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1.
Clastogen-induced chromosomal breakage as a marker for first trimester prenatal diagnosis of Fanconi anemia 总被引:5,自引:0,他引:5
Arleen D. Auerbach Zhang Min Rita Ghosh Eugene Pergament Yuri Verlinsky Henriette Nicolas Joëlle Boué 《Human genetics》1986,73(1):86-88
Summary Using cultured trophoblast cells obtained by chorionic villus biopsy, we diagnosed Fanconi anemia (FA) in two pregnancies and excluded it in eight pregnancies at risk for the syndrome. Baseline chromosomal breakage and breakage induced by diepoxybutane (DEB) were analyzed. Increased breakage was used as a marker for the syndrome. Our results were unambiguous and provide a reliable method for prenatal detection of FA in the first trimester of pregnancy. 相似文献
2.
The Kinetics of Sodium Transport in the Toad Bladder : I. Determination of the transport pool 总被引:4,自引:3,他引:1
A compartmental model of toad bladder sodium content has been developed, whereby it is possible to measure the four unidirectional fluxes across the opposite faces of the transport compartment, as well as the amount of sodium in the compartment. 24Na is added to the mucosal medium of a short-circuited bladder mounted between halves of a chamber in which the fluid is stirred by rotating impellers. After a steady state is reached, nonradioactive medium is flushed through both sides of the chamber, collected, and counted. The data from each chamber are fitted to sums of exponentials and interpreted in terms of conventional compartmental analysis. Three exponentials are required, with half-times of 0.2, 2.2, and 14.0 min. It is shown that the first of these represents chamber washout, the second the transport pool, and the third a tissue compartment which is not involved in active sodium transport and which does not communicate with the transport pool. The second compartment contains 10.5 µEq of sodium per 100 mg dry weight, an amount equal to approximately 30% of total tissue sodium. The results also indicate, as expected from electrophysiological data, that the mucosal-facing side of the transport compartment is over 10 times as permeable to sodium as the serosal, or pump, side. 相似文献
3.
Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex 总被引:10,自引:0,他引:10
Willis DM Loewy AP Charlton-Kachigian N Shao JS Ornitz DM Towler DA 《The Journal of biological chemistry》2002,277(40):37280-37291
4.
Bidder M Shao JS Charlton-Kachigian N Loewy AP Semenkovich CF Towler DA 《The Journal of biological chemistry》2002,277(46):44485-44496
5.
Hypomorphic mutations in the gene encoding a key Fanconi anemia protein, FANCD2, sustain a significant group of FA-D2 patients with severe phenotype
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Kalb R Neveling K Hoehn H Schneider H Linka Y Batish SD Hunt C Berwick M Callen E Surralles J Casado JA Bueren J Dasi A Soulier J Gluckman E Zwaan CM van Spaendonk R Pals G de Winter JP Joenje H Grompe M Auerbach AD Hanenberg H Schindler D 《American journal of human genetics》2007,80(5):895-910
FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a key role in DNA double-strand-type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 patients with FA from 23 families and 4 additional unrelated patients to complementation group FA-D2. This amounts to 3%-6% of FA-affected patients registered in various data sets. Malformations are frequent in FA-D2 patients, and hematological manifestations appear earlier and progress more rapidly when compared with all other patients combined (FA-non-D2) in the International Fanconi Anemia Registry. FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected total of 66 mutated alleles, 34 of which result in aberrant splicing patterns. Many mutations are recurrent and have ethnic associations and shared allelic haplotypes. There were no biallelic null mutations; residual FANCD2 protein of both isotypes was observed in all available patient cell lines. These analyses suggest that, unlike the knockout mouse model, total absence of FANCD2 does not exist in FA-D2 patients, because of constraints on viable combinations of FANCD2 mutations. Although hypomorphic mutations arie involved, clinically, these patients have a relatively severe form of FA. 相似文献
6.
Auerbach AD Burn J Cassiman JJ Claustres M Cotton RG Cutting G den Dunnen JT El-Ruby M Vargas AF Greenblatt MS Macrae F Matsubara Y Rimoin DL Vihinen M Van Broeckhoven C 《Nature reviews. Genetics》2011,12(12):881; discussion 881
7.
FANCJ/BRIP1 encodes a helicase that has been implicated in the maintenance of genomic stability. Here, to better understand
FANCJ function in DNA damage responses, we have examined the regulation of its cellular localization. FANCJ nuclear foci assemble
spontaneously during S phase and are induced by various stresses. FANCJ foci colocalize with the replication fork following
treatment with hydroxyurea, but not spontaneously. Using FANCJ mutants, we find that FANCJ helicase activity and the capacity
to bind BRCA1 are both involved in FANCJ recruitment. Given similarities to the recruitment of another Fanconi anemia protein,
FANCD2, we tested for colocalization of FANCJ and FANCD2. Importantly, these proteins show substantial colocalization, and
FANCJ promotes the assembly of FANCD2 nuclear foci. This process is linked to the proper localization of FANCJ itself since
both FANCJ and FANCD2 nuclear foci are compromised by FANCJ mutants that abrogate its helicase activity or interaction with
BRCA1. Our results suggest that FANCJ is recruited in response to replication stress and that FANCJ/BRIP1 may serve to link
FANCD2 to BRCA1. 相似文献
8.
Morales JF Song T Auerbach AD Wittkowski KM 《Statistical applications in genetics and molecular biology》2008,7(1):Article 19
As the field of genomics matures, more complex genotypes and phenotypes are being studied. Fanconi anemia (FA), for example, is an inherited chromosome instability syndrome with a complex array of variable disease phenotypes including congenital malformations, hematological manifestations, and cancer. To better understand specific aspects of the genetic etiology of FA and other rare diseases with complex phenotypes, it is often necessary to reduce the dimensions of the disease phenotype information. Towards this end, we extend a novel non-parametric approach to include information about a hierarchical structure among disease phenotypes. The proposed extension increases information content of the phenotype scores obtained and, thereby, the power of genotype-phenotype relationships studies. 相似文献
9.
Vicky Cho Yan Mei Arleen Sanny Stephanie Chan Anselm Enders Edward M Bertram Andy Tan Christopher C Goodnow T Daniel Andrews 《Genome biology》2014,15(1):R26
Background
Retention of a subset of introns in spliced polyadenylated mRNA is emerging as a frequent, unexplained finding from RNA deep sequencing in mammalian cells.Results
Here we analyze intron retention in T lymphocytes by deep sequencing polyadenylated RNA. We show a developmentally regulated RNA-binding protein, hnRNPLL, induces retention of specific introns by sequencing RNA from T cells with an inactivating Hnrpll mutation and from B lymphocytes that physiologically downregulate Hnrpll during their differentiation. In Ptprc mRNA encoding the tyrosine phosphatase CD45, hnRNPLL induces selective retention of introns flanking exons 4 to 6; these correspond to the cassette exons containing hnRNPLL binding sites that are skipped in cells with normal, but not mutant or low, hnRNPLL. We identify similar patterns of hnRNPLL-induced differential intron retention flanking alternative exons in 14 other genes, representing novel elements of the hnRNPLL-induced splicing program in T cells. Retroviral expression of a normally spliced cDNA for one of these targets, Senp2, partially corrects the survival defect of Hnrpll-mutant T cells. We find that integrating a number of computational methods to detect genes with differentially retained introns provides a strategy to enrich for alternatively spliced exons in mammalian RNA-seq data, when complemented by RNA-seq analysis of purified cells with experimentally perturbed RNA-binding proteins.Conclusions
Our findings demonstrate that intron retention in mRNA is induced by specific RNA-binding proteins and suggest a biological significance for this process in marking exons that are poised for alternative splicing. 相似文献10.
Larry M. Palato Shannon Pilcher Alissa Oakes Arleen Lamba Jaris Torres Litza I. Ledesma Monjaraz Crystabel Munoz Edward Njoo Dillon J. Rinauro Kate Alexandra Menefee Angela Tun Betssy L. Jauregui Sarah Shapiro Olivia H. Nossiff Eileen Olivares Kevin Chang Viviane Nguyen Luiza A. Nogaj David A. Moffet 《Journal of peptide science》2019,25(8)
The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP. 相似文献