Spontaneous deletion mutants resulting from a frameshift insertion in the simian virus 40 agnogene
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Abstract:
The 61-amino-acid agnoprotein is a nonessential polypeptide encoded by the late leader region of simian virus 40 which appears to play a role in viral assembly. A 2-base-pair (bp) insertion mutant (in2379) was created by altering the coding region of this protein. This mutation prevents the synthesis of the agnoprotein and, in contrast to the more extensive deletion mutations previously described in this region, might be expected to have a lesser effect on the template for late viral transcription. In fact, the 2-bp insertion mutant grew significantly less well than most mutants containing larger deletions in the agnoprotein region and frequently gave rise to stock containing second-site alterations in the same region. These observations suggested that the defect in mutant in2379 extends beyond the loss of the agnoprotein. Characterization of a number of second-site mutants indicated that all of them grew more efficiently than the original 2-bp insertion mutant. Based on the nucleotide sequence of these mutants, we suggest possibilities for the deleterious effect induced by the insertion in mutant in2379.Keywords:
Coding region
Simian
Insertion
Objective To explore germline mutation frequencies and features of mismatch repaired gene MSH6 in persons with different kinds of endometrial cancer.Methods The papers about MSH6 mutations were reviewed and information was derived from studies published between 1997 and 2008,data were analyzed by statistical methods.Results MSH6 mutation in all endometrial cancer patients was 9.77%;Substitute mutation and frameshift mutation were the main types of the mutation,and each mutation frequency was 1.70%;exon 4 was the main mutable site,and the mutation frequency was 3.69%;the mean age at onset of MSH6 mutation carriers was(54.8±2.8) years old.Conclusions The mutation frequencies of MSH6 in persons with different kinds of endometrial cancer were higher;substitute mutation and frameshift mutation were the main types of the mutation,exon 4 was the main mutable site,the mean age of onset was higher.
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BRCA Mutation
Mutation frequency
Mutation Testing
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In-frame and frameshift mutations were introduced into the pre-S region (1,212 base pairs) of duck hepatitis B virus. The in-frame mutants retained the inserted 12 nucleotides, while the frameshift mutants either reverted to wild type or exhibited a 10-nucleotide compensatory deletion downstream of the original mutation site. Thus, although duck hepatitis B virus has a compact and highly economical genome organization, it can replicate despite alterations of up to 9 amino acid codons in the pre-S and P open reading frames.
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Idiopathic congenital nystagmus (ICN) is a common oculomotor disorder characterized by bilateral involuntary, periodic, and predominantly ocular oscillations. X-linked ICN (XLICN) with incomplete penetrance in females is the most common inheritance form, and FERM domain containing (FRMD7) mutation is the major reason for XLICN families. To date, 39 FRMD7 mutations have been identified, and 50% of the XLICN pedigrees have yielded FRMD7 mutations in the Western population. In this study, we identified a novel frameshift mutation (c.1274–1275delTG) in the FRMD7 gene in six XLICN pedigrees. Incorporated with data reported from other two Chinese groups, approximately 47% XLICN pedigrees were caused by the FRMD7 mutation in China. Therefore, this study showed that mutation analysis of the FRMD7 gene had diagnostic value not only in the Western population but also in one of the biggest Eastern populations, Chinese XLICN families. In addition, the results indicated the type of FRMD7 mutation associated with the penetrance of female carriers of XLICN.
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Chinese population
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This study explored the role of TCOF1 insertion mutations in Taiwanese patients with craniofacial anomalies. Twelve patients with single or multiple, asymmetrical congenital craniofacial anomalies were enrolled. Genomic DNA was prepared from leukocytes; the coding regions of TCOF1 were analyzed by polymerase chain reaction and direct sequencing. Clinical manifestations were correlated to the TCOF1 mutation. Six of 12 patients diagnosed with hemifacial microsomia exhibited a novel insertion mutation 4127 ins G (frameshift) in exon 24 in the TCOF1 gene. All six patients were diagnosed with anomalies on the left side. In addition, four of these six patients had hearing impairment; three had other major anomalies; and two had developmental delay. The insertion caused a frameshift, an early truncation, the loss of two putative nuclear localization signals (residues 1404-1420 and 1424-1440), and the loss of coiled coil domain (1406-1426) in treacle protein. These findings support the existence of two regulators of growth of the mandibular condyles.
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Mutations in the RP2 gene located on Xp11.23 are associated with X-linked retinitis pigmentosa (XLRP), a severe form of progressive retinal degeneration which leads to complete loss of vision in affected males. To date, 14 different mutations in the RP2 gene have been reported to cause XLRP, the majority of which lead to a coding frameshift within the gene and predicted truncation of the protein product. We here report two novel frameshift mutations in RP2 identified in XLRP families by PCR-SSCP and direct sequencing, namely 723delT and 796-799del. Four single nucleotide polymorphisms (SNPs) within the coding region of RP2 are also described (105A>T, 597T>C, 844C>T, 1012G>T), the first polymorphisms to be reported within this gene of unknown function, two of which alter the amino acid sequence. The current study extends the XLRP mutation profile of RP2 and highlights non-pathogenic coding sequence variations which may facilitate both functional studies of the gene and analysis of intragenic allelic contribution to the phenotype. Hum Mutat 15:580, 2000. © 2000 Wiley-Liss, Inc.
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A novel heterozygous mutation (c.325dup) was identified in EXT1 gene from the proband and the affected family members; this mutation was absent in all the unaffected family members. The identification of the novel frameshift insertion mutation (c.325dup) expands the mutation spectrum of HME, which provides new evidence for HME diagnosis.
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Hereditary multiple exostoses
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Chinese family
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Mutation Testing
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Cerebellar ataxia
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"Adaptive mutation" denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac(-)Escherichia coli cells on lactose medium induces Lac(+)revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele. A crucial distinction between alternative hypotheses for the mechanisms of adaptive mutation hinges on whether these amplification and frameshift mutation events are distinct, or whether amplification is a molecular intermediate, producing an intermediate cell type, in colonies on a pathway to frameshift mutation. The latter model allows the evolutionarily conservative idea of increased mutations (per cell) without increased mutation rate (by virtue of extra gene copies per cell), whereas the former requires an increase in mutation rate, potentially accelerating evolution. To resolve these models, we probed early events leading to rare adaptive mutations and report several results that show that amplification is not the precursor to frameshift mutation but rather is an independent adaptive outcome. (i) Using new high-resolution selection methods and stringent analysis of all cells in very young (micro)colonies (500-10,000 cells), we find that most mutant colonies contain no detectable lac-amplified cells, in contrast with previous reports. (ii) Analysis of nascent colonies, as young as the two-cell stage, revealed mutant Lac(+)cells with no lac-amplified cells present. (iii) Stringent colony-fate experiments show that microcolonies of lac-amplified cells grow to form visible colonies of lac-amplified, not mutant, cells. (iv) Mutant cells do not overgrow lac-amplified cells in microcolonies fast enough to mask the lac-amplified cells. (v)lac-amplified cells are not SOS-induced, as was proposed to explain elevated mutation in a sequential model. (vi) Amplification, and not frameshift mutation, requires DNA polymerase I, demonstrating that mutation is separable from amplification, and also illuminating the amplification mechanism. We conclude that amplification and mutation are independent outcomes of adaptive genetic change. We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression.
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