scholarly journals Increased rate of base substitution in a hamster mutator strain obtained during serial selection for gene amplification.

1990 ◽  
Vol 10 (12) ◽  
pp. 6805-6808 ◽  
Author(s):  
M A Caligo ◽  
W Armstrong ◽  
B J Rossiter ◽  
M Meuth
Keyword(s):  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Lower Proportion ◽  
Base Substitution ◽  
Gene Rearrangements ◽  
Wild Type ◽  
Replication Process ◽  
Mutator Strain ◽  
Mutator Gene ◽  
Selection For

The pattern of mutations produced by a mutator gene (obtained during serial selection for amplification of the dihydrofolate reductase [dhfr] locus) shows a pronounced shift from that found in wild-type cells. The rate of certain types of base substitutions (particularly transitions) is dramatically increased, while gene rearrangements constitute a lower proportion of mutations. These data suggest a lower fidelity of the replication process in the mutator strain.

Increased rate of base substitution in a hamster mutator strain obtained during serial selection for gene amplification

1990 ◽  
Vol 10 (12) ◽  
pp. 6805-6808
Author(s):  
M A Caligo ◽  
W Armstrong ◽  
B J Rossiter ◽  
M Meuth
Keyword(s):  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Lower Proportion ◽  
Base Substitution ◽  
Gene Rearrangements ◽  
Wild Type ◽  
Replication Process ◽  
Mutator Strain ◽  
Mutator Gene ◽  
Selection For

The pattern of mutations produced by a mutator gene (obtained during serial selection for amplification of the dihydrofolate reductase [dhfr] locus) shows a pronounced shift from that found in wild-type cells. The rate of certain types of base substitutions (particularly transitions) is dramatically increased, while gene rearrangements constitute a lower proportion of mutations. These data suggest a lower fidelity of the replication process in the mutator strain.

scholarly journals Selection for and against a canalized phenotype in Drosophila melanogaster

1967 ◽  
Vol 10 (1) ◽  
pp. 21-33 ◽  
Author(s):  
S. S. Y. Young
Keyword(s):  
Drosophila Melanogaster ◽  
Lower Proportion ◽  
Modifier Genes ◽  
Wild Type ◽  
Appreciable Change ◽  
Bristle Number ◽  
Alternative Hypotheses ◽  
Males And Females ◽  
Selection For ◽  
Relative Change

Selection for and against the canalized phenotype in scutellar bristles was attempted in two selection lines and a randomly selected line was used as control. The selection lines were the Decanalization line (D) and the Canalization line (N). The D line was maintained by matings of scute males (scwbl) with three scutellars with wild-type females (scwbl/yw) with five bristles, in the N line scute males with four bristles were mated with wild-type females also with four bristles, while in the C line males and females of the above genotypes were selected at random. The lines were established from a sample of flies taken from a line selected for high scutellar numbers.After eighteen generations of selection the C line was characterized by a regression of mean bristle number without appreciable change in variance. Relative to the N line, the D population showed a lower proportion of flies having four scutellars, a higher variance in bristle numbers, and a higher proportion of four-bristle scute flies having abnormal patterns.Two alternative hypotheses were advanced to account for the results of this experiment. The first postulated a relative change in the widths of the four-bristle canalization zones in the selection lines, while the second suggested a relative change in frequencies of specific modifier genes for scutellars in scute and in wild-type genotypes of the lines. The evidence favours the latter hypothesis.

129 Genomic Relationship Between PRRSV Wild-type Infection and PRRSV Vaccination for Antibody Response and Reproductive Performance

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 18-18
Author(s):  
Leticia P Sanglard ◽  
Felipe Hickmann ◽  
Yijian Huang ◽  
Kent A Gray ◽  
Daniel Linhares ◽  
...  
Keyword(s):  
Antibody Response ◽  
Reproductive Performance ◽  
Genetic Correlations ◽  
Clinical Signs ◽  
Respiratory Syndrome Virus ◽  
Wild Type ◽  
Large White ◽  
Selection For ◽  
Indicator Trait ◽  
Type Infection

Abstract Immunoglobulin G antibody response, measured as sample-to-positive (S/P) ratio, to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) has been proposed as an indicator trait for improved reproductive performance in PRRSV-infected purebred sows and PRRSV-vaccinated crossbred gilts. In this study, we investigated the genetic correlations (rg) of S/P ratio following a PRRSV outbreak and PRRSV-vaccination with performance in non-exposed and PRRSV-exposed sows. PRRSV outbreak phase was defined based on previously described methodologies after the detection of typical clinical signs of PRRSV infection. 541 Landrace sows had S/P ratio measured at ~54 days after the beginning of the PRRSV outbreak (S/Poutbreak), and 906 Landrace x Large White naïve F1 gilts had S/P ratio measured at ~50 days after vaccination with a commercial modified live PRRSV vaccine (S/PVx). 711 and 428 Landrace sows had reproductive performance recorded before and during the PRRSV outbreak, respectively. 811 vaccinated F1 animals had farrowing performance for up to 3 parities. All animals were genotyped for ~28K SNPs. The estimate of rg of S/Poutbreakwith S/PVx was high (rg±SE = 0.72±0.18). Estimates of rg of S/Poutbreak with reproductive performance in F1 sows were low to moderate, ranging from 0.05±0.23 (number stillborn) to 0.30±0.20 (total number born). Estimates of rg of S/PVxwith reproductive performance in non-infected purebred sows were moderate and favorable with number born alive (0.50±0.23), but low (0 to -0.11±0.23) with litter mortality traits. Estimates of rg of S/PVx were moderate and negative (-0.47±0.18) with the number of mummies in PRRSV-infected purebred sows and low with other traits (-0.29±0.18 for total number born to 0.05±0.18 for number stillborn). These results indicate that selection for antibody response following a PRRSV outbreak collected in purebred sows and to PRRSV vaccination collected in commercial crossbred gilts may increase litter size of non-infected and PRRSV-exposed purebred and commercial crossbred sows.

Developing a Genetic System in Deinococcus radiodurans for Analyzing Mutations

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 661-668
Author(s):  
Mandy Kim ◽  
Erika Wolff ◽  
Tiffany Huang ◽  
Lilit Garibyan ◽  
Ashlee M Earl ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Deinococcus Radiodurans ◽  
Genetic System ◽  
Base Change ◽  
Base Substitution ◽  
Wild Type ◽  
Base Pairs ◽  
E Coli ◽  
Radiation Induced ◽  
Induced Mutagenesis

Abstract We have applied a genetic system for analyzing mutations in Escherichia coli to Deinococcus radiodurans, an extremeophile with an astonishingly high resistance to UV- and ionizing-radiation-induced mutagenesis. Taking advantage of the conservation of the β-subunit of RNA polymerase among most prokaryotes, we derived again in D. radiodurans the rpoB/Rif r system that we developed in E. coli to monitor base substitutions, defining 33 base change substitutions at 22 different base pairs. We sequenced >250 mutations leading to Rif r in D. radiodurans derived spontaneously in wild-type and uvrD (mismatch-repair-deficient) backgrounds and after treatment with N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and 5-azacytidine (5AZ). The specificities of NTG and 5AZ in D. radiodurans are the same as those found for E. coli and other organisms. There are prominent base substitution hotspots in rpoB in both D. radiodurans and E. coli. In several cases these are at different points in each organism, even though the DNA sequences surrounding the hotspots and their corresponding sites are very similar in both D. radiodurans and E. coli. In one case the hotspots occur at the same site in both organisms.

scholarly journals Novel DNA rearrangements are associated with dihydrofolate reductase gene amplification.

1984 ◽  
Vol 259 (14) ◽  
pp. 9127-9140
Author(s):  
N A Federspiel ◽  
S M Beverley ◽  
J W Schilling ◽  
R T Schimke
Keyword(s):  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Dna Rearrangements ◽  
Reductase Gene

scholarly journals TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Edaise M. da Silva ◽  
Pier Selenica ◽  
Mahsa Vahdatinia ◽  
Fresia Pareja ◽  
Arnaud Da Cruz Paula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Genetic Alterations ◽  
Wild Type ◽  
Histologic Subtype ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Hotspot Mutations ◽  
Or Gene

AbstractMetaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher’s exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher’s exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers.

scholarly journals Kenyan Plasmodium falciparum Field Isolates: Correlation between Pyrimethamine and Chlorcycloguanil Activity In Vitro and Point Mutations in the Dihydrofolate Reductase Domain

1998 ◽  
Vol 42 (1) ◽  
pp. 164-169 ◽  
Author(s):  
A. Nzila-Mounda ◽  
E. K. Mberu ◽  
C. H. Sibley ◽  
C. V. Plowe ◽  
P. A. Winstanley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Drug Response ◽  
Point Mutations ◽  
Distinct Group ◽  
Wild Type ◽  
Field Isolates ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT Sixty-nine Kenyan Plasmodium falciparum field isolates were tested in vitro against pyrimethamine (PM), chlorcycloguanil (CCG), sulfadoxine (SD), and dapsone (DDS), and their dihydrofolate reductase (DHFR) genotypes were determined. The in vitro data show that CCG is more potent than PM and that DDS is more potent than SD. DHFR genotype is correlated with PM and CCG drug response. Isolates can be classified into three distinct groups based on their 50% inhibitory concentrations (IC50s) for PM and CCG (P< 0.01) and their DHFR genotypes. The first group consists of wild-type isolates with mean PM and CCG IC50s of 3.71 ± 6.94 and 0.24 ± 0.21 nM, respectively. The second group includes parasites which all have mutations at codon 108 alone or also at codons 51 or 59 and represents one homogeneous group for which 25- and 6-fold increases in PM and CCG IC50s, respectively, are observed. Parasites with mutations at codons 108, 51, and 59 (triple mutants) form a third distinct group for which nine- and eightfold increases in IC50s, respectively, of PM and CCG compared to the second group are observed. Surprisingly, there is a significant decrease (P < 0.01) of SD and DDS susceptibility in these triple mutants. Our data show that more than 92% of Kenyan field isolates have undergone at least one point mutation associated with a decrease in PM activity. These findings are of great concern because they may indicate imminent PM-SD failure, and there is no affordable antimalarial drug to replace PM-SD (Fansidar).

scholarly journals Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected withPlasmodium falciparum Malaria Parasites

1998 ◽  
Vol 42 (7) ◽  
pp. 1811-1814 ◽  
Author(s):  
Leonardo K. Basco ◽  
Rachida Tahar ◽  
Pascal Ringwald
Keyword(s):  
Dihydrofolate Reductase ◽  
Point Mutations ◽  
Gene Mutations ◽  
Adult Patients ◽  
Wild Type ◽  
Dihydropteroate Synthase ◽  
Reductase Gene ◽  
Parasite Populations

ABSTRACT In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.

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