DNA Sequence Similarity Research Articles

Molecular evidence that GBS early neonatal sepsis results from ascending infection: comparative hybrid genomics analyses show that microorganisms in the vaginal ecosystem, amniotic fluid, chorioamniotic membranes, and neonatal blood are the same.

Streptococcus agalactiae, or Group B Streptococcus (GBS), is a leading cause of neonatal sepsis. Materno-fetal transmission of the microorganisms present in the lower genital tract/perineum is considered to be the most frequent mode for acquisition of infection. It has also been proposed that, in a subset of cases, GBS causes acute chorioamnionitis, intraamniotic infection, and fetal/neonatal sepsis. However, the evidence to support this ascending pathway is derived from microbiologic studies that rely on cultivation methods, which do not have the resolution to determine if the microorganisms causing neonatal sepsis are the same as those found in the amniotic fluid and the vaginal ecosystem. We used whole genome sequencing of the microorganisms isolated from the vagina, amniotic fluid, chorioamniotic membranes, and neonatal blood (four isolates) in a case of early neonatal sepsis. Using hybrid genome assembly, we characterized the genomic features including virulence factors and antimicrobial resistance in four isolates from the same mother, placenta, and newborn. Whole genome sequencing revealed that the microorganisms in the four clinical isolates corresponded to S. agalactiae sequence type 1, clonal complexes 1, and serotype Ib. Comparative genomic analysis illustrated similar DNA sequences of the four genomes. This study presents the first evidence of the genomic similarity of microorganisms in the vaginal ecosystem, the space between the chorioamniotic membranes of the placenta, amniotic fluid, and neonatal blood.

Use of 3D chaos game representation to quantify DNA sequence similarity with applications for hierarchical clustering

A 3D chaos game is shown to be a useful way for encoding DNA sequences. Since matching subsequences in DNA converge in space in 3D chaos game encoding, a DNA sequence’s 3D chaos game representation can be used to compare DNA sequences without prior alignment and without truncating or padding any of the sequences. Two proposed methods inspired by shape-similarity comparison techniques show that this form of encoding can perform as well as alignment-based techniques for building phylogenetic trees. The first method uses the volume overlap of intersecting spheres and the second uses shape signatures by summarizing the coordinates, oriented angles, and oriented distances of the 3D chaos game trajectory. The methods are tested using: (1) the first exon of the beta-globin gene for 11 species, (2) mitochondrial DNA from four groups of primates, and (3) a set of synthetic DNA sequences. Simulations show that the proposed methods produce distances that reflect the number of mutation events; additionally, on average, distances resulting from deletion mutations are comparable to those produced by substitution mutations.

Unveiling Similarities in the Code of Life: A Detailed Exploration of DNA Sequence Matching Algorithm

Identifying similar DNA sequences is crucial in various biological research endeavors. This paper delves into the intricate workings of a specific algorithm designed for this purpose. We provide a systematic explanation, exploring how the algorithm handles user input, reads stored DNA sequences, utilizes the Word2Vec model for vector representation, and calculates sequence similarity using diverse metrics like Cosine Similarity and Neutrosophic Distance. Additionally, the paper explores the incorporation of neutrosophic values to account for uncertainty in the comparisons. Finally, we discuss the extraction of results, including matched sequences, similarity scores, and accuracy measures. This in-depth exploration provides a clear understanding of the algorithm's capabilities and fosters its effective application in DNA sequence analysis.

Lelliottia wanjuensis sp. nov. Isolated from Korean Lettuce in Wanju, South Korea

Ten Gram stain-negative, oxidase-negative, catalase-positive, rod-shaped strains were isolated from lettuce in the city Wanju in South Korea. Comparative 16S rRNA gene analysis and multilocus sequence analysis indicated that the strains grouped closely together with all other Lelliottia (L.)-type strains. The average nucleotide identity (ANI) comparisons of the isolates showed a high relationship between the strains, as the ANI values of all strains ranged from 91.01 to 91.31% when compared to the L. jeotgali-type strain PFL01T. All isolates showed the highest genomic DNA sequence similarity to the L. jeotgali PFL01T strain at 43.3% when compared with digital DNA–DNA hybridization (dDDH). Strain V104_15T of the proposed novel Lelliottia species showed 91.2% and 43.3% similarity with the most closely related L. jeotgali PFL01T-type strain in the ANI and dDDH comparisons, respectively. Strain V104_15T could not grow at 45 °C and 7% NaCl, while L. jeotgali PFL01T strain could grow at both these conditions. Strain V104_15T showed ß-glucosidase activity but not α-glucosidase activity, while the L. jeotgali PFL01T strain was α-glucosidase positive but ß-glucosidase negative. The major cellular fatty acids of strain V104_15T were C16:0 and cyclo-C17:0 including summed features. The mol % G + C content of the genomic DNA of strain V104_15T was 55.74%. Phenotypic and biochemical characteristics, as well as the phylogenomic analysis indicated that the strain V104_15T represents a novel species of the genus Lelliottia, for which the name Lelliottia wanjuensis sp. nov. is proposed. The type strain is V104_15T (= LMG 32996 T = DSM 115585 T).

Graph-based analysis of DNA sequence comparison in closed cotton species: A generalized method to unveil genetic connections.

Graph theory provides a systematic method for modeling and analysing complicated biological data as an effective bioinformatics tool. Based on current trends, the number of DNA sequences in the DNA database is growing quickly. To determine the origin of a species and identify homologous sequences, it is crucial to detect similarities in DNA sequences. Alignment-free techniques are required for accurate measures of sequence similarity, which has been one of the main issues facing computational biologists. The current study provides a mathematical technique for comparing DNA sequences that are constructed in graph theory. The sequences of each DNA were divided into pairs of nucleotides, from which weighted loop digraphs and corresponding weighted vectors were computed. To check the sequence similarity, distance measures like Cosine, Correlation, and Jaccard were employed. To verify the method, DNA segments from the genomes of ten species of cotton were tested. Furthermore, to evaluate the efficacy of the proposed methodology, a K-means clustering method was performed. This study proposes a proof-of-model that utilises a distance matrix approach that promises impressive outcomes with future optimisations to be made to the suggested solution to get the hundred percent accurate result. In the realm of bioinformatics, this paper highlights the use of graph theory as an effective tool for biological data study and sequence comparison. It's expected that further optimization in the proposed solution can bring remarkable results, as this paper presents a proof-of-concept implementation for a given set of data using the proposed distance matrix technique.

Molecular similarities between the genes for Trypanosoma cruzi microtubule-associated proteins, mammalian interferons, and TRIMs

Initial studies using bioinformatics analysis revealed DNA sequence similarities between Trypanosoma cruzi GenBank® M21331, coding for Antigen 36 (Ag 36), and tripartite motif (TRIM) genes. TRIM40 showed 9.7% identity to GenBank M21331, and four additional TRIM genes had identities greater than 5.0%. TRIM37 showed a continuous stretch of identity of 12 nucleotides, that is, at least 25% longer than any of the other TRIMs. When we extended our analysis on the relationships of GenBank M21331 to further innate immune genes, using the Needleman-Wunsch (NW) algorithm for alignment, identities to human IFN-α, IFN-β, and IFN-γ genes of 13.6%, 12.6%, and 17.9%, respectively, were found. To determine the minimum number of genes coding for proteins closely related to Ag 36, a BLAST-p search was conducted with it versus the T. cruzi genome. The BLAST-p search revealed that T. cruzi GenBank M21331 had 14 gene sequences homologous to microtubule-associated protein (MAP) genes with 100% amino acid sequence identity. To verify the similarities in non-human genes, a study comparing TRIM21 region sequences among mammalian species to the comparable human TRIM21 region showed that related sequences were also present in 11 mammalian species. The MAP genes homologous to Ag 36 form a family of at least 14 genes which mimic human immune genes in the IFN and TRIM families. This mimicry is of gene sequences and not their protein products or epitopes. These results appear to be the first description of molecular mimicry of immune genes in humans by a protozoan parasite.

A Review of Probe-Based Enrichment Methods to Inform Plant Virus Diagnostics.

Modern diagnostic techniques based on DNA sequence similarity are currently the gold standard for the detection of existing and emerging pathogens. Whilst individual assays are inexpensive to use, assay development is costly and carries risks of not being sensitive or specific enough to capture an increasingly diverse range of targets. Sequencing can provide the entire nucleic acid content of a sample and may be used to identify all pathogens present in the sample when the depth of coverage is sufficient. Targeted enrichment techniques have been used to increase sequence coverage and improve the sensitivity of detection within virus samples, specifically, to capture sequences for a range of different viruses or increase the number of reads from low-titre virus infections. Vertebrate viruses have been well characterised using in-solution hybridisation capture to target diverse virus families. The use of probes for genotyping and strain identification has been limited in plants, and uncertainty around sensitivity is an impediment to the development of a large-scale virus panel to use within regulatory settings and diagnostic pipelines. This review aims to compare significant studies that have used targeted enrichment of viruses to identify approaches to probe design and potential for use in plant virus detection and characterisation.

Advancements in DNA analysis for distinguishing wild boar and domestic pig: a mini-review on research developments for food authentication studies

Abstract Ensuring food authenticity is integral to quality control and food safety, demanding traceability of food ingredient origins to be prominently featured on labels. Pork, a widely consumed and processed animal protein source, is susceptible to adulteration with wild boar meat, primarily driven by factors such as production costs and profitability. Complicating matters, the quality of wild boar meat obtained through game hunting lacks guarantees for hygienic standards, posing potential harm to consumers. Recent outbreaks of African Swine Fever in pigs and wild boars further emphasize the critical link between food safety and meat authenticity. This study addresses the need for research in distinguishing between pork and wild boar meat to uphold food quality control standards. Establishing the meat origin is not only crucial for quality control but also vital for mapping and tracing meat distribution patterns. The study adopts a DNA-based approach, utilizing biomarkers to distinguish domestic pig and wild boar meat. However, researchers encounter significant challenges due to their shared species (Sus scrofa) and high DNA sequence similarity. The pursuit of robust biomarkers and analytical methods becomes imperative. Exploring both nuclear and mitochondrial DNA, this mini-review outlines the research developments in identifying resilient biomarkers and employing various analytical methods, including conventional PCR, PCR-RFLP, Real-time PCR, microsatellite (STR), and deep sequencing (NGS or GWAS). The paper provides a concise overview of the ongoing efforts to find effective biomarkers and analytical methods based on DNA approaches for distinguishing domestic pigs and wild boars, showcasing their potential applications in food authentication.

Cooperative Gsx2-DNA binding requires DNA bending and a novel Gsx2 homeodomain interface.

The conserved Gsx homeodomain (HD) transcription factors specify neural cell fates in animals from flies to mammals. Like many HD proteins, Gsx factors bind A/T-rich DNA sequences prompting the following question: How do HD factors that bind similar DNA sequences in vitro regulate specific target genes in vivo? Prior studies revealed that Gsx factors bind DNA both as a monomer on individual A/T-rich sites and as a cooperative homodimer to two sites spaced precisely 7 bp apart. However, the mechanistic basis for Gsx-DNA binding and cooperativity is poorly understood. Here, we used biochemical, biophysical, structural and modeling approaches to (i) show that Gsx factors are monomers in solution and require DNA for cooperative complex formation, (ii) define the affinity and thermodynamic binding parameters of Gsx2/DNA interactions, (iii) solve a high-resolution monomer/DNA structure that reveals that Gsx2 induces a 20° bend in DNA, (iv) identify a Gsx2 protein-protein interface required for cooperative DNA binding and (v) determine that flexible spacer DNA sequences enhance Gsx2 cooperativity on dimer sites. Altogether, our results provide a mechanistic basis for understanding the protein and DNA structural determinants that underlie cooperative DNA binding by Gsx factors.

Phenotypic and Genotypic Characterization of Sheep Breeds in Diverse Habitats of Baluchistan Province through the Analysis of the vertnin Gene

This study was conducted to identify the vertnin gene in four different sheep breeds of Balochistan by studying their genetic characteristics and analyzing molecular markers. For this purpose, four different sheep breeds, Balochi, Rakhshani, Harnai, and Bibrik, were selected. A total of 10 animals from each breed were chosen to study the impact of breed and the vertnin gene on carcass features. The selection of animals was based on their phenotypic characteristics such as age and teeth. Blood samples of 10 ml were collected and transported to the Laboratory of Molecular Genetics at the Faculty of Veterinary and Animal Sciences, LUAWMS Uthal, Balochistan. Genomic DNA (gDNA) extraction was carried out using a modified inorganic method. The results showed that Balochi had a change in amino acid cytosine (C) > into thymine (T) mutation, Rakhshani had a change in guanine (G) > into adenine (A) mutation, Bibrik had a change in adenine (A) > into cytosine (C) mutation, and Harnai had a change in thymine (T) > into cytosine (C) mutation. The maximum divergence was 0.15715 bp in relation to the comparison in all studied sheep breeds. The phylogenetic results showed that the Balochi breed has 95–97% similarities with the other breeds when sequences were compared. The results revealed that the gel-electrophoresis bands of the Balochi breed were slightly higher, respectively. It was concluded that the vertnin gene exists in different breeds of sheep and might show a broad range of differences, even with similar DNA sequences. However, the purity based on the vertnin gene is at high risk, as a notable difference was found between the Balochi and Harnai sheep.

Optimization and Performance Analysis of CAT Method for DNA Sequence Similarity Searching and Alignment.

Bioinformatics is a rapidly developing field enabling scientific experiments via computer models and simulations. In recent years, there has been an extraordinary growth in biological databases. Therefore, it is extremely important to propose effective methods and algorithms for the fast and accurate processing of biological data. Sequence comparisons are the best way to investigate and understand the biological functions and evolutionary relationships between genes on the basis of the alignment of two or more DNA sequences in order to maximize the identity level and degree of similarity. This paper presents a new version of the pairwise DNA sequences alignment algorithm, based on a new method called CAT, where a dependency with a previous match and the closest neighbor are taken into consideration to increase the uniqueness of the CAT profile and to reduce possible collisions, i.e., two or more sequence with the same CAT profiles. This makes the proposed algorithm suitable for finding the exact match of a concrete DNA sequence in a large set of DNA data faster. In order to enable the usage of the profiles as sequence metadata, CAT profiles are generated once prior to data uploading to the database. The proposed algorithm consists of two main stages: CAT profile calculation depending on the chosen benchmark sequences and sequence comparison by using the calculated CAT profiles. Improvements in the generation of the CAT profiles are detailed and described in this paper. Block schemes, pseudo code tables, and figures were updated according to the proposed new version and experimental results. Experiments were carried out using the new version of the CAT method for DNA sequence alignment and different datasets. New experimental results regarding collisions, speed, and efficiency of the suggested new implementation are presented. Experiments related to the performance comparison with Needleman-Wunsch were re-executed with the new version of the algorithm to confirm that we have the same performance. A performance analysis of the proposed algorithm based on the CAT method against the Knuth-Morris-Pratt algorithm, which has a complexity of O(n) and is widely used for biological data searching, was performed. The impact of prior matching dependencies on uniqueness for generated CAT profiles is investigated. The experimental results from sequence alignment demonstrate that the proposed CAT method-based algorithm exhibits minimal deviation, which can be deemed negligible if such deviation is considered permissible in favor of enhanced performance. It should be noted that the performance of the CAT algorithm in terms of execution time remains stable, unaffected by the length of the analyzed sequences. Hence, the primary benefit of the suggested approach lies in its rapid processing capabilities in large-scale sequence alignment, a task that traditional exact algorithms would require significantly more time to perform.

NeuralBeds: Neural embeddings for efficient DNA data compression and optimized similarity search

The availability of high throughput sequencing tools coupled with the declining costs in the production of DNA sequences has led to the generation of enormous amounts of omics data curated in several databases such as NCBI and EMBL. Identification of similar DNA sequences from these databases is one of the fundamental tasks in bioinformatics. It is essential for discovering homologous sequences in organisms, phylogenetic studies of evolutionary relationships among several biological entities, or detection of pathogens. Improving DNA similarity search is of outmost importance because of the increased complexity of the evergrowing repositories of sequences. Therefore, instead of using the conventional approach of comparing raw sequences, e.g., in fasta format, a numerical representation of the sequences can be used to calculate their similarities and optimize the search process. In this study, we analyzed different approaches for numerical embeddings, including Chaos Game Representation, hashing, and neural networks, and compared them with classical approaches such as principal component analysis. It turned out that neural networks generate embeddings that are able to capture the similarity between DNA sequences as a distance measure and outperform the other approaches on DNA similarity search, significantly.

Variability of pMGA/vlhA sequences among Mycoplasma gallisepticum field strains isolated from laying hens and their deformed eggs.

Mycoplasmosis, attributed to Mycoplasma gallisepticum, poses a significant challenge to poultry farming, leading to substantial economic losses and persistent infections within flocks. This bacterium harbours various surface proteins that are crucial for adhesion, transporter activity and evasion of the host immune response, facilitating its pathogenicity. One such key surface lipoprotein, referred to as pMGA or vlhA haemagglutinin, plays a pivotal role in adhesion processes. In this study, the clonal regions pMGA1.2 and pMGA1.3, as reported by Markham (M83178.1), were investigated to elucidate differences or similarities in the whole DNA sequences of M. gallisepticum field strains. The aim was to analyse sequence diversity within this region. Six internal primers were designed to amplify the target sequence, and isolates were obtained from both eggs and chickens sourced from laying hen flocks. Identification revealed 17 strains of M. gallisepticum and four strains of Mycoplasma synoviae, which were confirmed through the mgc2 and 16S rRNA genes, respectively. Positive and negative controls were established using the MGS6 and MSWUV1853 strains. Amplification results indicated a higher frequency of amplification proximal to the C-terminal region, with segments 4 (33.3 %) and 6 (27.8 %) being the most prevalent. Notably, none of the field strains exhibited the same amplification pattern as MGS6, and none of the strains characterized as M. synoviae amplified any primer set. Upon translation, the amino acid sequences from segments 4 and 6 were found to be compatible with conserved sequences within the Myco_haema protein domains of the genus Mycoplasma, specifically corresponding to Q7NAP3_MYCGA VlhA.3.04. The observed homology suggests a potential genetic transfer, while the variability identified in the pMGA or vlhA gene region of the field strains may have significant implications for protection against M. gallisepticum infection in chickens.

Fungicide-Resistant Botrytis in Forest Nurseries May Impact Disease Control in Norway Spruce.

Gray mold, caused by Botrytis spp., is a serious problem in Norway spruce seedling production in forest nurseries. From 2013 to 2019, 125 isolates of Botrytis were obtained from eight forest nurseries in Norway: 53 from Norway spruce seedlings, 16 from indoor air, 52 from indoor surfaces, and four from weeds growing close to seedlings. The majority of isolates were identified as B. cinerea, and over 60% of these were characterized as Botrytis group S. B. pseudocinerea isolates were obtained along with isolates with DNA sequence similarities to B. prunorum. Fungicide resistance was assessed with a mycelial growth assay, and resistance was found for the following: boscalid (8.8%), fenhexamid (33.6%), fludioxonil (17.6%), pyraclostrobin (36.0%), pyrimethanil (13.6%), and thiophanate-methyl (50.4%). Many isolates (38.4%) were resistant to two to six different fungicides. A selection of isolates was analyzed for the presence of known resistance-conferring mutations in the cytb, erg27, mrr1, sdhB, and tubA genes, and mutations leading to G143A, F412S, ΔL497, H272R, and E198A/F200Y were detected, respectively. Detection of fungicide resistance in Botrytis from Norway spruce and forest nursery facilities reinforces the necessity of employing resistance management strategies to improve control and delay development of fungicide resistance in the gray mold pathogens.[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Stability and dynamics of extradenticle modulates its function

Extradenticle (EXD) is a partner protein of the HOX transcription factors and plays an important role in the development of Drosophila. It confers increased affinity and specificity of DNA-binding to the HOX proteins. However, the DNA-binding homeodomain of EXD has a significantly weaker affinity to DNA compared to the HOX homeodomains. Here, we show that a glycine residue (G290) in the middle of the EXD DNA-binding helix primarily results in this weaker binding. Glycine destabilizes helices. To probe its role in the stability and function of the protein, G290 was mutated to alanine. The intrinsic stability of the DNA-binding helix increased in the G290A mutant as observed by NMR studies and molecular dynamics (MD) simulation. Also, NMR dynamics and MD simulation show that dynamic motions present in the wild-type protein are quenched in the mutant. This in turn resulted in increased stability of the entire homeodomain (ΔΔGG→A of −2.6 kcal/mol). Increased protein stability resulted in three-fold better DNA-binding affinity of the mutant as compared to the wild-type protein. Molecular mechanics with generalized Born and surface area solvation (MMGBSA) analysis of our MD simulation on DNA-bound models of both wild-type and mutant proteins shows that the contribution to binding is enhanced for most of the interface residues in the mutant compared to the wild-type. Interestingly, the flexible N-terminal arm makes more stable contact with the DNA minor groove in the mutant. We found that the two interaction sites i.e. the DNA-binding helix and the unstructured N-terminal arm influence each other via the bound DNA. These results provide an interesting conundrum: alanine at position 290 enhances both the stability and the DNA-binding affinity of the protein, however, evolution prefers glycine at this position. We have provided several plausible explanations for this apparent conundrum. The function of the EXD as a HOX co-factor requires its ability to discriminate similar DNA sequences, which is most likely compromised by the quenching of its flexibility and enhancement of its stability and DNA-binding affinity.

Molecular characterization of mitochondrial COI gene sequences in Micraspis allardi from Pakistan.

The Coccinellidae is a highly diversified family of order Coleoptera. Coccinellid ladybirds are well known for their role as biological control agent against varied range of agricultural pests. The samples of coccinellid ladybird collected from Pakistan were identified and characterized as Micraspis allardi (Mulsant, 1866). This is one of the least-studied ladybird species with limited work on its ecological distribution as a biological control agent. The genus Micraspis has vast genetic diversity with a possible presence of unknown number of cryptic species. Sequence information of some species of the genus Micraspis are present in NCBI database. However, least molecular data or sequences describing M. allardi could be available from database. Therefore, morphological and molecular characterization was imperative for this species. Here, the samples collected from sugarcane field of Faisalabad District of Pakistan and were identified by using morphological and molecular protocols. For molecular identification, two different regions of mitochondrial cytochrome c oxidase I (COI) gene (COI-5' and COI- 3') were used as molecular markers for the identification of the species. Morphological appearance, DNA sequence similarity searches and phylogenetic analysis collectively indicated it as M. allardi. To the best of our knowledge, this is the first report providing molecular evidence of M. allardi using mitochondrial DNA barcode region (658bp) as well as mtCOI-3' sequences (817bp). The study will help in understanding population genetics through diversity analysis, ecological role, and phenotypic structures associated with the geographic range of this species.

Plasmonic Probing of Deoxyribonucleic Acid Hybridization at the Single Base Pair Resolution.

Partial DNA duplex formation greatly impacts the quality of DNA hybridization and has been extensively studied due to its significance in many biological processes. However, traditional DNA sensing methods suffer from time-consuming amplification steps and hinder the acquisition of information about single-molecule behavior. In this work, we developed a plasmonic method to probe the hybridization process at a single base pair resolution and study the relationship between the complementarity of DNA analytes and DNA hybridization behaviors. We measured single-molecule hybridization events with Au NP-modified ssDNA probes in real time and found two hybridization adsorption events: stable and transient adsorption. The ratio of these two hybridization adsorption events was correlated with the length of the complementary sequences, distinguishing DNA analytes from different complementary sequences. By using dual incident angle excitation, we recognized different single-base complementary sequences. These results demonstrated that the plasmonic method can be applied to study partial DNA hybridization behavior and has the potential to be incorporated into the identification of similar DNA sequences, providing a sensitive and quantitative tool for DNA analysis.

Prokaryotic virus host prediction with graph contrastive augmentaion.

Prokaryotic viruses, also known as bacteriophages, play crucial roles in regulating microbial communities and have the potential for phage therapy applications. Accurate prediction of phage-host interactions is essential for understanding the dynamics of these viruses and their impacts on bacterial populations. Numerous computational methods have been developed to tackle this challenging task. However, most existing prediction models can be constrained due to the substantial number of unknown interactions in comparison to the constrained diversity of available training data. To solve the problem, we introduce a model for prokaryotic virus host prediction with graph contrastive augmentation (PHPGCA). Specifically, we construct a comprehensive heterogeneous graph by integrating virus-virus protein similarity and virus-host DNA sequence similarity information. As the backbone encoder for learning node representations in the virus-prokaryote graph, we employ LGCN, a state-of-the-art graph embedding technique. Additionally, we apply graph contrastive learning to augment the node representations without the need for additional labels. We further conducted two case studies aimed at predicting the host range of multi-species phages, helping to understand the phage ecology and evolution.

Recombinase-independent chromosomal rearrangements between dispersed inverted repeats in Saccharomyces cerevisiae meiosis.

DNA double-strand break (DSB) repair by homologous recombination (HR) uses a DNA template with similar sequence to restore genetic identity. Allelic DNA repair templates can be found on the sister chromatid or homologous chromosome. During meiotic recombination, DSBs preferentially repair from the homologous chromosome, with a proportion of HR events generating crossovers. Nevertheless, regions of similar DNA sequence exist throughout the genome, providing potential DNA repair templates. When DSB repair occurs at these non-allelic loci (termed ectopic recombination), chromosomal duplications, deletions and rearrangements can arise. Here, we characterize in detail ectopic recombination arising between a dispersed pair of inverted repeats in wild-type Saccharomyces cerevisiae at both a local and a chromosomal scale-the latter identified via gross chromosomal acentric and dicentric chromosome rearrangements. Mutation of the DNA damage checkpoint clamp loader Rad24 and the RecQ helicase Sgs1 causes an increase in ectopic recombination. Unexpectedly, additional mutation of the RecA orthologues Rad51 and Dmc1 alters-but does not abolish-the type of ectopic recombinants generated, revealing a novel class of inverted chromosomal rearrangement driven by the single-strand annealing pathway. These data provide important insights into the role of key DNA repair proteins in regulating DNA repair pathway and template choice during meiosis.

Vers une généralisation du diagnostic prénatal non-invasif des maladies monogéniques ? État des lieux et perspectives

The screening of fetal aneuploidies and non-invasive prenatal diagnosis of monogenic diseases (NIPD-MD) both rely on the study of free fetal DNA in maternal circulation, but their respective rise was unequal. Development of NIPD-MD has taken longer as it represents a less attractive commercial dynamic for industry, but also because it usually involves the development of tailored tests specific to each pathogenic variant. We have carried out a review of the literature on the various indications and technologies involved in the use of NIPD-MM. We present its current implementation and its development in France. To date, NIPD-MD has been routinely offered in France for several years by the laboratories of the French NIPD-MD network but remains mostly limited to the exclusion of paternal or de novo variants, the exclusion DPNI-MD. Indeed, it is still difficult to study the transmission of maternal variants from circulating free DNA analysis, due to its biological complexity: coexistence and predominance of similar DNA sequences of maternal origin. Different strategies, either direct or indirect, are being evaluated to establish fetal status regardless of the parental origin of the disease or its transmission mode. The emergence of commercial screening solutions for monogenic diseases complements the arsenal of prenatal exploration tools for these diseases. The multitude of existing technologies and protocols may complicate the information provided during antenatal consultations, but mastery of know-how and knowledge of ethical issues of NIPD-MD will ensure optimal service and better management of pregnancies at risk of transmitting monogenic disease.