Misdiagnosis of a β-Thalassemia Heterozygote Using a Reverse Dot-Blot Method may be Caused by a Polymorphic Locus in the Wild Type Sequence of the β-Globin Gene

Hemoglobin ◽  
2010 ◽  
Vol 34 (2) ◽  
pp. 191-195
Author(s):  
Ping Yi ◽  
Jianxin Guo ◽  
Zhuqin Chen ◽  
Qiang Liu ◽  
Lili Yu ◽  
...  
Keyword(s):  
Polymorphic Locus ◽  
Globin Gene ◽  
Wild Type ◽  
Dot Blot ◽  
Wild Type Sequence ◽  
In The Wild ◽  
Type Sequence ◽  
Reverse Dot Blot

Amino acid modifications in the wild type sequence p53 232-240 overcome the poor immunogenicity of this self tumour epitope

2002 ◽  
Vol 8 (7) ◽  
pp. 327-334 ◽  
Author(s):  
Myriam Baratin ◽  
Mich�le Kayibanda ◽  
Marianne Ziol ◽  
Raph�elle Romieu ◽  
Jean-Paul Briand ◽  
...  
Keyword(s):  
Amino Acid ◽  
Wild Type ◽  
The Poor ◽  
Wild Type Sequence ◽  
In The Wild ◽  
Type Sequence

A highly revertible cyc1 mutant of yeast contains a small tandem duplication.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 57-62
Author(s):  
G Das ◽  
S Consaul ◽  
F Sherman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Tandem Duplication ◽  
Direct Repeat ◽  
High Rate ◽  
Reversion Rate ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Wild Type Sequence ◽  
In The Wild ◽  
Type Sequence

Abstract A mutant, cyc1-96, that reverts spontaneously at an extremely high rate, was uncovered after examining approximately 500 cyc1 mutants which lack or have defective iso-1-cytochrome c in the yeast Saccharomyces cerevisiae. Cloning and DNA sequencing of appropriate fragments revealed that the cyc1-96 mutation contained a 19 bp duplication whereas the spontaneously arising revertants contained the normal wild-type sequence. Because the 19 bp segment in the wild-type sequence is flanked by a 5 bp repeat and because the cyc1-96 mutation arose spontaneously, the 19 bp duplication may have arisen by slippage and misalignment during DNA synthesis. The high reversion rate was not diminished in strains containing the rad52 mutation, which generally reduces mitotic recombination, including recombination associated with the elimination of a segment of a long direct repeat. Thus the loss of segments from short and long duplications occur by different mechanisms. We suggest that the high reversion rates of cyc1-96 and other short duplications are due to misalignment errors during replication.

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

2003 ◽  
Vol 285 (4) ◽  
pp. R747-R753 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Masakatsu Tamaki ◽  
Yo-ichi Suzuki ◽  
Michiko Iwase ◽  
Takuji Shirasawa ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Globin Gene ◽  
Open Circuit ◽  
Mutant Mice ◽  
Whole Body ◽  
Wild Type ◽  
Peripheral Tissues ◽  
Ventilatory Responses ◽  
Significant Difference ◽  
In The Wild

The purpose of this study was to test whether chronically enhanced O2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO2 in O2) and hypoxia (10 and 15% O2 in N2) were assessed in mutant mice expressing Hb Presbyterian (mutation in the β-globin gene, β108 Asn → Lys). O2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial PCO2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O2) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures.

Wild-Type Sequence ofTP53, Intron 7

2001 ◽  
Vol 155 (4) ◽  
pp. 641-641 ◽  
Author(s):  
Wolfgang Eicheler ◽  
Michael Baumann
Keyword(s):  
Wild Type ◽  
Wild Type Sequence ◽  
Type Sequence

scholarly journals Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 239-242 ◽  
Author(s):  
A Maggio ◽  
A Giambona ◽  
SP Cai ◽  
J Wall ◽  
YW Kan ◽  
...  
Keyword(s):  
Globin Gene ◽  
Blot Hybridization ◽  
Beta Thalassemia ◽  
Dot Blot ◽  
Hemoglobin C ◽  
Mediterranean Regions ◽  
Analysis Application ◽  
Working Day ◽  
Dot Blot Analysis ◽  
Reverse Dot Blot

Abstract The molecular lesions causing beta-thalassemia in Sicily can be subdivided into two groups. One that occurs at a 71% frequency and consists of the beta 39, IVS 1,110 and IVS 1,6 mutations and the other group at a 20% frequency comprising the -87, beta s, IVS 1,1 and IVS 2,745 mutations. The identification of all these mutations by polymerase chain reaction (PCR) and conventional dot-blot hybridization has been time consuming and expensive. In this article, we describe the implementation of the reverse dot-blot (RDB) hybridization as a rapid nonradioactive method for the identification of the nine most frequent molecular lesions in the beta-globin gene (-87, beta s, beta c, IVS 1,1, IVS 1,6, IVS 1,110, beta 39, IVS 2,1, IVS 2,745) in Sicily. Sixty prenatal diagnoses were performed by this RDB assay, each of which was confirmed by dot-blot/ASO hybridization; thus demonstrating the accuracy of the RDB. The main advantage of this assay is the rapid typing of an individual's DNA for many mutations in a single working day. Because the mutations in this assay are representative for the Mediterranean region, this mutational panel can also be extended to the screening of beta-thalassemia from other Mediterranean regions.

Mutational Analysis of BCR-Abl From Subjects with Relapsed Ph+ALL Treated On the COG Protocol AALL0031: a Report From the Children's Oncology Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2634-2634
Author(s):  
Bill H Chang ◽  
Stephanie G Willis ◽  
Linda C. Stork ◽  
Stephen P Hunger ◽  
William L. Carroll ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Philadelphia Chromosome ◽  
Late Relapse ◽  
Cell Transplant ◽  
Wild Type ◽  
Wild Type Sequence ◽  
Early Results ◽  
Type Sequence

Abstract Abstract 2634 Poster Board II-610 Background: Philadelphia chromosome positive Acute Lymphoblastic Leukemia (Ph+ALL) occurs in 2–5% of pediatric ALL and is associated with a poor prognosis. COG AALL0031 treated children with an intensified chemotherapy backbone plus imatinib. All subjects received imatinib at 340mg/m^2 daily. Exposure to imatinib progressively increased in each of five cohorts. Patients had a total imatinib exposure (before maintenance) of 42 days in cohort 1, 63 days in cohort 2, 84 days in cohort 3, 126 days in cohort 4, and 280 days in cohort 5. All groups received an additional 336 days of imatinib exposure in maintenance cycles 1 through 12 for approximately 2 years (with imatinb given on 21 day cycles for maintenance cycles 1 – 4, and a two-week on/two-week off schedule for maintenance cycles 5 - 12). Early results of this trial show encouraging outcome with a 3-year event free survival of 80±11% (95% CI 64 – 90%) for patients in cohort 5. In studies of adults with Ph+ALL treated with imatinib many patients recurred with imatinib resistant BCR-Abl mutations. To date, there are no data on the occurrence of BCR-Abl mutations in pediatric Ph+ALL. Patients and Methods: We performed nested PCR to identify BCR-Abl point mutations in nine samples obtained at bone marrow (BM) relapse from Ph+ALL subjects on AALL0031. Results: (Table 1) Three samples from cohort 1 that had no exposure to imatinib prior to relapse showed wild-type sequence. There were 5 of 6 samples that also showed wild-type sequence. One sample was from cohort 2 and 3 samples were from cohort 3. Each subject relapsed 1 to 2 years after diagnosis while receiving varying amounts of imatinib with continued intensive therapy. One subject recurred after stem cell transplant in first remission. One sample from cohort 4 recurred after the completion of chemotherapy and imatinib. One subject from cohort 5 carried the histidine 396 to proline (H396P) mutation. This mutation, which increases the imatinib IC50 by 10-fold, has been previously described to occur in adults with CML and Ph+ALL treated with imatinib. The subject from cohort 5 recurred 1 year after diagnosis on therapy with imatinib. Conclusions: Only 1 resistant mutation in BCR-Abl has been identified among nine children with Ph+ALL treated on AALL0031. Therefore, unlike results in the adults, resistant mutations do not appear to drive early recurrence in Ph+ALL. Further studies will be needed to identify whether BCR-Abl mutations are identified in subjects who develop a late relapse after treatment with AALL0031 or subsequent treatment studies. Disclosures: Druker: OHSU patent #843 - Mutate ABL Kinase Domains: Patents & Royalties; MolecularMD: Equity Ownership; Roche: Consultancy; Cylene Pharmaceuticals: Consultancy; Calistoga Pharmaceuticals: Consultancy; Avalon Pharmaceuticals: Consultancy; Ambit Biosciences: Consultancy; Millipore via Dana-Farber Cancer Institute: Patents & Royalties; Novartis, ARIAD, Bristol-Myers Squibb: Research Funding. Schultz:novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Improvement in Sensitivity of Allele-specific PCR Facilitates Reliable Noninvasive Prenatal Detection of Cystic Fibrosis

2004 ◽  
Vol 50 (4) ◽  
pp. 694-701 ◽  
Author(s):  
Ourania Nasis ◽  
Shanel Thompson ◽  
Tom Hong ◽  
Margaret Sherwood ◽  
Shawn Radcliffe ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Alterations ◽  
Wild Type Allele ◽  
Wild Type ◽  
Type Allele ◽  
Specific Pcr ◽  
Wild Type Sequence ◽  
Allele Specific ◽  
Allele Specific Pcr ◽  
Type Sequence

Abstract Background: Cell-free fetal DNA circulating in maternal blood has potential as a safer alternative to invasive methods of prenatal testing for paternally inherited genetic alterations, such as cystic fibrosis (CF) mutations. Methods: We used allele-specific PCR to detect mutated CF D1152H DNA in the presence of an excess of the corresponding wild-type sequence. Pfx buffer (Invitrogen) containing replication accessory proteins and Taq polymerase with no proofreading activity was combined with TaqMaster PCR Enhancer (Eppendorf) to suppress nonspecific amplification of the wild-type allele. The procedure was tested on DNA isolated from plasma drawn from 11 pregnant women (gestational age, 11–19.2 weeks), with mutation confirmation by chorionic villus sampling. Results: The method detected 5 copies of the CF D1152H mutant allele in the presence of up to ∼100 000 copies of wild-type allele without interference from the wild-type sequence. The D1152H mutation was correctly identified in one positive sample; the only false-positive result was seen in a mishandled sample. Conclusions: This procedure allows for reliable detection of the paternally inherited D1152H mutation and has potential application for detection of other mutations, which may help reduce the need for invasive testing.

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