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Mouse chromosome 19 and distal rat chromosome 1: a chromosome segment conserved in evolution.

Through a combination of radiation hybrid mapping and studies by FISH and zoo-FISH we have made a comparative investigation of the distal portion of rat chromosome 1 (RNO1) and the entire mouse chromosome 19 (MMU19). It was found that homologous segments of RNO1 and MMU19 are similar in banding morphology and in length as determined by several different methods, and that the gene order of the 46 genes studied appears to be conserved across the homologous segments in the two species. High-resolution zoo-FISH techniques showed that MMU19 probes highlight only a continuous segment on RNO1 (1q43-qter), with no detectable signals on other rat chromosomes. We conclude that these data suggest the evolutionary conservation of a chromosomal segment from a common rodent ancestor. This segment now constitutes the entire MMU19 and a large segment distally on RNO1q in the mouse and rat, respectively.

Animals↗

Studies on metatherian sex chromosomes. III. The use of tritiated uridine-induced chromosome aberrations to distinguish active and inactive X chromosomes.

The paternal X inactivation system of kangaroos has been investigated in this study by using tritiated uridine-induced chromosome aberrations to distinguish the active from the inactive X. Previous work in eutherian mammals has demonstrated that constitutive heterochromatic chromosome regions are less susceptible to breakage by tritiated uridine than euchromatic regions. The results of a comparison between the paternal X chromosome of a wallaroo X red kangaroo hybrid female and the two X chromosomes of a red kangaroo female suggested that the facultative heterochromatin of the X is also less susceptible to breakage by this treatment. However there were significantly more breaks of the paternal X in fibroblasts than in lymphocytes of the hybrid female, which agrees with biochemical findings suggesting activation of the paternal X in fibroblasts. Our results strengthen the suggestion of other workers that the reduced number of aberrations in heterochromatin occurs because such breaks occur principally when the DNA and labelled RNA are in apposition during transcription. Some evidence was found of an apparent toxicity effect of the tritiated uridine solution on the cells.

Animals↗

Mapping through somatic cell hybrids and cDNA probes of protein C to chromosome 2, factor X to chromosome 13, and alpha 1-acid glycoprotein to chromosome 9.

The previously unassigned gene coding for the anti-coagulatory protein C has been mapped on chromosome 2 using a cDNA probe and genomic blots from a human-hamster somatic cell hybrid panel. The assignments of the genes coding for the coagulation factor X to chromosome 13, and for alpha 1-acid glycoprotein to chromosome 9 have been confirmed using a similar direct approach.

Animals↗

Analysis of chromosome loss and chromosome segregation in cytokinesis-blocked human lymphocytes: non-disjunction is the prevalent mistake in chromosome segregation produced by low dose exposure to ionizing radiation.

The aim of the present work was to examine in human lymphocytes, firstly, whether in vitro gamma-rays as compared with X-rays also induce chromatid malsegregation and at higher frequencies than chromosome loss and, secondly, whether the cytokinesis-blocked micronucleus assay combined with fluorescence in situ hybridization might be useful for the biomonitoring of individuals exposed to ionizing radiation. After irradiation, the relative frequencies of centromere-positive micronuclei decreased from 39.2% at 0.1 Gy to 21. 63% at higher doses. There was no statistically significant increase in MNCen+ frequencies at doses below 1 Gy (0.1, 0.25 and 0.5 Gy), but a statistically significant increase at 1 (P < 0.05) and 2 Gy (P < 0.001) was observed for all the donors. No significant differences in baseline and gamma-ray-induced non-disjunction frequencies for chromosomes 1 (P = 0.9) and 17 (P = 0.8) between individuals were detected. For radiation-induced non-disjunction, lower doses (0.1, 0. 25 and 0.5 Gy) of gamma-rays did not induce a statistically significant increase in non-disjunction frequencies whereas 1 Gy and above clearly induced a statistically significant increase in the total non-disjunction frequencies for all the donors (P < 0.05 at 1 Gy and P < 0.0001 at 2 Gy). The aneugenic effect of radiation is less clearly dose dependent at the lower doses, suggesting an apparent threshold below which no change could be demonstrated. At high radiation doses the major mechanism for gamma-ray-induced aneuploidy is related to chromosome loss through non-disjunction, as has been demonstrated using X-rays, and not through the formation of micronuclei.

Adult↗

A pericentric inversion of chromosome 9 and a rearrangement involving chromosomes 9 and 10, observed in two generations. Clinical description of chromosome 9 (p12-p21) deletion syndrome.

The clinical picture associated with a deletion of a central part of the short arm of chromosome no. 9 is described in two siblings. The clinical signs differ from those described in deletion of the terminal part of the short arm. Pericentric inversion of chromosome no. 9, combined with a rearrangement involving chromosomes 9 and 10, was found in the mother and the maternal grandmother of the propositus.

Abnormalities, Multiple↗

The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12.

A genomic DNA fragment containing the rat epimorphin gene sequence was cloned from a rat DNA cosmid library using a mouse epimorphin cDNA probe. Within the cosmid insert, nine epimorphin exons were identified and sequenced. The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively. Consistent with the developmentally related expression pattern of the mouse epimorphin gene, transcripts of the rat epimorphin gene were detected in 17-day postfertilization rat embryos. The gene, designated Epim, was assigned to rat chromosome 12 by somatic cell hybrid analysis and localized to 12q16 by fluorescence in situ hybridization. The mouse and human homologs of this gene were localized on mouse chromosome 5 and human chromosome 7 by linkage analysis and chromosomal in situ hybridization, respectively.

Amino Acid Sequence↗

Gene localization by chromosome fractionation: globin genes are on at least two chromosomes and three estrogen-inducible genes are on three chromosomes.

Chicken metaphase chromosomes were partially purified by rate zonal centrifugation, and DNA was prepared from each of the fractions of the sucrose gradient. The DNA was digested with various restriction enzymes and subjected to electrophoresis in agarose gels. The DNA was transferred to nitrocellulose filters (as described by Southern), and the filters were hybridized with cDNA probes. Four globin genes alpha A, alpha D, beta, and rho or epsilon are located on at least two chromosomes, and three of the estrogen-inducible genes of the hen oviduct--ovalbumin, ovomucoid, and transferrin--are on three different chromosomes. These experiments also confirm our earlier assignment of the endogenous viral sequence related to Rous-associated virus-0 to a separate (and larger) chromosome than the cellular sequence related to the transforming gene of avian sarcoma virus (cellular sarc), although it now appears that cellular sarc is on a small macrochromosome, rather than on a microchromosome.

Animals↗

Chromosome studies in hypoptopomatinae (Pisces, Siluriformes, Loricariidae). II. ZZ/ZW sex-chromosome system, B chromosomes, and constitutive heterochromatin differentiation in Microlepidogaster leucofrenatus.

Cytogenetic analysis of two local populations of Microlepidogaster leucofrenatus showed a basic diploid chromosome number (2N) of 54 in both populations. Some fishes were found to have a 2N = 55 or 56 chromosomes due to the presence of one or two large heterochromatic B chromosomes. Specimens of M. leucofrenatus from the Poço Grande stream had 24 metacentrics, 24 submetacentrics, four subtelocentrics, and one submetacentric homomorphic pair in males and one submetacentric/subtelocentric heteromorphic pair in females, whereas individuals of this species from the Marumbi River had 22 metacentrics, 24 submetacentrics, four subtelocentrics, two acrocentrics, and one submetacentric/subtelocentric heteromorphic pair in females. The occurrence of the heteromorphic pair in the females was due to the presence of an extra C-banded segment on the W chromosome. Ag-NORs in both populations were located interstitially on the short arm of the largest metacentric pair. The Poço Grande population had less constitutive heterochromatin than did the Marumbi River population. The speciation process in this fish species is discussed on the basis of heterochromatin distribution.

Aneuploidy↗

Chromosomal localization of the human heme oxygenase genes: heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13.3.

Heme oxygenase catalyzes the oxidation of heme to biliverdin, the precursor of the bile pigment bilirubin, and carbon monoxide, a putative neurotransmitter. We have employed polymerase chain reaction and fluorescence in situ hybridization to determine the chromosome localization of the genes coding for the two known heme oxygenase isozymes. Heme oxygenase-1 (HMOX1), the inducible form, was localized to human chromosome 22q12, while heme oxygenase-2 (HMOX2), the constitutive form, was localized to chromosome 16p13.3.

Animals↗

Four human chromosome 3q and four human chromosome 21 loci map onto sheep chromosome 1q.

Eight new loci have been assigned to sheep Chromosome (Chr) 1q by use of a chromosomally characterized minipanel of sheep x hamster cell hybrids. Four loci, which have been mapped to the distal region of human Chr 3q, are ceruloplasmin (CP), sucrase isomaltase (SI), glucose transporter 2 (GLUT2), and ectopic viral integration site 1 (EVI1). The other four loci, on human Chr 21, include interferon alpha receptor (IFNAR); interferon inducible protein p78, murine (MX1); collagen type VI, alpha 1 (COL6A1); and S100 protein, beta polypeptide (S100B). All of these loci, except GLUT2 and MX1, have been mapped onto bovine Chr 1 or are syntenic with loci on this chromosome. The in situ localization of transferrin (TF) to sheep Chr 1q42-q45 confirms our previous assignment of this locus and independently anchors the eight new syntenic loci to sheep Chr 1q.

Animals↗

Chromosomal localization of a cytochrome b5 gene to human chromosome 18 and a cytochrome b5 pseudogene to the X chromosome.

We have isolated cDNA clones that code for human cytochrome b5. Owing to the high degree of evolutionary conservation of cytochrome b5 sequences and the existence of human and rodent cytochrome b5 processed pseudogenes, we were unable to map unambiguously the chromosomal localization of the human gene(s) by Southern blot hybridization of DNA from human-rodent somatic cell hybrids. An alternative approach, based on restriction enzyme digestion of PCR-amplified DNA, enabled us to map the human cytochrome b5 gene(s) to chromosome 18 and one of its processed pseudogenes to the X chromosome. We propose the designations CYB5 and CYB5P1 for the gene and pseudogene loci, respectively.

Animals↗

Chromosome and replisome dynamics in E. coli: loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation.

Chromosome and replisome dynamics were examined in synchronized E. coli cells undergoing a eukaryotic-like cell cycle. Sister chromosomes remain tightly colocalized for much of S phase and then separate, in a single coordinate transition. Origin and terminus regions behave differently, as functionally independent domains. During separation, sister loci move far apart and the nucleoid becomes bilobed. Origins and terminus regions also move. We infer that sisters are initially linked and that loss of cohesion triggers global chromosome reorganization. This reorganization creates the 2-fold symmetric, ter-in/ori-out conformation which, for E. coli, comprises sister segregation. Analogies with eukaryotic prometaphase suggest that this could be a primordial segregation mechanism to which microtubule-based processes were later added. We see no long-lived replication "factory"; replication initiation timing does not covary with cell mass, and we identify changes in nucleoid position and state that are tightly linked to cell division. We propose that cell division licenses the next round of replication initiation via these changes.

Chromosome Mapping↗

Parental origin of the X chromosome, X chromosome mosaicism and screening for "hidden" Y chromosome in 45,X Turner syndrome ascertained cytogenetically.

Our study confirms the finding that about 85% of X chromosomes in Turner girls are maternally derived. A new observation is the detection of a high frequency of mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have a pure 45,X karyotype. DNA examination of the material was done by hybridization with digoxigenin labelled, non-radioactive probes, and PCR products for microsatellite analysis were run on polyacrylamide gels. We screened for the presence of "hidden" Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3, DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel "hidden" Y chromosome mosaics, we did not find any positive cases. A precise technical protocol for these new techniques is given, and the advantages are discussed.

Chromosome Banding↗

The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16.

The human amyloid beta protein is the major constituent of the brain amyloid plaques found in Alzheimer disease. The gene that encodes this protein is located on chromosome 21, and individuals with Down syndrome (trisomy 21) also exhibit an early onset form of Alzheimer disease. We have used the cloned human amyloid beta protein gene and a panel of somatic cell hybrids to map the location of the mouse homolog of this gene. We report here that the mouse gene is located on chromosome 16 within the region 16C3----ter, in common with three other genes which map within the Down syndrome region of human chromosome 21.

Amyloid↗

The gene encoding the transcriptional repressor BERF-1 maps to a region of conserved synteny on mouse chromosome 16 and human chromosome 3 and a related pseudogene maps to mouse chromosome 8.

We have recently identified and characterized a Kruppel-like zinc finger protein (BERF-1), that functions as a repressor of beta enolase gene transcription. By interspecific backcross analysis the gene encoding BERF-1 was localized 4.7 cM proximal to the Mtv6 locus on mouse chromosome 16, and an isolated pseudogene was localized to mouse chromosome 8, about 5.3 cM distal to the D8Mit4 marker. Nucleotide sequence identity and chomosome location indicate that the gene encoding BERF-1 is the mouse homologue (Zfp148) of ZNF148 localized to human chromosome 3q21, a common translocation site in acute myeloid leukemia patients.

Animals↗

Assignment of transcription factor NFAT5 to human chromosome 16q22.1, murine chromosome 8D and porcine chromosome 6p1.4 and comparison of the polyglutamine domains.

To date, transcription factors of the NFAT family (nuclear factors of activated T cells) have been described for mouse and man. Recently, we mapped the human NFAT5 gene to chromosome 16 by PCR using DNA from hybrid cell lines. Here we report the exact position of the human gene between D16S496 and WI5254 within the 16q22.1 subband, the localization of the murine gene at chromosome 8D, and the identification and mapping of the porcine counterpart to chromosome 6p1.4.

Animals↗

A functional mouse ornithine decarboxylase gene (Odc) maps to chromosome 12: further evidence of homoeology between mouse chromosome 12 and the short arm of human chromosome 2.

We have used a DNA probe specific for a functional mouse ornithine decarboxylase gene (Odc) in conjunction with a panel of Chinese hamster x mouse somatic cell hybrids to assign Odc to mouse chromosome 12. This assignment provides further evidence of genetic homoeology between a region of mouse chromosome 12 and the distal short arm of human chromosome 2.

Animals↗

Localization by fluorescence in situ hybridization (FISH) of human mitochondrial polymerase gamma (POLG) to human chromosome band 15q24-->q26, and of mouse mitochondrial polymerase gamma (Polg) to mouse chromosome band 7E, with confirmation by direct sequence analysis of bacterial artificial chromosomes (BACs).

Cloned cDNAs for the human mitochondrial DNA polymerase gamma (POLG) were identified by homology with the yeast mitochondrial DNA polymerase catalytic subunit (MIP). Fluorescence in situ hybridization (FISH) of human and mouse bacterial artificial chromosomes (BACs), hybridized by radioactively labeled POLG cDNAs, mapped to human chromosome band 15q24-->q26, as well as to mouse chromosome band 7E. Direct sequencing of the BAC DNA without subcloning confirmed the presence of both human POLG and mouse mitochondrial DNA polymerase gamma (Polg) in the respective BACs.

Animals↗