Dinucleotide repeat polymorphisms at the D8S85, D8S87, and D8S88 loci.
Explore the source record for details and available documents.
Base Sequence↗
Biomedical subjects
D Patterson
Publications and source records attributed to D Patterson.
Analysis of human chromosome 21: correlation of physical and cytogenetic maps; gene and CpG island distributions.
Human chromosome 21 has been analyzed by pulsed-field gel electrophoresis using somatic cell hybrids containing limited regions of the chromosome and greater than 60 unique sequence probes. Thirty-three independent NotI fragments have been identified, totalling 43 million bp. This must account for essentially the entire long arm, and therefore gaps remaining in the map must be small. The extent of the pulsed-field map has allowed the direct correlation of the physical map with the cytogenetic map: translocation breakpoints can be unambiguously positioned along the long arm and the distances between them measured in base pairs. Three breakpoints have been identified, providing physical confirmation of cytogenetic landmarks. Information on sequence organization has been obtained: (i) 60% of the unique sequence probes are located within 11 physical linkage groups which can be contained in only 20% of the long arm; (ii) 9/21 genes are clustered within 4%; (iii) translocation breakpoints appear to occur within CpG island regions, making their identification difficult by pulsed-field techniques. This analysis contributes to the human genome mapping effort, and provides information to guide the rapid investigation of the biology of chromosome 21.
Base Composition↗
Sublocalization on chromosome 21 of human interferon-alpha receptor gene and the gene for an interferon-gamma response protein.
The cellular responses to alpha and beta interferons (IFN-alpha and -beta) are mediated through the IFN-alpha/beta (type I) receptor, while the response to IFN-gamma is mediated through the IFN-gamma (type II) receptor. The receptors for IFN-alpha/beta and IFN-gamma are encoded by genes on human chromosomes 21 and 6q, respectively. The presence of chromosome 21q confers both ligand binding and responsiveness to human IFN-alpha/beta, whereas chromosome 6q confers binding of Hu-IFN-gamma, but not cellular responsiveness on somatic cell hybrids. Chromosome 6q (i.e., the Hu-IFN-gamma receptor gene) and chromosome 21q are both necessary for the cellular response of somatic cell hybrids (from fibroblasts) to Hu-IFN-gamma. It is conceivable that the factor mediating activity through the IFN-gamma receptor is, in fact, the IFN-alpha receptor, or that the two genes are distinct but part of an "interferon response" region. Here we more precisely localize on human chromosome 21 the genes for the IFN-alpha receptor and for the factor(s) mediating the action of IFN-gamma through the chromosome 6-encoded receptor. Hamster-human somatic cell hybrids containing various fragments of human chromosome 21 were used. The presence of the human IFN-alpha/beta receptor was determined by binding 32P-labeled human IFN-alpha to cells, covalently cross-linking the [32P]IFN-alpha-receptor complex, and analyzing it by SDS-polyacrylamide gel electrophoresis. The presence of the IFN-gamma receptor-related factor mediating cellular responsiveness was determined by HLA induction in hybrid cells containing the IFN-gamma receptor (chromosome 6q), a transfected copy of the human HLA-B7 gene, and various portions of chromosome 21. In all hybrids examined, the two genes cosegregate. Specifically, both genes are localized to the region of chromosome 21 containing the markers D21S58, D21S65, and GART and appear to be proximal to D21S58. The implications for IFN action are discussed.
Animals↗
Physical mapping of chromosome 21 DNA markers in Alzheimer's disease region using somatic cell hybrids.
From a chromosome 21 phage library, we selected 10 clones located proximal of the senile plaque amyloid precursor protein gene. Since a locus for Alzheimer's disease (AD) has been localized in the pericentromeric region of chromosome 21, the selected phage clones are potential candidate probes for genetic analysis of AD. In this study, we subcloned single-copy fragments of the selected phage clones, refined their physical localization, and examined their chromosomal distribution in relation to their position on chromosome 21. The results indicated that the phage clones are identifying nine chromosome 21 loci, which, if polymorphic, may be helpful in localizing the AD locus more precisely. Moreover, since all phage clones are located close to the centromere of chromosome 21, they can be used to determine the parental origin of nondisjunction in trisomy 21 with high reliability.
Alzheimer Disease↗
Gaining access to community resources: breaking the cycle of adolescent pregnancy.
Explore the source record for details and available documents.
Adolescent↗
Translocations and rearrangements involving chromosome 21.
Explore the source record for details and available documents.
Animals↗
Effect of nitrous oxide inactivation of vitamin B12-dependent methionine synthetase on the subcellular distribution of folate coenzymes in rat liver.
The effects of nitrous oxide inactivation of the vitamin B12-dependent enzyme, methionine synthetase (EC 2.1.1.13), on the subcellular distribution of hepatic folate coenzymes was determined. In controls, cytosolic folates were 5-methyltetrahydrofolate (45%), 5- and 10-formyltetrahydrofolate (9 and 19%, respectively), and tetrahydrofolate (27%). Exposure of rats to an atmosphere containing 80% nitrous oxide for 18 h resulted in a marked shift in this distribution pattern to 5-methyltetrahydrofolate, 84%; 5- and 10-formyltetrahydrofolate, 2.1 and 9.1%, respectively; and tetrahydrofolate, 4.7%. Activity of the cytosolic enzyme, methionine synthetase, was reduced by about 84% as compared to that of air breathing controls. In controls, mitochondrial folates were 5-methyltetrahydrofolate (7.3%), 5- and 10-formyltetrahydrofolate (11.5 and 33.1%, respectively), and tetrahydrofolate (48.1%). This distribution did not change after exposure to nitrous oxide. These results show that the effects of nitrous oxide inactivation of vitamin B12 are confined to the cytosol, at least in the short term, and suggest that there is little, if any, transport of free folates between the cytosolic and mitochondrial compartments.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
Characterization of an unusual and complex chromosome 21 rearrangement using somatic cell genetics and cloned DNA probes.
In a previous case of a newborn infant with typical Down syndrome, chromosome analysis indicated the presence of an unusual and complex translocation of chromosome 21. The patient's cells contained one normal chromosome 21 and a rearranged, F group-sized submetacentric chromosome. This abnormal chromosome appeared to involve duplication of the distal portion of 21q with translocation to the short arm, and a deletion of C-band-positive centromeric heterochromatin. Using linearly ordered cloned DNA probes, we report the detailed molecular examination of this abnormal chromosome, which has been isolated on a hamster background in a hybrid cell line. Both short arm and pericentromeric sequences are present on this chromosome, as well as distal 21q sequences. However, a substantial portion of proximal 21q is deleted. The distal boundary of this deleted section can be pinpointed within the region between two loci (D21S8 and D21S54), a distance of about 5,000 kb. This study illustrates the power of using precisely mapped, linearly ordered DNA probes to characterize this type of rearrangement. In addition, this hybrid cell line can also be used as a member of a mapping panel to map DNA sequences regionally on chromosome 21.
Animals↗
Mapping of the gene encoding the multifunctional protein carrying out the first three steps of pyrimidine biosynthesis to human chromosome 2.
The CAD gene encodes a trifunctional protein that carries the activities of the first three enzymes (carbamyl phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase) of de novo pyrimidine biosynthesis. Genomic fragments of the human CAD gene have been obtained by screening a human genomic library in bacteriophage lambda using a Syrian hamster cDNA clone as a probe. These human genomic clones have been used to assign the CAD gene to human chromosome 2 using in situ hybridization to human metaphase chromosomes and Southern blot hybridization analysis of DNA isolated from a panel of Chinese hamster/human hybrid cells. In situ hybridization analysis has allowed further localization of this gene to the chromosomal region 2p21-p22.
Amidohydrolases↗
Drosophila purine auxotrophy: new alleles of adenosine 2 exhibiting a complex visible phenotype.
New mutant alleles of the adenosine2 locus (ade2; 2-17.7) have been isolated using the eye-color phenotype exhibited by the prototype auxotrophic allele ade2 as the screening criterion. The new mutants form a single complementation group, suggesting that they all exhibit purine auxotrophy and defective formylglycineamide ribotide amidotransferase enzyme, like ade2. Tests carried out on particular new alleles confirm these suggestions. The new mutants all exhibit more extreme physical defects than the prototype. They have wing abnormalities like mutants defective in pyrmidine biosynthesis and reduced bristles like those defective in protein synthesis; thus they exhibit the combined visible phenotype of rudimentary wings, rosy eyes, and bobbed bristles. Cytogenetic analysis places the locus in the interband proximal to 26B1-2.
Adenosine↗
Aging: effect on hepatic metabolism and transport of folate in the rat.
Effects of aging on hepatic folate metabolism and transport were assessed in male Fisher 344 rats. Total serum and hepatic folate levels were measured. Hepatic folates were measured by high-performance liquid chromatography and by Lactobacillus casei assay. Transport of 5-methyltetrahydrofolate (5-CH3-H4PteGlu) was measured in isolated hepatocytes. Serum folate declined with aging; however, neither the total folate level nor the distribution of hepatic folate coenzymes was affected by the aging process. The level of liver folate monoglutamates was not significantly different in any group. The initial rate of uptake of 5-CH3-H4PteGlu was significantly decreased in hepatocytes from the 24-mo-old rats, as was the ability to concentrate this folate from the medium. Aged rats maintain apparently normal levels of hepatic folates despite decreased serum levels and decreased ability to take up folates, suggesting that membrane transport of folates may not be a limiting factor in hepatic folate assimilation.
Aging↗
Effects of extracorporeal shock wave lithotripsy on single chamber rate response and dual chamber pacemakers.
This study evaluated effects of extracorporeal shock wave lithotripsy on four models of Medtronic implantable cardiac pacemakers. In vitro testing consisted of: (1) unsynchronized pacemaker strapped on the patient with extracorporeal shock synchronized to the patient's native heart rate; and (2) pacemakers suspended alone in water 6 inches from the focal point, synchronizing the extracorporeal shock to pacemaker output. Unsynchronized shocks affected each model of pacemaker differently, i.e., single chamber constant rate pacemakers experienced extended periods of inhibition for more than three pacing cycles while activity-triggered rate response pacemakers exhibited rate increases to the upper rate setting. Dual chamber synchronous pacemakers exhibited intermittently a 59% decrease and a 20% increase in ventricular rate due to inhibition and triggering, respectively, from shock oversensing. Synchronized shocks did not alter the rate of single chamber constant rate pacemakers, but did cause the rate to increase to the upper rate setting for activity-triggered rate response pacemakers. The shock was synchronized to the initial atrial output from the dual chamber pacemaker and caused frequent inhibition of the ventricular stimulus when the ventricular-safety-pace (VSP) feature was programmed off. Programming VSP on reduced the incidence of ventricular inhibition resulting in near normal pacemaker operation. There was neither observable damage to pacemaker components nor spurious reprogramming of pacemaker parameters during the tests. Our studies with one manufacturer's pacemakers suggests that lithotripsy shock effects on implantable pacemakers can be tolerated provided: (1) the single chamber pacemaker is programmed to the demand constant rate modality; (2) the dual chamber pacemaker is programmed to VSP on or to the VVI mode; and (3) the pacemaker distance to the focal point is greater than 6 inches.(ABSTRACT TRUNCATED AT 250 WORDS)
Equipment Design↗
Resolution of the intermediates of de novo purine biosynthesis by ion-pair reversed-phase high-performance liquid chromatography.
An ion-pair reversed-phase high-performance liquid chromotographic procedure capable of resolving twelve of the fourteen intermediates of de novo purine biosynthesis is presented. The method utilizes isocratic elution and detection by ultraviolet light absorption. Separation of all twelve intermediates can be achieved in 90 min.
Chromatography, High Pressure Liquid↗
Combined trisomy 1q and monosomy 17p due to translocation t(1;17) in a patient with myelodysplastic syndrome.
A nonconstitutional translocation, t(1;17)(q21;p11), has been observed in bone marrow cells from a young patient with myelodysplastic syndrome during a 4-year period. Cytogenetic findings and some clinical aspects are briefly discussed.
Adolescent↗
D22S15--a fetal brain cDNA with BanII and SacI RFLP.
Explore the source record for details and available documents.
Brain↗
Isolation of DNA sequences on human chromosome 21 by application of a recombination-based assay to DNA from flow-sorted chromosomes.
By merging two efficient technologies, bivariate flow sorting of human metaphase chromosomes and a recombination-based assay for sequence complexity, we isolated 28 cloned DNA segments homologous to loci on human chromosome 21. Subregional mapping of these DNA segments with a somatic cell hybrid panel showed that 26 of the 28 cloned DNA sequences are distributed along the long arm of chromosome 21, while the other 2 hybridize with sequences on the short arm of both chromosome 21 and other chromosomes. This new collection of probes homologous to chromosome 21 should facilitate molecular analyses of trisomy 21 by providing DNA probes for the linkage map of chromosome 21, for studies of nondisjunction, for chromosome walking in clinically relevant subregions of chromosome 21, and for the isolation of genes on chromosome 21 following the screening of cDNA libraries.
Animals↗
Mapping of bovine PRGS and PAIS genes in hybrid somatic cells: syntenic conservation with human chromosome 21.
Somatic cell genetics coupled with enzyme electrophoresis has facilitated the mapping of PRGS and PAIS genes in cattle. Individual cow-hamster hybrid cell lines established by fusion of mutant CHO cells, ade-C and ade-G, with cattle leukocytes required complementing bovine genes for PRGS and PAIS, respectively, when propogated on selective media. Homogenates of 12 PRGS+ hybrid clones and 12 PAIS+ hybrid clones retained the bovine electromorph of SOD1 while extensively segregating 14 biochemical markers of other cattle syntenic groups. Secondary cattle-hamster hybrid subclones which segregated bovine PRGS and PAIS in late passages on nonselective media concordantly segregated bovine SOD1. These data support a syntenic relationship among PRGS, PAIS, and SOD1 on cattle syntenic group U10. An interferon receptor locus, IFREC, is also syntenic with SOD1. This synteny represents an extensive conservation of bovine U10 and the "Down syndrome region" of human chromosome 21.
Animals↗
Irradiation-reduced human chromosome 21 hybrids.
Rodent-human somatic cell hybrids have been constructed which contain fragments of human chromosome 21 as their only human material. This was done by irradiating rodent-human somatic cell hybrids containing a complete chromosome 21 to fragment the genome and then rescuing human GAR synthetase and various amounts of flanking chromosome 21 DNA by fusing with GAR synthetase-deficient hamster cells and selecting for growth in purine-free medium. Four irradiation-reduction hybrids were produced by this method and contain the distal, proximal, and central portions of the long arm of human chromosome 21, all centered about GAR synthetase. These irradiation-reduction hybrids were used as a panel to regionally map single-copy and individual copies of repetitive sequences. Using these hybrids along with another independently constructed hybrid, the GAR synthetase gene was mapped distal to SOD-1 and proximal to CP21G1(D21S60). Of special interest is the regional mapping of the gene for the amyloid beta-protein distal to pPW236B(D21S11) and proximal to SOD-1.
Animals↗