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Results for “Chromosome segmentation”

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At least 253 records · Page 14Linked to original sources

PubMed1999

Type-specific contributions to chromosome size differences in Escherichia coli.

The Escherichia coli genome varies in size from 4.5 to 5.5 Mb. It is unclear whether this variation may be distributed finely throughout the genome or is concentrated at just a few chromosomal loci or on plasmids. Further, the functional correlates of size variation in different genome copies are largely unexplored. We carried out comparative macrorestriction mapping using rare-restriction-site alleles (made with the Tn10dRCP2 family of elements, containing the NotI, BlnI, I-CeuI, and ultra-rare-cutting I-SceI sites) among the chromosomes of laboratory E. coli K-12, newborn-sepsis-associated E. coli RS218, and uropathogenic E. coli J96. These comparisons showed just a few large accessory chromosomal segments accounting for nearly all strain-to-strain size differences. Of 10 sepsis-associated and urovirulence genes, previously isolated from the two pathogens by scoring for function, all were colocalized exclusively with one or more of the accessory chromosomal segments. The accessory chromosomal segments detected in the pathogenic strains from physical, macrorestriction comparisons may be a source of new virulence genes, not yet isolated by function.

Alleles↗

PubMed1995

Chromosome painting with human chromosome-specific DNA libraries reveals the extent and distribution of conserved segments in bovine chromosomes.

Commercially available human chromosome-specific DNA libraries covering the whole karyotype were hybridized to normal bovine metaphase spreads to characterize the conserved chromosomal segments between man and cattle. All chromosome libraries except the Y chromosome library displayed a signal on at least part of one or more bovine chromosomes. The labeling was clearly visualized and permitted precise delineation of the hybridized bovine chromosomal segments. This study indicates that the reorganization of the genetic material between human and bovine genomes is not as great as expected from classical comparative cytogenetics based on banding patterns. However, apart from interchromosomal rearrangements between ancestral forms of human and bovine chromosomes, a majority of intrachromosomal rearrangements must have occurred in these species during evolution to explain the differences in the banding patterns of their chromosomes. These results show that chromosome painting with heterologous chromosome-specific DNA libraries can provide useful information in comparative studies on karyotypes and gene maps of distantly related mammalian species. The observations are discussed in relation to published data on gene mapping in man and cattle.

Animals↗

PubMed1993

Mapping of MYF5, C1R, MYHL, TPI1, IAPP, A2MR and RNR onto sheep chromosome 3q.

Five new loci, myogenic factor 5 (MYF5), complement 1 receptor (CIR), myosin-like heavy chain (MYHL), islet amyloid polypeptide (IAPP), and alpha-2-macroglobulin receptor (A2MR), were mapped onto sheep chromosome 3q by Southern hybridization to a panel of chromosomally characterized sheep x hamster cell hybrid lines. The location of the triose phosphate isomerase (TPI1) gene and one of the nucleolar organizer regions (RNR) on sheep 3q was confirmed by Southern analysis. This study provides further evidence for the existence of a large conserved chromosomal segment comprising much of sheep chromosome 3q, cattle chromosome 5, and human chromosome 12. The distal evolutionary breakpoint on human chromosome 12, producing the chromosomal segment U23 in cattle marked by aldehyde dehydrogenase (ALDH2), also produces a separate segment in sheep. Neither ALDH2 nor pancreatic lipase (PLA2), which is also distally located on human chromosome 12, were mapped onto sheep chromosome 3q.

Amyloid↗

PubMed2004

PCC-FISH in skin fibroblasts for local dose assessment: biodosimetric analysis of a victim of the Georgian radiological accident.

We propose a new method of biodosimetry that could be applied in cases of localized irradiation. The approach is based on excess chromosome segments determination by the PCC-FISH technique in fibroblasts isolated from skin biopsy. Typically, 0 to 10 Gy ex vivo gamma-irradiated human skin biopsies were dissociated and fibroblasts were isolated and grown for several days. Cells next underwent PCC-FISH painting of whole chromosome 4, and the number of excess chromosome segments per metaphase was determined. An ex vivo reference curve correlating the number of excess chromosome segments per metaphase to the radiation dose was established and used to assess the dose delivered to the skin of one of the victims of the radiological accident that occurred at Lia in Georgia in December 2001. Specifically, the victim suffering from moist desquamation underwent skin excision in Hospital Percy (France). Measurement of excess chromosome segments per metaphase was done in fibroblasts isolated and grown from removed wounded skin and subsequent conversion to radiation doses was performed. The radiation dose map obtained was shown to be in accordance with clinical data and physical dosimetry as well as with conventional biodosimetry. These results demonstrated that PCC-FISH painting applied to skin fibroblasts may be a suitable technique for dose estimation. To assess its worth, this approach needs to be extended to future accidents involving localized radiation exposure.

Apoptosis↗

PubMed1989

Double in situ hybridization in combination with digital image analysis: a new approach to study interphase chromosome topography.

Double in situ hybridization with mercurated and biotinylated chromosome specific DNA probes in combination with digital image analysis provides a new approach to compare the distribution of homologous and nonhomologous chromosome targets within individual interphase nuclei. Here we have used two DNA probes representing tandemly repeated sequences specific for the constitutive heterochromatin of the human chromosomes 1 and 15, respectively, and studied the relative arrangements of these chromosome targets in interphase nuclei of human lymphocytes, amniotic fluid cells, and fibroblasts, cultivated in vitro. We have developed a 2D-image analysis approach which allows the rapid evaluation of large numbers of interphase nuclei. Models to test for a random versus nonrandom distribution of chromosome segments are discussed taking into account the three-dimensional origin of the evaluated 2D-distribution. In all three human diploid cell types the measurements of target-target and target-center distances in the 2D-nuclear image revealed that the labeled segments of the two chromosomes 15 were distributed both significantly closer to each other and closer to the center of the nuclear image than the labeled chromosome 1 segments. This result can be explained by the association of nucleolus organizer regions on the short arm of chromosome 15 with nucleoli located more centrally in these nuclei and does not provide evidence for a homologous association per se. In contrast, evaluation of the interphase positioning of the two chromosome 1 segments fits the random expectation in amniotic fluid and fibroblast cells, while in experiments using lymphocytes a slight excess of larger distances between these homologous targets was occasionally observed. 2D-distances between the labeled chromosome 1 and 15 segments showed a large variability in their relative positioning. In conclusion our data do not support the idea of a strict and permanent association of these homologous and nonhomologous targets in the cell types studied so far.

Cell Nucleolus↗

PubMed2002

Sheep/human comparative map in a chromosome region involved in scrapie incubation time shows multiple breakpoints between human chromosomes 14 and 15 and sheep chromosomes 7 and 18.

A chromosome region involved in scrapie incubation time was identified on sheep chromosome 18 (OAR18). Since OAR18 (and OAR7) share conserved chromosome segments with human chromosomes HSA14 and HSA15, a dense map of type I markers was constructed by FISH mapping of bacterial artificial chromosomes containing genes located on these human chromosomes. In this study, we used the complete human sequence information (gene positions in megabases, Mb) to locate approximately one gene every 2 Mb on HSA15 (19 genes mapped between 19.51 and 66.02 Mb) and on HSA14 (11 genes between 73.24 and 102.62 Mb). Combined with previous work carried out in cattle and goats, our results made it possible to refine the comparative map between ruminants and humans for these two highly rearranged chromosomes (10 segments on HSA15 and 7 on HSA14). Furthermore, we identified relatively short intervals containing evolutionary breakpoints, which is a prerequisite to position them precisely. This work is also the first step in the cloning of the region involved in scrapie incubation period in sheep.

Animals↗

PubMed1989

A Salmonella typhimurium virulence gene linked to flg.

Isogenic pairs of strains of Salmonella typhimurium which differed only in whether or not they were flagellate were found to be equally virulent in C57BL/6J mice infected orally, intravenously, or intraperitoneally. Therefore, we investigated the genetic basis for our previous observation that in this mouse model, nonflagellate delta flagABCDE25 strains were reduced in virulence compared with isogenic wild-type flagellate strains. The recombinant plasmid pMH6, which contains several flg+ genes and a segment of the S. typhimurium chromosome adjacent to the flg genes, was introduced into a delta flgABCDE25 mutant. This restored virulence in mice challenged intraperitoneally, which suggested that a virulence gene occurs adjacent to the flg genes. When plasmid pMH64, which lacks the chromosomal segment adjacent to the flg genes, was introduced into the same delta flgABCDE25 mutant, virulence was not restored. In contrast, the introduction of pMH71, a plasmid which retains the chromosomal segment adjacent to the flg genes, restored virulence. We concluded that a hitherto unknown virulence gene, which we have named mviS, occurs adjacent to the flg genes and that its absence in delta flgABCDE25 mutants, rather than the nonflagellate phenotype of the delta flgABCDE25 mutants, caused the previously reported attenuation of such mutants.

Animals↗

PubMed1995

Comparative maps: the mammalian jigsaw puzzle.

Chromosomal rearrangements such as inversions and translocations have played an important role in defining genome organization in existing mammals. The number of rearrangements that have occurred since divergence from the 'primordial' mammal has been modest and the distribution of these rearrangements among chromosomes seems to be random. As a result, each mammalian species has a unique arrangement of conserved and disrupted chromosomal segments as compared to other mammalian species. Genes are excellent markers for these chromosomal segments because homologies can be detected in highly divergent species. By comparing the chromosomal location of homologous genes in different species, maps of conserved chromosomal segments can be obtained. These comparative maps can be used to predict gene locations in other species, identify candidate disease genes, characterize the genetic basis for complex traits, and find modulators of disease susceptibility. Equally important is the use of comparative maps for addressing questions about genome organization and evolution.

Animals↗

PubMed1982

Ultrastructural characterization of the meiotic prophase. A tool in the assessment of radiation damage in man.

The three-dimensional reconstruction of meiotic nuclei from serial sections micrographed in the electron microscope has provided information about man and several other organisms that is not obtainable by light microscopy or biochemical analysis. At zygotene, the previously unpaired chromosomes align and form synaptonemal complexes between homologous chromosome segments either by progressive initiation from the telomeres or by interstitial recognition. Chromosome and bivalent interlocking at zygotene is a regular phenomenon and occurs at a frequency of 0.7-4.0 per nucleus in samples of meiocytes analyzed from different organisms. This frequency is reduced to 0.1 per nucleus at pachytene. The interlockings are resolved by breakage and precise rejoining of the broken ends. This breakage and rejoining can also occur in the absence of the DNA nicking and repair involved in crossing-over. The synaptonemal complexes combining homologous chromosome segments are stabilized by recombination nodules, after which a second round of synaptonemal complex formation between as yet unpaired or unstably paired chromosome segments occurs, apparently for optimization of bivalent formation. Non-homologous pairing with the synaptonemal complex can take place in this phase of pachytene. Continuity between recombination nodules and chromatin chiasmata has been traced at the ultrastructural level but not all nodules lead to chiasmata. The distributions of recombination nodules among the bivalents and along the bivalents at successive stages of meiotic prophase show that the nodules are placed at random at early-zygotene after which bivalents without nodules have preference for the acquisition of these structures. Chiasma interference appears as a consequence of the limited number of recombination nodules available together with a decreased affinity of a bivalent arm with a nodule for additional ones. The relevance of these observations in the study of genetic damage by radiation is discussed.

Aneuploidy↗

PubMed1996

Pathogenicity island evaluation in Escherichia coli K1 by crossing with laboratory strain K-12.

In bacterial pathogens, strain-specific chromosomal segments often contain genes encoding strain-specific traits, and because these genes often appear to be dedicated to pathogenic interactions with eucaryotic hosts, the segments containing them may be considered so-called pathogenicity islands (G. Blum, M. Ott, A. Lischewski, A. Ritter, H. Imrich, H. Tschape, and J. Hacker, Infect. Immun. 62:606-614, 1994). We evaluated the contribution to pathogenesis of a recently identified strain-specific chromosomal segment from an Escherichia coli K1 mammalian-newborn sepsis strain: transfer of E. coli K-12 DNA sequences near 64 min, by P1 transduction, into K1 strain RS218 resulted in an RS218-K-12 chimera that (i) contained a shortened NotIotl restriction fragment (relative to wild-type RS218) encompassing the 64-min region; (ii) lacked invasiveness in newborn rats; and (iii) grew in vitro, in both rich and minimal laboratory media, indistinguishably from strain RS218. In addition, genomic DNA from the chimera failed to hybridize with sequences of the K1 capsule genes from strain RS218, suggesting that the chromosomal segment near 64 min which was lost contained these sequences and indeed contained K1-specific virulence genes. Transfer of K-12 sequences resulting in deletion of E. coli pathogen-specific chromosomal segments may afford a general method of detecting genes encoding virulence and/or other distinguishing traits.

Animals↗

PubMed1982

Abnormalities of chromosome #13 in retinoblastomas from individuals with normal constitutional karyotypes.

Constitutional chromosome abnormalities have been associated with retinoblastoma, Wilm's tumor, and a familial form of renal carcinoma. For each tumor type, the particular chromosome segment involved in the observed rearrangements is different: in retinoblastoma, that segment is band q14 on chromosome #13. We now present evidence that in retinoblastoma, structural abnormalities involving the particular chromosome segment identified in the constitutional cases can also occur in the tumors of individuals with normal constitutional karyotypes. Six cases with retinoblastoma in one or both eyes were analyzed; deletions/rearrangements involving 13q14 were found in the tumor cell karyotypes of five of the six. These observations suggest that changes in a gene or genes at a common site (13q14) play a role in tumorigenesis in all forms of retinoblastoma, sporadic as well as heritable.

Child, Preschool↗

PubMed1996

LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.

A major cytogenetic subgroup of lipomas is characterized by recurrent chromosome aberrations, mainly translocations, that involve chromosome segment 12q13-q15. Multiple chromosomes have been found as the translocation partners of chromosome 12 but 3q27-q28 is preferentially involved. In previous studies, it has been shown that the high mobility group (HMG) protein gene HMGIC at 12q15 is consistently rearranged as a consequence of these translocations. Here, we report the identification and characterization of the chromosome 3-derived translocation partner gene, which we have designated LPP (lipoma preferred partner gene). Using 3'-RACE analysis of HMGIC fusion transcripts in lipoma cell line Li-501/SV40, ectopic genetic sequences were obtained, which by CASH (chromosome assignment using somatic cell hybrids) and FISH (fluorescence in situ hybridization) analysis were found to originate from chromosome segment 3q27-q28. In Northern blot analysis, an mRNA of over 10 kb was detected by these ectopic sequences in a variety of human tissues but not in brain and peripheral blood leukocytes. Upon partial cDNA cloning, features of the genetic organization of LPP were established. The gene was found to span a genomic region of over 400 kb. Nucleotide sequence analysis of a composite cDNA of LPP revealed an open reading frame of 1836 nucleotides encoding a proline-rich protein containing a leucine-zipper motif in its amino-terminal region and three LIM domains in its carboxy-terminal region. The LPP-encoded protein should be classified as a novel member of the group 3 proteins of the LIM protein gene family. Using reverse transcriptase combined with polymerase chain reactions in the analysis of a number of lipoma cell lines and primary lipomas, it appeared that LPP is frequently rearranged also in cases without a cytogenetically detectable involvement of 3q27-q28. Two alternative HMGIC/LPP hybrid transcripts have been detected; the difference between them is mainly the presence of either two or three LIM domains in the predicted HMGI-C/LPP fusion proteins.

Alternative Splicing↗

PubMed1995

Alterations of CDKN2 (p16) in non-small cell lung cancer.

The cyclin-dependent kinase inhibitor known as p16 (CDK41, CDKN2, INK4A, MTS1) has been proposed as a tumor suppressor gene on chromosome segment 9p21. We have evaluated CDKN2 alterations in 34 non-small cell lung cancers (NSCLCs) with matched normal tissue controls and in 9 NSCLC cell lines by Southern blotting, single-strand conformation polymorphism (SSCP) with the polymerase chain reaction, and direct sequencing. In addition, loss of heterozygosity at chromosome segment 9p21, with the use of the microsatellite marker D9S171, was studied in these samples. Whereas CDKN2 was either deleted or mutated in NSCLC cell lines at a high frequency (6/9, 67%), alterations were much less frequent (7/34, 21%) in primary tumor samples. Only one sample contained a point mutation in exon 1 of CDKN2. In addition, two samples had homozygous deletions of CDKN2 in exon 1; one had a homozygous and three a hemizygous deletion of exon 2. Possibly normal tissue contaminating our tumor samples may have masked homozygous deletions in these cases. Four patient samples had LOH in the region of CDKN2 on chromosome segment 9p21; two of these samples had potentially inactivating alterations of CDKN2; one sample had a mutation of CDKN2, and the other had a homozygous deletion of exon 1. In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancer cannot be eliminated.

Base Sequence↗

PubMed1986

Possible derivation of the laboratory mouse genome from multiple wild Mus species.

Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to estimate the extent of the non-domesticus contribution to laboratory mouse genomes, and to determine whether it could account for observed variation, we have used computer simulations to investigate the properties of genetically marked chromosomal segments and the distribution of residual allogenicity at various times during inbreeding. A locus or chromosomal segment is allogenic if it is unfixed within a lineage at a given time. The odds of fixation of a foreign chromosome segment are predicted to be an exponentially decreasing function of its length. The median segment length is predicted to be 17 centimorgans. Available data for markers of chromosomes 1, 9 and 12 in recombinant inbred strain sets conform to these predictions. Together, the results suggest that introgression of non-domesticus chromosomes and segregation of residual allogenicity are sufficient to account for the genetic diversity observed among inbred mouse strains and substrains.

Alleles↗

PubMed1998

Conformation of replicated segments of chromosome fibres in human S-phase nucleus.

Recent statistical analysis of the folding of G0/G1 chromosomes using fluorescence in situ hybridization (FISH) allowed development of a random walk/giant loop model of chromosome structure. According to this model there are two levels of organization of G0/G1 chromosome fibres. On the first level, the fibres are arranged in giant loops several Mbp in size, and within each loop the fibres are randomly folded. On the second level, the loop attachment sites form a chromosome backbone that also shows random folding. Newly replicated segments of mammalian chromosomes may be directly visualized at high resolution in S-phase nuclei using immunofluorescent methods and appear as worm-like fibres. In our earlier study, we analysed conformation of the fibres in human cells blocked for 16 h at the G1/S boundary with 5-fluorodeoxyuridine (FdU) and then released into S-phase by the addition of a DNA precursor. However, long treatment of cells with FdU induces very short replicons and may promote apoptosis. In this study we analysed conformation of the fibres in normally proliferating human cells that had not been blocked with FdU for a long time. It has been found that replicated chromosome fibres visualized just after 2 h of incubation of the cells with a non-radioactively labelled DNA precursor behave as flexible polymer chains without major constraints, and that their local conformation in the range of several microns of their contour length may be considered as random. Confocal analysis of human X chromosomes visualized in HeLa cells using FISH with a specific painting probe shows that in S-phase the chromosomes occupy distinct nuclear territories and their apparent size does not differ from that in non-S-phase cells. This observation indicates that the second level of chromosome organization also exists in S-phase chromosomes. It appears, therefore, that the random walk/giant loop model developed earlier for G0/G1 chromosomes is also valid for S-phase chromosomes.

Cell Nucleus↗

PubMed2003

Homologous fission event(s) implicated for chromosomal polymorphisms among five species in the genus Equus.

The genus Equus is unusual in that five of the ten extant species have documented centric fission (Robertsonian translocation) polymorphisms within their populations, namely E. hemionus onager, E. hemionus kulan, E. kiang, E. africanus somaliensis, and E. quagga burchelli. Here we report evidence that the polymorphism involves the same homologous chromosome segments in each species, and that these chromosome segments have homology to human chromosome 4 (HSA4). Bacterial artificial chromosome clones containing equine genes SMARCA5 (ECA2q21 homologue to HSA4q31. 21) and UCHL1 (ECA3q22 homologue to HSA4p13) were mapped to a single metacentric chromosome and two unpaired acrocentrics by FISH mapping for individuals possessing odd numbers of chromosomes. These data suggest that the polymorphism is either ancient and conserved within the genus or has occurred recently and independently within each species. Since these species are separated by 1-3 million years of evolution, this polymorphism is remarkable and worthy of further investigations.

Adenosine Triphosphatases↗

PubMed1975

Familial Down syndrome due to t(10;21) translocation: evidence that the Down phenotype is related to trisomy of a specific segment of chromosome 21.

This report deals with a reciprocal t(10;21) translocation which is observed in three generations of a family. Included are examples of the balanced translocation, adjacent-2 segregation producing three patients with trisomy of the distal long arm of chromosome 21 and the Down syndrome, and 3-1 disjunction producing trisomy of the proximal segment of chromosome 21 in a mildly mentally retarded boy without phenotypic features of the Down syndrome. These data provide evidence that the Down phenotype is attributable to trisomy of the distal long arm of chromosome 21.

Chromosome Aberrations↗

PubMed1987

Specific chromosome aberration in human renal cell carcinoma.

Using G-banding technique, the chromosomes were studied in short-term cultures of 25 primary renal-cell carcinomas (RCC). Phytohaemagglutinin-stimulated peripheral blood lymphocytes or normal kidney cells of the same patients growing in primary cultures were analysed to define the constitutional karyotype. The modal chromosome number of 23 RCC's was found to be pseudo-diploid or near-diploid with only few structural rearrangements, 22 of the RCC's showed an aberration of chromosome 3, deletion of 3p, or translocation of different chromosome segments to the deleted chromosome 3, leading to the loss of variable segments of chromosome 3. The break-points in rearrangements of chromosome 3 clustered in the region 3p11.2-p13. Shortest-region overlap analysis localized a consistent change to a small area of 3p13-pter. In 8 of the 25 RCCs, the rearrangement of chromosome 3 was the only karyotype change determined, and 4 other tumours had only one chromosomal rearrangement in addition to the aberration of chromosome 3. These results suggest that the aberration of chromosome 3 is the first cytogenetic event in the clonal evolution of RCCs. Translocation 3;5 was preferentially involved in the rearrangements between chromosome 3p and other chromosomes. The breakpoint on chromosome 3 was constant at p13, but the breaks on chromosome 5 varied between bands q11.2 and q22. Monosomy 14 was observed in 10 cases and loss of Y chromosome was detected in 6 of 14 tumours obtained from male patients. Since the normal somatic cells were free of chromosomal aberrations, one may conclude that the loss of 3p13-pter segment is an acquired, consistent chromosomal aberration which marks human RCCs.

Adult↗