bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of the centromere as a mechanism for achieving stability of a dicentric chromosome
Authors: Vianna-Morgante A.M. , Rosenberg C.
Published: May 2008

A patient with primary amenorrhea and a terminal rearrangement of chromosomes 13 and 20 is described. The stability of the dicentric translocation chromosome was achieved by suppression of the activity of the centromere of chromosome 20 and actual deletion of the centromere of chromosome 13. These two mechanisms may be fundamentally similar if centromere inactivation results from a visually undetectable deletion.
Human ornithine decarboxylase sequences map to chromosome regions 2pter→p23 and 7cen→qter but are not coamplified with the NMYC oncogene
Authors: Winqvist R. , Mäkelä T.P. , Seppänen P. , Jänne O.A. , Alhonen-Hongisto L. , Jänne J. , Grzeschik K.-H. , Alitalo K.
Published: May 2008

Using a mouse cDNA probe for ornithine decarboxylase (ODC), we have identified and isolated an ODC cDNA clone from a λ gt11 recombinant library prepared from human liver cell mRNA. The 2.0-kb insert of this clone hybridizes with several mouse genomic ODC DNA restriction fragments under conditions of low stringency, but reacts with only few human DNA fragments and a polyA+ RNA species of 2.2 kb under both nonstringent and stringent hybridization conditions. This suggests that, unlike the mouse genome, there are only few ODC genes in the human genome. The human ODC DNA fragments segregate with chromosome regions 2pter→p23 and 7cen→qter in mouse × human somatic cell hybrid clones containing normal, translocated, and deleted human chromosomes. Sequences of the short arm of chromosome 2 containing the NMYC oncogene at 2p23→p24 are often involved in DNA amplification in neuroblastomas and small-cell lung cancers. However, in at least three cases—one neuroblastoma cell line, one neuroblastoma tumor, and one lung carcinoma—the ODC sequences are not coamplified with the NMYC oncogene.
Cytogenetic analysis of lymphoblastoid cell lines
Authors: Abruzzo M.A. , Hunt P.A. , Mayer M. , Jacobs P.A. , Wang J.-C.C. , Erbe R.W.
Published: May 2008

Cytogenetic abnormalities were discovered in more than half of 16 lymphoblastoid cell lines established from fragile X individuals and their relatives upon routine cytogenetic analysis of early passage cultures. Subsequently, a second series of lymphoblastoid lines was analyzed to determine if the aneuploidy was (1) a characteristic of lymphoblastoid cell lines derived from fragile X families or (2) a result of the use of cyclosporin A in the establishment of these lines. In the second series of 33 lymphoblastoid cultures, no aneuploid clones were found in the fragile X group, while two were detected in the control cultures, one in a line initiated with cyclosporin A and the other in a line established without cyclosporin A. We conclude that the abnormal clones in our preliminary series were not a characteristic of lines derived from fragile X families and probably not due to the use of cyclosporin A. However, the finding of chromosome abnormalities in a large proportion of lines during the first 3 mo of culture contrasts with previous reports of chromosome stability for the first 12–18 mo of cultivation and indicates that the chromosomes of lymphoblastoid lines should be monitored in any experiment in which a normal diploid complement is critical.
Nucleolar dominance in diploid and triploid parthogenetic lizards of hybrid origin
Authors: Ward O.G. , Cole C.J.
Published: May 2008

Silver staining of nucleolus organizer regions (NORs) in diploid cells of bisexual species of whiptail lizards (Cnemidophorus) indicated codominance of the rRNA genes on homologous chromosomes, However, a nucleolar dominance hierarchy was revealed by inactivity of specific NORs in diploid and triploid cells from natural unisexual clones of hybrid origin. Often, only one NOR was active in cells of these diploid or triploid parthenogenetic species, and activity depended on the dominance hierarchy, not maternal inheritance or dosage compensation. This is in striking contrast to the gene activity previously observed in the same lizards but based on the electrophoretic analysis of other gene products, in which there was codominance of all alleles at each locus studied in triploid and tetraploid lizards. These results indicate that ribosomes produced by the dominant rRNA gene of one ancestor in hybrid cells function adequately in synthesizing polypeptides encoded by other codominant genes from two or three ancestors.
Random acrocentric bivalent associations in human pachytene spermatocytes
Authors: Guichaoua M.R. , Devictor M. , Hartung M. , Luciani J.M. , Stahl A.
Published: May 2008

Acrocentric bivalent associations were studied in 232 human male germ cells at pachytene in order to understand better the preferential involvement of chromosomes 13, 14, and 21 in Robertsonian translocations. The tendency of each acrocentric bivalent to associate with another was not correlated with NOR activity, as measured by silver staining. Good agreement was noticed between their ability to associate and the amount of satellite DNA in human acrocentric chromosomes. The distribution of two-by-two acrocentric bivalent associations was random. In order to reconcile this result with the nonrandom distribution of Robertsonian translocations, a molecular hypothesis is proposed. The model is based on homology of recom-binational sites, interspersed at regular interval in satellite DNA, which could increase the probability of accidental unequal crossing-over between two specific acrocentric chromosomes.
Localization of a β-crystallin gene, HuβA3/A1 (gene symbol: CRYB1), to the long arm of human chromosome 17
Authors: Law M.L. , Cai G.-Y. , Hartz J. , Kao F-T. , Hogg D. , Breitman M.L. , Tsui L.-C.
Published: May 2008

We have assigned a human β-crystallin gene, HuβA3/A1 (gene symbol: CRYB1), to chromosome 17 using a panel of 19 human-hamster somatic cell hybrids and blot-hybridization analysis of cell hybrid DNA. Positive probe-hybridization signal was detected in a hybrid that had lost the short arm of human chromosome 17 but retained the long arm, translocated to a hamster chromosome. In addition, in situ hybridization analysis of metaphase chromosome spreads of this cell line suggested that the most probable location for CR YB1 is on the long arm of chromosome 17, in the region q21.
The murine Hox-2 cluster of homeo box containing genes maps distal on chromosome 11 near the tail-short (Ts) locus
Authors: Münke M. , Cox D.R. , Jackson I.J. , Hogan B.L.M. , Francke U.
Published: May 2008

Two probes derived from a mouse recombinant λ-clone (H24.1), that contains a sequence closely homologous to the Drosophila antennapedia homeo box, were mapped to mouse chromosome (MMU) 11 by filter hybridization of somatic cell hybrid DNA. This sequence is highly homologous to a human homeo box gene (HoX2) and appears to represent one of the two genes in the Hox-2 cluster previously assigned to MMU 11. To regionally map the Hox-2 cluster, we have carried out in situ hybridization of the two H24.1 probes and of an independently isolated Hox-2 probe. The autoradiographic silver grain distributions were similar in all three experiments with a peak over band 11 D. This region contains the locus for the tail-short (Ts) mutation which causes skeletal abnormalities in heterozygotes and early embryonic death in homozygotes.
Cytogenetic studies of Hynobiidae (Urodela)
Authors: Kuro-o M. , Ikebe C. , Kohno S.
Published: May 2008

The R-banding technique of Dutrillaux et al. (1973) was modified in order to analyze the chromosomes of salamanders in the genus Hynobius. Embryonic cells of Hynobius nigrescens Stejneger from Nakakubiki County, Niigata Prefecture, and Hakui County, Ishikawa Prefecture, were cultured in medium containing 5-bromodeoxyuridine (BrdU). Banded metaphases were obtained by the FPG (fluorescent-plus-Giemsa) technique (Perry and Wolff, 1974), with slight modifications. With this modified R-banding technique, multiple, clear DNA replication bands were obtained on the chromosomes, and 18 of 28 chromosome pairs could be identified easily by their replication patterns in embryos collected from Nakakubiki County. A distinct heteromorphism in banding pattern was detected on the long arm of chromosome 9 in these embryos, but the frequency of this variant was too low for chromosome 9 to be a sex chromosome. Chromosomes 1 14, except for 6, 12 (for which the data were not satisfactory), and 9 (the variant type from Nakakubiki County), had the same replication patterns in embryos obtained from Nakakubiki and Hakui Counties.
Determination of the baseline sister chromatid exchange frequency in human and mouse peripheral lymphocytes using monoclonal antibodies and very low doses of bromodeoxyuridine
Authors: Tucker J.D. , Christensen M.L. , Strout C.L. , Carrano A.V.
Published: May 2008

We measured the frequency of sister chromatid exchanges (SCEs) in human and mouse peripheral lymphocytes using doses of bromodeoxyuridine (BrdU) ranging from 30 ΠM to 100 µM (human) and from 10 nM to 10 µM (mouse). Heparinized peripheral blood was obtained from five healthy nonsmokers and from six C57B1/6 male mice. The blood was stimulated with PHA (human) or lipopolysaccharide (LPS, mouse) and grown for the first of two cell cycles in BrdU. Metaphase chromosomes were denatured and exposed to a monoclonal antibody reactive to single-stranded DNA containing BrdU. A second antibody was used to label the first antibody with fluorescein, and propidium iodide was used as a counterstain. Second-division metaphases were thus differentially stained red to indicate DNA content and yellow-green to indicate the presence of BrdU. The results indicate that the baseline SCE frequency in human and mouse peripheral lymphocytes is 3.6 and 2.4 SCEs per cell per generation, and that in the human these frequencies are invariant at the lowest BrdU levels. This suggests that SCEs are an integral part of DNA replication, even in the absence of agents known to induce SCEs. The distribution of SCEs per chromosome was analyzed and found to be Poisson-distributed in all 24 murine cultures and in 25 of 36 human cultures. The distribution of SCEs per chromosome may be due to either species-specific chromosome packaging or to karyotypic differences between the species.
Toward early diagnosis of myotonic dystrophy:construction and characterization of a somatic cell hybrid with a single human der(19) chromosome
Authors: Hulsebos T. , Wieringa B. , Hochstenbach R. , Smeets D. , Schepens J. , Oerlemans F. , Zimmer J. , Ropers H.-H.
Published: May 2008

We have constructed a somatic cell hybrid line, designated 908K1, with a single human der(19) chromosome on a Chinese hamster background by employing conventional as well as microcell-mediated cell fusion techniques. The der(19) chromosome comprises the 19p13.1→q13.2 segment, as well as the distal (Xq24→qter) portion of the X chromosome long arm, and is stably retained by HAT selection. Extensive characterization of this hybrid line and comparison with other somatic cell hybrids has enabled us to regionally assign PGK2 to the distal short arm of chromosome 19 and to narrow down the assignments of CYP1, TGFB, and ERCC1 on 19q. Moreover, a cosmid library has been constructed from this microcell hybrid. By screening this library, as well as a chromosome 19-enriched library obtained elsewhere, 14 single-copy probes have been isolated that map on the 19p13.1→q13.2 segment, and 5 probes were assigned to the distal Xq. It is anticipated that these probes will be useful for the diagnosis of myotonic dystrophy and fra(X) mental retardation.
Construction of fifteen human chromosome-specific DNA libraries from flow-purified chromosomes
Authors: Fuscoe J.C. , Clark L.M. , Van Dilla M.A.
Published: May 2008

We report the construction of 15 human chromosome-specific DNA libraries. Metaphase chromosomes were purified by flow sorting and the DNA was extracted and cleaved with Hindlll before cloning into the λ vector Charon 21 A. A sensitive miniblot hybridization method was used to monitor the physical and biochemical steps in the cloning procedure. Using this method, we have developed a highly efficient protocol for producing large numbers of recombinant phage from 0.2–1.0 × 106 sorted chromosomes. DNA from the following chromosomes was cloned: #4, 6, 8, 9, 11, 13, 14+15, 16, 17, 18, 19, 20, 21, 22 and Y. These libraries are available to the scientific research community and will be valuable in the genetic analysis of the human genome.
Many oncogenes are transcribed in the D98AH2 derivative of the HeLa carcinoma cell line
Authors: O’Hara B. , Klinger H.P. , Blair D.G.
Published: May 2008

As a first step in an ongoing study on the correlation of oncogene expression and tumorigenicity in hybrids made by fusing D98AH2 (D98) carcinoma cells with normal diploid human fibroblasts, we determined which oncogenes are expressed in the D98 cells. Northern blot determinations of the RNA levels of 21 oncogenes revealed moderate to abundant transcripts of 13 oncogenes. The remaining eight oncogenes for which no RNA was found normally show a very restricted pattern of expression among cell types. The presence of RNAs for nine of the 13 that were transcribed was not unexpected as they have been found in many other cell types. Three of the oncogene RNAs that were detected in D98 cells have not been well characterized for tissue or cell type specificity. FOS RNA was unexpectedly detected at high levels in nonsynchronized D98 cells suggesting aberrant expression of this oncogene. A comparison of human oncogene RNAs described by other workers with those observed in the D98 cells revealed no alterations in the sizes of the RNAs. Abundant transcripts of human papilloma virus 18, which is frequently associated with human cervical tumors, were also found in the D98 cells. Despite the high levels of oncogene specific RNAs detected, transfection of murine NIH3T3 cells with DNA of D98 cells did not result in malignant transformation of the murine fibroblasts.
The 724 family of DNA sequences is interspersed about the pericentromeric regions of human acrocentric chromosomes
Authors: Kurnit D.M. , Roy S. , Stewart G.D. , Schwedock J. , Neve R.L. , Bruns G.A.P. , Van Keuren M.L. , Patterson D.
Published: May 2008

We describe the organization of the complex, interspersed 724 family of DNA sequences that is distributed in multiple copies about the pericentromeric region of human acrocentric chromosomes. 724 family members were isolated using an efficient recombination-based assay for nucleotide sequence homology to screen a human genomic library. Eight related but distinct 724 family members were isolated that hybridized to a total of 20 different human-genomic EcoRl DNA fragments spanning 100,000 base pairs. In contrast with tandemly clustered satellite and ribosomal DNA sequences also located on the short arms of human acrocentric chromosomes, 724 family members are interspersed. No evidence for local interspersion or homology between 724 family members and ribosomal or satellite DNA sequences was found. Juxtaposition of the complex 724 family to the nucleolus organizer region was a recent event in primate evolution. The unique organization of 724 family members on each of the five human acrocentric chromosomes indicates that the 724 family continues to evolve within the human karyotype.
A polymorphic human myosin heavy chain locus is linked to an anonymous single copy locus (D17S1) at 17pl3
Authors: Schwartz C.E. , McNally E. , Leinwand L. , Skolnick M.H.
Published: May 2008

Restriction fragment length polymorphisms (RFLPs) have been developed for an adult human skeletal muscle myosin heavy chain gene which was previously mapped to the short arm of human chromosome 17. Using RFLP analysis of DNA from 140 individuals, we have found tight linkage (LOD score of 6.9) between this myosin heavy chain gene and the anonymous DNA probe, D17S1.
The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23→q24) and on mouse chromosome 19
Authors: Yang-Feng T.L. , Landau N.R. , Baltimore D. , Francke U.
Published: May 2008

Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase expressed in immature lymphocytes of the thymus and bone marrow, as well as certain leukemic cells. Chromosomal assignment of the gene coding for human TdT was accomplished by in situ hybridization of a 3H-labeled cDNA probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs. The human TdT gene was mapped to the region q23→q24 of chromosome 10. Breaks at this site have been reported in different translocations in human leukemias. The mouse TdT gene was assigned to chromosome 19 by Southern blot analysis of mouse × Chinese hamster somatic cell hybrids. This result adds a fourth locus to the conserved syntenic group on mouse chromosome 19 and human chromosome 10.
Chromosomal mapping of four different integration sites of Moloney murine leukemia virus including the locus for α1(I) collagen in mouse
Authors: Münke M. , Harbers K. , Jaenisch R. , Francke U.
Published: May 2008

Infection of mouse embryos with Moloney murine leukemia virus (M-MuLV) has yielded several mouse substrains with stable germ line integration of retroviral DNA at distinct chromosomal loci (Mov loci; Jaenisch et al., 1981). There is evidence that flanking DNA sequences can have an effect on virus expression and, conversely, inserted viral DNA may affect the expression of adjacent host genes. As part of our studies on the interaction of inserted M-MuLV with the mouse genome, we have chromosomally mapped four different Mov loci by hybridizing single-copy mouse sequences, flanking the proviral DNA, to interspecies somatic cell hybrids. Furthermore, these sequences were assigned regionally by in situ hybridization to mouse metaphase chromosomes. In Mov-13 mice, M-MuLV had inserted into the α1(I) collagen gene leading to early embryonic death in homozygotes. We have assigned this locus to the distal region of chromosome 11. Thus, the al(I) collagen gene is part of an evolutionarily conserved linkage group with the homologous genes on human chromosome 17. Three other proviral integration sites were mapped to chromosome 1, bands BC (Mov-7), chromosome 11, bands BC (Mov-9), and chromosome 3, bands FG (Mov-10). The Mov-70-specific probe detects an EcoRI-specific restriction fragment length polymorphism, which can make this probe a useful genetic marker.
Assignment of the pepsinogen gene complex (PGA) to human chromosome region llql3 by in situ hybridization
Authors: Nakai H. , Byers M.G. , Shows T.B. , Taggart R.T.
Published: May 2008

The genes coding for human pepsinogen (PGA3, PGA4, and PGA5) were assigned to chromosome region 11q13 by in situ hybridization. Previously we localized the PGA gene complex to a centromeric region of chromosome 11 (p11→q13) by Southern blot analysis of mouse-human somatic cell hybrids. Our in situ hybridization results confirm this assignment and further localize the genes to a smaller region on the long arm.
Mapping of the gene for anti-Müllerian hormone to the short arm of human chromosome 19
Authors: Cohen-Haguenauer O. , Picard J.Y. , Mattéi M.-G. , Serero S. , Van Cong Nguyen , de Tand M.-F. , Guerrier D. , Hors-Cayla M.-C. , Josso N. , Frézal J.
Published: May 2008

The gene coding for human anti-Müllerian hormone (AMH) was localized to subbands p13.2→p13.3 on chromosome 19, using in situ hybridization and Southern blot analysis of a panel of man-mouse and man-hamster somatic cell hybrids.
The gene for galactosyltransferase maps to mouse chromosome 4
Authors: Shaper N.L. , Shaper J.H. , Hollis G.F. , Chang H. , Kirsch I.R. , Kozak C.A.
Published: May 2008

The chromosomal localization of the gene for UDP-galactosyltransferase (glycoprotein 4-B-galactosyltransferase, EC 2.4.1.38) has been determined to be on mouse chromosome 4 by the use of mouse × hamster somatic cell hybrids. It has been proposed that galactosyltransferase is associated with the mouse T/t complex which has been localized to mouse chromosome 17. These results show that galactosyltransferase is not encoded within the T/t complex.
Localisation of a sequence, 7C22, showing close linkage to the cystic fibrosis locus
Authors: Buckle V.J. , Scambler P.J. , Wainwright B.J.
Published: May 2008

The DNA sequence 7C22 is known to show close linkage to the cystic fibrosis locus on chromosome 7. We present a regional localisation for this sequence by in situ hybridisation to 7q31.1→q31.2.
A scanning electron microscopy study of double minutes from a human tumour cell line
Authors: Jack E.M. , Waters J.J. , Harrison C.J.
Published: May 2008

Double minutes from a human tumour cell line were examined in intact metaphase spreads using scanning electron microscopy. They were discrete, acentromeric, compact spheres of chromatin fibres similar to the chromatin of the metaphase chromosomes within the same cells. They were closely associated with the telomeres and chromatids of the metaphase chromosomes.
Cytogenetic studies of Hynobiidae (Urodela)
Authors: Kuro-o M. , Ikebe C. , Kohno S.
Published: May 2008

Chromosome analysis was done in salamanders belonging to the genus Hynobius using the R-banding (RBG) technique. The embryonic cells of H. leechii Boulenger from Korea and H. nebulosus (Schlegel), H. tokyoensis Tago, H. nigrescens Stejneger, and H. retardatus Dunn from Japan were cultured in medium containing 5-bromodeoxyuridine. R-banding patterns in these five species were analyzed, except for most of the small-sized chromosomes. Eighteen out of 28 chromosome pairs in H. leechii, H. nebulosus, H. tokyoensis, and H. nigrescens, and 16 out of 20 chromosome pairs in H. retardatus could be identified by their R-banding patterns. The R-banding patterns in H. leechii, H. nebulosus, H. tokyoensis, and H. nigrescens were very similar to one another as are their karyotypes. Among these four species, about 90% of the total lengths of the karyotypes in each species showed homoeologous R-banding patterns, while among all the five species, including H. retardatus, homoeologies decreased to about 65%. The results imply that H. leechii, H. nebulosus, H. tokyoensis, and H. nigrescens are extremely close to one another phylogenetically, and that H. retardatus is a near phylogenetic relation to the other species of this study.
The rat vitamin D binding protein (Gc-globulin) gene is syntenic with the rat albumin and α-fetoprotein genes on chromosome 14
Authors: Cooke N.E. , Levan G. , Szpirer J.
Published: May 2008

Using a panel of mouse × rat somatic cell hybrids and a characterized rat vitamin D binding protein (DBP) cDNA probe, we assigned the gene coding for rat DBP to chromosome 14. We conclude that the genes for DBP, albumin, and α-fetoprotein, all of which derive from a common precursor, are syntenic in the rat, as they are in man.
Chromosomal evolution of the Canidae
Authors: Wayne R.K. , Nash W.G. , O’Brien S.J.
Published: May 2008

The Giemsa banding patterns of seven canid species, including the grey wolf (Canis lupus), the maned wolf (Chrysocyon brachyurus), the bush dog (Speothos venaticus), the crab-eating fox (Cerdocyon thous), the grey fox (Urocyon cinereoargenteus), the bat-eared fox (Otocyon megalotis), and the fennec (Fennecus zerda), are presented and compared. Relative to other members of Canidae, these species have high diploid complements (2n > 64) consisting of largely acrocentric chromosomes. They show a considerable degree of chromosome homoeology, but relative to the grey wolf, each species is either missing chromosomes or has unique chromosomal additions and rearrangements. Differences in chromosome morphology among the seven species were used to reconstruct their phylogenetic history. The results suggest that the South American canids are closely related to each other and are derived from a wolf-like progenitor. The fennec and the bat-eared fox seem to be recent derivatives of a lineage that branched early from the wolf-like canids and which also includes the grey fox.
Chromosomal evolution of the Canidae
Authors: Wayne R.K. , Nash W.G. , O’Brien S.J.
Published: May 2008

The Giemsa-banding patterns of chromosomes from the arctic fox (Alopex lagopus), the red fox (Vulpes vulpes), the kit fox (Vulpes macrotis), and the raccoon dog (Nyctereutes procyonoides) are compared. Despite their traditional placement in different genera, the arctic fox and the kit fox have an identical chromosome morphology and G-banding pattern. The red fox has extensive chromosome arm homoeology with these two species, but has only two entire chromosomes in common. All three species share some chromosomes with the raccoon dog, as does the high diploid-numbered grey wolf (Canis lupus, 2n = 78). Moreover, some chromosomes of the raccoon dog show partial or complete homoeology with metacentric feline chromosomes which suggests that these are primitive canid chromosomes. We present the history of chromosomal rearrangements within the Canidae family based on the assumption that a metacentric-dominated karyotype is primitive for the group.
A somatic cell hybrid with a single human chromosome 22 corrects the defect in the CHO mutant (Ade–I) lacking adenylosuccinase activity
Authors: Van Keuren M.L. , Hart I.M. , Kao F.-T. , Neve R.L. , Bruns G.A.P. , Kurnit D.M. , Patterson D.
Published: May 2008

Adenine-requiring Chinese hamster ovary (CHO-K1) auxotrophs of the complementation group Ade–I were hybridized with various human cells, and hybrids were isolated under selective conditions in which retention of the complementing gene on the human chromosome is necessary for survival. Ade–I cells are deficient in adenylosuccinase activity. This enzyme carries out two independent, but similar, steps of purine biosynthesis: (1) the removal of a fumarate from succinylaminoimidazole carboxamide ribotide to produce aminoimidazole carboxamide ribotide and (2) the removal of fumarate from adenylosuccinate to produce AMP. These are the 9th and 13th steps of adenylate biosynthesis, respectively. Analysis of hybrids by cytogenetics and by Southern blot techniques using chromosome 22 specific DNA probes, one of which encodes an antigen expressed in human fetal brain, indicated that human chromosome 22 was 100% concordant for growth without adenine. One hybrid subclone, isolated after two successive rounds of subcloning, was found to be capable of growth without adenine; the only human chromosome present was 22. In addition, segregants that had lost the ability to grow in adenine-free media had also lost human chromosome 22. These results suggest that the human gene for adenylosuccinase resides on chromosome 22.
Differences in the location of nucleolus organizer regions in European vespertilionid bats
Authors: Volleth M.
Published: May 2008

The karyotypes of European vespertilionid bats are distinguished by only a few, easily detectable differences in their G-banding patterns. Most rearrangements can be identified as Robertsonian translocations. Yet, there are surprising differences in the location of active nucleolus organizer regions (NORs), as revealed by silver staining. The ancestral position of the NOR is considered to be a secondary constriction on chromosome 15, as is the case in the genera Eptesicus, Nyctalus, and Vespertilio and in three of four Pipistrellus species. The remaining genera show multiple NOR sites located on minute short arms close to the centromere. In P. pipistrellus, differences in the location of the NORs correlate with the geographical origin of the animals. Some Myotis species possess NORs on numerous chromosomes and show great interindividual variability. In addition, two sibling species, M. brandtii and M. mystacinus, show completely different NOR locations.
Enhancement and attenuation of cytogenetic damage by vitamin C in cultured human lymphocytes exposed to Thiotepa or L-ethionine
Authors: Lialiaris T. , Mourelatos D. , Dozi-Vassiliades J.
Published: May 2008

Vitamin C (vit C) at 2 mM enhanced sister chromatid exchange (SCE) frequencies induced by Thiotepa (THIO) or L-ethionine (L-ETH) in cultured human lymphocytes. However, when vit C was tested at 0.02 mM and 0.2 mM a rather protective effect on SCE rates induced by THIO or L-ETH was identified. Vit C (2 mM) caused a cell division delay in cultures treated with THIO or L-ETH. Division delays caused by THIO or L-ETH were reversed in the presence of 0.02 mM or 0.2 mM vit C. Mitotic indices (Mis) in cultures treated with THIO or L-ETH continued to be suppressed in the presence of 2 mM vit C. However, vit C at 0.02 mM reversed suppression of Mis caused by L-ETH or THIO. These findings illustrate the complexity of the interactions of vit C in biological systems and indicate that with different concentrations vit C can cause or prevent genetic toxicity.
Variant Philadelphia translocations in chronic myeloid leukemia
Authors: De Braekeleer M.
Published: May 2008

Up to the beginning of 1986, some 327 variant Philadelphia translocations were reported in chronic myeloid leukemia. The present study represents an attempt to determine which factors (sex, age, geographic localization, etc.) influence the occurrence and chromosome involvement of these variant Philadelphia (Ph1) translocations. Clinical data indicated that band 9q34 was always rearranged in the variant Ph1 translocations and no difference existed between the hematologic and prognostic features among patients with the standard and the variant translocations. An uneven geographic distribution of the variant Ph1 translocations was found. Whether this was due to populations with different ethnic backgrounds or to environmental factors could not be determined. Twenty-eight bands were shown to be rearranged more frequently than expected (P < 0.05); 27 of them are known to contain a fragile site and/or an oncogene and/or are rearranged more frequently than expected in other malignancies. The chromosomes involved in these variant Ph1 translocations were found to show a very particular geographic distribution, which cannot be explained at present.
Correlation of pachytene chromomeres and metaphase bands of human chromosomes, and distinctive properties of telomeric regions
Authors: Ambros P.F. , Sumner A.T.
Published: May 2008

By means of double staining with DAPI and chromomycin A3, we show that the chromomeres of human pachytene chromosomes are generally DAPI positive and chromomycin negative, like the G- or Q-bands of mitotic chromosomes. Thus we have demonstrated, using an objective technique not based on morphological comparisons, that chromomeres and G-bands are equivalent. However, terminal chromomeres and the ends of mitotic chromosomes, as well as a few other sites, are chromomycin positive and DAPI negative. The ends of human chromosomes appear, therefore, to contain a distinctive class of GC-rich DNA.
Offspring of a trisomic cow
Authors: Mayr B. , Schellander K. , Auer H. , Tesarik E. , Schleger W. , Sasshofer K. , Glawischnig E.
Published: May 2008

A cow, trisomic for chromosome 22, became pregnant and gave birth to a karyotypically normal and healthy calf. Thus, a second example of reproductive capability in autosomal trisomies in mammals, in addition to trisomy 21 in man, is provided.
The gene for human carbonic anhydrase II (CA2) is located at chromosome 8q22
Authors: Nakai H. , Byers M.G. , Venta P.J. , Tashian R.E. , Shows T.B.
Published: May 2008

The gene CA2 for the human carbonic anhydrase II isozyme is encoded in band q22 of chromosome 8. These data and supporting evidence predict that the genes for carbonic anhydrase I and III are also physically closely linked in this chromosomal region.
High-resolution in situ hybridization technique using biotinylated NMYC oncogene probe reveals periodic structure of HSRs in human neuroblastoma
Authors: Garson J.A. , van den Berghe J.A. , Kemshead J.T.
Published: May 2008

Gene amplification in mammalian cells commonly manifests itself as homogeneously staining chromosomal regions (HSRs). These are frequently seen in neuroblastoma and have been shown to be the site of amplification of the NMYC oncogene. We have used a nonisotopic, high-resolution in situ hybridization technique to reveal a hitherto unrecognized periodic microstructure within HSRs of a human neuroblastoma cell line.
Live haploid-diploid and other unusual mosaic chickens (Gallus domesticus)
Authors: Thorne M.H. , Collins R.K. , Sheldon B.L.
Published: May 2008

Sixteen haploid-diploid chickens, four diploid-triploids, and one haploid-diploid-triploid chicken have been found in a layer line of crossbred origin. Live haploid-euploid vertebrates have not been reported previously. Flow cytometric analysis revealed 1–80% haploid red blood cells (RBCs) in the haploid-euploid chickens and 5–30% triploid RBCs in the diploid-triploids. Mosaic cell lines were also found in leukocytes and many tissues. The haploid-diploid chickens were all phenotypically normal and fertile, but the phenotype and fertility of the diploid-triploid chickens depended on their sex-chromosome complements and the ratio of diploid to triploid cells. The haploid cell lines are thought to originate from supernumerary spermatozoa, and the diploid-triploids from binucleated oocytes with meiotic errors. It is likely that genetic factors are partly responsible for the occurrence of these mosaic chickens.
Mapping of alpha-spectrin on distal mouse chromosome 1
Authors: Seldin M.F. , Morse, III H.C. , D’Hoostelaere L. , Britten J.L. , Steinberg A.D.
Published: May 2008

DNAs from different strains of inbred mice and feral Mus spretus were found to exhibit restriction fragment length polymorphisms (RFLP) when hybridized with a probe prepared from a c-DNA clone of the mouse α-spectrin (Spna-1) gene. Studies of five recombinant inbred strains and (C57BL/6 × M. spretus) F1× C57BL/6 backcross mice demonstrated that these RFLPs were allelic and that Spna-1 is closely linked to Ly-9 and Ly-17 on the distal region of chromosome 1.
Chromosome localization of the human renin gene (REN) by in situ hybridization
Authors: McGill J.R. , Chirgwin J.M. , Moore C.M. , McCombs J.L.
Published: May 2008

Previous studies by Southern blot analysis of human × mouse somatic cell hybrids localized the renin gene to region p21→qter of human chromosome 1. Using a DNA insert encoding exons 2–5, the renin gene was mapped to human chromosome bands 1q25→q32 by in situ hybridization. The sublocalization of the renin gene will facilitate subsequent detailed linkage analysis of human chromosome 1.
Localization of a unique DNA sequence to band p16 of human chromosome 4
Authors: Thayer R.E. , Harper M.E. , Sawyer J. , Singer M.F. , McBride O.W.
Published: May 2008

Southern blot analysis of DNA from human-rodent cell hybrids and in situ hybridization to metaphase chromosomes allowed the assignment of a unique human DNA sequence associated with satellite DNA to band p16 of human chromosome 4.
Elimination of the largest chromosome pair during differentiation into somatic cells in the Japanese hagfish, Myxine garmani (Cyclostomata, Agnatha)
Authors: Nakai Y. , Kohno S.
Published: May 2008

The modal number of chromosomes in Myxine garmani was 14 in somatic cells from three tissues, 16 in spermatogonia, and eight in first spermatocytes. The amount of DNA in a somatic cell averaged 70.2% of the amount in a spermatogonium. The largest pair of chromosomes present in spermatogonia was absent from the somatic cells. These results indicate that, in M. garmani, chromosome elimination takes place during the early stages of cleavage, except in the ancestral germ line cells. The chromosome number of M. garmani is extremely small as compared with 48–54 in germ lines and 34–36 in somatic cells of the order Myxinida, and is the lowest in the literature on fishes.
Chromosomal assignment of amplified genes in hydroxyurea-resistant hamster cells
Authors: Tonin P.N. , Stallings R.L. , Carman M.D. , Bertino J.R. , Wright J.A. , Srinivasan P.R. , Lewis W.H.
Published: May 2008

We have shown previously that cDNAs for the Ml and M2 subunits of ribonucleotide reductase, ornithine decarboxylase (ODC), and p5–8, a 55,000-Dalton protein, hybridize to amplified genomic sequences in a highly hydroxyurea-resistant hamster cell line. We have extended these observations to include two additional, independently isolated, hydroxyurea-resistant cell lines: SC8, a single-step hamster ovary cell line, and KH450, a multistep human myeloid leukemic cell line, have also undergone genomic amplification for sequences homologous to ODC and p5–8 cDNAs. However, neither SC8 nor KH450 contains amplified genomic sequences homologous to an Ml cDNA probe. A panel of mouse-hamster somatic cell hybrids was used to map sequences homologous to Ml, M2, ODC, and 5–8 cDNAs in the hamster genome. The M2, ODC, and p5–8 cDNAs hybridized to DNA fragments that segregated with hamster chromosome 7. In contrast, Ml cDNA hybridized to DNA fragments that segregated with hamster chromosome 3. These data suggest that the genes RRM2, (M2), ODC, and p5–8, but not RRM1 (Ml), are linked and may have been co-amplified in the selection of the hydroxyurea-resistant hamster and human cell lines.
Direct chromosome preparations from chorionic villi: a method for obtaining extended chromosomes and recognizing mosaicism confined to the placenta
Authors: Cheung S.W. , Crane J.P. , Kyine M. , Cui M.Y.
Published: May 2008

A modified technique is described for obtaining extended metaphase chromosomes (600 bands) from direct preparations of chorionic villi, allowing rapid detection of subtle structural aberrations with minimal risk of maternal-cell contamination. Analysis of multiple individually processed villus fragments may be helpful in recognizing mosaicism confined to chorionic villi.
A specific chromosomal abnormality in rhabdomyosarcoma
Authors: Douglass E.C. , Valentine M. , Etcubanas E. , Parham D. , Webber B.L. , Houghton P.J. , Green A.A.
Published: May 2008

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal. Cytogenetic hallmarks of gene amplification (double minute chromosomes and homogeneously staining regions) were apparent in three cases. Other frequent abnormalities included rearrangements of chromosome 1p and trisomy of chromosome 8. The absence of the t(2;13) in more than 100 cases of other pediatric solid tumors investigated in our laboratory indicates its specificity for rhabdomyosarcoma. These cytogenetic findings suggest directions for further investigation of the molecular events underlying the genesis of this tumor.
Equine half sibs with an unbalanced X;15 translocation or trisomy 28
Authors: Power M.M.
Published: May 2008

Two unrelated chromosome abnormalities were found in equine half sibs. The proposita, Case 1, which was short in stature and infertile, had a de novo unbalanced X;15 translocation involving loss of Xp. Replication studies indicated that the translocated X was preferentially late replicating and that this late replication spread variably into the autosomal segment. Case 2, a half brother of the proposita, was short in stature, had cryptorchidism, and was trisomic for chromosome 28. Cytogenetic analysis of the dam, the sire of Case 1, and two other phenotypically normal half sibs revealed normal chromosome complements. Five further normal pregnancies were reported. The finding of two unrelated chromosome abnormalities is therefore probably fortuitous in this family. This is the first case of an unbalanced X-autosome translocation and the first case of an autosome trisomy to be reported in the horse.
Rearrangements of chromosome region 12q13→q15 in pleomorphic adenomas of the human salivary gland (PSA)
Authors: Bullerdiek J. , Bartnitzke S. , Weinberg M. , Chilla R. , Haubrich J. , Schloot W.
Published: May 2008

Nine of 40 pleomorphic salivary gland adenomas (PSAs) showed clonal aberrations of chromosome 12, with a breakpoint at 12q13→q15. The cytogenetic findings in these cases and those of nine additional cases reported in the literature suggest that this type of aberration is a primary change directly involved in the genesis of PSA.
Two different XY-quadrivalent associations and impairment of fertility in men
Authors: Johannisson R. , Löhrs U. , Wolff H.H. , Schwinger E.
Published: May 2008

One sterile and one subfertile man with balanced reciprocal autosomal translocations, a t(9;15), and a t(14;21), were analyzed using whole mount pachytene spreads, histology, and semen analyses. In both probands with different types of quadrivalent complexes lack of pairing near the translocation breakpoints and significant associations with XY bivalents were found. Variability in the frequency of XY-quadrivalent contacts and an increase in late pachytene to 52% in t(9;15) and 90% in t(14;21) could be observed. The lower rate was associated with reduced postmeiotic spermatogenesis and the higher rate with complete spermatogenic arrest. In both translocation carriers the XY-quadrivalent association is considered to be the main cause for testicular malfunction rather than nonpaired segments in the multivalent complexes.
KLF2 Primes the Antioxidant Transcription Factor Nrf2 for Activation in Endothelial Cells
Authors: Fledderus Joost O. , Boon Reinier A. , Volger Oscar L. , Hurttila Hanna , Ylä-Herttuala Seppo , Pannekoek Hans , Levonen Anna-Liisa , Horrevoets Anton J.G.
Published: May 2008

Objective—

Atheroprotective blood flow induces expression of anti-inflammatory Krüppel-like factor 2 (KLF2) and activates antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in vascular endothelium. Previously, we obtained KLF2-induced gene expression profiles in ECs, containing several Nrf2 target genes. Our aim was to investigate the role of KLF2 in shear stress–mediated activation of Nrf2 in human umbilical vein endothelial cells (HUVECs).

Methods and Results—

Expression of Nrf2 and its targets NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase (HO-1) was elevated by shear and KLF2. KLF2 knockdown showed that shear-induced expression of NQO1 but not Nrf2 was dependent on KLF2. KLF2 overexpression in absence of flow resulted in more efficient activation of Nrf2 by tert-butyl hydroquinone (tBHQ) through enhanced nuclear localization, and promoted expression of a large panel of Nrf2-dependent genes resulting in superior protection against oxidative stress. Comparison of shear-, KLF2-, and Nrf2-induced transcriptomes showed that the majority of shear-modulated gene sets is influenced by KLF2 or Nrf2.

Conclusions—

We report that KLF2 substantially enhances antioxidant activity of Nrf2 by increasing its nuclear localization and activation. The synergistic activity of these two transcription factors forms a major contribution to the shear stress–elicited transcriptome in endothelial cells.
Arrhythmogenic Effects of β
2
-Adrenergic Stimulation in the Failing Heart Are Attributable to Enhanced Sarcoplasmic Reticulum Ca Load
Authors: DeSantiago Jaime , Ai Xun , Islam Mohammed , Acuna Georgia , Ziolo Mark T. , Bers Donald M. , Pogwizd Steven M.
Published: May 2008

Ventricular tachycardia in heart failure (HF) can initiate by nonreentrant mechanisms such as delayed afterdepolarizations. In an arrhythmogenic rabbit model of HF, we have shown that isoproterenol induces ventricular tachycardia in vivo and aftercontractions and transient inward currents in HF myocytes. To determine whether β
2
-adrenergic receptor (β
2
-AR) stimulation contributes, we performed in vivo drug infusion, in vitro myocyte and biochemical studies. Intravenous zinterol (2.5 μg/kg) led to ventricular arrhythmias, including ventricular tachycardia up to 13 beats long in 4 of 6 HF rabbits (versus 0 of 5 controls,
P
<0.01), an effect blocked by β
2
-AR antagonist ICI-118,551 (0.2 mg/kg). In field-stimulated myocytes (0.5 to 4 Hz, 37°C), β
2
-AR stimulation (1 μmol/L zinterol+300 nmol/L β
1
-AR antagonist CGP-29712A) induced aftercontractions and Ca aftertransients in 88% of HF versus 0% of control myocytes (
P
<0.01). β
2
-AR stimulation in HF (but not control) myocytes increased Ca transient amplitude (by 29%), sarcoplasmic reticulum (SR) Ca load (by 28%), the rate of [Ca]
i
decline (by 28%; n=12, all
P
<0.05), and phospholamban phosphorylation at Ser16, but Ca current was unchanged. All of these effects in HF myocytes were blocked by ICI-118,551 (100 nmol/L). Although total β-AR expression was reduced by 47% in HF rabbit left ventricle, β
2
-AR number was unchanged, indicating more potent β
2
-AR–dependent SR Ca uptake and arrhythmogenesis in HF. Human HF myocytes showed similar β
2
-AR–induced aftercontractions, aftertransients, and enhanced Ca transient amplitude, SR Ca load and twitch [Ca]
i
decline rate. Thus, β
2
-AR stimulation is arrhythmogenic in HF, mediated by SR Ca overload-induced spontaneous SR Ca release and aftercontractions.
Transcription Factor Tbx3 Is Required for the Specification of the Atrioventricular Conduction System
Authors: Bakker Martijn L. , Boukens Bastiaan J. , Mommersteeg Mathilda T.M. , Brons Janynke F. , Wakker Vincent , Moorman Antoon F.M. , Christoffels Vincent M.
Published: May 2008

The cardiac conduction system consists of distinctive heart muscle cells that initiate and propagate the electric impulse required for coordinated contraction. The conduction system expresses the transcriptional repressor Tbx3, which is required for vertebrate development and controls the formation of the sinus node. In humans, mutations in
Tbx3
cause ulnar–mammary syndrome. Here, we investigated the role of Tbx3 in the molecular specification of the atrioventricular conduction system. Expression analysis revealed early delineation of the atrioventricular bundle and proximal bundle branches by
Tbx3
expression in human, mouse, and chicken.
Tbx3
-deficient mice, which die between embryonic day 12.5 and 15.5, ectopically expressed genes for connexin (Cx)43, atrial natriuretic factor (Nppa), Tbx18, and Tbx20 in the atrioventricular bundle and proximal bundle branches.
Cx40
was precociously upregulated in the atrioventricular bundle of
Tbx3
mutants. Moreover, the atrioventricular bundle and branches failed to exit the cell cycle in
Tbx3
mutant embryos. Finally,
Tbx3
-deficient embryos developed outflow tract malformations and ventricular septal defects. These data reveal that Tbx3 is required for the molecular specification of the atrioventricular bundle and bundle branches and for the development of the ventricular septum and outflow tract. Our data suggest a mechanism in which Tbx3 represses differentiation into ventricular working myocardium, thereby imposing the conduction system phenotype on cells within its expression domain.