genes were chosen either because their murine homologues lie in imprinted regions or because they are potentially important in embryogenesis. Once imprinted candidate genes have been identified, their methylation status and expression in normal, early embryonic failure and uniparental disomy 21 pregnancies will be studied. At the same time, a larger number of cases of EEF are being examined to further investigate the incidence of UPD21 in this group.

  13. 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.

  14. 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

  15. High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.

    Science.gov (United States)

    van Koningsbruggen, Silvana; Gierlinski, Marek; Schofield, Pietá; Martin, David; Barton, Geoffey J; Ariyurek, Yavuz; den Dunnen, Johan T; Lamond, Angus I

    2010-11-01

    The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.

  16. 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.

  17. Peopling of the North Circumpolar Region--insights from Y chromosome STR and SNP typing of Greenlanders.

    Directory of Open Access Journals (Sweden)

    Jill Katharina Olofsson

    Full Text Available The human population in Greenland is characterized by migration events of Paleo- and Neo-Eskimos, as well as admixture with Europeans. In this study, the Y-chromosomal variation in male Greenlanders was investigated in detail by typing 73 Y-chromosomal single nucleotide polymorphisms (Y-SNPs and 17 Y-chromosomal short tandem repeats (Y-STRs. Approximately 40% of the analyzed Greenlandic Y chromosomes were of European origin (I-M170, R1a-M513 and R1b-M343. Y chromosomes of European origin were mainly found in individuals from the west and south coasts of Greenland, which is in agreement with the historic records of the geographic placements of European settlements in Greenland. Two Inuit Y-chromosomal lineages, Q-M3 (xM19, M194, L663, SA01 and L766 and Q-NWT01 (xM265 were found in 23% and 31% of the male Greenlanders, respectively. The time to the most recent common ancestor (TMRCA of the Q-M3 lineage of the Greenlanders was estimated to be between 4,400 and 10,900 years ago (y. a. using two different methods. This is in agreement with the theory that the North Circumpolar Region was populated via a second expansion of humans in the North American continent. The TMRCA of the Q-NWT01 (xM265 lineage in Greenland was estimated to be between 7,000 and 14,300 y. a. using two different methods, which is older than the previously reported TMRCA of this lineage in other Inuit populations. Our results indicate that Inuit individuals carrying the Q-NWT01 (xM265 lineage may have their origin in the northeastern parts of North America and could be descendants of the Dorset culture. This in turn points to the possibility that the current Inuit population in Greenland is comprised of individuals of both Thule and Dorset descent.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-01

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

  4. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular r...

  5. Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.

    Science.gov (United States)

    Vakili, Hana; Jin, Yan; Cattini, Peter A

    2014-11-01

    Levels of pituitary growth hormone (GH), a metabolic homeostatic factor with strong lipolytic activity, are decreased in obese individuals. GH declines prior to the onset of weight gain in response to excess caloric intake and hyperinsulinemia; however, the mechanism by which GH is reduced is not clear. We used transgenic mice expressing the human GH (hGH) gene, GH1, to assess the effect of high caloric intake on expression as well as the local chromosome structure of the intact GH1 locus. Animals exposed to 3 days of high caloric intake exhibited hyperinsulinemia without hyperglycemia and a decrease in both hGH synthesis and secretion, but no difference in endogenous production of murine GH. Efficient GH1 expression requires a long-range intrachromosomal interaction between remote enhancer sequences and the proximal promoter region through "looping" of intervening chromatin. High caloric intake disrupted this interaction and decreased both histone H3/H4 hyperacetylation and RNA polymerase II occupancy at the GH1 promoter. Incorporation of physical activity muted the effects of excess caloric intake on insulin levels, GH1 promoter hyperacetylation, chromosomal architecture, and expression. These results indicate that energy homeostasis alters postnatal hGH synthesis through dynamic changes in the 3-dimensional chromatin structure of the GH1 locus, including structures required for cell type specificity during development.

  6. Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence

    Energy Technology Data Exchange (ETDEWEB)

    Sztrolovics, R.; Grover, J.; Roughley, P.J. [McGill Univ., Montreal (Canada)] [and others

    1994-10-01

    This report describes the cloning of the 3{prime}-untranslated region of the human fibromodulin cDNA and its use to map the gene. For somatic cell hybrids, the generation of the PCR product was concordant with the presence of chromosome 1 and discordant with the presence of all other chromosomes, confirming that the fibromodulin gene is located within region q32 of chromosome 1. The physical mapping of genes is a critical step in the process of identifying which genes may be responsible for various inherited disorders. Specifically, the mapping of the fibromodulin gene now provides the information necessary to evaluate its potential role in genetic disorders of connective tissues. The analysis of previously reported diseases mapped to chromosome 1 reveals two genes located in the proximity of the fibromodulin locus. These are Usher syndrome type II, a recessive disorder characterized by hearing loss and retinitis pigmentosa, and Van der Woude syndrome, a dominant condition associated with abnormalities such as cleft lip and palate and hyperdontia. The genes for both of these disorders have been projected to be localized to 1q32 of a physical map that integrates available genetic linkage and physical data. However, it seems improbable that either of these disorders, exhibiting restricted tissue involvement, could be linked to the fibromodulin gene, given the wide tissue distribution of the encoded proteoglycan, although it remains possible that the relative importance of the quantity and function of the proteoglycan may avry between tissues. 11 refs., 1 fig.

  7. 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

  8. 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).

  9. Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves, Dendrocolaptidae): Evidence of a chromosome inversion.

    Science.gov (United States)

    de Oliveira Barbosa, Marcelo; da Silva, Rubens Rodrigues; de Sena Correia, Vanessa Carolina; Dos Santos, Luana Pereira; Garnero, Analía Del Valle; Gunski, Ricardo José

    2013-03-01

    Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.

  10. Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves, Dendrocolaptidae: evidence of a chromosome inversion

    Directory of Open Access Journals (Sweden)

    Marcelo de Oliveira Barbosa

    2013-01-01

    Full Text Available Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs. Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.

  11. 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)

  12. DNA segment containing C/sub β1/, a gene for the constant region of the β chain of the T-cell antigen receptor, was inserted into chromosome 6 in cells from one patients with human T-cell leukemia

    International Nuclear Information System (INIS)

    Ino, T.; Kurosawa, Y.; Yoshida, M.C.; Hirano, M.

    1987-01-01

    DNA rearrangements that occurred in the vicinity of T-cell antigen receptor β-chain gene clusters residing on chromosome 7 were examined in human T-cell acute lymphoblastic leukemia cells. In one patient, it was observed that, for the T-cell receptor β-chain genes, a D/sub β 1/-J/sub β2.3/ (where D is diversity and J is joining) junction was found on one chromosome, while the other chromosome kept the germ-line configuration. If this D/sub β/-J/sub β/ junction was formed by the customary deletion mechanism, the C/sub β1/ gene (where C is constant) located between the D/sub β1/ and J/sub Β2.3/ loci should have disappeared from this chromosome. The C/sub β1/ gene indeed was absent from the rearranged chromosome 7, but it was found on chromosome 6 as an inserted segment. The implications of the observations are discussed

  13. Characterization of chromosomal regions conserved in Yersinia pseudotuberculosis and lost by Yersinia pestis.

    Science.gov (United States)

    Pouillot, Flavie; Fayolle, Corinne; Carniel, Elisabeth

    2008-10-01

    The transformation of the enteropathogenic bacterium Yersinia pseudotuberculosis into the plague bacillus, Yersinia pestis, has been accompanied by extensive genetic loss. This study focused on chromosomal regions conserved in Y. pseudotuberculosis and lost during its transformation into Y. pestis. An extensive PCR screening of 78 strains of the two species identified five regions (R1 to R5) and four open reading frames (ORFs; orf1 to orf4) that were conserved in Y. pseudotuberculosis and absent from Y. pestis. Their conservation in Y. pseudotuberculosis suggests a positive selective pressure and a role during the life cycle of this species. Attempts to delete two ORFs (orf3 and orf4) from the chromosome of strain IP32953 were unsuccessful, indicating that they are essential for its viability. The seven remaining loci were individually deleted from the IP32953 chromosome, and the ability of each mutant to grow in vitro and to kill mice upon intragastric infection was evaluated. Four loci (orf1, R2, R4, and R5) were not required for optimal growth or virulence of Y. pseudotuberculosis. In contrast, orf2, encoding a putative pseudouridylate synthase involved in RNA stability, was necessary for the optimal growth of IP32953 at 37 degrees C in a chemically defined medium (M63S). Deletion of R1, a region predicted to encode the methionine salvage pathway, altered the mutant pathogenicity, suggesting that the availability of free methionine is severely restricted in vivo. R3, a region composed mostly of genes of unknown functions, was necessary for both optimal growth of Y. pseudotuberculosis at 37 degrees C in M63S and for virulence. Therefore, despite their loss in Y. pestis, five of the nine Y. pseudotuberculosis-specific chromosomal loci studied play a role in the survival, growth, or virulence of this species.

  14. 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.

  15. Cytogenetic analysis chromosomal status of subjects from the regions in the vicinity of uranium-contaminated areas

    International Nuclear Information System (INIS)

    Jovicic, D.; Milacie, S.; Kovacevic, R.; Petrovic, I.

    2004-01-01

    The past application of nuclear technology has brought about free emission of numerous Due to the military application of the depleted uranium (DU) in our country, the problem of its radioactivity and hemo toxicity if actualized. Likewise every heavy metal, its is highly toxic and, in addition to it, also radioactive: Interaction of the water-soluble uranium forms with soil is an important effect. In this way, it penetrates into food chain and endangers human health. The study was aimed at determining possible karyotype genotoxic effects in individuals from the regions close to the contaminated areas. Biological dosimetry was performed using modified Moorthead's micromethod. Our studies included the targeted group of 29 patients from the affected regions. The subjects were averagely aged 39.5±2.8 years. Average age of the control group (k), unexposed to the effects of the known genotoxic agents comprising 22 individuals was 28.3±1.2 years. The presented data evidenced that increased incidence of the chromosomal aberrations was found in 6 subjects,accounting for 20.6%. Dicentric type changes were evidence, as well ring chromosomes and eccentric fragments, which are, at the same time the most frequent aberrations. The changes are considered reparable aberrations accounting for 2-3% in metaphases of the unexposed individuals. Statistical data processing evidenced significant difference (p<0.005) between structural chromosomal aberrations in the studied and control groups, as well as in the number of chromatid aberrations (p<0.05).Based on the obtained data it may be concluded that human karyotype changes were present in the studied group, resulting from interaction of ionizing irradiation and other genotoxic agents, with possibility of potent synergistic effects. It is necessary to stress the importance of further monitoring and control of the general population health, particularly due to possible late genetic effects that may affect future generations. (Author) 10

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  1. Structure of the human vitreoretinal border region

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1994-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human......Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human...

  2. Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA

    International Nuclear Information System (INIS)

    Smits, H.L.; Raadsheer, E.; Rood, I.; Mehendale, S.; Slater, R.M.; van der Noordaa, J.; Ter Schegget, J.

    1988-01-01

    Human embryonic fibroblasts with a large deletion (11p11.11p15.1) in the short arm of one chromosome 11 (del-11 cells) appeared to be susceptible to transformation by early human papillomavirus type 16 (HPV-16) DNA, whereas diploid human embryonic fibroblasts were not. This difference in susceptibility might be explained by the absence of a tumor suppressor gene located within the deleted part on the short arm of chromosome 11. The presence of abundant viral early-gene transcripts in transformed cells suggests that transformation was induced by an elevated level of an HPV-16 early-gene product(s). The low transcriptional activity of HPV-16 in diploid cells may indicate that cellular genes affect viral transcription. Interruption of the HPV-16 E2 early open reading frame is probably required for high-level HPV-16 early-gene expression driven from the homologous enhancer-promoter region

  3. 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

  4. DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer.

    Science.gov (United States)

    Ma, Stephanie; Chan, Yuen Piu; Woolcock, Bruce; Hu, Liang; Wong, Kai Yau; Ling, Ming Tat; Bainbridge, Terry; Webber, Douglas; Chan, Tim Hon Man; Guan, Xin-Yuan; Lam, Wan; Vielkind, Juergen; Chan, Kwok Wah

    2009-05-15

    Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. (c) 2008 Wiley-Liss, Inc.

  5. 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.

  6. 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

  7. 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...

  8. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. (Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States)); Weber, J.L. (Marshfield Medical Research Foundation, WI (United States)); Yuen, J.; Reinker, K. (Univ. of Hawaii, Honolulu, HI (United States))

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  9. 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

  10. 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

  11. Qualitative and quantitative expression status of the human chromosome 20 genes in cancer tissues and the representative cell lines.

    Science.gov (United States)

    Wang, Quanhui; Wen, Bo; Yan, Guangrong; Wei, Junying; Xie, Liqi; Xu, Shaohang; Jiang, Dahai; Wang, Tingyou; Lin, Liang; Zi, Jin; Zhang, Ju; Zhou, Ruo; Zhao, Haiyi; Ren, Zhe; Qu, Nengrong; Lou, Xiaomin; Sun, Haidan; Du, Chaoqin; Chen, Chuangbin; Zhang, Shenyan; Tan, Fengji; Xian, Youqi; Gao, Zhibo; He, Minghui; Chen, Longyun; Zhao, Xiaohang; Xu, Ping; Zhu, Yunping; Yin, Xingfeng; Shen, Huali; Zhang, Yang; Jiang, Jing; Zhang, Chengpu; Li, Liwei; Chang, Cheng; Ma, Jie; Yan, Guoquan; Yao, Jun; Lu, Haojie; Ying, Wantao; Zhong, Fan; He, Qing-Yu; Liu, Siqi

    2013-01-04

    Under the guidance of the Chromosome-centric Human Proteome Project (C-HPP), (1, 2) we conducted a systematic survey of the expression status of genes located at human chromosome 20 (Chr.20) in three cancer tissues, gastric, colon, and liver carcinoma, and their representative cell lines. We have globally profiled proteomes in these samples with combined technology of LC-MS/MS and acquired the corresponding mRNA information upon RNA-seq and RNAchip. In total, 323 unique proteins were identified, covering 60% of the coding genes (323/547) in Chr.20. With regards to qualitative information of proteomics, we overall evaluated the correlation of the identified Chr.20 proteins with target genes of transcription factors or of microRNA, conserved genes and cancer-related genes. As for quantitative information, the expression abundances of Chr.20 genes were found to be almost consistent in both tissues and cell lines of mRNA in all individual chromosome regions, whereas those of Chr.20 proteins in cells are different from tissues, especially in the region of 20q13.33. Furthermore, the abundances of Chr.20 proteins were hierarchically evaluated according to tissue- or cancer-related distribution. The analysis revealed several cancer-related proteins in Chr.20 are tissue- or cell-type dependent. With integration of all the acquired data, for the first time we established a solid database of the Chr.20 proteome.

  12. Two populations of double minute chromosomes harbor distinct amplicons, the MYC locus at 8q24.2 and a 0.43-Mb region at 14q24.1, in the SW613-S human carcinoma cell line.

    Science.gov (United States)

    Guillaud-Bataille, M; Brison, O; Danglot, G; Lavialle, C; Raynal, B; Lazar, V; Dessen, P; Bernheim, A

    2009-01-01

    High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level MYC amplification in the form of double minutes (DM(+) cells) and non tumorigenic cells exhibiting low-level MYC amplification in the form of homogeneously staining regions (DM(-) cells). Both cell types were studied at genomic and functional levels. The DM(+) cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the PLEK2, PIGH, ARG2, VTI1B, RDH11, and ZFYVE26 genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level MYC amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM MYC copies or after transfection of DM(-) cells with a MYC gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs. Copyright 2009 S. Karger AG, Basel.

  13. 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

  14. 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)

  15. Construction of a yeast artifical chromosome contig spanning the spinal muscular atrophy disease gene region

    Energy Technology Data Exchange (ETDEWEB)

    Kleyn, P.W.; Wang, C.H.; Vitale, E.; Pan, J.; Ross, B.M.; Grunn, A.; Palmer, D.A.; Warburton, D.; Brzustowicz, L.M.; Gilliam, T.G. (New York State Psychiatric Institute, NY (United States)); Lien, L.L.; Kunkel, L.M. (Howard Hughes Medical Institute, Boston, MA (United States))

    1993-07-15

    The childhood spinal muscular atrophies (SMAs) are the most common, serious neuromuscular disorders of childhood second to Duchenne muscular dystrophy. A single locus for these disorders has been mapped by recombination events to a region of 0.7 centimorgan (range, 0.1-2.1 centimorgans) between loci D5S435 and MAP1B on chromosome 5q11.2-13.3. By using PCR amplification to screen yeast artificial chromosome (YAC) DNA pools and the PCR-vectorette method to amplify YAC ends, a YAC contig was constructed across the disease gene region. Nine walk steps identified 32 YACs, including a minimum of seven overlapping YAC clones (average size, 460 kb) that span the SMA region. The contig is characterized by a collection of 30 YAC-end sequence tag sites together with seven genetic markers. The entire YAC contig spans a minimum of 3.2 Mb; the SMA locus is confined to roughly half of this region. Microsatellite markers generated along the YAC contig segregate with the SMA locus in all families where the flanking markers (D5S435 and MAP1B) recombine. Construction of a YAC contig across the disease gene region is an essential step in isolation of the SMA-encoding gene. 26 refs., 3 figs., 1 tab.

  16. 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)

  17. Efficient assembly of de novo human artificial chromosomes from large genomic loci

    Directory of Open Access Journals (Sweden)

    Stromberg Gregory

    2005-07-01

    Full Text Available Abstract Background Human Artificial Chromosomes (HACs are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning, manipulating and transferring large segments of the genome. However, development of HACs for the transfer of large genomic loci into mammalian cells has been limited by difficulties in manipulating high-molecular weight DNA, as well as by the low overall frequencies of de novo HAC formation. Indeed, to date, only a small number of large (>100 kb genomic loci have been reported to be successfully packaged into de novo HACs. Results We have developed novel methodologies to enable efficient assembly of HAC vectors containing any genomic locus of interest. We report here the creation of a novel, bimolecular system based on bacterial artificial chromosomes (BACs for the construction of HACs incorporating any defined genomic region. We have utilized this vector system to rapidly design, construct and validate multiple de novo HACs containing large (100–200 kb genomic loci including therapeutically significant genes for human growth hormone (HGH, polycystic kidney disease (PKD1 and ß-globin. We report significant differences in the ability of different genomic loci to support de novo HAC formation, suggesting possible effects of cis-acting genomic elements. Finally, as a proof of principle, we have observed sustained ß-globin gene expression from HACs incorporating the entire 200 kb ß-globin genomic locus for over 90 days in the absence of selection. Conclusion Taken together, these results are significant for the development of HAC vector technology, as they enable high-throughput assembly and functional validation of HACs containing any large genomic locus. We have evaluated the impact of different genomic loci on the frequency of HAC formation and identified segments of genomic DNA that appear to facilitate de novo HAC formation. These genomic loci

  18. Isolation of the Drosophila melanogaster dunce chromosomal region and recombinational mapping of dunce sequences with restriction site polymorphisms as genetic markers

    OpenAIRE

    Davis, Ronald L.; Davidson, Norman

    1984-01-01

    Using the method of chromosomal walking, we have isolated a contiguous region of the Drosophila melanogaster X chromosome which corresponds to salivary gland chromosome bands 3C12 to 3D4. This five-band region contains approximately 100 kilobases of DNA, including those sequences comprising dunce, a gene which functions in memory and cyclic nucleotide metabolism. Genome blots of DNA from flies carrying several different chromosomal aberrations with breakpoints in the region have been probed w...

  19. 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.

  20. Allelic imbalance on chromosome 1 in human breast cancer. I. Minisatellite and RFLP analysis.

    Science.gov (United States)

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

    1995-01-01

    In order to characterise the role of chromosome 1 more fully in breast cancer, polymorphic markers mapping along the length of the whole chromosome were used to assess a panel of 71 tumour-lymphocyte pairs for allelic imbalance. Complex patterns of alterations were established that are consistent with cytogenetic data in the literature. Deletion mapping of individuals with loss of heterozygosity identified five independent smallest common regions of deletion, two of which are novel. There are also three discrete regions showing a gain in copy number of one homologue. The two arms of the chromosome may be subject to different events; the short arm primarily undergoes interstitial deletions, whereas the long arm is subject to whole arm events (as both gains and losses) as well as regional deletions.

  1. 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

  2. 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.

  3. 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).

  4. Human Y Chromosome Haplogroup N: A Non-trivial Time-Resolved Phylogeography that Cuts across Language Families.

    Science.gov (United States)

    Ilumäe, Anne-Mai; Reidla, Maere; Chukhryaeva, Marina; Järve, Mari; Post, Helen; Karmin, Monika; Saag, Lauri; Agdzhoyan, Anastasiya; Kushniarevich, Alena; Litvinov, Sergey; Ekomasova, Natalya; Tambets, Kristiina; Metspalu, Ene; Khusainova, Rita; Yunusbayev, Bayazit; Khusnutdinova, Elza K; Osipova, Ludmila P; Fedorova, Sardana; Utevska, Olga; Koshel, Sergey; Balanovska, Elena; Behar, Doron M; Balanovsky, Oleg; Kivisild, Toomas; Underhill, Peter A; Villems, Richard; Rootsi, Siiri

    2016-07-07

    The paternal haplogroup (hg) N is distributed from southeast Asia to eastern Europe. The demographic processes that have shaped the vast extent of this major Y chromosome lineage across numerous linguistically and autosomally divergent populations have previously been unresolved. On the basis of 94 high-coverage re-sequenced Y chromosomes, we establish and date a detailed hg N phylogeny. We evaluate geographic structure by using 16 distinguishing binary markers in 1,631 hg N Y chromosomes from a collection of 6,521 samples from 56 populations. The more southerly distributed sub-clade N4 emerged before N2a1 and N3, found mostly in the north, but the latter two display more elaborate branching patterns, indicative of regional contrasts in recent expansions. In particular, a number of prominent and well-defined clades with common N3a3'6 ancestry occur in regionally dissimilar northern Eurasian populations, indicating almost simultaneous regional diversification and expansion within the last 5,000 years. This patrilineal genetic affinity is decoupled from the associated higher degree of language diversity. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism.

    Science.gov (United States)

    Bosch, Nina; Morell, Marta; Ponsa, Immaculada; Mercader, Josep Maria; Armengol, Lluís; Estivill, Xavier

    2009-12-14

    The human chromosome 8p23.1 region contains a 3.8-4.5 Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals. We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescent in situ hybridization (FISH). The variability of the 8p23.1 orientation in 150 HapMap samples was predicted using this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentially expressed (pinversion occurred. Moreover, an impact of 8p23.1 inversion on gene expression levels cannot be ruled out, since four genes from this region have statistically significant different expression levels depending on the inversion status. FISH results in lymphoblastoid cell lines suggest the presence of mosaicism regarding the 8p23.1 inversion.

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

    Directory of Open Access Journals (Sweden)

    Hasmik Mkrtchyan

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

  7. Major Chromosomal Breakpoint Intervals in Breast Cancer Co-Localize with Differentially Methylated Regions

    Energy Technology Data Exchange (ETDEWEB)

    Eric Tang, Man-Hung [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Varadan, Vinay; Kamalakaran, Sitharthan [Philips Research North America, Briarcliff Manor, NY (United States); Zhang, Michael Q. [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); The University of Texas at Dallas, Richardson, TX (United States); Tsinghua University, Beijing (China); Dimitrova, Nevenka, E-mail: nevenka.dimitrova@philips.com [Philips Research North America, Briarcliff Manor, NY (United States); Hicks, James, E-mail: hicks@cshl.edu [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States)

    2012-12-27

    Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple chromosomal loci (copy number variation, or CNV), and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape, the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation, but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls (Wiedswang et al., 2003), where each sample has both high-resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions (DMR), coupled with additional genomic parameters, such as repeat elements and designated “fragile sites” in the reference genome. Through this analysis, we have identified a set of 93 regional loci called breakpoint enriched DMR (BEDMRs) characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1 Mb. BEDMR loci are further associated with local hypomethylation (66%), concentrations of the Alu SINE repeats within 3 Mb (35% of the cases), and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. Furthermore, BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors, e.g., JMJD1B, which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA

  8. Molecular cloning of a cDNA and chromosomal localization of a human theta-class glutathione S-transferase gene (GSTT2) to chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Tan, K.L.; Baker, R.T.; Board, P.G. [Australian National Univ., Canberra (Australia)] [and others

    1995-01-20

    Until recently the Theta-class glutathione S-transferases (GSTs) were largely overlooked due to their low activity with the model substrate 1-chloro-2,4-dinitrobenzene (CDNB) and their failure to bind to immobilized glutathione affinity matrices. Little is known about the number of genes in this class. Recently, Pemble et al. reported the cDNA cloning of a human Theta-class GST, termed GSTT1. In this study, we describe the molecular cloning of a cDNA encoding a second human Theta-class GST (GSTT2) from a {lambda}gt11 human liver 5{prime}-stretch cDNA library. The encoded protein contains 244 amino acids and has 78.3% sequence identity with the rat subunit 12 and only 55.0% identity with human GSTT1. GSTT2 has been mapped to chromosome 22 by somatic cell hybrid analysis. The precise position of the gene was localized to subband 22q11.2 by in situ hybridization. The absence of other regions of hybridization suggests that there are no closely related sequences (e.g., reverse transcribed pseudogenes) scattered throughout the genome and that if there are closely related genes, they must be clustered near GSTT2. Southern blot analysis of human DNA digested with BamHI shows that the size of the GSTT2 gene is relatively small, as the coding sequence falls within a 3.6-kb BamHI fragment. 35 refs., 6 figs.

  9. Study of Y Chromosome Microdeletion in AZF Region in Infertile Males of Isfahan Population

    Directory of Open Access Journals (Sweden)

    M Motovali-Bashi

    2013-02-01

    Full Text Available Abstract Background & aim: One of the main genetic factors of infertility is the deletions in the chromosome Y. Accordingly this study was conducted to determine the frequency of microdeletion of AZF region in infertile men of Isfahan, Iran. Methods: In this case-control study, 100 infertile men referred to the Infertility Center of Isfahan and 100 fertile men as controls were randomly selected. Genomic DNA was extracted from their blood and amplified by sequence tagged sites-polymerase chain reaction (STS-PCR method. The presence of microdeletion in AZF locus was diagnosed. Results: No AZFa, AZFb or AZFc deletions were found in the control group. Microdeletions were observed in one patient in AZFb region, eight patients in AZFc region and two patients in AZFa region. Conclusion: The incidence of Yq microdeletions in Iranian population is similar to the international frequency. Our data agree with other studies regarding microdeletions of AZFc, but for microdeletions of AZFa (2% our results show smaller frequency and differ significantly with many studies. Key words: Infertility, Y chromosome, Microdeletion

  10. 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.

  11. 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

  12. Meiotic synapsis of homogeneously staining regions (HSRs) in chromosome 1 of Mus musculus.

    Science.gov (United States)

    Winking, H; Reuter, C; Traut, W

    1993-05-01

    About 50 copies of a long-range repeat DNA family with a repeat size of roughly 100 kb and with sequence homology to mRNAs are clustered in the G-light band D of chromosome 1 of the house mouse, Mus musculus. We studied amplified versions of the cluster which are found in many wild populations of M. musculus. They are cytogenetically conspicuous as one or two C-band positive homogeneously staining regions (single- and double band HSRs) which increase the mitotic length of chromosome 1. The double band HSR was phylogenetically derived from a single band HSR by a paracentric inversion. In homozygous condition, such HSRs contribute, albeit not as much as expected from their mitotic length, to the synaptonemal complex (SC) length of chromosome 1. In HSR heterozygous animals an elongation of the SCs was not noticeable. In single band HSR heterozygous males, synapsis proceeds regularly and continuously from the distal telomere towards the centromeric end without forming buckles. Thus, the single band HSR has no adverse effect on pairing. The same straight pairing behaviour was found in the majority of double band HSR heterozygous spermatocytes. This shows that extensive nonhomologous pairing can take place in the earliest phase of synapsis. Synapsis was discontinuous, leaving the central part of the bivalent 1 asynapsed, in only 14.3% of double band HSR heterozygous cells. In such cells the chromosome 1 SC is completed at a later stage of meiosis. The delay is presumably an effect of the inversion that includes one HSR band and the segment between the two HSR bands.

  13. 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

  14. 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.

  15. The cld mutation: narrowing the critical chromosomal region and selecting candidate genes.

    Science.gov (United States)

    Péterfy, Miklós; Mao, Hui Z; Doolittle, Mark H

    2006-10-01

    Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the tw73 haplotype on mouse Chromosome 17. While the cld mutation results in lipase proteins that are inactive, aggregated, and retained in the endoplasmic reticulum (ER), it maps separately from the lipase structural genes. We have narrowed the gene critical region by about 50% using the tw18 haplotype for deletion mapping and a recombinant chromosome used originally to map cld with respect to the phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs). To identify the affected gene, we have selected candidates based on their known role in associated biological processes, cellular components, and molecular functions that best fit with the predicted function of the cld gene. A secondary approach was based on differences in mRNA levels between mutant (cld/cld) and unaffected (+/cld) cells. Using both approaches, we have identified seven functional candidates with an ER localization and/or an involvement in protein maturation and folding that could explain the lipase deficiency, and six expression candidates that exhibit large differences in mRNA levels between mutant and unaffected cells. Significantly, two genes were found to be candidates with regard to both function and expression, thus emerging as the strongest candidates for cld. We discuss the implications of our mapping results and our selection of candidates with respect to other genes, deletions, and mutations occurring in the cld critical region.

  16. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    International Nuclear Information System (INIS)

    Ledbetter, D.H.; Ledbetter, S.A.; vanTuinen, P.

    1989-01-01

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region

  17. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, S.G.; O' Connell, P. (Univ. of Texas Health Science Center, San Antonio (United States)); Dixon, M.J. (Univ. of Manchester (United Kingdom)); Nigro, M.A. (Wayne State Univ., Detroit, MI (United States)); Kelts, K.A. (Black Hills Neurology, Rapid City, SD (United States)); Markand, O.N. (Indiana Univ., Indianopolis (United States)); Shiang, R.; Wasmuth, J.J. (Univ. of California, Irvine (United States)); Terry, J.C.

    1992-12-01

    Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. The authors performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. 45 refs., 4 figs., 4 tabs.

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

    Directory of Open Access Journals (Sweden)

    Xianfa Xie

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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. DDX11L: a novel transcript family emerging from human subtelomeric regions

    Directory of Open Access Journals (Sweden)

    D'Urso Michele

    2009-05-01

    Full Text Available Abstract Background The subtelomeric regions of human chromosomes exhibit an extraordinary plasticity. To date, due to the high GC content and to the presence of telomeric repeats, the subtelomeric sequences are underrepresented in the genomic libraries and consequently their sequences are incomplete in the finished human genome sequence, and still much remains to be learned about subtelomere organization, evolution and function. Indeed, only in recent years, several studies have disclosed, within human subtelomeres, novel gene family members. Results During a project aimed to analyze genes located in the telomeric region of the long arm of the human X chromosome, we have identified a novel transcript family, DDX11L, members of which map to 1pter, 2q13/14.1, 2qter, 3qter, 6pter, 9pter/9qter, 11pter, 12pter, 15qter, 16pter, 17pter, 19pter, 20pter/20qter, Xpter/Xqter and Yqter. Furthermore, we partially sequenced the underrepresented subtelomeres of human chromosomes showing a common evolutionary origin. Conclusion Our data indicate that an ancestral gene, originated as a rearranged portion of the primate DDX11 gene, and propagated along many subtelomeric locations, is emerging within subtelomeres of human chromosomes, defining a novel gene family. These findings support the possibility that the high plasticity of these regions, sites of DNA exchange among different chromosomes, could trigger the emergence of new genes.

  5. 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.

  6. 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).

  7. 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.

  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. Interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q

    International Nuclear Information System (INIS)

    Le Beau, M.M.; Epstein, N.D.; O'Brien, S.J.; Nienhuis, A.W.; Yang, Y.C.; Clark, S.C.; Rowley, J.D.

    1987-01-01

    The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, the authors localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33[del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent from the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF, CSF-1, and FMS. The findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q- chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q)

  10. 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...

  11. 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.

  12. 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

  13. Recombination in the human Pseudoautosomal region PAR1.

    Directory of Open Access Journals (Sweden)

    Anjali G Hinch

    2014-07-01

    Full Text Available The pseudoautosomal region (PAR is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

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

    International Nuclear Information System (INIS)

    Rowley, J.D.

    1991-06-01

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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3

    Energy Technology Data Exchange (ETDEWEB)

    Heiber, M.; Marchese, A.; O`Dowd, B.F. [Univ. of Toronto, Ontario (Canada)] [and others

    1996-03-05

    We used sequence similarities among G-protein-coupled receptor genes to discover a novel receptor gene. Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor encoded by GPR15 with other receptors revealed that it shared sequence identity with the angiotensin II AT1 and AT2 receptors, the interleukin 8b receptor, and the orphan receptors GPR1 and AGTL1. GPR15 was mapped to human chromosome 3q11.2-q13.1. 12 refs., 2 figs.

  7. 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...

  8. 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

  9. 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 ...

  10. 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...

  11. 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....

  12. Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins

    Directory of Open Access Journals (Sweden)

    Kahlem Pascal

    2006-06-01

    Full Text Available Abstract Background Trisomy of human chromosome 21 (Chr21 results in Down's syndrome, a complex developmental and neurodegenerative disease. Molecular analysis of Down's syndrome, however, poses a particular challenge, because the aneuploid region of Chr21 contains many genes of unknown function. Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. Following this idea, we used a transfected-cell array technique to perform a rapid and cost-effective analysis of the intracellular distribution of Chr 21 proteins. Results We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb to MCM3AP (46.6 Mb, with part of them expressed aberrantly in the Down's syndrome mouse model. Open reading frames of these genes were cloned into a mammalian expression vector with an amino-terminal His6 tag. All of the constructs were arrayed on glass slides and reverse transfected into HEK293T cells for protein expression. Co-localization detection using a set of organelle markers was carried out for each Chr21 protein. Here, we report the subcellular localization properties of 52 proteins. For 34 of these proteins, their localization is described for the first time. Furthermore, the alteration in cell morphology and growth as a result of protein over-expression for claudin-8 and claudin-14 genes has been characterized. Conclusion The cell array-based protein expression and detection approach is a cost-effective platform for large-scale functional analyses, including protein subcellular localization and cell phenotype screening. The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome.

  13. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

    Directory of Open Access Journals (Sweden)

    Pierce Levi CT

    2009-01-01

    Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

  14. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

  15. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    International Nuclear Information System (INIS)

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs

  16. Sequencing and association analysis of the type 1 diabetes – linked region on chromosome 10p12-q11

    Directory of Open Access Journals (Sweden)

    Barratt Bryan J

    2007-05-01

    Full Text Available Abstract Background In an effort to locate susceptibility genes for type 1 diabetes (T1D several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with T1D. Results Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs and found no association with T1D. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex T1D families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05 – 0.0026, located near the PAPD1 gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the T1D families. We also tested 13 polymorphisms in the PAPD1 gene and in five other loci in 1,612 T1D patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPD1 showed nominal evidence of association in both T1D families and in the case-control sample (P = 0.037 and 0.03, respectively. Conclusion We conclude that polymorphisms in the CREM and SDF1 genes have no major effect on T1D. The weak T1D association that we detected in the association scan near the PAPD1 gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region.

  17. The Paternal Landscape along the Bight of Benin - Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers.

    Directory of Open Access Journals (Sweden)

    Maarten H D Larmuseau

    Full Text Available Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample

  18. 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).

  19. Clastogenic effects of different Ureaplasma urealyticum serovars on human chromosomes

    Directory of Open Access Journals (Sweden)

    R.A.F Cunha

    1997-06-01

    Full Text Available The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 103 CCU (color changing units/ml, 104 CCU/ml and 105 CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (103 CCU/ml, 104 CCU/ml or 105 CCU/ml of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0% and chromatid breaks (13.9% were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated

  20. Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

    1994-09-01

    Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

  1. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes.

    Science.gov (United States)

    Pongsavee, Malinee

    2009-10-30

    Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

  2. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    Directory of Open Access Journals (Sweden)

    Pongsavee Malinee

    2009-10-01

    Full Text Available Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI. The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  4. 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.

  5. Phylogeography of Y-chromosome haplogroup O3a2b2-N6 reveals patrilineal traces of Austronesian populations on the eastern coastal regions of Asia

    Science.gov (United States)

    Teo, Yik-Ying; Huang, Yun-Zhi; Wang, Ling-Xiang; Yu, Ge; Saw, Woei-Yuh; Ong, Rick Twee-Hee; Lu, Yan; Zhang, Chao; Xu, Shu-Hua; Jin, Li; Li, Hui

    2017-01-01

    Austronesian diffusion is considered one of the greatest dispersals in human history; it led to the peopling of an extremely vast region, ranging from Madagascar in the Indian Ocean to Easter Island in Remote Oceania. The Y-chromosome haplogroup O3a2b*-P164(xM134), a predominant paternal lineage of Austronesian populations, is found at high frequencies in Polynesian populations. However, the internal phylogeny of this haplogroup remains poorly investigated. In this study, we analyzed -seventeen Y-chromosome sequences of haplogroup O3a2b*-P164(xM134) and generated a revised phylogenetic tree of this lineage based on 310 non-private Y-chromosome polymorphisms. We discovered that all available O3a2b*-P164(xM134) samples belong to the newly defined haplogroup O3a2b2-N6 and samples from Austronesian populations belong to the sublineage O3a2b2a2-F706. Additionally, we genotyped a series of Y-chromosome polymorphisms in a large collection of samples from China. We confirmed that the sublineage O3a2b2a2b-B451 is unique to Austronesian populations. We found that O3a2b2-N6 samples are widely distributed on the eastern coastal regions of Asia, from Korea to Vietnam. Furthermore, we propose- that the O3a2b2a2b-B451 lineage represents a genetic connection between ancestors of Austronesian populations and ancient populations in North China, where foxtail millet was domesticated about 11,000 years ago. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree of O3a2b2-N6 will be helpful to explore the origin of proto-Austronesians and the early diffusion process of Austronesian populations. PMID:28380021

  6. A histone map of human chromosome 20q13.12.

    Directory of Open Access Journals (Sweden)

    Pelin Akan

    Full Text Available We present a systematic search for regulatory elements in a 3.5 Mb region on human chromosome 20q13.12, a region associated with a number of medical conditions such as type II diabetes and obesity.We profiled six histone modifications alongside RNA polymerase II (PolII and CTCF in two cell lines, HeLa S3 and NTERA-2 clone D1 (NT2/D1, by chromatin immunoprecipitation using an in-house spotted DNA array, constructed with 1.8 kb overlapping plasmid clones. In both cells, more than 90% of transcription start sites (TSSs of expressed genes showed enrichments with PolII, di-methylated lysine 4 of histone H3 (H3K4me2, tri-methylated lysine 4 of histone H3 (H3K4me3 or acetylated H3 (H3Ac, whereas mono-methylated lysine 4 of histone H3 (H3K4me1 signals did not correlate with expression. No TSSs were enriched with tri-methylated lysine 27 of histone H3 (H3K27me3 in HeLa S3, while eight TSSs (4 expressed showed enrichments in NT2/D1. We have also located several CTCF binding sites that are potential insulator elements.In summary, we annotated a number of putative regulatory elements in 20q13.12 and went on to verify experimentally a subset of them using dual luciferase reporter assays. Correlating this data to sequence variation can aid identification of disease causing variants.

  7. Assignment of adenosine deaminase complexing protein (ADCP) gene(s) to human chromosome 2 in rodent-human somatic cell hybrids.

    Science.gov (United States)

    Herbschleb-Voogt, E; Grzeschik, K H; Pearson, P L; Meera Khan, P

    1981-01-01

    The experiments reported in this paper indicate that the expression of human adenosine deaminase complexing protein (ADCP) in the human-rodent somatic cell hybrids is influenced by the state of confluency of the cells and the background rodent genome. Thus, the complement of the L-cell derived A9 or B82 mouse parent apparently prevents the expression of human ADCP in the interspecific somatic cell hybrids. In the a3, E36, or RAG hybrids the human ADCP expression was not prevented by the rodent genome and was found to be proportional to the degree of confluency of the cell in the culture as in the case of primary human fibroblasts. An analysis of human chromosomes, chromosome specific enzyme markers, and ADCP in a panel of rodent-human somatic cell hybrids optimally maintained and harvested at full confluency has shown that the expression of human ADCP in the mouse (RAG)-human as well as in the hamster (E36 or a3)-human hybrids is determined by a gene(s) in human chromosome 2 and that neither chromosome 6 nor any other of the chromosomes of man carry any gene(s) involved in the formation of human ADCP at least in the Chinese hamster-human hybrids. A series of rodent-human hybrid clones exhibiting a mitotic separation of IDH1 and MDH1 indicated that ADCP is most probably situated between corresponding loci in human chromosome 2.

  8. Epigenetic basis of neuronal plasticity: Association with R/G-band boundaries on human chromosomes

    Directory of Open Access Journals (Sweden)

    Yoshihisa Watanabe

    2016-09-01

    Full Text Available Epigenetic mechanisms have been suggested to have roles in neuroplasticity, in particular with regard to learning and memory formation, and in a range of neural diseases. In addition to epigenetic marks, the human genome also contains large-scale compartmentalized structures that might also influence neuroplasticity and neural disease. These structures result from variations in the amounts of GC% and in the timing of DNA replication and give rise to longitudinal differentiation (light and dark bands along chromosomes after the appropriate staining. Here we describe our current understanding of the biological importance of the boundaries between these light and dark bands (the so-called R/G boundaries. We propose that the R/G-band boundaries on human chromosomes can be altered by epigenetic mechanisms, and that these changes may affect neuroplasticity, which is important to memory and learning, and may also have a role in the development of neural diseases associated with genomic instability.

  9. Yeast artificial chromosome cloning in the glycerol kinase and adrenal hypoplasia congenita region of Xp21

    Energy Technology Data Exchange (ETDEWEB)

    Worley, K.C.; Ellison, K.A.; Zhang, Y.H.; Wang, D.F.; Mason, J.; Roth, E.J.; Adams, V.; Fogt, D.D.; Zhu, X.M.; Towbin, J.A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1993-05-01

    The adrenal hypoplasia congenita (AHC) and glycerol kinase (GK) loci are telomeric to the Duchenne muscular dystrophy locus in Xp21. The authors developed a pair of yeast artificial chromosome (YAC) contigs spanning at least 1.2 Mb and encompassing the region from the telomeric end of the Duchenne muscular dystrophy (DMD) locus to beyond YHX39 (DXS727), including the genes for AHC and GK. The centromeric contig consists of 13 YACs reaching more than 600 kb from DMD through GK. The telomeric contig group consists of 8 YACs containing more than 600 kb including the markers YHX39 (DXS727) and QST-59 (DXS319). Patient deletion breakpoints in the region of the two YAC contigs define at least eight intervals, and seven deletion breakpoints are contained within these contigs. In addition to the probes developed from YAC ends, they have mapped eight Alu-PCR probes amplified from a radiation-reduced somatic cell hybrid, two anonymous DNA probes, and one Alu-PCR product amplified from a cosmid end, for a total of 26 new markers within this region of 2 Mb or less. One YAC in the centromeric contig contains an insert encompassing the minimum interval for GK deficiency defined by patient deletion breakpoints, and this clone includes all or part of the GK gene. 33 refs., 3 figs., 5 tabs.

  10. 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

  11. Report of the first international workshop on human chromosome 14 mapping 1993

    Energy Technology Data Exchange (ETDEWEB)

    Cox, D.W.

    1995-06-01

    The first International Workshop on Human Chromosome 14 mapping was held at Novotel in Toronto, Canada on June 9-12, 1993. There were 23 participants from nine countries. The goals of the workshop were to compile physical maps and a consensus linkage map, to consolidate available data on disease loci, to catalogue and facilitate distribution of resources and to encourage new collaborations and data sharing.

  12. Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

    OpenAIRE

    Pongsavee Malinee

    2009-01-01

    Abstract Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0...

  13. Sex, rebellion and decadence: the scandalous evolutionary history of the human Y chromosome.

    Science.gov (United States)

    Navarro-Costa, Paulo

    2012-12-01

    It can be argued that the Y chromosome brings some of the spirit of rock&roll to our genome. Equal parts degenerate and sex-driven, the Y has boldly rebelled against sexual recombination, one of the sacred pillars of evolution. In evolutionary terms this chromosome also seems to have adopted another of rock&roll's mottos: living fast. Yet, it appears to have refused to die young. In this manuscript the Y chromosome will be analyzed from the intersection between structural, evolutionary and functional biology. Such integrative approach will present the Y as a highly specialized product of a series of remarkable evolutionary processes. These led to the establishment of a sex-specific genomic niche that is maintained by a complex balance between selective pressure and the genetic diversity introduced by intrachromosomal recombination. Central to this equilibrium is the "polish or perish" dilemma faced by the male-specific Y genes: either they are polished by the acquisition of male-related functions or they perish via the accumulation of inactivating mutations. Thus, understanding to what extent the idiosyncrasies of Y recombination may impact this chromosome's role in sex determination and male germline functions should be regarded as essential for added clinical insight into several male infertility phenotypes. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. High-resolution YAC-cosmid-STS map of human chromosome 13.

    Science.gov (United States)

    Cayanis, E; Russo, J J; Kalachikov, S; Ye, X; Park, S H; Sunjevaric, I; Bonaldo, M F; Lawton, L; Venkatraj, V S; Schon, E; Soares, M B; Rothstein, R; Warburton, D; Edelman, I S; Zhang, P; Efstratiadis, A; Fischer, S G

    1998-01-01

    We have assembled a high-resolution physical map of human chromosome 13 DNA (approximately 114 Mb) from hybridization, PCR, and FISH mapping data using a specifically designed set of computer programs. Although the mapping of 13p is limited, 13q (approximately 98 Mb) is covered by an almost continuous contig of 736 YACs aligned to 597 contigs of cosmids. Of a total of 10,789 cosmids initially selected from a chromosome 13-specific cosmid library (16,896 colonies) using inter-Alu PCR probes from the YACs and probes for markers mapped to chromosome 13, 511 were assembled in contigs that were established from cross-hybridization relationships between the cosmids. The 13q YAC-cosmid map was annotated with 655 sequence tagged sites (STSs) with an average spacing of 1 STS per 150 kb. This set of STSs, each identified by a D number and cytogenetic location, includes database markers (198), expressed sequence tags (93), and STSs generated by sequencing of the ends of cosmid inserts (364). Additional annotation has been provided by positioning 197 cosmids mapped by FISH on 13q. The final (comprehensive) map, a list of STS primers, and raw data used in map assembly are available at our Web site (genome1.ccc.columbia.edu/ approximately genome/) and can serve as a resource to facilitate accurate localization of additional markers, provide substrates for sequencing, and assist in the discovery of chromosome 13 genes associated with hereditary diseases.

  15. Structure of the human gene encoding the associated microfibrillar protein (MFAP1) and localization to chromosome 15q15-q21

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, H.; Chow, M.; Abrams, W.R. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1994-09-15

    Microfibrils with a diameter of 10-12 nm, found either in assocation with elastin or independently, are an important component of the extracellular matrix of many tissues. To extend understanding of the proteins composing these microfibrils, the cDNA and gene encoding the human associated microfibril protein (MRAP1) have been cloned and characterized. The coding portion is contained in 9 exons, and the sequence is very homologous to the previously described chick cDNA, but does not appear to share homology or domain motifs with any other known protein. Interestingly, the gene has been localized to chromosome 15q15-q21 by somatic hybrid cell and chromosome in situ analyses. This is the same chromosomal region to which the fibrillin gene, FBN1, known to be defective in the Marfan syndrome, has been mapped. MFAP1 is a candidate gene for heritable diseases affecting microfibrils. 38 refs., 6 figs.

  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. Relative biological effectiveness of tritiated water on human chromosomes of lymphocytes and bone marrow cells

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Sawada, Shozo; Kamada, Nanao

    1992-01-01

    One of the major toxic effluent from nuclear power industries is tritiated water (HTO), which is released into the environment in large quantities. Low dose radiation effects and dose rate effects of HTO on human lymphocytes and bone marrow cells are not well studied. The present study was performed to investigate dose-response relationship for chromosome aberration frequencies in the human lymphocytes and bone marrow cells, by HTO in-vitro exposure at low dose ranges of 0.1 to 1 Gy. Go lymphocytes and bone marrow cells were incubated for 10 - 150 minutes with HTO at 2 cGy/min. Also 60 Co γ and 137 Cs γ rays were used as controls. Dicentric chromosomes were scored in 1,000 to 2,000 cells of each experimental series. The RBE values of HTO at low dose range for the induction of dicentric chromosomes and chromatid type aberrations were 2.7 in lymphocytes and approximately 3.8 in bone marrow cells with respect to 60 Co γ ray, respectively. Also lymphocytes were chronically exposed to HTO for 24 to 72 hrs at lower dose rates (0.2 and 0.05 cGy/min). The yields of dicentrics and rings decreased with the reduction in the dose rate of HTO, presenting a clear dose rate effects of HTO. These results provide an useful information for the assessment for health risk in humans exposed to low concentration level to HTO. (author)

  18. Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.

    Science.gov (United States)

    Slovak, M L; Hoeltge, G A; Ganapathi, R

    1986-08-01

    B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.

  19. 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.

  20. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    Science.gov (United States)

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  1. The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    George, Kerry; Hada, Megumi; Cucinotta, F. A.

    2011-01-01

    Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

  2. Regional localization of DNA probes on the short arm of chromosome 11 using aniridia-Wilms' tumor-associated deletions

    NARCIS (Netherlands)

    Mannens, M.; Slater, R. M.; Heyting, C.; Geurts van Kessel, A.; Goedde-Salz, E.; Frants, R. R.; van Ommen, G. J.; Pearson, P. L.

    1987-01-01

    We are interested in the precise localization of various DNA probes on the short arm of chromosome 11 for our research on the aniridia-Wilms' tumor association (AWTA), assigned to region 11p13 (Knudson and Strong 1972; Riccardi et al. 1978). For this purpose we have screened lymphocyte DNA and

  3. Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.

    Science.gov (United States)

    D'Agostini, F; Caimo, A; De Filippi, S; De Flora, S

    1999-07-01

    Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels.

  4. Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhou, Y.Z.; Slagle, B.L.; Donehower, L.A.; van Tuinen, P.; Ledbetter, D.H.; Butel, J.S.

    1988-01-01

    Hepatitis B virus (HBV) is clearly a factor in the development of hepatocellular carcinoma, but its mechanism of action remains obscure. One possibility is that the HBV integration event alters the expression of a nearby growth-regulatory cellular gene. A 9-kilobase (kb) DNA fragment containing an HBV insert plus flanking cellular sequences was cloned from a hepatoma specimen from Shanghai, People's Republic of China. Restriction mapping of the insert revealed a large inverted repeat structure consisting of both viral sequences (encompassing all of the core and pre-S regions and portions of the X and S genes) and at least 3 kb of unique cellular sequences. The virus-cell junction mapped 11 nucleotides from the DRI region, in a position within the HBV X gene and included in the cohesive overlap region. A probe generated from 1.0 kb of the flanking cellular DNA mapped the viral insert to chromosome 17 in the region designated 17p11.2-17p12, which is near the human proto-oncogene p53. Sequence data from a portion of the flanking cellular DNA revealed a stretch of approximately 70 base pairs that showed highly significant homology with a conserved region of a number of functional mammalian DNA, including the human autonomously replicating sequence 1 (ASRI)

  5. Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

    Science.gov (United States)

    Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

    2018-02-01

    Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

  6. A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts

    NARCIS (Netherlands)

    Noordam, M. J.; van Daalen, S. K. M.; Hovingh, S. E.; Korver, C. M.; van der Veen, F.; Repping, S.

    2011-01-01

    BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1

  7. Gold nanoparticle-assisted primer walking for closing the human chromosomal gap

    DEFF Research Database (Denmark)

    Li, H; Shi, B; Li, X

    2013-01-01

    The finished sequence of the human genome still contains 260 euchromatic gaps. All the PCR-based genome walking techniques used to close gaps have common limitations, such as low efficiency and low specificity. We herein describe a strategy to solve this problem by employing gold nanoparticles (Au......NPs) to improve the efficiency in primer walking amplification. We used this strategy to close a gap in human chromosome 5 containing a DNA stretch composed of the 12SAT repeat. The obtained gap sequence is highly conserved among several mammalian genomes. The demonstrated AuNP-assisted primer walking strategy...

  8. Effect of mobile phone station on micronucleus frequency and chromosomal aberrations in human blood cells.

    Science.gov (United States)

    Yildirim, M S; Yildirim, A; Zamani, A G; Okudan, N

    2010-01-01

    The use of mobile telephones has rapidly increased worldwide as well as the number of mobile phone base stations that lead to rise low level radiofrequency emissions which may in turn have possible harm for human health. The national radiation protection board has published the known effects of radio waves exposure on humans living close to mobile phone base stations. However, several studies have claimed that the base station has detrimental effects on different tissues. In this study, we aimed to evaluate the effects of mobile phone base stations on the micronucleus (MN) frequency and chromosomal aberrations on blood in people who were living around mobile phone base stations and healthy controls. Frequency of MN and chromosomal aberrations in study and control groups was 8.96 +/- 3.51 and 6.97 +/- 1.52 (p: 0.16); 0.36 +/- 0.31 and 0.75 +/- 0.61 (p: 0.07), respectively. Our results show that there was not a significant difference of MN frequency and chromosomal aberrations between the two study groups. The results claim that cellular phones and their base stations do not produce important carcinogenic changes.

  9. 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)

  10. 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.

  11. 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.

  12. Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21–q22

    Science.gov (United States)

    Shiina, Takashi; Ando, Asako; Suto, Yumiko; Kasai, Fumio; Shigenari, Atsuko; Takishima, Nobusada; Kikkawa, Eri; Iwata, Kyoko; Kuwano, Yuko; Kitamura, Yuka; Matsuzawa, Yumiko; Sano, Kazumi; Nogami, Masahiro; Kawata, Hisako; Li, Suyun; Fukuzumi, Yasuhito; Yamazaki, Masaaki; Tashiro, Hiroyuki; Tamiya, Gen; Kohda, Atsushi; Okumura, Katsuzumi; Ikemura, Toshimichi; Soeda, Eiichi; Mizuki, Nobuhisa; Kimura, Minoru; Bahram, Seiamak; Inoko, Hidetoshi

    2001-01-01

    Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under

  13. 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

  14. 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)

  15. 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

  16. Repression of hTERT transcription by the introduction of chromosome 3 into human oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nishio, Sachiyo; Ohira, Takahito; Sunamura, Naohiro; Oshimura, Mitsuo; Ryoke, Kazuo; Kugoh, Hiroyuki

    2015-01-01

    Telomerase is a ribonucleoprotein enzyme that maintains telomere length. Telomerase activity is primarily attributed to the expression of telomerase reverse transcriptase (TERT). It has been reported that introduction of an intact human chromosome 3 into the human oral squamous cell carcinoma cell line HSC3 suppresses the tumorigenicity of these cells. However, the mechanisms that regulate tumorigenicity have not been elucidated. To determine whether this reduction in tumorigenicity was accompanied by a reduction in telomerase activity, we investigated the transcriptional activation of TERT in HSC3 microcell hybrid clones with an introduced human chromosome 3 (HSC3#3). HSC#3 cells showed inhibition of hTERT transcription compared to that of the parental HSC3 cells. Furthermore, cell fusion experiments showed that hybrids of HSC3 cells and cells of the RCC23 renal carcinoma cell line, which also exhibits suppression of TERT transcription by the introduction of human chromosome 3, also displayed suppressed TERT transcription. These results suggested that human chromosome 3 may carry functionally distinct, additional TERT repressor genes. - Highlights: • hTERT mRNA expression level decreased in the chromosome 3 introduced HSC3 clones. • hTERT mRNA expression level was tend to suppressed in HSC3 and RCC23 hybrid cells. • We provide evidence that human chromosome 3 carries at least two distinct hTERT regulatory factors.

  17. Repression of hTERT transcription by the introduction of chromosome 3 into human oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Sachiyo [Division of Oral and Maxillofacial Biopathological Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503 (Japan); Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Ohira, Takahito; Sunamura, Naohiro [Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Oshimura, Mitsuo [Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, 683-8503 (Japan); Ryoke, Kazuo [Division of Oral and Maxillofacial Biopathological Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503 (Japan); Kugoh, Hiroyuki, E-mail: kugoh@med.tottori-u.ac.jp [Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, 683-8503 (Japan)

    2015-10-30

    Telomerase is a ribonucleoprotein enzyme that maintains telomere length. Telomerase activity is primarily attributed to the expression of telomerase reverse transcriptase (TERT). It has been reported that introduction of an intact human chromosome 3 into the human oral squamous cell carcinoma cell line HSC3 suppresses the tumorigenicity of these cells. However, the mechanisms that regulate tumorigenicity have not been elucidated. To determine whether this reduction in tumorigenicity was accompanied by a reduction in telomerase activity, we investigated the transcriptional activation of TERT in HSC3 microcell hybrid clones with an introduced human chromosome 3 (HSC3#3). HSC#3 cells showed inhibition of hTERT transcription compared to that of the parental HSC3 cells. Furthermore, cell fusion experiments showed that hybrids of HSC3 cells and cells of the RCC23 renal carcinoma cell line, which also exhibits suppression of TERT transcription by the introduction of human chromosome 3, also displayed suppressed TERT transcription. These results suggested that human chromosome 3 may carry functionally distinct, additional TERT repressor genes. - Highlights: • hTERT mRNA expression level decreased in the chromosome 3 introduced HSC3 clones. • hTERT mRNA expression level was tend to suppressed in HSC3 and RCC23 hybrid cells. • We provide evidence that human chromosome 3 carries at least two distinct hTERT regulatory factors.

  18. Regulated expression of genes inserted at the human chromosomal β-globin locus by homologous recombination

    International Nuclear Information System (INIS)

    Nandi, A.K.; Roginski, R.S.; Gregg, R.G.; Smithies, O.; Skoultchi, A.I.

    1988-01-01

    The authors have examined the effect of the site of integration on the expression of cloned genes introduced into cultured erythroid cells. Smithies et al. reported the targeted integration of DNA into the human β-globin locus on chromosome 11 in a mouse erythroleukemia-human cell hybrid. These hybrid cells can undergo erythroid differentiation leading to greatly increased mouse and human β-globin synthesis. By transfection of these hybrid cells with a plasmid carrying a modified human β-globin gene and a foreign gene composed of the coding sequence of the bacterial neomycin-resistance gene linked to simian virus 40 transcription signals (SVneo), cells were obtained in which the two genes are integrated at the β-globin locus on human chromosome 11 or at random sites. When they examined the response of the integrated genes to cell differentation, they found that the genes inserted at the β-globin locus were induced during differentiation, whereas randomly positioned copies were not induced. Even the foreign SVneo gene was inducible when it had been integrated at the β-globin locus. The results show that genes introduced at the β-globin locus acquire some of the regulatory properties of globin genes during erythroid differentiation

  19. Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors

    International Nuclear Information System (INIS)

    Bystroem, C.; Larsson, C.; Blomberg, C.; Nordenskjoeld, M.; Sandelin, K.; Falkmer, U.; Werner, S.; Skogseid, B.; Oeberg, K.

    1990-01-01

    The gene for multiple endocrine neoplasia type 1 (MEN1), and inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. The authors now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, they could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas

  20. Gain of chromosomal region 20q and loss of 18 discriminates between Lynch syndrome and familial colorectal cancer

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Jönsson, Göran; Dominguez-Valentin, Mev

    2013-01-01

    Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours...... are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FCCTX with comparison to 23 Lynch syndrome tumours and to 45 sporadic colorectal cancers. FCCTX tumours showed genomic complexity with frequent gains on chromosomes 20q, 19 and 17 and losses of 18, 8p...... and 15. Gain of genetic material in two separate regions encompassing, 20q12-13.12 and 20q13.2-13.32, was identified in 65% of the FCCTX tumours. Gain of material on chromosome 20q and loss on chromosome 18 significantly discriminated colorectal cancers associated with FCCTX from Lynch syndrome, which...

  1. Cytogenetic evaluation of human glial tumors: correlation of overexpression of epidermal growth factor receptor (EGFB) with abnormalities of chromosome 7

    International Nuclear Information System (INIS)

    Bell, C.W.

    1987-01-01

    Chromosome banding analysis of human glial tumors were performed using G- and Q-banding techniques in an attempt to establish recurring sites of chromosome change. Results revealed a nonrandom karyotypic profile including aneuploidy and considerable variation in chromosome number (range 40 → 200). All tumors examined displayed numerical abnormalities, with the most common numeric change being a gain of chromosome 7. An attempt was then made to correlate the observed chromosome 7 changes with activation of the cellular proto-oncogene c-erb-B, whose produce is the epidermal growth factor receptor (EGFR). Six human glial tumors were analyzed for 125 I-EGF binding, EGFR gene copy number, EGFR gene rearrangement, mRNA expression, and karyotypic profile. Saturation analysis at 4 0 C revealed significant numbers of EGFR's in all 6 tumors. Southern blotting analysis utilizing cDNA probes for the EGFR failed to demonstrate significant amplification or structural rearrangement of the EFGR gene. The results suggest that overexpression of the EGFR may be related to an alternative mechanism, other than gene amplification and elevated mRNA levels, such as the regulation of receptor biosynthesis and degradation. In summary, findings indicate that alterations of chromosome 7 are the most prevalent chromosomal change in human glial tumors, and that these alterations may lead to overexpression of the protooncogene c-erb-B

  2. Chromosomal aberrations induced by low-dose γ-irradiation: Study of R-banded chromosomes of human lymphocytes

    International Nuclear Information System (INIS)

    Al-Achkar, W.; Lefrancois, D.; Aurias, A.

    1991-01-01

    The effect of low-dose (0-0.5 Gy) γ-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas the of deletions decreases. (author). 6 refs., 3 figs., 2 tabs

  3. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    DEFF Research Database (Denmark)

    Huebner, K; Kastury, K; Druck, T

    1994-01-01

    "adapter" proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human......Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding...... hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ...

  4. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents

    International Nuclear Information System (INIS)

    Albertsen, H.M.; Abderrahim, H.; Cann, H.M.; Dausset, J.; Le Paslier, D.; Cohen, D.

    1990-01-01

    Prior to constructing a library of yeast artificial chromosomes (YACs) containing very large human DNA fragments, the authors performed a series of preliminary experiments aimed at developing a suitable protocol. They found an inverse relationship between YAC insert size and transformation efficiency. Evidence of occasional rearrangement within YAC inserts was found resulting in clonally stable internal deletions or clonally unstable size variations. A protocol was developed for preparative electrophoretic enrichment of high molecular mass human DNA fragments from partial restriction digests and ligation with the YAC vector in agarose. A YAC library has been constructed from large fragments of DNA from an Epstein-Barr virus-transformed human lymphoblastoid cell line. The library presently contains 50,000 clones, 95% of which are greater than 250 kilobase pairs in size. The mean YAC size of the library, calculated from 132 randomly isolated clones, is 430 kilobase pairs. The library thus contains the equivalent of approximately seven haploid human genomes

  5. Nucleolar organizer regions and a new chromosome number for Rhea americana (Aves: Rheiformes

    Directory of Open Access Journals (Sweden)

    Ricardo José Gunski

    1998-06-01

    Full Text Available Sequential banding analysis (Giemsa-C-banding-Ag NOR of chromosomes of the common rhea (Rhea americana was performed. Metaphases were obtained by peripheral blood lymphocyte culture and monolayer embryo cell culture. The diploid chromosome number was 80, different from the 2n = 82 in previous reports. Macrochromosome pairs 1, 2 and 5 were submetacentric and pair 3, subacrocentric. The 4th pair was acrocentric and all of the microchromosomes appeared to be acrocentric, with the exception of a clearly metacentric pair which was fully heterochromatic. The Z was slightly larger than the W, both being acrocentric and C-band negative. Nucleolar organizer regions were observed in the secondary constriction of a microchromosome pair. Correct identification of the NOR-bearing pair was possible only by sequential analyses, Giemsa staining followed by the Ag-NOR technique.Foram efetuadas análises seqüenciais de bandeamento cromossômico (Giemsa-banda-C-AgNOR em material da espécie Rhea americana (ema com o objetivo de identificar os cromossomos portadores de regiões organizadoras de nucléolos e confirmar o cariótipo desta espécie. As metáfases foram obtidas de culturas de leucócitos e de células de embrião. O número diplóide de cromossomos, determinado pela análise de metáfases oriundas de 19 espécimes, foi de 80 (2n = 80, NF = 95, o que difere da literatura. Os pares de macrocromossomos números 1, 2 e 5 eram submetacêntricos e o par 3 era sub-acrocêntrico, confirmado pelo bandeamento C. O par 4 era acrocêntrico, bem como todos os microcromossomos, com exceção de um metacêntrico inteiramente heterocromático. O cromossomo Z era ligeiramente maior que o W, sendo ambos acrocêntricos e banda-C negativos. A região organizadora de nucléolos foi observada na constrição secundária de um par de microcromossomos. A correta identificação do par portador da NOR só foi possível com a utilização da análise seqüencial de colora

  6. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini)

    Science.gov (United States)

    2009-01-01

    In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus,Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates. PMID:21637455

  7. 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

  8. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini).

    Science.gov (United States)

    Gifalli-Iughetti, Cristiani; Koiffmann, Célia P

    2009-10-01

    In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus,Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

  9. Detection of chromosomal instability in α-irradiated and bystander human fibroblasts

    International Nuclear Information System (INIS)

    Ponnaiya, Brian; Jenkins-Baker, Gloria; Bigelow, Alan; Marino, Stephen; Geard, Charles R.

    2004-01-01

    There is increasing evidence biological responses to ionizing radiation are not confined to those cells that are directly hit, but may be seen in the progeny at subsequent generations (genomic instability) and in non-irradiated neighbors of irradiated cells (bystander effects). These so called non-targeted phenomena would have significant contributions to radiation-induced carcinogenesis, especially at low doses where only a limited number of cells in a population are directed hit. Here we present data using a co-culturing protocol examining chromosomal instability in α-irradiated and bystander human fibroblasts BJ1-htert. At the first cell division following exposure to 0.1 and 1 Gy α-particles, irradiated populations demonstrated a dose dependent increase in chromosome-type aberrations. At this time bystander BJ1-htert populations demonstrated elevated chromatid-type aberrations when compared to controls. Irradiated and bystander populations were also analyzed for chromosomal aberrations as a function of time post-irradiation. When considered over 25 doublings, all irradiated and bystander populations had significantly higher frequencies of chromatid aberrations when compared to controls (2-3-fold over controls) and were not dependent on dose. The results presented here support the link between the radiation-induced phenomena of genomic instability and the bystander effect

  10. Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini

    Directory of Open Access Journals (Sweden)

    Cristiani Gifalli-Iughetti

    2009-01-01

    Full Text Available In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus, Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62. The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

  11. Lethality of radiation-induced chromosome aberrations in human tumour cell lines with different radiosensitivities.

    Science.gov (United States)

    Coco-Martin, J M; Ottenheim, C P; Bartelink, H; Begg, A C

    1996-03-01

    In order to find an explanation for the eventual disappearance of all chromosome aberrations in two radiosensitive human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two radiosensitive and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two radiosensitive lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or G1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for radiosensitivity.

  12. Contrasting patterns of Y-chromosome variation in South Siberian populations from Baikal and Altai-Sayan regions.

    Science.gov (United States)

    Derenko, Miroslava; Malyarchuk, Boris; Denisova, Galina A; Wozniak, Marcin; Dambueva, Irina; Dorzhu, Choduraa; Luzina, Faina; Miścicka-Sliwka, Danuta; Zakharov, Ilia

    2006-01-01

    In order to investigate the genetic history of autochthonous South Siberian populations and to estimate the contribution of distinct patrilineages to their gene pools, we have analyzed 17 Y-chromosomal binary markers (YAP, RPS4Y(711), SRY-8299, M89, M201, M52, M170, 12f2, M9, M20, 92R7, SRY-1532, DYS199, M173, M17, Tat, and LLY22 g) in a total sample of 1,358 males from 14 ethnic groups of Siberia (Altaians-Kizhi, Teleuts, Shors, Tuvinians, Todjins, Tofalars, Sojots, Khakassians, Buryats, Evenks), Central/Eastern Asia (Mongolians and Koreans) and Eastern Europe (Kalmyks and Russians). Based on both, the distribution pattern of Y-chromosomal haplogroups and results on AMOVA analysis we observed the statistically significant genetic differentiation between the populations of Baikal and Altai-Sayan regions. We suggest that these regional differences can be best explained by different contribution of Central/Eastern Asian and Eastern European paternal lineages into gene pools of modern South Siberians. The population of the Baikal region demonstrates the prevalence of Central/Eastern Asian lineages, whereas in the populations of Altai and Sayan regions the highest paternal contribution resulted from Eastern European descent is revealed. Yet, our data on Y-chromosome STRs variation demonstrate the clear differences between the South Siberian and Eastern European R1a1-lineages with the evolutionary ages compatible with divergence time between these two regional groups.

  13. Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

    LENUS (Irish Health Repository)

    Buckley, Patrick G

    2011-03-01

    Loss of chromosome 1p\\/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p\\/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p\\/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p\\/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p\\/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p\\/19q-deleted tumor phenotype inthese samples.

  14. Induction of chromosomal instability in human lymphoblasts by low doses of γ-radiation

    International Nuclear Information System (INIS)

    Gibbons, C.F.; Grosovsky, A.J.

    2003-01-01

    Full text: Genomic instability is a hallmark of tumorigenic progression, and a similar phenotype is also observed in a high fraction (10 - 50%) of cells that survive exposure to ionizing radiation. In both cases unstable clones are characterized by non-clonal chromosomal rearrangements, which are indicative of a high rate of genetic change during the outgrowth of an unstable parental cell. We postulate that the remarkably high frequency of radiation-induced genomic instability is incompatible with a mutational mechanism for a specific gene, or even a large family of genes. Rather, we hypothesize that a major portion of instability is attributable to the formation of chromosomal rearrangement junction sequences that act as de novo chromosomal breakage hotspots. We further suggest that critical target sequences, which represent at least 10% of the genome and include repetitive DNA sequences such as those found in centromeric heterochromatin, can be involved in breakage and rearrangement hotspots that drive persistent genomic instability and karyotypic heterogeneity. Since chromosomal damage is induced even by low dose radiation exposure, we hypothesize that this phenotype can be efficiently induced at doses that are relevant to environmental, occupational, or medical exposure. In the present study, TK6 human B-lymphoblastoid cells were irradiated with 0, 10, 20 and 200cGy, in order to provide a set of data points for single, low dose exposures. Independent clones were analyzed karyotypically approximately 40 generations after radiation exposure. Preliminary results suggest that the fraction of clones exhibiting genomic instability after 20 cGy (0.16) is similar to and statistically indistinguishable from the fraction of unstable clones following 200 cGy (0.2) exposure. These findings support the hypothesis that instability following radiation, and perhaps also in cancer, primarily reflects non-mutational mechanisms

  15. Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Hisakatsu Nawata

    Full Text Available A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression.

  16. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenic forms of Burkitt lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Neri, A.; Barriga, F.; Knowles, D.M.; Magrath, I.T.; Dalla-Favera, R.

    1988-04-01

    The authors show that endemic (eBL), sporadic (sBL), and acquired immunodeficiency syndrome-associated (AIDS-BL) forms of Burkitt lymphoma (BL) carrying t(8; 14) chromosomal translocations display different breakpoints within the immunoglobulin heavy-chain locus (IGH) on chromosome 14. In sBL (7 out of 11) and AIDS-BL (5 out of 6), the breakpoints occurred within or near the IGH ..mu.. switch (S/sub mu/) region on chromosome 14 and within the c-myc locus (MYC) on chromosome 8. In most eBL (13 out of 16) the breakpoints were mapped within or 5' to the IGH joining J/sub H/ region on chromosome 14 and outside the MYC locus on chromosome 8. Cloning and sequencing of the (8; 14) chromosomal junctions from two eBL cell lines and one eBL biopsy sample show that the recombination do not involve IGH-specific recombination signals on chromosome 14 or homologous sequences on chromosome 8, suggesting that these events are not likely to be mediated by the same mechanisms or enzymes as in IGH rearrangements. In general, these data have implications for the timing of occurrence of chromosomal translocations during B-cell differentiation in different BL types.

  17. Integration sites of Epstein-Barr virus genome on chromosomes of human lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wuu, K.D.; Chen, Y.J.; Wang-Wuu, S. [Institute of Genetics, Taipei (Taiwan, Province of China)

    1994-09-01

    Epstein-Barr virus (EBV) is the pathogen of infectious mononucleosis. The viral genome is present in more than 95% of the African cases of Burkitt lymphoma and it is usually maintained in episomal form in the tumor cells. Viral integration has been described only for Nanalwa which is a Burkitt lymphoma cell line lacking episomes. In order to examine the role of EBV in the immortalization of human Blymphocytes, we investigated whether the EBV integration into the human genome is essential. If the integration does occur, we would like to know whether the integration is randomly distributed or whether the viral DNA integrates preferentially at certain sites. Fourteen in vitro immortalized human lymphoblastoid cell lines (LCLs) were examined by fluorescence in situ hybridization (FISH) with a biotinylated EBV BamHI w DNA fragment as probe. The episomal form of EBV DNA was found in all cells of these cell lines, while only about 65% of the cells have the integrated viral DNA. This might suggest that integration is not a pre-requisite for cell immortalization. Although all chromosomes, except Y, have been found with integrated viral genome, chromsomes 1 and 5 are the most frequent EBV DNA carrier (p<0.05). Nine chromosome bands, namely, 1p31, 1q31, 2q32, 3q13, 3q26, 5q14, 6q24, 7q31 and 12q21, are preferential targets for EBV integration (p<0.001). Eighty percent of the total 938 EBV hybridization signals were found to be at G-band-positive area. This suggests that the mechanism of EBV integration might be different from that of the retroviruses, which specifically integrate to G-band-negative areas. Thus, we conclude that the integration of EBV to host genome is non-random and it may have something to do with the structure of chromosome and DNA sequences.

  18. The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3

    Energy Technology Data Exchange (ETDEWEB)

    Kapfhamer, D.; Sufalko, D.; Warren, S. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-08-01

    Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene. 31 refs., 2 figs.

  19. A unique genomic sequence in the Wolf-Hirschhorn syndrome [WHS] region of humans is conserved in the great apes.

    Science.gov (United States)

    Tarzami, S T; Kringstein, A M; Conte, R A; Verma, R S

    1996-10-01

    The Wolf-Hirschhorn syndrome (WHS) is caused by a partial deletion in the short arm of chromosome 4 band 16.3 (4p 16.3). A unique-sequence human DNA probe (39 kb) localized within this region has been used to search for sequence homology in the apes' equivalent chromosome 3 by FISH-technique. The WHS loci are conserved in higher primates at the expected position. Nevertheless, a control probe, which detects alphoid sequences of the pericentromeric region of humans, is diverged in chimpanzee, gorilla, and orangutan. The conservation of WHS loci and divergence of DNA alphoid sequences have further added to the controversy concerning human descent.

  20. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, L.M. (Department of Molecular Genetics, Institute of Genetics, Sofia (Bulgaria)); Mullenders, L.H.F.; Natarajan, A.T. (J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden (Netherlands))

    1994-12-01

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations.

  1. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    International Nuclear Information System (INIS)

    Stoilov, L.M.; Mullenders, L.H.F.; Natarajan, A.T.

    1994-01-01

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

  2. Radiation exposure and chromosome abnormalities. Human cytogenetic studies at the National Institute of Radiological Sciences, Japan, 1963-1988

    International Nuclear Information System (INIS)

    Ishihara, T.; Kohno, S.; Minamihisamatsu, M.

    1990-01-01

    The results of human cytogenetic studies performed at the National Institute of Radiological Sciences (NIRS), Chiba, Japan for about 25 years are described. The studies were pursued primarily under two major projects: one involving people exposed to radiation under various conditions and the other involving patients with malignant diseases, especially leukemias. Whereas chromosome abnormalities in radiation-exposed people are excellent indicators of radiation exposure, their behavior in bone marrow provide useful information for a better understanding of chromosome abnormalities in leukemias and related disorders. The role of chromosome abnormalities in the genesis and development of leukemia and related disorders is considered, suggesting a view for future studies in this field

  3. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    Directory of Open Access Journals (Sweden)

    Lucie Šedová

    Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

  4. 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.

  5. Structural and functional organization of the HF.10 human zinc finger gene (ZNF35) located on chromosome 3p21-p22

    DEFF Research Database (Denmark)

    Lanfrancone, L; Pengue, G; Pandolfi, P P

    1992-01-01

    We report the structural and functional characterization of the HF.10 zinc finger gene (ZNF35) in normal human cells, as well as a processed pseudogene. The HF.10 gene spans about 13 kb and it is interrupted by three introns. All 11 zinc finger DNA-binding domains are contiguously encoded within...... and partial nucleotide sequencing of the HF.10 pseudogene indicated that it has arisen by retroposition of spliced HF.10 mRNA. In situ hybridization experiments revealed that both the functional locus and the pseudogene map to chromosome 3p21p22, a region that is frequently deleted in small cell lung...... and renal carcinomas. Hybridization of the HF.10 gene and the HF.10 pseudogene DNA probes to metaphases from a small cell lung carcinoma cell line with the 3p deletion revealed that both loci are part of the deleted chromosome region....

  6. Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

    Directory of Open Access Journals (Sweden)

    Sivaramakurup Sreekumar

    2010-01-01

    Full Text Available In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

  7. Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism

    International Nuclear Information System (INIS)

    Huang, L.; Miller, D.A.; Bruns, G.A.P.; Breslow, J.L.

    1986-01-01

    ApoB is a large glycoprotein with an apparent molecular mass of 550 kDa on NaDodSO 4 /PAGE. Recently, apoB cDNA clones have been isolated from an expression library made with mRNA from a human hepatoma cell line. These clones, which were all 1.5-1.6 kilobases (kb) long and corresponded to the 3' end of apoB mRNA, were used to demonstrate that hepatic apoB mRNA is ≅ 22 kb long. In the current report, a probe derived from one of these cDNA clones, pB8, was used for in situ hybridization experiments to map the human gene for apoB, APOB, to the distal half of the short arm of chromosome 2. This probe was also used to analyze somatic cell hybrids and, in agreement with the in situ hybridization studies, concordancy was demonstrated with chromosome 2. In addition, two hybrids with chromosome 2 translocations that contain only the short arm reacted with the pB8 probe. A third hybrid with a complex rearrangement of chromosome 2, which deleted an interstitial region and the tip of the short arm of chromosome 2, did not react. These data indicate that APOB maps to either 2p21-p23 or 2p24-pter. In further studies, DNA from normal individuals, digested with the restriction endonuclease EcoRI and subjected to Southern blot analysis with the pB8 probe, revealed a two-allele restriction fragment length polymorphism (RFLP). The mapping studies provide the means for understanding the relationship of the APOB locus to others in the human genome, whereas the demonstration of an APOB RFLP increases their ability to assess the role of this locus in determining plasma lipoprotein levels

  8. On-line sorting of human chromosomes by centromeric index, and identification of sorted populations by GTG-banding and fluorescent in situ hybridization

    NARCIS (Netherlands)

    Boschman, G. A.; Rens, W.; Manders, E.; van Oven, C.; Barendsen, G. W.; Aten, J. A.

    1990-01-01

    Using slit-scan flow cytometry, the shape of human metaphase chromosomes, as expressed in their centromeric index (CI), and the DNA content of the chromosomes have been used as parameters in bivariate flow karyotyping. The resolution of the DNA vs CI flow karyogram of the larger chromosomes up to

  9. Thinking regionally: narrative, the medical humanities and region.

    Science.gov (United States)

    Waddington, Keir

    2015-06-01

    Drawing on multiple literatures from history, geography, anthropology, sociology and literature, this essay asks questions about what we mean by region and why narratives of region should matter to the medical humanities. The essay surveys how region can be used as a lens of analysis, exploring the various academic approaches to region and their limitations. It argues that regions are dynamic but also unstable as a category of analysis and are often used uncritically by scholars. In encouraging scholars working in the medical humanities to be aware that regions are not simple objective or analytical boxes, the essay shows how an awareness of region helps challenge metropolitan whiggism and ideas of core and periphery to give a more prominent place to hinterlands, market towns and rural environments. Furthermore, the essay considers how incorporating region into our understanding of illness can offer new insights. It demonstrates the need for scholars to be attuned to the narratives constructed around regions, suggesting that regions can be viewed as discursive formations that provide a frame for understanding both collective and personal ideas of, and responses to, health and illness, disease and healing, to create what Megan Davies calls a more nuanced 'intellectual cartography'. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

    Science.gov (United States)

    Coignet, L J; Lima, C S; Min, T; Streubel, B; Swansbury, J; Telford, N; Swanton, S; Bowen, A; Nagai, M; Catovsky, D; Fonatsch, C; Dyer, M J

    1999-07-01

    Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.

  11. Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig.

    Science.gov (United States)

    Fan, B; Glenn, K L; Geiger, B; Mileham, A; Rothschild, M F

    2008-08-01

    Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

  12. The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, F. A.

    2011-01-01

    Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

  13. [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.

  14. A genome-wide identification of chromosomal regions determining nitrogen use efficiency components in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Cormier, Fabien; Le Gouis, Jacques; Dubreuil, Pierre; Lafarge, Stéphane; Praud, Sébastien

    2014-12-01

    This study identified 333 genomic regions associated to 28 traits related to nitrogen use efficiency in European winter wheat using genome-wide association in a 214-varieties panel experimented in eight environments. Improving nitrogen use efficiency is a key factor to sustainably ensure global production increase. However, while high-throughput screening methods remain at a developmental stage, genetic progress may be mainly driven by marker-assisted selection. The objective of this study was to identify chromosomal regions associated with nitrogen use efficiency-related traits in bread wheat (Triticum aestivum L.) using a genome-wide association approach. Two hundred and fourteen European elite varieties were characterised for 28 traits related to nitrogen use efficiency in eight environments in which two different nitrogen fertilisation levels were tested. The genome-wide association study was carried out using 23,603 SNP with a mixed model for taking into account parentage relationships among varieties. We identified 1,010 significantly associated SNP which defined 333 chromosomal regions associated with at least one trait and found colocalisations for 39 % of these chromosomal regions. A method based on linkage disequilibrium to define the associated region was suggested and discussed with reference to false positive rate. Through a network approach, colocalisations were analysed and highlighted the impact of genomic regions controlling nitrogen status at flowering, precocity, and nitrogen utilisation on global agronomic performance. We were able to explain 40 ± 10 % of the total genetic variation. Numerous colocalisations with previously published genomic regions were observed with such candidate genes as Ppd-D1, Rht-D1, NADH-Gogat, and GSe. We highlighted selection pressure on yield and nitrogen utilisation discussing allele frequencies in associated regions.

  15. Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf–Hirschhorn syndrome

    Science.gov (United States)

    South, Sarah T; Lortz, Amanda; Hensel, Charles H; Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Peiffer, Andreas; Lambert, Christophe G; Calhoun, Amy; Carey, John C; Battaglia, Agatino

    2016-01-01

    Background Wolf–Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Methods Using chromosomal microarray analysis, we finely mapped the breakpoints of copy number variants (CNVs) in 48 individuals with WHS. Seizure phenotype data were collected through parent-reported answers to a comprehensive questionnaire and supplemented with available medical records. Results We observed a significant correlation between the presence of an interstitial 4p deletion and lack of a seizure phenotype (Fisher's exact test p=3.59e-6). In our cohort, there were five individuals with interstitial deletions with a distal breakpoint at least 751 kbp proximal to the 4p terminus. Four of these individuals have never had an observable seizure, and the fifth individual had a single febrile seizure at the age of 1.5 years. All other individuals in our cohort whose deletions encompass the terminal 751 kbp region report having seizures typical of WHS. Additional examples from the literature corroborate these observations and further refine the candidate seizure susceptibility region to a region 197 kbp in size, starting 368 kbp from the terminus of chromosome 4. Conclusions We identify a small terminal region of chromosome 4p that represents a seizure susceptibility region. Deletion of this region in the context of WHS is sufficient for seizure occurrence. PMID:26747863

  16. Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Ho, Karen S; South, Sarah T; Lortz, Amanda; Hensel, Charles H; Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Peiffer, Andreas; Lambert, Christophe G; Calhoun, Amy; Carey, John C; Battaglia, Agatino

    2016-04-01

    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Using chromosomal microarray analysis, we finely mapped the breakpoints of copy number variants (CNVs) in 48 individuals with WHS. Seizure phenotype data were collected through parent-reported answers to a comprehensive questionnaire and supplemented with available medical records. We observed a significant correlation between the presence of an interstitial 4p deletion and lack of a seizure phenotype (Fisher's exact test p=3.59e-6). In our cohort, there were five individuals with interstitial deletions with a distal breakpoint at least 751 kbp proximal to the 4p terminus. Four of these individuals have never had an observable seizure, and the fifth individual had a single febrile seizure at the age of 1.5 years. All other individuals in our cohort whose deletions encompass the terminal 751 kbp region report having seizures typical of WHS. Additional examples from the literature corroborate these observations and further refine the candidate seizure susceptibility region to a region 197 kbp in size, starting 368 kbp from the terminus of chromosome 4. We identify a small terminal region of chromosome 4p that represents a seizure susceptibility region. Deletion of this region in the context of WHS is sufficient for seizure occurrence. 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/

  17. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage

    DEFF Research Database (Denmark)

    Hagmar, L; Brøgger, A; Hansteen, I L

    1994-01-01

    Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target...... tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange.......0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk....

  18. Mitotic chromosome structure

    International Nuclear Information System (INIS)

    Heermann, Dieter W.

    2012-01-01

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

  19. Mitotic chromosome structure

    Energy Technology Data Exchange (ETDEWEB)

    Heermann, Dieter W., E-mail: heermann@tphys.uni-heidelberg.de

    2012-07-15

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

  20. Biological effects of tritiated water in low concentration of human lymphocyte chromosome

    International Nuclear Information System (INIS)

    Tanaka, K.; Kamada, N.; Sawaeda, S.

    1992-01-01

    This study was undertaken to investigate the dose-response relationship of tritiated water (HTO) for chromosome aberration in the human lymphocytes, at low dose in vitro exposure ranging from 0.1-1 Gy. The Relative Biological Effectiveness values of HTO with respect to 60 Co gamma ray at a dose rate of 2 cGy/min(15 mCi/ml), at low dose range for the induction of dicentric and centric ring chromosomes were 2.7 in lymphocytes. Also lymphocytes were chronically exposed to HTO for 67 to 80 hrs at different lower dose rates (0.5 and 0.02 cGy/min). There was a 77% decrease in the yields of dicentrics and centric rings, at the dose rate of 0.02cGy/min of HTO, presenting a clear dose rate effect of HTO. The RBE value of HTO relative to 137 Cs gamma ray was 2.0 at the dose rate of 0.02cGy/min(0.15mCi/ml). This suggests that a higher dose rate of HTO exposure has a higher risk and a decrease of RBE value at low dose rate. These results provide useful information for the assessment of health risks in humans specially exposed to low concentration of HTO. (author). 6 refs., 2 figs

  1. Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

    International Nuclear Information System (INIS)

    Hori, T.; Moriya, Junko; Nakai, Sayaka

    1978-01-01

    Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

  2. Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration.

    Science.gov (United States)

    Gilbert-Girard, Shella; Gravel, Annie; Artusi, Sara; Richter, Sara N; Wallaschek, Nina; Kaufer, Benedikt B; Flamand, Louis

    2017-07-15

    Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency ( P integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A. IMPORTANCE HHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3' extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the

  3. Human chromosome-specific changes in a human-hamster hybrid cell line (AL) assessed by fluorescent in situ hybridization (fish)

    International Nuclear Information System (INIS)

    Geard, Charles R.; Jenkins, Gloria

    1995-01-01

    Purpose: To quantitatively assess all gamma-ray induced chromosomal changes confined to one human chromosome using fluorescence microscopy and in situ hybridization with a fluorescently labeled human chromosome specific nucleic acid probe. Methods and Materials: Synchronized human-hamster hybrid cells containing human chromosome 11 were obtained by a modified mitotic shake-off procedure. G1 phase cells (> 95%) were irradiated with 137 Cs gamma rays (0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, and 10.0 Gy) at a dose rate of 1.1 Gy/min and mitotic cells collected 16-20 h later; chromosomal spreads were prepared, denatured, and hybridized with a fluorescein-tagged nucleic acid probe against total human DNA. Chromosomes were examined by fluorescence microscopy and all categories of change involving the human chromosome 11 as target, recorded. Results: Overall, of the 3104 human-hamster hybrid cells examined, 82.1% were euploid, of which 88.6% contained one copy of human chromosome 11, 6.2% contained two copies, and 5.2% contained 0 copies. This is compatible with mitotic nondisjunction in a small fraction of cells. Of the remaining 17.9% of cells, 85.2% were tetraploid cells with two copies of human chromosome 11. For all aberrations involving human chromosome 11 there was a linear relationship between yield and absorbed dose of 0.1 aberrations per chromosome per Gy. The yield of dicentrics, translocations, and terminal deletions that involve one lesion on the human chromosome was linear, while the yield of interstitial deletions that arise from two interacting lesions on the human chromosome was curvilinear. The frequencies of dicentrics and translocations were about equal, while there was a high (40-60%) incidence of incomplete exchanges between human and hamster chromosomes. Conclusions: Fluorescent in situ hybridization (FISH) procedures allow for the efficient detection of a broad range of induced changes in target chromosomes. Symmetrical exchanges induced in G1

  4. Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology.

    Science.gov (United States)

    Fajkus, J; Simícková, M; Maláska, J

    2002-04-29

    The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

  5. Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Seyyedi, S. S.; Mozdarani, H.; Rezaei Tavirani, M.; Heydari, S.

    2010-01-01

    Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to extremely low-frequency electromagnetic fields may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Materials and Methods: Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields (3, 50 and 60 Hz, sinusoidal, 3h, and 4 m T). Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous extremely low-frequency electromagnetic fields (50 Hz, sinusoidal, 3 h, 4 m T). Metaphase plates Were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of extremely low-frequency electromagnetic fields on primary or established cell lines. Results: Results indicate that by increasing the frequency of extremely low-frequency electromagnetic fields, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Conclusion: Results obtained indicate that extremely low-frequency electromagnetic fields has the potential for induction of chromosomal aberrations in all cell types.

  6. Flagellar region 3b supports strong expression of integrated DNA and the highest chromosomal integration efficiency of the Escherichia coli flagellar regions.

    Science.gov (United States)

    Juhas, Mario; Ajioka, James W

    2015-07-01

    The Gram-negative bacterium Escherichia coli is routinely used as the chassis for a variety of biotechnology and synthetic biology applications. Identification and analysis of reliable chromosomal integration and expression target loci is crucial for E. coli engineering. Chromosomal loci differ significantly in their ability to support integration and expression of the integrated genetic circuits. In this study, we investigate E. coli K12 MG1655 flagellar regions 2 and 3b. Integration of the genetic circuit into seven and nine highly conserved genes of the flagellar regions 2 (motA, motB, flhD, flhE, cheW, cheY and cheZ) and 3b (fliE, F, G, J, K, L, M, P, R), respectively, showed significant variation in their ability to support chromosomal integration and expression of the integrated genetic circuit. While not reducing the growth of the engineered strains, the integrations into all 16 target sites led to the loss of motility. In addition to high expression, the flagellar region 3b supports the highest efficiency of integration of all E. coli K12 MG1655 flagellar regions and is therefore potentially the most suitable for the integration of synthetic genetic circuits. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  7. The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Wasco, W.; Tanzi, R.E. (Harvard Medical School, Boston, MA (United States)); Brook, J.D. (Center for Medical Genetics, Nottingham (United Kingdom))

    1993-01-01

    We have recently isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid [beta] protein precursor (APP; 16). This 653-amino-acid amyloid precursor-like protein (APLP) is similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are particularly strong in three distinct regions of the proteins where the identities are 47, 54, and 56% (16). All three of these regions are also conserved in the Drosophila APP-like gene, APPL (11). Notably, 12 cysteine residues and a N -glyco-sylation site are conserved in the extracellular portion of APLP and APP, and a clathrin-binding domain is conserved in the cytoplasmic domain. The cytoplasmic domain is also conserved in a partial CDNA reported to encode an APP-like gene in rat testes (17), These data suggest that APLP and APP are members of a highly conserved gene family. A panel of DNAs from 31 human-rodent somatic cell lines of known karyotype was digested with EcoR1. These DNAs were then probed with the human APLP cDNA clone and the hybridization pattern was consistent with the assignment of the APLP locus to chromosome 19. 17 refs., 1 fig.

  8. The use of premature chromosome condensation to study in interphase cells the influence of environmental factors on human genetic material

    Directory of Open Access Journals (Sweden)

    Vasiliki I. Hatzi

    2006-01-01

    Full Text Available Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics.

  9. Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

    Directory of Open Access Journals (Sweden)

    Shamone R Gore-Panter

    Full Text Available Atrial Fibrillation (AF, the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS have identified that the single nucleotide polymorphisms (SNPs most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

  10. Genetic and physical mapping of two centromere-proximal regions of chromosome IV in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Aleksenko, Alexei Y.; Nielsen, Michael Lynge; Clutterbuck, A.J.

    2001-01-01

    revision of the genetic map of the chromosome, including the position of the centromere, Comparison of physical and genetic maps indicates that meiotic recombination is low in subcentromeric DNA, its frequency being reduced from 1 crossover per 0.8 Mb to approximately 1 crossover per 5 Mb per meiosis...

  11. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn

    2008-01-01

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

  12. Chromosomal radiosensitivity: a study of the chromosomal G2 assay in human blood lymphocytes indicating significant inter-individual variability

    International Nuclear Information System (INIS)

    Smart, V.; Curwen, G.B.; Whitehouse, C.A.; Edwards, A.; Tawn, E.J.

    2003-01-01

    The G 2 chromosomal radiosensitivity assay is a technically demanding assay. To ensure that it is reproducible in our laboratory, we have examined the effects of storage and culture conditions by applying the assay to a group of healthy controls and determined the extent of intra- and inter-individual variations. Nineteen different individuals provided one or more blood samples resulting in a total of 57 successful tests. Multiple cultures from a single blood sample showed no statistically significant difference in the number of chromatid type aberrations between cultures. A 24 h delay prior to culturing the lymphocytes did not significantly affect the induced G 2 score. Intra-individual variation was not statistically significant in seven out of nine individuals. Inter-individual variation was highly statistically significant (P<0.001), indicating that there is a real difference between individuals in the response to radiation using this assay

  13. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

    International Nuclear Information System (INIS)

    Benkhaled, L.; Xuncla, M.; Caballin, M.R.; Barrios, L.; Barquinero, J.F.

    2008-01-01

    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (∼0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM

  14. 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.)

  15. 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)

  16. 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.

  17. 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

  18. 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.

  19. The first cytogenetic data on Strumigenys louisianae Roger, 1863 (Formicidae: Myrmicinae: Dacetini: the lowest chromosome number in the Hymenoptera of the neotropical region.

    Directory of Open Access Journals (Sweden)

    Ana Paula Alves-Silva

    Full Text Available In the present study, the first cytogenetic data was obtained for the ant species Strumigenys louisianae, from a genus possessing no previous cytogenetic data for the Neotropical region. The chromosome number observed was 2n = 4, all possessing metacentric morphology. Blocks rich in GC base pairs were observed in the interstitial region of the short arm of the largest chromosome pair, which may indicate that this region corresponds to the NORs. The referred species presented the lowest chromosome number observed for the subfamily Myrmicinae and for the Hymenoptera found in the Neotropical region. Observation of a low chromosome number karyotype has been described in Myrmecia croslandi, in which the occurrence of tandem fusions accounts for the most probable rearrangement for its formation. The accumulation of cytogenetic data may carry crucial information to ensure deeper understanding of the systematics of the tribe Dacetini.

  20. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis

    International Nuclear Information System (INIS)

    Klinger, K.W.; Winqvist, R.; Riccio, A.

    1987-01-01

    The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer

  1. Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

    Directory of Open Access Journals (Sweden)

    Volfovsky Natalia

    2009-01-01

    Full Text Available Abstract Background Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes. Results Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb region, (ii those with at least one exact copy found nearby, and (iii those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429 were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans. Conclusion Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are

  2. Interstitial deletion in the "critical region" of the long arm of the X chromosome in a mentally retarded boy and his normal mother

    DEFF Research Database (Denmark)

    Tabor, A; Andersen, O; Lundsteen, C

    1983-01-01

    A family in which an intestitial deletion of the X chromosome, del(X)(q13q21.3), is segregating was ascertained through a boy with cleft lip and palate, agenesis of the corpus callosum, and severe mental retardation. The possible causal relationship to his chromosome abnormality is discussed. Alt....... Although the deletion occurred within the critical region, the mother showed no signs of gonadal dysgenesis. A phenotypically normal daughter was, as her mother, monosomic for this region of the X, and both showed random inactivation of the X chromosome....

  3. Chromosomal aberrations and DNA damage in human populations exposed to the processing of electronics waste.

    Science.gov (United States)

    Liu, Qiang; Cao, Jia; Li, Ke Qiu; Miao, Xu Hong; Li, Guang; Fan, Fei Yue; Zhao, Yong Cheng

    2009-05-01

    It has been known that the pollutants of electronic wastes (E-wastes) can lead to severe pollution to the environment. It has been reported that about 50% to 80% of E-wastes from developed countries are exported to Asia and Africa. It has become a major global environmental problem to deal with 'E-wastes'. E-waste recycling has remained primitive in Jinghai, China. This not only produces enormous environmental pollution but also can bring about toxic or genotoxic effects on the human body, threatening the health of both current residents and future generations living in the local environment. The concentration of lead in the blood of children in the E-waste polluted area in China is higher than that of the control area. But little is known about the cytogenetic effect to human beings caused by the pollution of E-wastes. In the present study, experiments have been performed to investigate the genetics of permanent residents of three villages with numerous E-waste disposal sites and to analyze the harmful effects of exposure to E-wastes. In total, 171 villagers (exposed group) were randomly selected from permanent residents of three villages located in Jinghai County of Tianjin, China, where there has been massive disposal of E-wastes. Thirty villagers were selected from the neighboring towns without E-waste disposal sites to serve as controls. Chromosomal aberrations and cytokinesis blocking micronucleus were performed to detect the cytogenetic effect, dic + r (dicentric and ring chromosome), monomer, fragments (acentric fragments, minute chromosomes, and acentric rings), translocation, satellite, quadriradial, total aberrations, and micronuclear rate were scored for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes. The total chromosome aberration rates (5.50%) and micronuclear rates (16.99%) of the exposure group

  4. Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders.

    Science.gov (United States)

    Webb, Amy; Miller, Bruce; Bonasera, Stephen; Boxer, Adam; Karydas, Anna; Wilhelmsen, Kirk C

    2008-11-01

    An inverted region on chromosome 17 has been previously linked to many Pick complex diseases. Due to the inversion, an exact causal locus has been difficult to identify, but the microtubule-associated protein tau gene is a likely candidate gene for its involvement in these diseases with tau inclusion. To search for variants that confer susceptibility to 4 tauopathies and clinically related disorders. Genomewide association study. University research laboratory. A total of 231 samples were genotyped from an unrelated white population of patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia, and frontotemporal dementia with amyotrophy. Unaffected individuals from the same population were used as controls. The results from an inverted region of chromosome 17 that contains the MAPT gene. Genotypes of cases and controls were compared using a Fisher exact test on a marker-by-marker basis. Haplotypes were determined by visually inspecting genotypes. Comparing any particular disease and controls, the association was constant across the inverted chromosome segment. Significant associations were seen for PSP and PSP combined with CBD. Of the 2 haplotypes seen in the region, H1 was overrepresented in PSP and CBD cases compared with controls. As expected, the markers are highly correlated and the association is seen across the entire region, which makes it difficult to narrow down a disease-causing variant or even a possible candidate gene. However, considering the pathologic abnormalities of these diseases and the involvement of tau mutations seen in familial forms, the MAPT gene represents the most likely cause driving the association.

  5. 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)

  6. Chromosome dosimetry: the influence of culture media on the proliferation of irradiated and unirradiated human lymphocytes

    International Nuclear Information System (INIS)

    Purrott, R.J.; Lloyd, D.C.; Vulpis, N.

    1981-01-01

    The proliferation of phytohaemagglutinin stimulated human lymphocytes in four types of synthetic culture medium has been studied using the fluorescence plus Giemsa staining technique to determine cell cycle status. 48 hour cultures of unirradiated cells containing Ham's F10 or RPMI 1640 media yielded significant numbers of second cycle metaphases. Cultures containing Eagle's MEM or TC 199 media, however, required longer incubation times to produce appreciable numbers of second division cells. Intrinsic differences between donors in the rate of proliferation had little effect on the relative ranking of the media. Radiation induced mitotic delay of about 1 hour per Gray was observed for each medium. The relevance of these results to the accuracy of radiation dose estimation by chromosome aberration analysis is discussed. (author)

  7. Assignment of FUT8 to chicken chromosome band 5q1.4 and to human chromosome 14q23.2-->q24.1 by in situ hybridization. Conserved and compared synteny between human and chicken

    NARCIS (Netherlands)

    Coullin, Ph.; Crooijmans, R.P.M.A.; Groenen, M.A.M.; Heilig, R.; Mollicone, R.; Oriol, R.; Candelier, J.J.

    2002-01-01

    The human FUT8 gene is implicated in crucial developmental stages and is overexpressed in some tumors and other malignant diseases. Based on three different experiments we have assigned the FUT8 gene to chromosome bands 14q23.2 --> q24.1 and not 14q24.3 as previously shown (Yamaguchi et al.,

  8. Inversion of the chromosomal region between two mating type loci switches the mating type in Hansenula polymorpha.

    Science.gov (United States)

    Maekawa, Hiromi; Kaneko, Yoshinobu

    2014-11-01

    Yeast mating type is determined by the genotype at the mating type locus (MAT). In homothallic (self-fertile) Saccharomycotina such as Saccharomyces cerevisiae and Kluveromyces lactis, high-efficiency switching between a and α mating types enables mating. Two silent mating type cassettes, in addition to an active MAT locus, are essential components of the mating type switching mechanism. In this study, we investigated the structure and functions of mating type genes in H. polymorpha (also designated as Ogataea polymorpha). The H. polymorpha genome was found to harbor two MAT loci, MAT1 and MAT2, that are ∼18 kb apart on the same chromosome. MAT1-encoded α1 specifies α cell identity, whereas none of the mating type genes were required for a identity and mating. MAT1-encoded α2 and MAT2-encoded a1 were, however, essential for meiosis. When present in the location next to SLA2 and SUI1 genes, MAT1 or MAT2 was transcriptionally active, while the other was repressed. An inversion of the MAT intervening region was induced by nutrient limitation, resulting in the swapping of the chromosomal locations of two MAT loci, and hence switching of mating type identity. Inversion-deficient mutants exhibited severe defects only in mating with each other, suggesting that this inversion is the mechanism of mating type switching and homothallism. This chromosomal inversion-based mechanism represents a novel form of mating type switching that requires only two MAT loci.

  9. New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes for radiation molecular cytogenetics

    Directory of Open Access Journals (Sweden)

    Repin Mikhail V

    2009-06-01

    Full Text Available Abstract Background The objective of this work is to obtain the correct relative DNA contents of chromosomes in the normal male and female human diploid genomes for the use at FISH analysis of radiation-induced chromosome aberrations. Results The relative DNA contents of chromosomes in the male and female human diploid genomes have been calculated from the publicly available international Human Genome Project data. New sequence-based data on the relative DNA contents of human chromosomes were compared with the data recommended by the International Atomic Energy Agency in 2001. The differences in the values of the relative DNA contents of chromosomes obtained by using different approaches for 15 human chromosomes, mainly for large chromosomes, were below 2%. For the chromosomes 13, 17, 20 and 22 the differences were above 5%. Conclusion New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes were obtained. This approach, based on the genome sequence, can be recommended for the use in radiation molecular cytogenetics.

  10. Electron microscope mapping of the pericentric and intercalary heterochromatic regions of the polytene chromosomes of the mutant Suppressor of underreplication in Drosophila melanogaster.

    Science.gov (United States)

    Semeshin, F; Belyaeva, S; Zhimulev, F

    2001-12-01

    Breaks and ectopic contacts in the heterochromatic regions of Drosophila melanogaster polytene chromosomes are the manifestations of the cytological effects of DNA underreplication. Their appearance makes these regions difficult to map. The Su(UR)ES gene, which controls the phenomenon, has been described recently. Mutation of this locus gives rise to new blocks of material in the pericentric heterochromatic regions and causes the disappearance of breaks and ectopic contacts in the intercalary heterochromatic regions, thereby making the banding pattern distinct and providing better opportunities for mapping of the heterochromatic regions in polytene chromosomes. Here, we present the results of an electron microscope study of the heterochromatic regions. In the wild-type salivary glands, the pericentric regions correspond to the beta-heterochromatin and do not show the banding pattern. The most conspicuous cytological effect of the Su(UR)ES mutation is the formation of a large banded chromosome fragment comprising at least 25 bands at the site where the 3L and 3R proximal arms connect. In the other pericentric regions, 20CF, 40BF and 41BC, 15, 12 and 9 new bands were revealed, respectively. A large block of densely packed material appears in the most proximal part of the fourth chromosome. An electron microscope analysis of 26 polytene chromosome regions showing the characteristic features of intercalary heterochromatin was also performed. Suppression of DNA underreplication in the mutant transforms the bands with weak spots into large single bands.

  11. Phylogeography of haplotypes of five microsatellites located in a low-recombination region of the X chromosome: studies worldwide and in Brazilian populations.

    Science.gov (United States)

    Pereira, Rinaldo Wellerson; Pena, Sérgio D J

    2006-01-01

    We studied five microsatellites (DXS995, DXS8076, DXS8114, DXS1002 and DXS1050) located in a region of very low recombination rate in the long arm of the human X chromosome (Xq13.3-Xq21.3). No recombination was seen in 291 meioses in CEPH families. To test whether haplotypes composed of the five microsatellites could differentiate among distinct human continental populations, we studied an international panel containing 72 males from Africa, Europe, Asia and the America. Haplotypic diversity was very high within these groups and no haplotypes were shared among them. This led to the hope that we might be able to identify continent-specific lineages. However, in a median joining network there was no clear discrimination of the different continental groups. We then tested whether we could identify X chromosomal lineages from different continental origins in Brazilians. We typed 180 white Brazilians from four different geographical regions and examined their proportions of haplotype sharing with Africans, Asians, Europeans and Amerindians. No phylogeographical patterns emerged from the data. Moreover, there were several instances of the same haplotype being shared by many (and in one instance all) groups, suggesting that recombination might be occurring. We thus studied pairwise the level of linkage disequilibrium (LD) between the microsatellites. No detectable linkage disequilibrium between the most external loci DXS995 and DXS1050 was observed. Thus, even though recombination may be absent on short time spans, as seen in the CEPH pedigrees, on a long term basis it occurs often enough to dissipate all linkage disequilibrium. On the other hand, we observed very strong linkage disequilibrium between the pairs DXS995/DXS8076 and DXS1002/DXS8114, raising the possibility of resequencing the segment between them to identify single nucleotide polymorphisms (SNPs) in their intervals. The combination of X-linked microsatellites and SNPs in strong linkage disequilibrium might

  12. Mapping of the human NMDA receptor subunit (NMDAR1) and the proposed NMDA receptor glutamate-binding subunit (NMDARA1) to chromosomes 9q34.3 and chromosome 8, respectively

    DEFF Research Database (Denmark)

    Collins, C; Duff, C; Duncan, A M

    1993-01-01

    to human chromosome 8 using a somatic cell hybrid panel. Because the gene causing HD has been localized to chromosome 4p16.3, the chromosome assignments reported here are inconsistent with either of these genes playing a causative role in the molecular pathology of HD. However, it is noteworthy......A role for the N-methyl-D-aspartate (NMDA) receptor in the molecular pathology underlying Huntington disease (HD) has been proposed on the basis of neurochemical studies in HD and the ability of the NMDA receptor to mediate neuronal cell death. The molecular cloning of the human NMDA receptor...

  13. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Leana-Cox, J. (Univ. of Maryland School of Medicine, Baltimore, MD (United States)); Jenkins, L. (Kaiser Permanente Medical Group, San Jose, CA (United States)); Palmer, C.G.; Plattner, R. (Indiana School of Medicine, Indianapolis, IN (United States)); Sheppard, L. (Palo Verde Laboratory, Inc., Chandler, AZ (United States)); Flejter, W.L. (Univ. of Michigan, Ann Arbor, MI (United States)); Zackowski, J. (Univ. of Florida Health Science Center, Gainsville, FL (United States)); Tsien, F. (Tulane Univ. School of Medicine, New Orleans, LA (United States)); Schwartz, S. (Case Western Reserve Univ., Cleveland, OH (United States))

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  14. 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.

  15. 4p16.3 microdeletions and microduplications detected by chromosomal microarray analysis: New insights into mechanisms and critical regions.

    Science.gov (United States)

    Bi, Weimin; Cheung, Sau-Wai; Breman, Amy M; Bacino, Carlos A

    2016-10-01

    Deletions in the 4p16.3 region cause Wolf-Hirschhorn syndrome, a well known contiguous microdeletion syndrome with the critical region for common phenotype mapped in WHSCR2. Recently, duplications in 4p16.3 were reported in three patients with developmental delay and dysmorphic features. Through chromosomal microarray analysis, we identified 156 patients with a deletion (n = 109) or duplication (n = 47) in 4p16.3 out of approximately 60,000 patients analyzed by Baylor Miraca Genetics Laboratories. Seventy-five of the postnatally detected deletions encompassed the entire critical region, 32 (43%) of which were associated with other chromosome rearrangements, including six patients (8%) that had a duplication adjacent to the terminal deletion. Our data indicate that Wolf-Hirschhorn syndrome deletions with an adjacent duplication occur at a higher frequency than previously appreciated. Pure deletions (n = 14) or duplications (n = 15) without other copy number changes distal to or inside the WHSCR2 were identified for mapping of critical regions. Our data suggest that deletion of the segment from 0.6 to 0.9 Mb from the terminus of 4p causes a seizure phenotype and duplications of a region distal to the previously defined smallest region of overlap for 4p16.3 microduplication syndrome are associated with neurodevelopmental problems. We detected seven Wolf-Hirschhorn syndrome deletions and one 4p16.3 duplication prenatally; all of the seven are either >8 Mb in size and/or associated with large duplications. In conclusion, our study provides deeper insight into the molecular mechanisms, the critical regions and effective prenatal diagnosis for 4p16.3 deletions/ duplications. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Slit-scanning technique using standard cell sorter instruments for analyzing and sorting nonacrocentric human chromosomes, including small ones

    NARCIS (Netherlands)

    Rens, W.; van Oven, C. H.; Stap, J.; Jakobs, M. E.; Aten, J. A.

    1994-01-01

    We have investigated the performance of two types of standard flow cell sorter instruments, a System 50 Cytofluorograph and a FACSTar PLUS cell sorter, for the on-line centromeric index (CI) analysis of human chromosomes. To optimize the results, we improved the detection efficiency for centromeres

  17. First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

    NARCIS (Netherlands)

    Pratt, JJ; de Wolf, BTHM; Mantingh, A

    Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

  18. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  19. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, M. P.; van Leeuwen, A. M.; Hollema, H.; Quint, W. G.; Pieters, W. J.

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  20. Suppression of topoisomerase IIα expression and function in human cells decreases chromosomal radiosensitivity

    International Nuclear Information System (INIS)

    Terry, Samantha Y.A.; Riches, Andrew C.; Bryant, Peter E.

    2009-01-01

    The mechanism behind chromatid break formation is as yet unclear, although it is known that DNA double-strand breaks (DSBs) are the initiating lesions. Chromatid breaks formed in cells in the G2-phase of the cell-cycle disappear ('rejoin') as a function of time between radiation exposure and cell fixation. However, the kinetics of disappearance of chromatid breaks does not correspond to those of DSB rejoining, leading us to seek alternative models. We have proposed that chromatid breaks could be formed indirectly from DSB and that the mechanism involves topoisomerase IIα. In support of this hypothesis we have recently shown that frequencies of radiation-induced chromatid breaks are lower in two variant human promyelocytic leukaemic cell lines with reduced topoisomerase IIα expression. Here we report that suppression of topoisomerase IIα in human hTERT-RPE1 cells, either by its abrogation using specific siRNA or by inhibition of its catalytic activity with the inhibitor ICRF-193, causes a reduction in frequency of chromatid breaks in radiation-exposed cells. The findings support our hypothesis for the involvement of topoisomerase IIα in the formation of radiation-induced chromatid breaks, and could help explain inter-individual variation in human chromosomal radiosensitivity; elevation of which has been linked with cancer susceptibility.

  1. Assembling the Setaria italica L. Beauv. genome into nine chromosomes and insights into regions affecting growth and drought tolerance.

    Science.gov (United States)

    Tsai, Kevin J; Lu, Mei-Yeh Jade; Yang, Kai-Jung; Li, Mengyun; Teng, Yuchuan; Chen, Shihmay; Ku, Maurice S B; Li, Wen-Hsiung

    2016-10-13

    The diploid C 4 plant foxtail millet (Setaria italica L. Beauv.) is an important crop in many parts of Africa and Asia for the vast consumption of its grain and ability to grow in harsh environments, but remains understudied in terms of complete genomic architecture. To date, there have been only two genome assembly and annotation efforts with neither assembly reaching over 86% of the estimated genome size. We have combined de novo assembly with custom reference-guided improvements on a popular cultivar of foxtail millet and have achieved a genome assembly of 477 Mbp in length, which represents over 97% of the estimated 490 Mbp. The assembly anchors over 98% of the predicted genes to the nine assembled nuclear chromosomes and contains more functional annotation gene models than previous assemblies. Our annotation has identified a large number of unique gene ontology terms related to metabolic activities, a region of chromosome 9 with several growth factor proteins, and regions syntenic with pearl millet or maize genomic regions that have been previously shown to affect growth. The new assembly and annotation for this important species can be used for detailed investigation and future innovations in growth for millet and other grains.

  2. Cell Culture Systems To Study Human Herpesvirus 6A/B Chromosomal Integration.

    Science.gov (United States)

    Gravel, Annie; Dubuc, Isabelle; Wallaschek, Nina; Gilbert-Girard, Shella; Collin, Vanessa; Hall-Sedlak, Ruth; Jerome, Keith R; Mori, Yasuko; Carbonneau, Julie; Boivin, Guy; Kaufer, Benedikt B; Flamand, Louis

    2017-07-15

    Human herpesviruses 6A/B (HHV-6A/B) can integrate their viral genomes in the telomeres of human chromosomes. The viral and cellular factors contributing to HHV-6A/B integration remain largely unknown, mostly due to the lack of efficient and reproducible cell culture models to study HHV-6A/B integration. In this study, we characterized the HHV-6A/B integration efficiencies in several human cell lines using two different approaches. First, after a short-term infection (5 h), cells were processed for single-cell cloning and analyzed for chromosomally integrated HHV-6A/B (ciHHV-6A/B). Second, cells were infected with HHV-6A/B and allowed to grow in bulk for 4 weeks or longer and then analyzed for the presence of ciHHV-6. Using quantitative PCR (qPCR), droplet digital PCR, and fluorescent in situ hybridization, we could demonstrate that HHV-6A/B integrated in most human cell lines tested, including telomerase-positive (HeLa, MCF-7, HCT-116, and HEK293T) and telomerase-negative cell lines (U2OS and GM847). Our results also indicate that inhibition of DNA replication, using phosphonoacetic acid, did not affect HHV-6A/B integration. Certain clones harboring ciHHV-6A/B spontaneously express viral genes and proteins. Treatment of cells with phorbol ester or histone deacetylase inhibitors triggered the expression of many viral genes, including U39 , U90 , and U100 , without the production of infectious virus, suggesting that the tested stimuli were not sufficient to trigger full reactivation. In summary, both integration models yielded comparable results and should enable the identification of viral and cellular factors contributing to HHV-6A/B integration and the screening of drugs influencing viral gene expression, as well as the release of infectious HHV-6A/B from the integrated state. IMPORTANCE The analysis and understanding of HHV-6A/B genome integration into host DNA is currently limited due to the lack of reproducible and efficient viral integration systems. In the

  3. Evolution of postmating reproductive isolation: measuring the fitness effects of chromosomal regions containing hybrid male sterility factors.

    Science.gov (United States)

    Johnson, N A; Wu, C I

    1993-08-01

    At least six regions of the X chromosome can cause male sterility when introgressed from Drosophila mauritiana into Drosophila simulans. In this article, we present the results of the other fitness effects caused by two X-linked regions that contain hybrid male sterility factors. In both regions, females that are heterozygous for an introgression with such a sterility factor produce substantially-fewer offspring than females heterozygous for an introgression that lacks the sterility factor. Thus, the hybrid male sterility factors, or other genes nearby, have substantial effects on female productivity. In contrast, hybrid male sterility factors have little or no effect on the relative viabilities of either sex. The evolutionary implications of these findings are discussed.

  4. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S

    1999-01-01

    the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint...

  5. 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.

  6. 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

  7. Dose response curve for prematurely condensed chromosome fragments of human lymphocytes after 60Co-γ ray exposure

    International Nuclear Information System (INIS)

    Gao Jinsheng; Zheng Siying; Bao Hong

    1992-06-01

    The dose-effect relationship of premature condensed chromosome fragments in human lymphocytes irradiated by 60 Co gamma ray was studied by PCC method (premature condensed chromosomes). In addition, The conventional cellular genetics method was also used in the study. The response curve of both methods can represented by two linear equations. The ratio of two slopes, K PCC /K M1 , is about 28. Comparing with conventional method, the PCC method has many advantages such as faster, simpler, more sensitive and accurate. The PCC method used in the studying of radiation damage is also discussed

  8. Proteomic analysis of human metaphase chromosomes reveals Topoisomerase II alpha as an Aurora B substrate

    DEFF Research Database (Denmark)

    Morrison, Ciaran; Henzing, Alexander J; Jensen, Ole Nørregaard

    2002-01-01

    B in the presence of radioactive ATP. Immunoblot analysis confirmed the HeLa scaffold fraction to be enriched for known chromosomal proteins including CENP-A, CENP-B, CENP-C, ScII and INCENP. Mass spectrometry of bands excised from one-dimensional polyacrylamide gels further defined the protein......The essential Aurora B kinase is a chromosomal passenger protein that is required for mitotic chromosome alignment and segregation. Aurora B function is dependent on the chromosome passenger, INCENP. INCENP, in turn, requires sister chromatid cohesion for its appropriate behaviour. Relatively few...... composition of the extracted chromosome fraction. Cloning, fluorescent tagging and expression in HeLa cells of the putative GTP-binding protein NGB/CRFG demonstrated it to be a novel mitotic chromosome protein, with a perichromosomal localisation. Identi fication of the protein bands corresponding to those...

  9. CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis.

    Science.gov (United States)

    Smolikov, Sarit; Schild-Prüfert, Kristina; Colaiácovo, Mónica P

    2008-06-06

    The synaptonemal complex (SC), a tripartite proteinaceous structure that forms between homologous chromosomes during meiosis, is crucial for faithful chromosome segregation. Here we identify CRA-1, a novel and conserved protein that is required for the assembly of the central region of the SC during C. elegans meiosis. In the absence of CRA-1, central region components fail to extensively localize onto chromosomes at early prophase and instead mostly surround the chromatin at this stage. Later in prophase, central region proteins polymerize along chromosome axes, but for the most part fail to connect the axes of paired homologous chromosomes. This defect results in an inability to stabilize homologous pairing interactions, altered double-strand break (DSB) repair progression, and a lack of chiasmata. Surprisingly, DSB formation and repair are required to promote the polymerization of the central region components along meiotic chromosome axes in cra-1 mutants. In the absence of both CRA-1 and any one of the C. elegans homologs of SPO11, MRE11, RAD51, or MSH5, the polymerization observed along chromosome axes is perturbed, resulting in the formation of aggregates of the SC central region proteins. While radiation-induced DSBs rescue this polymerization in cra-1; spo-11 mutants, they fail to do so in cra-1; mre-11, cra-1; rad-51, and cra-1; msh-5 mutants. Taken together, our studies place CRA-1 as a key component in promoting the assembly of a tripartite SC structure. Moreover, they reveal a scenario in which DSB formation and repair can drive the polymerization of SC components along chromosome axes in C. elegans.

  10. Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

    International Nuclear Information System (INIS)

    Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

    2008-01-01

    Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-β-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells

  11. Localization of the homolog of a mouse craniofacial mutant to human chromosome 18q11 and evaluation of linkage to human CLP and CPO

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, A.J.; Burgess, D.L.; Kohrman, D.C.; Yu, J. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-06-15

    The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci. 23 refs., 4 figs., 2 tabs.

  12. Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

    Science.gov (United States)

    Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

    2015-01-01

    Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle. PMID:25992976

  13. The study of chromosome aberration yield in human lymphocytes as an indicator of radiation dose. 1. Techniques

    International Nuclear Information System (INIS)

    Purrott, R.J.; Lloyd, D.C.

    1972-08-01

    Estimates of exposure to ionizing radiation can be obtained by determining the yield of chromosome aberrations in cultured human lymphocytes. Chromosomes can only be conveniently examined during cell division. The lymphocytes, which do not normally divide whilst circulating, are stimulated to divide during a 48-hour culture period. Two types of culture technique are described, one of which employs a lymphocyte-enriched inoculum and the other which uses whole blood. After culture the cells are harvested, dispensed onto slides and prepared for microscopic examination. An account is also given of the analysis of various types of radiation-induced chromosome aberrations and of the construction of calibration curves for certain types and rates of radiation which are used to interpret the aberration yields in terms of dose. (author)

  14. Metabolic and molecular changes of the phenylpropanoid pathway in tomato (Solanum lycopersicum lines carrying different Solanum pennellii wild chromosomal regions

    Directory of Open Access Journals (Sweden)

    Maria Manuela Rigano

    2016-10-01

    Full Text Available Solanum lycopersicum represents an important dietary source of bioactive compounds including the antioxidants flavonoids and phenolic acids. We previously identified two genotypes (IL7-3 and IL12-4 carrying loci from the wild species Solanum pennellii, which increased antioxidants in the fruit. Successively, these lines were crossed and two genotypes carrying both introgressions at the homozygous condition (DHO88 and DHO88-SL were selected. The amount of total antioxidant compounds was increased in DHOs compared to both ILs and the control genotype M82. In order to understand the genetic mechanisms underlying the positive interaction between the two wild regions pyramided in DHO genotypes, detailed analyses of the metabolites accumulated in the fruit were carried out by colorimetric methods and LC/MS/MS. These analyses evidenced a lower content of flavonoids in DHOs and in ILs, compared to M82. By contrast, in the DHOs the relative content of phenolic acids increased, particularly the fraction of hexoses, thus evidencing a redirection of the phenylpropanoid flux towards the biosynthesis of phenolic acid glycosides in these genotypes. In addition, the line DHO88 exhibited a lower content of free phenolic acids compared to M82. Interestingly, the two DHOs analyzed differ in the size of the wild region on chromosome 12. Genes mapping in the introgression regions were further investigated. Several genes of the phenylpropanoid biosynthetic pathway were identified, such as one 4-coumarate:CoA ligase and two UDP-glycosyltransferases in the region 12-4 and one chalcone isomerase and one UDP-glycosyltransferase in the region 7-3. Transcriptomic analyses demonstrated a different expression of the detected genes in the ILs and in the DHOs compared to M82.These analyses, combined with biochemical analyses, suggested a central role of the 4-coumarate:CoA ligase in redirecting the phenylpropanoid pathways towards the biosynthesis of phenolic acids in the

  15. 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

  16. Positioning of chromosomes in human spermatozoa is determined by ordered centromere arrangement.

    Directory of Open Access Journals (Sweden)

    Olga S Mudrak

    Full Text Available The intranuclear positioning of chromosomes (CHRs is a well-documented fact; however, mechanisms directing such ordering remain unclear. Unlike somatic cells, human spermatozoa contain distinct spatial markers and have asymmetric nuclei which make them a unique model for localizing CHR territories and matching peri-centromere domains. In this study, we established statistically preferential longitudinal and lateral positioning for eight CHRs. Both parameters demonstrated a correlation with the CHR gene densities but not with their sizes. Intranuclear non-random positioning of the CHRs was found to be driven by a specific linear order of centromeres physically interconnected in continuous arrays. In diploid spermatozoa, linear order of peri-centromeres was identical in two genome sets and essentially matched the arrangement established for haploid cells. We propose that the non-random longitudinal order of CHRs in human spermatozoa is generated during meiotic stages of spermatogenesis. The specific arrangement of sperm CHRs may serve as an epigenetic basis for differential transcription/replication and direct spatial CHR organization during early embryogenesis.

  17. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    Energy Technology Data Exchange (ETDEWEB)

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L. [Oregon Health Sciences Univ. Portland, OR (United States)] [and others

    1994-09-01

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

  18. The gene order on Human Chromosome 15 and Chicken Chromosome 10 reveal multiple inter- and intrachromosomal rearrangements

    NARCIS (Netherlands)

    Crooijmans, R.P.M.A.; Dijkhof, R.J.M.; Veenendaal, T.; Poel, van der J.J.; Groenen, M.A.M.

    2001-01-01

    Comparative mapping between the human and chicken genomes has revealed a striking conservation of synteny between the genomes of these two species, but the results have been based on low-resolution comparative maps. To address this conserved synteny in much more detail, a high-resolution

  19. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer

    Science.gov (United States)

    Duffy, Supipi; Fam, Hok Khim; Wang, Yi Kan; Styles, Erin B.; Kim, Jung-Hyun; Ang, J. Sidney; Singh, Tejomayee; Larionov, Vladimir; Shah, Sohrab P.; Andrews, Brenda; Boerkoel, Cornelius F.; Hieter, Philip

    2016-01-01

    Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1. Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID:27551064

  20. Mitotic chromosome condensation in vertebrates

    International Nuclear Information System (INIS)

    Vagnarelli, Paola

    2012-01-01

    Work from several laboratories over the past 10–15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292–301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories—a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307–316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119–1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579–589] (Fig. 1A, A'). In prophase, when cyclin B