After 20 years researchers locate the mutant gene cloche

2019 ◽  
Author(s):  
Editage Insights
Keyword(s):  
Mutant Gene

Arg506GIn Factor V Mutation (Factor V Leiden) in Patients with Ischaemic Cerebrovascular Disease and Survivors of Myocardial Infarction

1995 ◽  
Vol 73 (04) ◽  
pp. 558-560 ◽  
Author(s):  
Kimmo Kontula ◽  
Antti Ylikorkala ◽  
Helena Miettinen ◽  
Alpo Vuorio ◽  
Ritva Kauppinen-Mäkelin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cerebrovascular Disease ◽  
Factor V Leiden ◽  
Mutant Gene ◽  
Arterial Disease ◽  
Cerebrovascular Diseases ◽  
Extensive Study ◽  
Carrier Status ◽  
Factor V ◽  
Ischaemic Attack

SummaryThe point mutation Arg506->Gln of factor V was recently shown to be an important and relatively common genetic cause of venous thromboembolism. Using a DNA technique based on polymerase chain reaction, we surveyed the blood samples of 236 patients with ischaemic stroke or a transient ischaemic attack, 122 survivors of myocardial infarction and 137 control subjects for the presence of this mutation. Although the frequency of the factor V mutation in patients with arterial disease (4.5%) was not significantly different from that in healthy blood donors (2.9%), a carrier status for this mutant gene was associated with symptoms of migraine and relatively mild angiographic abnormalities among patients with cerebrovascular disease. A more extensive study addressing the occurrence and significance of the mutant factor V mutation in patients with vasospastic cerebrovascular diseases seems to be warranted.

Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

2020 ◽  
Vol 17 (2) ◽  
pp. 104-113
Author(s):  
G.K. Udayaraja ◽  
I. Arnold Emerson
Keyword(s):  
Cytochrome P450 ◽  
Cancer Treatment ◽  
Cancer Susceptibility ◽  
Mutant Gene ◽  
Genome Project ◽  
Interdisciplinary Field ◽  
Precision Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer ◽  
Genetic Events

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescription. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy.

scholarly journals The BRCA2 p.N372 H i.a.1342A>C Could Regulate the Sensitivity of Ovarian Cancer Cells to Platinum-Based Drugs

2020 ◽  
Vol 19 ◽  
pp. 153303382098328
Author(s):  
Zhen-Hua Du ◽  
Yu Xia ◽  
Qing Yang ◽  
Song Gao
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Mutant Gene ◽  
Negative Control ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance ◽  
Over Expression ◽  
Ic50 Value ◽  
Brca2 Protein ◽  
Recombination Repair

Background and Objective: We have previously reported that BRCA2 N372 H i.a.1342A>C heterozygous variation presented in platinum-resistant patients. This study aimed to further investigate the mechanism of BRCA2 N372 H mutation in the development of platinum resistance in ovarian cancer. Methods: The BRCA2 N372 H i.a.1342A>C was synthesized and used to exchange 1 wildtype allele followed by sequencing to confirm the mutant allele sequence. Plasmids were constructed and transfected into the OVCAR-3 cells after lentiviral packaging. BRCA2 N372 H mRNA was detected by qPCR. BRCA2 protein was assessed by immunoblotting. Binding of the BRCA2 to Rad51 was detected by immunofluorescence staining. Sensitivity of the cells to cisplatin treatment was assessed with CCK-8 assay. Results: It was found that expression of BRCA2 protein in ovarian cancer cells transfected with BRCA2 N372 H i.a.1342A>C gene (2.177 ± 0.003) was significantly increased compared to that of the cells transfected with lenti-EGFP only (1.227 ± 0.003, P < 0.001). Binding of the BRCA2 and Rad51 proteins was significantly increased in the cells with BRCA2 N372 H i.a.1342A>C mutation (3.542 ± 0.24) than that in the cells transfected with lenti-EGFP (1.29 ± 0.32) or empty cells (1.363 ± 0.32, P < 0.001). Cell viability significantly increased in the cells transfected with BRCA2 N372 H mutant gene. The IC50 value was significantly higher in the cells transfected with BRCA2 N372 H mutant gene (1.963 ± 0.04) than that of the cells transfected with lenti-EGFP (0.955 ± 0.03, P < 0.01) or empty cells (1.043 ± 0.007, P < 0.01). Conclusion: Over expression of mRNA and protein of BRCA2 was detected in the cells with BRCA2 N372 H i.a.1342A>C mutation but not in the lentivirus negative control (lenti-EGFP) or the cells without transfection (empty cells), which may lead to resistance to platinum-based drugs in ovarian cancer cells through homologous recombination repair pathway.

scholarly journals A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.

1990 ◽  
Vol 171 (2) ◽  
pp. 519-531 ◽  
Author(s):  
A Matsuzawa ◽  
T Moriyama ◽  
T Kaneko ◽  
M Tanaka ◽  
M Kimura ◽  
...  
Keyword(s):  
Recessive Gene ◽  
Mutant Gene ◽  
Inbred Strains ◽  
Lymphoid Hyperplasia ◽  
Lymphoid Cells ◽  
Autoantibody Production ◽  
Genetic Studies ◽  
Inbred Strains Of Mice ◽  
Backcross Populations ◽  
Generalized Lymphadenopathy

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.

Dynamics of Telomeric DNA Turnover in Yeast

Genetics ◽  
2002 ◽  
Vol 160 (1) ◽  
pp. 63-73
Author(s):  
Michael J McEachern ◽  
Dana Hager Underwood ◽  
Elizabeth H Blackburn
Keyword(s):  
Kluyveromyces Lactis ◽  
Mutant Gene ◽  
Dna Repeats ◽  
Wild Type ◽  
Telomeric Dna ◽  
Cell Divisions ◽  
Dna Turnover ◽  
Length Regulation ◽  
Turn Over

Abstract Telomerase adds telomeric DNA repeats to telomeric termini using a sequence within its RNA subunit as a template. We characterized two mutations in the Kluyveromyces lactis telomerase RNA gene (TER1) template. Each initially produced normally regulated telomeres. One mutation, ter1-AA, had a cryptic defect in length regulation that was apparent only if the mutant gene was transformed into a TER1 deletion strain to permit extensive replacement of basal wild-type repeats with mutant repeats. This mutant differs from previously studied delayed elongation mutants in a number of properties. The second mutation, TER1-Bcl, which generates a BclI restriction site in newly synthesized telomeric repeats, was indistinguishable from wild type in all phenotypes assayed: cell growth, telomere length, and in vivo telomerase fidelity. TER1-Bcl cells demonstrated that the outer halves of the telomeric repeat tracts turn over within a few hundred cell divisions, while the innermost few repeats typically resisted turnover for at least 3000 cell divisions. Similarly deep but incomplete turnover was also observed in two other TER1 template mutants with highly elongated telomeres. These results indicate that most DNA turnover in functionally normal telomeres is due to gradual replicative sequence loss and additions by telomerase but that there are other processes that also contribute to turnover.

Cytogenetics and sex determination in man and mammals

1970 ◽  
Vol 2 (S2) ◽  
pp. 7-30 ◽  
Author(s):  
C. E. Ford
Keyword(s):  
Y Chromosome ◽  
External Genitalia ◽  
Mutant Gene ◽  
Normal Female ◽  
Human Female ◽  
Present Evidence ◽  
Male Development ◽  
Sex Development ◽  
Internal Genitalia ◽  
Male External Genitalia

SummarySex in man and probably throughout the class mammalia is normally determined by the presence of a Y chromosome (male) or its absence (female). The presence of genetic loci on both the long and the short arm of the X chromosome in double dose appears to be essential for the development of mature functional ovaries in the human female though a single X suffices in the female mouse.The development of masculine genital anatomy and phenotype is a consequence of prior formation of testes. In the absence of gonads of either kind, female internal and external genitalia are formed but secondary sex development fails. In rare human families a mutant gene suppresses the development of male external genitalia in 46, XY embryos but permits the development of testes and male internal genitalia. The external phenotype is normal female (syndrome of testicular feminization). A sex-linked mutant gene in the mouse has a similar effect.The locus or loci directly concerned with male development might lie wholly on the Y chromosome or might be located on another chromosome or chromosomes. In the latter case it (or they) must be repressed in the female and normally activated by a locus or loci on the Y chromosome in the male. Present evidence does not permit the exclusion of either possibility.

scholarly journals Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae.

1996 ◽  
Vol 16 (8) ◽  
pp. 4357-4365 ◽  
Author(s):  
D Huang ◽  
I Farkas ◽  
P J Roach
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Mutant Gene ◽  
Glycogen Synthase Kinase ◽  
Partial Purification ◽  
Glycogen Accumulation ◽  
Dependent Protein

In Saccharomyces cerevisiae, nutrient levels control multiple cellular processes. Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen. The impaired glycogen synthesis is due to maintenance of glycogen synthase in a hyperphosphorylated, inactive state. In a screen for second site suppressors of the glycogen storage defect of snf1 cells, we identified a mutant gene that restored glycogen accumulation and which was allelic with PHO85, which encodes a member of the cyclin-dependent kinase family. In cells with disrupted PHO85 genes, we observed hyperaccumulation of glycogen, activation of glycogen synthase, and impaired glycogen synthase kinase activity. In snf1 cells, glycogen synthase kinase activity was elevated. Partial purification of glycogen synthase kinase activity from yeast extracts resulted in the separation of two fractions by phenyl-Sepharose chromatography, both of which phosphorylated and inactivated glycogen synthase. The activity of one of these, GPK2, was inhibited by olomoucine, which potently inhibits cyclin-dependent protein kinases, and contained an approximately 36-kDa species that reacted with antibodies to Pho85p. Analysis of Ser-to-Ala mutations at the three potential Gsy2p phosphorylation sites in pho85 cells implicated Ser-654 and/or Thr-667 in PHO85 control of glycogen synthase. We propose that Pho85p is a physiological glycogen synthase kinase, possibly acting downstream of Snf1p.

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