Antibiotic resistance. A new kind of epidemic.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
SEARCH · PubMed Health
Results for “Translocation, Genetic”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Defective expression of Bruton's tyrosine kinase in acute lymphoblastic leukemia.
Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that serves an essential role in B cell signaling and development. We examined the BTK expression profile of primary leukemic cells from infants with newly diagnosed acute lymphoblastic leukemia (ALL) (N = 14) and from pediatric patients with newly diagnosed (N = 10) or relapsed (N = 5) B-lineage ALL. Analysis of BTK protein and mRNA expression in the infant patient cells (N = 14) showed variable levels of BTK expression with the majority of samples having reduced to absent BTK expression. Sequence analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products of Btk mRNA from infant leukemia cells revealed the presence of aberrant transcripts. These Btk transcripts were characterized by either deletion of exon 16 (delta16) alone or deletion of both exons 15 and 16 (delta15 and 16). These deletions involve exact exon skipping and encode BTK proteins with either a deleted (delta16), or truncated (delta15 and 16) kinase domain. Extension of these Btk transcript sequencing studies to 15 pediatric B-lineage ALL patients revealed expression of exon 16 deleted Btk transcripts in several pediatric patients, however, none of these pediatric patients expressed transcripts with the exon 15 and 16 deletion. Both reduced expression of Btk message and expression of aberrant deleted Btk transcripts would contribute to reduced BTK protein expression and function in B-lineage leukemia cells. Since BTK is required for radiation induced apoptosis, reduced to absent expression of functional BTK in infant ALL cells could contribute to their radiation resistance.
Adolescent↗
Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22.
In recent decades, comparative chromosomal banding, chromosome painting, and gene-order studies have shown strong conservation of gross chromosome structure and gene order in mammals. However, findings from the human genome sequence suggest an unprecedented degree of recent (<35 million years ago) segmental duplication. This dynamism of segmental duplications has important implications in disease and evolution. Here we present a chromosome-wide view of the structure and evolution of the most highly homologous duplications (> or = 1 kb and > or = 90%) on chromosome 22. Overall, 10.8% (3.7/33.8 Mb) of chromosome 22 is duplicated, with an average sequence identity of 95.4%. To organize the duplications into tractable units, intron-exon structure and well-defined duplication boundaries were used to define 78 duplicated modules (minimally shared evolutionary segments) with 157 copies on chromosome 22. Analysis of these modules provides evidence for the creation or modification of 11 novel transcripts. Comparative FISH analyses of human, chimpanzee, gorilla, orangutan, and macaque reveal qualitative and quantitative differences in the distribution of these duplications--consistent with their recent origin. Several duplications appear to be human specific, including a approximately 400-kb duplication (99.4%-99.8% sequence identity) that transposed from chromosome 14 to the most proximal pericentromeric region of chromosome 22. Experimental and in silico data further support a pericentromeric gradient of duplications where the most recent duplications transpose adjacent to the centromere. Taken together, these data suggest that segmental duplications have been an ongoing process of primate genome evolution, contributing to recent gene innovation and the dynamic transformation of genome architecture within and among closely related species.
Animals↗
Primary primitive neuroectodermal tumor of the kidney. Case report and review of the literature.
Small cell tumors are a heterogeneous group of neoplasms with similar morphologic features. They include lymphomas, carcinomas with variable degrees of neuroendocrine differentiation, rhabdomyosarcomas, and neuroblastomas. The authors describe a rare case of primitive neuroectodermal tumor (PNET) located in the kidney that was thoroughly studied with modern diagnostic techniques, including expression of protein P 30/32 MIC2 with the antibody 013 with subsequent demonstration of a genetic translocation consistent with t(11;22). The literature on small cell tumors of the kidney, with special emphasis on PNET, is reviewed.
Adult↗
The genetics of a small chromosome region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. IV: scutoid, an antimorphic mutation.
Exchange mapping locates the dominant mutation Scutoid to the right of Adh on chromosome arm 2L of D. melanogaster. However, deletion mapping indicates that Sco is to the left of Adh. The phenotype of Sco is sensitive to mutation, or deletion, of noc+ and of three genes, el, l(2)br22, and l(2)br29 mapping immediately distal to noc. The four contiguous loci, el, l(2)br22, l(2) br29 and noc, although separable by deletion end points, interact, because certain (or all) alleles of these four loci show partial failure of complementation, or even negative complementation. The simplest hypothesis is that Sco is a small reciprocal transposition, the genes noc, osp, and Adh exchanging places with three genes normally mapping proximal to them: l(2)br34, 1(2)br35 and rd. The Sco phenotype is thought to result from a position effect at the newly created noc/l(2)br28 junction.
Alcohol Oxidoreductases↗
Effects of mutagen-sensitive mus mutations on spontaneous mitotic recombination in Aspergillus.
Methyl methane-sulfonate (MMS)-sensitive, radiation-induced mutants of Aspergillus were shown to define nine new DNA repair genes, musK to musS. To test mus mutations for effects on mitotic recombination, intergenic crossing over was assayed between color markers and their centromeres, and intragenic recombination between two distinguishable adE alleles. Of eight mutants analyzed, four showed significant deviations from mus+ controls in both tests. Two mutations, musK and musL, reduced recombination, while musN and musQ caused increases. In contrast, musO diploids produced significantly higher levels only for intragenic recombination. Effects were relatively small, but averages between hypo- and hyperrec mus differed 15-20-fold. In musL diploids, most of the rare color segregants resulted from mitotic malsegregation rather than intergenic crossing over. This indicates that the musL gene product is required for recombination and that DNA lesions lead to chromosome loss when it is deficient. In addition, analysis of the genotypes of intragenic (ad+) recombinants showed that the musL mutation specifically reduced single allele conversion but increased complex conversion types (especially recombinants homozygous for ad+). Similar analysis revealed differences between the effects of two hyperrec mutations; musN apparently caused high levels solely of mitotic crossing over, while musQ increased various conversion types but not reciprocal crossovers. These results suggest that mitotic gene conversion and crossing over, while generally associated, are affected differentially in some of the mus strains of Aspergillus nidulans.
Aspergillus nidulans↗
The meiotic behavior of an inversion in Caenorhabditis elegans.
The rearrangement hIn1(I) was isolated as a crossover suppressor for the right end of linkage group (LG) I. By inducing genetic markers on this crossover suppressor and establishing the gene order in the homozygote, hIn1(I) was demonstrated to be the first genetically proven inversion in Caenorhabditis elegans. hIn1(I) extensively suppresses recombination in heterozygotes in the right arm of chromosome I from unc-75 to unc-54. This suppression is associated with enhancement of recombination in other regions of the chromosome. The enhancement observed maintains the normal distribution of events but does not extend to other chromosomes. The genetic distance of chromosome I in inversion heterozygotes approaches 50 map units (m.u.), approximately equal to one chiasma per meiosis. This value is maintained in hIn1(I)/szT1(I;X) heterozygotes indicating that small homologous regions can pair and recombine efficiently. hIn1(I)/hT2(I;III) heterozygotes share no uninverted homologous regions and segregate randomly, suggesting the importance of chiasma formation in proper segregation of chromosomes. The genetic distance of chromosome I in these heterozygotes is less that 1 m.u., indicating that crossing over can be suppressed along an entire chromosome. Since one of our goals was to develop an efficient balancer for the right end of LGI, the effectiveness of hIn1(I) as a balancer was tested by isolating and maintaining lethal mutations. The meiotic behaviour of hIn1(I) is consistent with other genetic and cytogenetic data suggesting the meiotic chromosomes are monocentric. Rare recombinants bearing duplications and deficiencies of chromosome I were recovered from hIn1(I) heterozygotes, leading to the proposal the inversion was paracentric.
Animals↗
Suppression of a lethal trisomic phenotype in Drosophila melanogaster by increased dosage of an unlinked locus.
One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo-lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and shown that the suppression is a gene dosage effect. Altered dosage of Isis in the presence of two copies of Tpl has no obvious effects. By examining the interactions between Isis dosage and Tpl we suggest that Isis does not directly repress Tpl expression, but acts downstream on the triplo-lethal phenotype of Tpl.
Animals↗
Genetic analysis of Rough sheath1 developmental mutants of maize.
Maize Rough sheath1 (Rs1) mutants are dominant and cause a proliferation of sheath-like tissue at the base of the blade and throughout the ligular region. They also cause ligule displacement, a chaotic pattern of vasculature and abnormal cellular structure of vascular bundles. The affected region of Rs1-O leaves displays genetic and morphological attributes of both sheath and auricle, suggesting an overlap of these genetic programs. The rs1 locus maps approximately 26 map units distal to opaque2 (o2) on chromosome 7S, defining a new distal-most locus on the genetic map. Three mutant alleles, Rs1-O, Rs1-1025 and Rs1-Z, all display similar phenotypes. The mutations are completely dominant and the Rs1-O phenotype is not affected by dosage of the chromosome arm carrying the rs1+ allele, indicating that these alleles are neomorphic. Analysis of genetic mosaics showed that the Rs1-O phenotype is non-cell-autonomous, suggesting that intercellular signals convey the phenotype. Rs1 mutant phenotypes are affected by modifiers present in particular genetic backgrounds. An enhancer of Rs1-O was identified; segregation data imply a single recessive gene, ers1. Rs1 mutants were also found to enhance the expression of unlinked rs2 and Rs4 mutants, suggesting that these mutations affect similar developmental processes. We discuss the phenotypic and genetic similarities between Rs1 and Knotted 1 (Kn1) mutants that led to the identification of rs1 as a kn1-like homeobox gene (unpublished data).
Crosses, Genetic↗
Developmental genetics of the essential Drosophila nucleoporin nup154: allelic differences due to an outward-directed promoter in the P-element 3' end.
Drosophila nup154 encodes a predicted nucleoporin homologous to yeast Nup170p, Nup157p, and vertebrate Nup155, all of which are major components of the nuclear pore complex (NPC). Unlike its yeast homologs, nup154 is essential for viability. Animals with strong loss-of-function nup154 mutations caused by P-element insertion in the 5'-UTR of the gene died as larvae with small discs, brains, and testes. nup154 mRNA expression appeared developmentally regulated in tissues of wild-type embryos, larvae, and adults, suggesting that new nup154 synthesis is required when assembly of new NPCs is required, as in proliferating or growing tissues. Two additional nup154 alleles also associated with different P-element inserts in the 5'-UTR were viable but had strong loss-of-function sterile phenotypes, including failure to maintain spermatogenic stem cells and failure to progress into vitellogenic stages of oogenesis. Lethality vs. viability correlated with orientation of the P-element inserts in the different alleles. Transcript analysis by 5'-RACE suggested a mechanism for allelic differences: an outward-directed promoter internal to the P-element 3' end able to drive sufficient expression of the nup154 transcript for viability but not for fertility.
Animals↗
Regulation of gene activity by dosage compensation at the chromosomal level in drosophila.
Two models of dosage compensation have been tested by the measurement of G6PD and 6PGD enzymatic specific activities in flies hyperploid for regions of the X chromosome. Females duplicated for the proximal half of the X chromosomes (2 1/2 X's) have an increased level of G6PD and a normal level of 6PGD. Females duplicated for the distal half of the X chromosome (2 1/2 X's) have a normal level of G6PD and an increased level of 6PGD. Males bearing duplications of various segments of the X chromosome show control levels of G6PD and 6PGD, except where the duplicated region includes the structural gene for G6PD or 6PGD. These results fail to provide evidence for either the presence of discrete X-linked compensator (regulator) genes reducing the activity of other X-linked genes, or for a factor in limiting supply necessary for the transcription of all the genes on the X chromosome. Superfemales (3 X chromosomes) have the same G6PD and 6PGD activity levels as their diploid sisters. It would appear that the regulation of gene activity by dosage compensation is a chromosomal phenomenon in that the level of activity per gene copy for loci on the X chromosome is modulated in a stepwise fashion according to the total number of X chromosomes present.
Aneuploidy↗
The use of duplication-generating rearrangements for studying heterokaryon incompatibility genes in Neurospora.
Heterokaryon (vegetative) incompatibility, governing the fusion of somatic hyphal filaments to form stable heterokaryons, is of interest because of its widespread occurrence in fungi and its bearing on cellular recognition. Conventional investigations of the genetic basis of heterokaryon incompatibility in N. crassa are difficult because in commonly used stocks differences are present at several het loci, all with similar incompatibility phenotypes. This difficulty is overcome by using duplications (partial diploids) that are unlikely to contain more than one het locus. A phenotypically expressed incompatibility reaction occurs when unlike het alleles are present within the same somatic nucleus, and this parallels the heterokaryon incompatibility reaction that occurs when unlike alleles in different haploid nuclei are introduced into the same somatic hypha by mycelial fusion. - Nontandem duplications were used to confirm that the incompatibility reactions in heterokaryons and in duplications are alternate expressions of the same genes. This was demonstrated for three loci which had previously been established by conventional heterokaryon test-het-e, het-c and mt. These were each obtained in duplications as recombinant chromosome rearrangements. The particular method of producing the duplications is irrelevant so long as the incompatibility alleles are heterozygous. - The duplication technique has made it possible to determine easily the het-e and het-c genotypes of numerous laboratory and wild strains of unknown constitution. In laboratory strains both loci are represented simply by two alleles. Analysis of het-c is more complicated in some wide strains, where differences have been demonstrated at one or more additional het loci within the duplication used and multiple allelism is also possible. - The results how that the duplication method can be used to identify and map additional vegetative incompatibility loci, without the necessity of heterokaryon tests.
Alleles↗
Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis.
X-linked ichthyosis (XLI) is often associated with a recurrent microdeletion at Xp22.31 due to non-allelic homologous recombination between the CRI-S232 low-copy repeat regions flanking the STS gene. The clinical features of these patients may include mental retardation (MR) and the VCX-A gene has been proposed as the candidate MR gene. Analysis of DNA from four XLI patients with MR by array-comparative genomic hybridization (array-CGH) on a 150 kb resolution X chromosome-specific array revealed a 1.5 Mb interstitial microdeletion with breakpoints in the CRI-S232 repeat sequences, each of which harbors a VCX gene. We demonstrate that the recombination sites in all four cases are situated in the 1 kb repeat unit 2 region present at the 3' ends of the VCX-A and VCX-B genes thereby deleting VCX-A and VCX-B1 but not VCX-B and VCX-C. Array-CGH with DNA of an XLI patient with MR and an inherited t(X;Y)(p22.31;q11.2) showed an Xpter deletion of 8.0 Mb resulting in the deletion of all four VCX genes and duplication of both VCY homologs. These data confirm the role of VCX-A in the occurrence of MR in XLI patients. Moreover, we propose a VCX/Y teamwork-dependent mechanism for the incidence of mental impairment in XLI patients.
Chromosomes, Human, X↗
Preimplantation genetic diagnosis for an insertional translocation.
Explore the source record for details and available documents.
Female↗
Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11).
A DNA binding protein was identified which binds to two novel target-like sequences: (i) at the 5' flanking site of the breakpoint junction of chromosome 8 in a patient with T-acute lymphoblastic leukemia (ALL) carrying the t(8;14)(q24;q11) rearrangement and (ii) on chromosome 1 in three of five T-ALL patients with the t(1;14)(p32;q11) rearrangement. This protein [provisionally called recombination hotspot associated factor (ReHF-1)] was also found to bind to a similar target sequence that is present immediately at the 3' end of the human V delta 3 gene segment. In a small number of lines tested, the ReHF-1 protein was expressed in gamma delta lineage T cells and in a number of B cell precursor ALLs whose TCR delta locus has been rearranged. The molecular weight of ReHF-1 protein was determined to be approximately 30 kDa by UV cross-linking analysis. Gel filtration chromatography and sedimentation velocity centrifugation analyses indicate that the ReHF-1 protein exists as a multimeric protein in its native form. These data might suggest a possible role for this protein in the rearrangement of the TCR delta locus. Furthermore, another protein, ReHF-2, that appears to have strict sequence specificity was found to bind only to the complementary single strand of the target sequence. The interaction of these proteins with a conserved target sequence at the chromosomal breakpoint junction might suggest that they are involved in a novel enzymatic mechanism reminiscent of the general features of DNA recombination or replication events in Escherichia coli or Saccharomyces cerevisiae.
Base Sequence↗
The XLR sequence family: dispersion on the X and Y chromosomes of a large set of closely related sequences, most of which are pseudogenes.
The XLR sequence family encodes RNA transcripts specific to late-stage T and B cells and their neoplasms. Only one apparently functional mRNA has been identified thus far and this encodes a novel 25 kDa nuclear protein. In this report, we find that the XLR gene family is composed of 50-75 copies per haploid genome which localize to at least two different portions of the mouse X chromosome. Neither of these locations are near the xid mutation that earlier work had correlated with XLR. In addition, some members of this family are also on the Y chromosome. Another surprising finding is that while the fourteen genomic clones examined to date have the same exon-intron structure and are closely related with respect to sequence conservation (90%), all appear (in most cases by multiple criteria) to be non-functional, raising the possibility that all but one of the members of this large semi-dispersed family are pseudogenes.
Animals↗
Towards new prognostic factors in diffuse large cell non-Hodgkin's lymphoma.
Explore the source record for details and available documents.
Gene Rearrangement↗
Chromosome extraction and revision of linkage group 2 in Tribolium castaneum.
We used a balancer chromosome to recover ethylmethanesulfonate-induced recessive mutations in a targeted region of the genome of the red flour beetle (Tribolium castaneum) by the technique of chromosome extraction. The experiments reported herein constitute the first successful application of this powerful technique in the order Coleoptera. Using the balancer chromosome maxillopedia-Dachs3 (mxpDch-3), we recovered seven recessive visible variants representing seven distinct loci and several dozen recessive lethal variants representing at least five distinct loci after screening 1,607 EMS-mutagenized chromosomes. A subset of the mxpDch-3-extracted mutations were positioned on the map of the second linkage group by a series of two-, three-, and four-point crosses. The orientation of the homeotic gene complex (HOM-C) on this linkage group was also determined. With the advent of better and more varied balancer chromosomes and the concomitant improvement of chromosome extraction procedures for genetic analysis of T. castaneum, saturation mutagenesis of targeted regions of the genome is now feasible in this species.
Animals↗