In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cell lines exhibiting different tissue-specific functions. Some of the rules we have determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (lii) Nontranscribed genes can replicate during any interval of S phase. (iv)Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of cobtiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.Early observations in many laboratories suggested a relationship among chromosome condensation, late DNA replication, and gene inactivity (for review, see reference 4). Examples include the DNA of the inactive X chromosome in female mammals or genes showing variegated patterns of inactivity in Drosophila melanogaster when they are transposed from their normal position to one proximal to centromeric late replicating heterochromatin. Several observations have been reported indicating that, during the S phase, the genome of higher eucaryotes replicates in a bipartite manner separated by a pause (27, 37 and references therein). It has been suggested that, after this pause, the genome could replicate in a manner that renders it transcriptionally incompetent (21). It has also been suggested that there are distinct early and late compartments for replication of genes for specialized functions (21, 51 and references therein).To study the relationship between replication and gene expression on a molecular basis, we carried out initial studies on the temporal replication of single-copy genes in mammalian cells (18). The a-globin gene replicates very early during S phase in the Friend virus-transformed murine erythroleukemia (MEL) cell line in which it is transcribed. In subsequent studies, we showed that several immunoglobulin heavy-chain constant-region (IgCH) and variable-region (IgVH) genes also replicate very early during S phase when they are transcribed (10). Here we examine the temporal order of replication of genes for specialized functions in several types of differentiated cells in which they either are trariscribed or are transcriptionally silent. Among the findings presented here is ...
Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its identification is important for risk stratification in acute leukemia (AL). The scoring proposal of the European Group for the Classification of Acute Leukemia (EGIL) is useful for this purpose, but its performance against objective benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from among 676 newly diagnosed AL patients. Mixed, small and large blast cells predominated, with FAB M2 and L1 constituting the majority. All patients were positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T) (8 or 34%) markers with two exceptional patients demonstrating trilineage phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In six (26%) patients myeloid lineage commitment was also demonstrable by electron cytochemistry. Abnormal findings were present in 19 (83%) patients by cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities (13%), and three (13%) new, previously unreported translocations t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the EGIL criteria for BAL appear robust when compared against molecular techniques that, if applied routinely, could aid in detecting BAL and help in risk stratification.
We measured the temporal order of replication of EcoRI segments from the murine immunoglobulin heavy-chain constant region (IgCH) gene cluster, including the joining (J) and diversity (D) contained mitochondrial origin sequences. Two independently isolated clones contained the same middle repetitive sequences. Thus, as expected of replication origins, these clones represent specific sets of sequences rather than a random sampling of genomic DNA.Studies by Heintz et al. (12) on methotrexate-resistant Chinese hamster ovary cells suggested that a 135-kb amplified region (amplicon) containing the dihydrofolate reductase gene may in fact be a replicon. Furthermore, the initiation of DNA synthesis in each amplicon was shown to be confined to a small subset of restriction segments during the first 40 min of the S phase. These studies suggested that the early replicating fragments contain or flank origins of replication.While specific origins appear to exist in the genome, the available evidence suggests that only a fraction of them are active in a single cell type (36). For example, more origins are active in early Drosophila melanogaster embryonic cells than at later stages in development (3). The arrest of cells in the S phase with fluorodeoxyuridine results in the initiation of DNA synthesis from additional sites after release from the block, suggesting the existence of potential origins that are not normally active (37). These authors (37) found that such potential origins are spaced about 12 kb apart. In a particular cell type, only a fraction of these origins may be used.The transcriptional activity of DNA also appears to influence the activation of origins. For example, some genes replicate early in the S phase in cell types in which they are expressed and at later times in cell types in which they are not expressed (6, 9, 10; Hatton et al., manuscript in preparation). It has also been suggested that the initiation of replication from an upstream origin is required for transcriptional activation of a gene (31,34). A recent study (13) 450 on May 11, 2018 by guest
Carbon-13 NMR longitudinal relaxation time and line-width studies are reported on the coacervate concentration (about 60% water by weight) of singly carbonyl carbon enriched polypentapeptides of elastin: specifically, (L-Val1-L-[1-13C]Pro2-Gly3-L-Val4-Gly5)n and (L-Val1-L-Pro2-Gly3-L-Val4-[1-13C]Gly5)n. On raising the temperature from 10 to 25 degrees C and from 40 to 70 degrees C, carbonyl mobility increases, but over the temperature interval from 25 to 40 degrees C, the mobility decreases. The results characterize an inverse temperature transition in the most fundamental sense of temperature being a measure of molecular motion. This transition in the state of the polypentapeptide indicates an increase in order of polypeptide on raising the temperature from 25 degrees C to physiological temperature. This fundamental NMR characterization corresponds with the results of numerous other physical methods, e.g., circular dichroism, dielectric relaxation, and electron microscopy, that correspondingly indicate an increase in order of the polypentapeptide both intramolecularly and intermolecularly for the same temperature increase from 25 to 40 degrees C. Significantly with respect to elastomeric function, thermoelasticity studies on gamma-irradiation cross-linked polypentapeptide coacervate show a dramatic increase in elastomeric force over the same interval that is here characterized by NMR as an inverse temperature transition. The temperature dependence of mobility above 40 degrees C indicates an activation energy of the order of 1.2 kcal/mol, which is the magnitude of barrier expected for elasticity.
BackgroundA newborn with ambiguous genitalia needs prompt evaluation to detect life-threatening conditions (e.g., salt-losing crisis in congenital adrenal hyperplasia [CAH]) and gender assignment. Sex assignment in these children continues to be a challenging diagnostic and therapeutic problem. We studied the causes and characteristics of ambiguous genitalia in children who were referred to a cytogenetic laboratory.Patients and MethodsWe retrospectively reviewed a total of 120 medical records of patients with a primary indication of ambiguous genitalia that were referred to the cytogenetic lab for karyotyping during the period of 1989 to 1999. Diagnosis was based on a clinical impression from the primary physician, who was primarily a staff pediatrician, endocrinologist and/or pediatric urologist.ResultsCAH was the underlying cause of ambiguous genitalia in 41 of 63 patients with ambiguity due to endocrine causes; 39 of these patients showed a 46,XX karyotype and 2 cases were 46,XY (both the 46,XY patients had 3 β-hydroxylase deficiency). In 57 patients, ambiguous genitalia were due to congenital developmental defects. The most common endocrine case of ambiguous genitalia was 21-OH deficiency. Seven patients were classified as idiopathic with six showing the 46,XY and one the 46,XX karyotype. Gender was reassigned at birth or at diagnosis in 15 patients.ConclusionThe etiology of ambiguous genitalia is variable. The physician managing these families could minimize the trauma of having a child with unidentified sex by providing appropriate genetic counseling so that the parents can make an early decision. Prenatal DNA testing in at-risk families should be considered and appropriate therapy offered to minimize or prevent genital ambiguity.
A patient with ring chromosome 6 had most of the manifestations previously reported in this syndrome and also had albinoid fundi and unilateral aniridia, findings not previously described. In most peripheral leukocyte metaphases analyzed, one chromosome 6 was replaced by a monocentric ring chromosome with deletion of the 6p and 6q. Fifteen other patients with a ring chromosome 6 have been reported. The most frequent findings were mental retardation, prenatal and postnatal failure, epicanthal folds, flat nasal bridge, short neck, apparently low-set and/or malformed ears, microphthalmia, and micrognathia. Studies of coagulation Factors XII and XIII and of the P blood group for possible assignment on distal 6p and 6q did not provide evidence for localization of the genes for these factors on the pter----p24 part of chromosome 6.
A 2-year-old male patient with dysmorphic facial features and multiple congenital anomalies suggestive of a chromosome syndrome is presented. The facial features consisted of a large and high forehead, mild metopic ridging, a small triangular face, depressed nasal bridge, microphthalmia (right more than the left), protruding ears, and mildly prominent anteverted nose with long and smooth philtrum. Cytogenetic analysis showed 46,XY,del(20)(q11.2q12). Parental karyotypes were normal. Molecular characterization of del(20)(q11.2q12) by high-resolution microarray comparative genomic hybridization (arrayCGH) showed an approximately 6.8 Mb deletion. To our knowledge this is the first report of a de novo interstitial del(20)(q11.2q12) characterized by arrayCGH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.