Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Recurrent mutation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMed2004

BRO beta-lactamase alleles, antibiotic resistance and a test of the BRO-1 selective replacement hypothesis in Moraxella catarrhalis.

OBJECTIVES: The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of the Moraxella catarrhalis BRO beta-lactamase was tested by examining the temporal distribution, antibiotic resistance and epidemiological characteristics of isolates from a long-term collection at a single locale. METHODS: A rapid, one-step PCR assay conducted on 354 isolates spanning 1984-1994 distinguished bro alleles in over 97% of the beta-lactamase-producing isolates. Probes of dot blots were used to distinguish PCR failure from non-beta-lactamase-mediated penicillin resistance. RESULTS: BRO-2 isolates comprised 0-10% of the population per year with no evidence of a decline over time. All beta-lactamase producers exceeded the clinical threshold for penicillin resistance. Bimodality of penicillin MICs for beta-lactamase producers was caused by variation within BRO-1 rather than differences between BRO-1 and BRO-2. Non-beta-lactamase factors also confer resistance to penicillin and may contribute to the BRO-1 bimodality. The 13 BRO-2 isolates were associated with diverse genotypes within which there was evidence of epidemiologically linked clusters. The exclusive association of BRO-2 with four unrelated genotypes suggested maintenance of BRO-2 by recurrent mutation or horizontal exchange. CONCLUSIONS: The relative rarity of BRO-2 throughout the study, the absence of a declining temporal trend, and genetic diversity within BRO-2 all failed to support the hypothesis that BRO-2 was more common in the past and has been selectively replaced by BRO-1.

Alleles↗
PubMed2006

SNP identification and analysis in part of intron 2 of goat MSTN gene and variation within and among species.

Part of intron 2 of the myostatin (MSTN) gene of 140 goats from 24 populations and 38 sheep from 8 breeds were sequenced, and similar sequences of different species from Gene bank were also obtained to study MSTN diversity within and among species. The results indicated that there were seven polymorphic sites in the sequenced region of goat, which have not been separated by recombination (or recurrent mutation), presented complete linkage disequilibrium, and could be sorted into three haplotypes. There was no polymorphic site in the sequenced region of sheep. The haplotype diversity, nucleotide diversity, and average number of single nucleotide polymorphism (SNP) differences of goats from the South group are higher than those of North group, and the corresponding value of the Foreign group is also higher than that of Chinese. The genetic differentiation (0.7558) between the Foreign and Chinese group is significant. There are two main haplotypes of the MSTN intron 2 in the goat, which may represent two ancestral types, in support of the theory that domestic goats in the world mainly originated from two ancestors based on morphology, history, archaeology, and molecular markers. The sequence differences of the MSTN intron 2 among species are greater than those within species.

Animals↗
PubMed2003

Transpecific polymorphisms in an inversion linked esterase locus in Drosophila buzzatii.

Nucleotide variation was studied in a 1.1 kb section of the coding region of an Esterase gene (Est-A) that maps in the center of the segments rearranged by polymorphic inversions in the cactophilic Drosophila buzzatii. We examine 30 homozygous second-chromosome lines differing in gene arrangement and three D. koepferae isofemale lines as outgroups. Our data show that Est-A is a highly polymorphic gene at both synonymous and replacement sites. Significant departures from homogeneity in the distribution of the ratio of silent polymorphism to divergence predicted by the neutral theory reveals a local excess of silent polymorphism. This is consistent with the presence of two apparent narrow peaks of elevated silent polymorphism surrounding nonconservative amino acid substitutions. These polymorphisms as well as others at synonymous and nonsynonymous sites are shared with D. koepferae. We suggest that the presence of shared nucleotide polymorphisms is probably due to interspecific gene flow and/or balancing selection acting on replacement variants and/or to a decreased probability of loss of ancestral polymorphisms caused by linkage to an adaptive inversion polymorphism. Recurrent mutation and persistence of neutral ancestral polymorphisms cannot, however, be ruled out. The analysis of the distribution of nucleotide variation among the three chromosomal arrangements sampled reveals that derived arrangements (J and JZ(3)) are less polymorphic than the ancestral ST, and that the widely distributed ST and J arrangements are genetically differentiated. However, a significant number of polymorphisms are shared between arrangements, suggesting frequent exchange either from gene conversion or from double crossovers in heterokaryotypes. Finally, our present results in combination with data of sequence variation at the breakpoints of inversion J suggest that this old gene arrangement has risen in frequency in relatively recent times.

Animals↗
PubMed2002

Rapid divergence of gene duplicates on the Drosophila melanogaster X chromosome.

The recent sequencing of several eukaryotic genomes has generated considerable interest in the study of gene duplication events. The classical model of duplicate gene evolution is that recurrent mutation ultimately results in one copy becoming a pseudogene, and only rarely will a beneficial new function evolve. Here, we study divergence between coding sequence duplications in Drosophila melanogaster as a function of the linkage relationship between paralogs. The mean K(a)/K(s) between all duplicates in the D. melanogaster genome is 0.2803, indicating that purifying selection is maintaining the structure of duplicate coding sequences. However, the mean K(a)/K(s) between duplicates that are both on the X chromosome is 0.4701, significantly higher than the genome average. Further, the distribution of K(a)/K(s) for these X-linked duplicates is significantly shifted toward higher values when compared with the distributions for paralogs in other linkage relationships. Two models of molecular evolution provide qualitative explanations of these observations-relaxation of selective pressure on the duplicate copies and, more likely, positive selection on recessive adaptations. We also show that there is an excess of X-linked duplicates with low K(s), suggesting a larger proportion of relatively young duplicates on the D. melanogaster X chromosome relative to autosomes.

Animals↗
PubMed2004

Analysis of factor VIII gene intron 1 inversion in Argentinian families with severe haemophilia A and a review of the literature.

Besides intron 22 factor VIII gene inversion (Inv22), intron 1 inversion (Inv1) has recently been reported as a further recurrent mutation that causes approximately 5% of severe haemophilia A (HA) cases. We analysed the presence of the Inv1 in a group of 64 severe HA-affected families from Argentina, and found only one positive case. This Inv1 patient has not developed a factor VIII inhibitor, and the screening for small mutations in the coding sequences of the factor VIII gene did not detect any additional defect in this case. The Inv1 genotyping was further applied to analyse the haemophilia carrier status of the proband's sister. In addition, we studied the accuracy of the current polymerase chain reaction-based method to investigate the Inv1, and confirmed the absence of amplimer length polymorphisms associated to the Inv1-specific polymerase chain reaction amplifications in 101 X-chromosome haplotypes from unrelated Argentinian healthy males. In order to discuss Inv1 mutation frequency in severe HA and the risk of inhibitor formation, a review of the literature was included. Our data highlight the importance of analysis of the Inv1 in Inv22-negative severe HA cases. This will benefit both genetic counselling and the study of the relationship between genotype and inhibitor development.

Argentina↗
PubMed2003

Community-acquired poliovirus infection in children with primary immunodeficiencies in Tunisia.

The global polio eradication program recommends the use of massive vaccination campaigns with live vaccine through National Immunization Days (NIDs) to displace the wild virus from the community. Immunodeficient patients may be indirectly infected and become chronic excretors and potential reservoirs of polioviruses, a concern for the posteradication era. This prospective study aimed to assess the risk of community-acquired infection of immunodeficient patients following NIDs, the dynamics of viral excretion and the genetic variation of excreted viruses. Sixteen children with various primary immunodeficiencies, who did not receive the vaccine during the campaign, were investigated. Stool samples were collected weekly, shortly after the NIDs, during at least 3 months, and were processed for viral isolation. Isolates were characterized by three intratypic differentiation methods and partial sequencing of the VP1/2A region. Polioviruses were detected in 4 out of 16 patients (serotype 1 in 3 patients and serotype 3 in 1 patient). Sequencing revealed more than 99% homology with homotypic Sabin strains, suggesting recent infection. Duration of viral excretion ranged from 1 to 7 weeks. Nine out of eleven isolates from the three poliovirus serotype 1-infected patients disclosed a non-Sabin-like phenotype by enzyme-linked immunosorbent assay and had recurrent mutations within or close to the neutralizing antigenic sites. In summary, the risk of secondary infection in immunodeficient patients is within the range previously reported for the general population. Although none of the four infected patients developed prolonged viral excretion, particular viral variants were selected and may be of epidemiological significance.

Child↗
PubMed1996

Clinical and genetic heterogeneity of hypochondroplasia.

Hypochondroplasia (HCH) is an autosomal dominant condition characterised by short stature, micromelia, and lumbar lordosis. In a series of 29 HCH probands (13 sporadic cases, 16 familial cases), we tested their DNA for the N540K recurrent mutation previously described in the proximal tyrosine kinase domain of the FGFR3 gene on chromosome 4p16.3, and we detected this mutation in 21/29 HCH patients. Interestingly, three familial cases were clearly unlinked to chromosome 4p16.3. Reviewing the clinical and radiological manifestations of the disease a posteriori, we observed that the N540K mutation was associated with relative macrocrania with a high and large forehead and short hands. By contrast, in the three pedigrees inconsistent with linkage to chromosome 4p16.3, the clinical phenotype was milder, macrocephaly and shortening of the long bones was less obvious, the hands were normal, and no metaphyseal flaring was noted. This study supports the view that HCH is a clinically and genetically heterogeneous condition.

Achondroplasia↗
PubMed2005

[Prevalence of frequent recessive diseases in the Spanish population through DNA analyses on samples from the neonatal screening].

BACKGROUND AND OBJECTIVE: Cystic fibrosis (CF) and the nonclassical forms of congenital adrenal hyperplasia (NC21OHD) are frequent autosomal recessive diseases. Their frequencies in the Caucasian population are the ones applied to the management of the diseases (1:2500 and 1:1000, respectively). The aim of this study was to learn about the adequacy of these figures to the Spanish population. MATERIAL AND METHOD: Study of the recurrent mutation (about 50% of alleles) in each entity, DF508 or Val281Leu, respectively, in 300 anonymous consecutive samples (600 alleles) from the Comunidad de Madrid neonatal screening. PCR specific amplifications of the CFTR and CYP21A2 genes and direct analyses of DF508 and Val281Leu mutations were performed. RESULTS: Allele frequencies of DF508 and Val281Leu were 0.005 and 0.038 (carrier frequencies 1.1% and 7.5%, respectively). Taking into consideration the percentage of these mutations in patient alleles, 48% for CF and for 57% NC21OHD, disease frequencies of about 1:8028 (CF) and 1:230 (NC21OHD) were estimated. The standard error calculated for these data were 0.6% and 1.5%. CONCLUSIONS: We have found that CF is less frequent and NC21OHD more frequent in the Spanish population than in other Caucasian populations.

Adrenal Hyperplasia, Congenital↗
PubMed2005

The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice.

The molecular characterization of leukemia has demonstrated that genetic alterations in the leukemic clone frequently fall into 2 classes, those affecting transcription factors (e.g., AML1-ETO) and mutations affecting genes involved in signal transduction (e.g., activating mutations of FLT3 and KIT). This finding has favored a model of leukemogenesis in which the collaboration of these 2 classes of genetic alterations is necessary for the malignant transformation of hematopoietic progenitor cells. The model is supported by experimental data indicating that AML1-ETO and FLT3 length mutation (FLT3-LM), 2 of the most frequent genetic alterations in AML, are both insufficient on their own to cause leukemia in animal models. Here we report that AML1-ETO collaborates with FLT3-LM in inducing acute leukemia in a murine BM transplantation model. Moreover, in a series of 135 patients with AML1-ETO-positive AML, the most frequently identified class of additional mutations affected genes involved in signal transduction pathways including FLT3-LM or mutations of KIT and NRAS. These data support the concept of oncogenic cooperation between AML1-ETO and a class of activating mutations, recurrently found in patients with t(8;21), and provide a rationale for therapies targeting signal transduction pathways in AML1-ETO-positive leukemias.

Animals↗
PubMed2026

Age- and sex-adjusted genomic differences between Korean and Beat AML cohorts.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Journal Article↗
PubMed2025

Evolution of SARS-CoV-2 in white-tailed deer in Pennsylvania 2021-2024.

SARS-CoV-2 continues to transmit and evolve in humans and animals. White-tailed deer (Odocoileus virginianus) have been previously identified as a zoonotic reservoir for SARS-CoV-2 with high rates of infection and probable spillback into humans. Here we report sampling 1,127 white-tailed deer (WTD) in Pennsylvania, and a genomic analysis of viral dynamics spanning 1,017 days between April 2021 and January 2024. To assess viral load and genotypes, RNA was isolated from retropharyngeal lymph nodes and analyzed using RT-qPCR and viral whole genome sequencing. Samples showed a 14.64% positivity rate by RT-qPCR. Analysis showed no association of SARS-CoV-2 prevalence with age, sex, or diagnosis with Chronic Wasting Disease. From the 165 SARS-CoV-2 positive WTD, we recovered 25 whole genome sequences and an additional 17 spike-targeted amplicon sequences. The viral variants identified included 17 Alpha, 11 Delta, and 14 Omicron. Alpha largely stopped circulating in humans around September 2021, but persisted in WTD as recently as March of 2023. Phylodynamic analysis of pooled genomic data from Pennsylvania documents at least 12 SARS-CoV-2 spillovers from humans into WTD, including a recent series of Omicron spillovers. Prevalence was higher in WTD in regions with crop coverage rather than forest, suggesting an association with proximity to humans. Analysis of seasonality showed increased prevalence in winter and spring. Multiple examples of recurrent mutations were identified associated with transmissions, suggesting WTD-specific evolutionary pressures. These data document ongoing infections in white-tailed deer, probable onward transmission in deer, and a remarkable rate of new spillovers from humans.

Animals↗
PubMed2026

Molecular subtyping of adrenocortical carcinoma reveals distinct subtypes with prognostic and therapeutic implications.

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with poor survival and limited treatment options. To comprehensively characterize its molecular landscape and identify clinically relevant subtypes, we performed an integrated genomic analysis - including whole-exome sequencing, RNA sequencing, and copy number variation profiling - on 61 Chinese patients with ACC. We identified recurrent mutations in TP53 (25%), CTNNB1 (15%), ZNRF3 (10%), and MEN1 (8%). Unsupervised clustering of transcriptomic data revealed four distinct molecular subtypes: cortisol-driven (CD, 14%), immune-suppressed (IS, 40%), cell cycle-altered (CCA, 22%), and immunomodulatory (IM, 24%). The CD subtype exhibited steroidogenic pathway activation; the IS subtype showed T cell receptor downregulation and the worst disease-free survival; the CCA subtype was marked by chromosomal instability and cell cycle gene overexpression; and the IM subtype displayed enriched immune signaling and favorable outcomes. Copy number analysis further uncovered focal amplifications (e.g. TERT, CDK4) and HLA-II deletions. This study establishes a novel molecular classification of ACC, providing a framework for subtype-specific therapeutic strategies, such as CDK4/6 inhibition for CCA and immunotherapy for IM tumors, while highlighting the clinical challenges of immune-cold IS tumors.

Humans↗
PubMed2005

Predictions of patterns of response to artificial selection in lines derived from natural populations.

The pattern of response to artificial selection on quantitative traits in laboratory populations can tell us something of the genetic architecture in the natural population from which they were derived. We modeled artificial selection in samples drawn from natural populations in which variation had been maintained by recurrent mutation, with genes having an effect on the trait, which was subject to real stabilizing selection, and a pleitropic effect on fitness (the joint-effect model). Natural selection leads to an inverse correlation between effects and frequencies of genes, such that the frequency distribution of genes increasing the trait has an extreme U-shape. In contrast to the classical infinitesimal model, an early accelerated response and a larger variance of response among replicates were predicted. However, these are reduced if the base population has been maintained in the laboratory for some generations by random sampling prior to artificial selection. When multiple loci and linkage are also taken into account, the gametic disequilibria generated by the Bulmer and Hill-Robertson effects are such that little or no increase in variance and acceleration of response in early generations of artificial selection are predicted; further, the patterns of predicted responses for the joint-effect model now become close to those of the infinitesimal model. Comparison with data from laboratory selection experiments shows that, overall, the analysis did not provide clear support for the joint-effect model or a clear case for rejection.

Artificial Intelligence↗
PubMed2004

Combining mathematical models and statistical methods to understand and predict the dynamics of antibiotic-sensitive mutants in a population of resistant bacteria during experimental evolution.

Temporarily discontinuing the use of antibiotics has been proposed as a means to eliminate resistant bacteria by allowing sensitive clones to sweep through the population. In this study, we monitored a tetracycline-sensitive subpopulation that emerged during experimental evolution of E. coli K12 MG1655 carrying the multiresistance plasmid pB10 in the absence of antibiotics. The fraction of tetracycline-sensitive mutants increased slowly over 500 generations from 0.1 to 7%, and loss of resistance could be attributed to a recombination event that caused deletion of the tet operon. To help understand the population dynamics of these mutants, three mathematical models were developed that took into consideration recurrent mutations, increased host fitness (selection), or a combination of both mechanisms (full model). The data were best explained by the full model, which estimated a high mutation frequency (lambda = 3.11 x 10(-5)) and a significant but small selection coefficient (sigma = 0.007). This study emphasized the combined use of experimental data, mathematical models, and statistical methods to better understand and predict the dynamics of evolving bacterial populations, more specifically the possible consequences of discontinuing the use of antibiotics.

Anti-Bacterial Agents↗
PubMed2005

Relative influences of crossing over and gene conversion on the pattern of linkage disequilibrium in Arabidopsis thaliana.

In this article we infer the rates of gene conversion and crossing over in Arabidopsis thaliana from population genetic data. Our data set is a genomewide survey consisting of 1347 fragments of length 600 bp sequenced in 96 accessions. It has several orders of magnitude more markers than any previous nonhuman study. This allows for more accurate inference as well as a detailed comparison between theoretical expectations and observations. Our methodology is specifically set to account for deviations such as recurrent mutations or a skewed frequency spectrum. We found that even if some components of the model clearly do not fit, the pattern of LD conforms to theoretical expectations quite well. The ratio of gene conversion to crossing over is estimated to be around one. We also find evidence for fine-scale variations of the crossing-over rate.

Arabidopsis↗
PubMed2005

Mitochondrial genome recombination in the zone of contact between two hybridizing conifers.

Variation in mitochondrial DNA was surveyed at four gene loci in and around the zone of contact between two naturally hybridizing conifers, black spruce (Picea mariana) and red spruce (P. rubens) in northeastern North America. Most of the mtDNA diversity of these species was found in populations next to or into the zone of contact, where some individuals bore rare mitotypes intermediate between the common mitotypes observed in the allopatric areas of each species. Sequence analysis and tests for mtDNA recombination point to this phenomenon, rather than to recurrent mutation, as the most tenable hypothesis for the origin of these rare mitotypes. From the 10 mitotypes observed, at least 4 would be the product of recombination between 4 of the 5 putative ancestral mitotypes. Tests for cytonuclear disequilibrium and geographical structure of the putative recombinant mitotypes suggest that mtDNA recombination is not frequent and relatively recent on the geological time scale. mtDNA recombination would have been promoted by transient heteroplasmy due to leakage of paternal mtDNA since the Holocene secondary contact between the two species.

Base Sequence↗
PubMed1979

Distribution and effects of the 1/29 Robertsonian translocation in cattle.

The distribution and effects of the 1/29 translocation in cattle, defined with chromosome banding techniques, are described. Findings in different parts of the world are reported, and the origin of the translocation in some cases is explained. Geographical distribution as known at present reflects the areas in which chromosome investigations have been carried out rather than the true distribution. It is not known whether the occurrence of the 1/29 translocation in different geographical areas and breeds is due to recurrent mutation or distribution of an ancient mutation, but many observations point to the latter. Although direct observations of an increased embryonic mortality are lacking, reduced fertility of males and females heterozygous for 1/29 is established. No correlations of the 1/29 translocation with other characteristics have been found, and variability in incidence between different populations is probably due to genetic drift. The importance in animal breeding of introducing eradication programs is emphasized, and it is stressed that cattle populations using artificial insemination should undergo routine cytogenetic investigations.

Animals↗
PubMed1999

Y-chromosome-specific microsatellite variation in Australian aboriginals.

The frequency distributions of 4 highly polymorphic Y-chromosome-specific microsatellites (DYS19, DYS390, DYS391, and DYS392) were determined in 79 unrelated Australian Aboriginal males from the Northern Territory. These results are compared with those observed in worldwide populations at both the locus and the haplotype level. Common alleles in Aboriginals are DYS19*15 (49%), DYS19*14 (28%), DYS390*19 (39%), DYS390*24 (20%), DYS391*10 (72%), DYS392*11 (63%), and DYS392*13 (28%). No evidence of reduced gene diversity was observed for these Y-chromosome alleles. DYS390 exhibits the most complex arrangement, displaying a bimodal distribution composed of common alleles (*22-*26), and rare short alleles (*18-*20), with an intermediate allele (*21) being absent. DYS390*20, previously reported only in Papuans and Samoans, is observed for the first time in Aboriginals. Compared with a recent study of Aboriginals, our sample exhibits considerable diversity in the haplotypes associated with the rare DYS390*19 allele, indicating that this allele is of considerable antiquity, if it arose as a single deletion event. Combining all 4 Y-chromosome-linked microsatellites produced 41 unique haplotypes, which were linked using a median-joining network. This network shows that most (78%) of our Aboriginal haplotypes fall into 2 distinct clusters, which likely represent 2 separate lineages. Seven haplotypes are shared with haplotypes found in a recent study of Aboriginals, and 7 are shared with a Spanish population. The cluster of Aboriginal haplotypes associated with the short DYS390 alleles does not share any haplotypes with the Spanish, indicating that this cluster of haplotypes is unique to Australian Aboriginals. Limited data from 4 worldwide populations used to construct haplotypes based on 3 loci (DYS19, DYS390, DYS392) show that only 4 of these haplotypes are seen in Australian Aboriginals. Shared haplotypes may be the result of admixture and/or recurrent mutation at these loci. Expanding the haplotype analysis to include biallelic markers on the Y chromosome will resolve this issue.

Alleles↗