Biology subjects

Becker, A.

Publications and source records attributed to Becker, A..

54 records · Page 3Linked to original sources

bioRxiv2021

Unipolar peptidoglycan synthesis in the Rhizobiales requires an essential class A penicillin-binding protein

Members of the Rhizobiales are polarly-growing bacteria that lack homologs of the canonical rod complex. To investigate the mechanisms underlying polar cell wall synthesis, we systematically probed the function of cell wall synthesis enzymes in the plant-pathogen Agrobacterium tumefaciens. The development of fluorescent O_SCPLOWDC_SCPLOW-amino acid dipeptide (FDAAD) probes, which are incorporated into peptidoglycan by penicillin-binding proteins in A. tumefaciens, enabled us to monitor changes in growth patterns in the mutants. Use of these fluorescent cell wall probes and peptidoglycan compositional analysis convincingly demonstrate that a single class A penicillin-binding protein is essential for polar peptidoglycan synthesis. Furthermore, we find evidence of an alternative mode of cell wall synthesis that likely requires O_SCPLOWLDC_SCPLOW-transpeptidase activity. Genetic analysis and cell wall targeting antibiotics reveal that the mechanism of unipolar growth is conserved in Sinorhizobium and Brucella. This work provides insights into unipolar peptidoglycan biosynthesis employed by the Rhizobiales during cell elongation.

microbiology↗

bioRxiv2021

Transcription factor action orchestrates the complex expression pattern of CRABS CLAW, a gynoecium developmental regulator in Arabidopsis

The flower of angiosperms is the most complex organ that plants generate and many transcription factors (TFs) are involved to regulate its morphogenesis in a coordinated way. In its center, the gynoecium develops consisting of specialized tissues such as secondary meristems, sites of postgenital fusion, ovules, pollen transmitting tract, all to assure successful sexual reproduction. Gynoecium development requires tight regulation of developmental regulators across time and tissues. However, while we know of several examples how simple on/off regulation of gene expression is achieved in plants, it remains unclear which regulatory processes generate complex expression patterns. Here, we use the gynoecium developmental regulator CRABS CLAW (CRC) from Arabidopsis to study regulatory mechanisms contributing to its sophisticated expression pattern. Using a combination of in silico promoter analyses, global TF-DNA interaction screens, co-expression and mutant analysis we find that miRNA action, DNA methylation, and chromatin remodeling do not contribute substantially to CRC regulation. We show that a plethora of TFs bind to the CRC promoter to fine-tune transcript abundance by activation of transcription, linking CRC to specific developmental processes but not biotic or abiotic stress. Interestingly, the temporal-spatial aspects of regulation of expression may be under the control of redundantly acting genes and may require higher order complex formation at TF binding sites. We conclude that endogenous regulation of complex expression pattern of Arabidopsis genes requires orchestrated transcription factor action on several conserved promotor sites over almost 4 kb in length. Significance statementDifferent to genes that are simply switched on or off, depending on an environmental cue we find that genes directing development in plants often show complex expression pattern dependent on internal factors only. Here, we addressed the question how an complex expression pattern is achieved and use the CRABS CLAW (CRC) gene required for gynoecium development as an example. Combining wet lab experiments and in silico analysis we find that epigenetic regulation plays only a minor role and that a large number of transcription factors activates the transcription of CRC. Single regulators may have a profound effect on CRC transcript abundance but less so on the pattern of expression. Complex patterns most likely require the interplay of several transcription factors.

genetics↗

bioRxiv2020

Cryo-EM structural studies of the agonist complexed human TRPV4 ion-channel reveals novel structural rearrangements resulting in an open-conformation

The human transient receptor potential vanilloid 4 (hTRPV4) ion channel plays a critical role in a variety of biological processes. Whilst the activation of hTRPV4 gating properties has been reported for a broad spectrum of stimuli, including synthetic 4-phorbols, the molecular basis of the activation is poorly understood. Here we report the novel cryo-EM structure of the hTRPV4 determined in the presence of the archetypical phorbol acid agonist, 4-PDD. Complementary mutagenesis experiments support the EM-identified binding site as well as allowing rationalization of disruptive mutants located outside of the 4-PDD binding site. This work represents the first structural information of hTRPV4 in a ligand-induced open conformation. Together, our data reveal the underlying molecular mechanisms resulting in the opening of the central pore and ion-channel activation and provide a structural template for designing inhibitors targeting the open-state conformation of hTRPV4.

molecular biology↗

bioRxiv2020

High-resolution temporal transcript profiling during Arabidopsis thaliana gynoecium morphogenesis uncovers the chronology of gene regulatory network activity and reveals novel developmental regulators

The gynoecium is the most complex organ formed by the flowering plants. It encloses the ovules, provides a surface for pollen contact and self-incompatibility reactions, allows pollen tube growth and, post fertilization, and develops into the fruit. Consequently, the regulation of gynoecium morphogenesis is complex and appropriate timing of this process in part determines reproductive success. However, little is known about the global control of gynoecium development, even though many regulatory genes have been characterized. Here, we characterized dynamic gene expression changes using laser-microdissected gynoecium tissue from four developmental stages in Arabidopsis. We provide a high-resolution map of global expression dynamics during gynoecium morphogenesis and link these to the gynoecium interactome. We reveal groups of genes acting together early and others acting late in morphogenesis. Clustering of co-expressed genes enables comparisons between the leaf, shoot apex, and gynoecium transcriptomes allowing the dissection of common and distinct regulators. Furthermore, our results lead to the discovery of the LESSER FERTILITY1-4 (LEF1-4) genes, which, when mutated, lead to impaired gynoecium expansion, illustrating that global transcriptome analyses reveal yet unknown developmental regulators. Our data show that highly interacting proteins, such as SEPALLATA3, AGAMOUS, and TOPLESS are expressed more evenly during development, but switch interactors in time, whereas stage-specific proteins have only few interactors. Our analysis connects specific transcriptional regulator activities, protein interactions, and underlying metabolic processes towards the development of a dynamic network model for gynoecium development.

plant biology↗

bioRxiv2020

Deep Learning for Virtual Screening: Five Reasons to Use ROC Cost Functions

Computer-aided drug discovery is an essential component of modern drug development. Therein, deep learning has become an important tool for rapid screening of billions of molecules in silico for potential hits containing desired chemical features. Despite its importance, substantial challenges persist in training these models, such as severe class imbalance, high decision thresholds, and lack of ground truth labels in some datasets. In this work we argue in favor of directly optimizing the receiver operating characteristic (ROC) in such cases, due to its robustness to class imbalance, its ability to compromise over different decision thresholds, certain freedom to influence the relative weights in this compromise, fidelity to typical benchmarking measures, and equivalence to positive/unlabeled learning. We also propose new training schemes (coherent mini-batch arrangement, and usage of out-of-batch samples) for cost functions based on the ROC, as well as a cost function based on the logAUC metric that facilitates early enrichment (i.e. improves performance at high decision thresholds, as often desired when synthesizing predicted hit compounds). We demonstrate that these approaches outperform standard deep learning approaches on a series of PubChem high-throughput screening datasets that represent realistic and diverse drug discovery campaigns on major drug target families.

pharmacology and toxicology↗

bioRxiv2020

Rapid community-driven development of a SARS-CoV-2 tissue simulator

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable "choke points" for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.

systems biology↗

bioRxiv2020

Tol-Pal system and Rgs proteins interact to promote unipolar growth and cell division in Sinorhizobium meliloti

Sinorhizobium meliloti is an -proteobacterium belonging to the Rhizobiales. Bacteria from this order elongate their cell wall at the new cell pole, generated by cell division. Screening for protein interaction partners of the previously characterized polar growth factors RgsP and RgsM, we identified the inner membrane components of the Tol-Pal system (TolQ and TolR) and novel Rgs (rhizobial growth and septation) proteins with unknown functions. TolQ, Pal and all Rgs proteins, except for RgsE, were indispensable for S. meliloti cell growth. Six of the Rgs proteins, TolQ and Pal localized to the growing cell pole in the cell elongation phase and to the septum in pre-divisional cells, and three Rgs proteins localized to growing cell pole only. The FtsN-like protein RgsS contains a conserved SPOR domain and is indispensable at the early stages of cell division. The components of the Tol-Pal system were required at the late stages of cell division. RgsE, a homolog of the Agrobacterium tumefaciens growth pole ring protein GPR, has an important role in maintaining the normal growth rate and rod cell shape. RgsD is a novel periplasmic protein with the ability to bind peptidoglycan. Analysis of the phylogenetic distribution of novel Rgs proteins showed that they are conserved in Rhizobiales and mostly absent from other -proteobacterial orders, suggesting a conserved role of these proteins in polar growth. IMPORTANCEBacterial cell proliferation involves cell growth and septum formation followed by cell division. For cell growth, bacteria have evolved different complex mechanisms. The most prevalent growth mode of rod shaped bacteria is cell elongation by incorporating new peptidoglycan in a dispersed manner along the sidewall. A small share of rod-shaped bacteria, including the -proteobacterial Rhizobiales, grow unipolarly. Here, we identified and initially characterized a set of Rgs (rhizobial growth and septation) proteins, which are involved in cell division and unipolar growth of Sinorhizobium meliloti and highly conserved in Rhizobiales. Our data expand the knowledge of components of the polarly localized machinery driving cell wall growth and suggest a complex of Rgs proteins with components of the divisome, differing in composition between the polar cell elongation zone and the septum.

microbiology↗

bioRxiv2019

Expansion and re-classification of the extracytoplasmic function (ECF) σ factor family

Extracytoplasmic function {sigma} factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As result, we identified [~]10 ECFs per bacterial genome on average and classified them into 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands the number of unique ECF sequences [~]50-fold relative to previous classification efforts, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences, enables the application of in silico tools for the prediction of important functional residues, and serves as a powerful hypothesis-generator to guide future research in the field.

bioinformatics↗

bioRxiv2019

Independent effects of socioeconomic status and genetics on adolescent cognition and brain development.

Genetic factors and socioeconomic (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used polygenic score for educational attainment (EduYears-PGS) as well as SES, in a longitudinal study of 551 adolescents, to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time-points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to non-verbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This is the first study demonstrating a regional association of EduYears-PGS and the independent prediction of SES on cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence. Significance statementThe influence of socioeconomic (SES) inequalities on brain and cognitive development is a hotly debated topic. However, previous studies have not considered that genetic factors overlap with SES. Here we showed, for the first time, that SES and EduYears-PGS (a score from thousands of genetic markers for educational attainment) have independent associations with both cognition and global cortical surface area in adolescents. EduYears-PGS also had a localized association in the brain: the intraparietal sulcus, a region related to non-verbal intelligence. In contrast, SES had global, but not regional, associations, and these persisted throughout adolescence. This suggests that the influence of SES inequalities is widespread - a result that opposes the current paradigm and can help inform policies in education.

neuroscience↗

bioRxiv2019

Transcriptional changes suggest a major involvement of Gibberellins in Trifolium pratense regrowth after mowing

Red clover (Trifolium pratense) is used worldwide as a fodder plant due its high nutritional value. In response to mowing, red clover exhibits specific morphological traits to compensate the loss of biomass. The morphological reaction is well described, but knowledge of the underlying molecular mechanisms are still lacking. Here we characterize the molecular genetic response to mowing of red clover by using comparative transcriptomics in greenhouse conditions and agriculturally used field. The analysis of mown and control plants revealed candidate genes possibly regulating crucial steps of the genetic network governing the regrowth reaction. In addition, multiple identified gibberellic acid (GA) related genes suggest a major role for GA in establishing the regrowth morphology of red clover. Mown red clover plants showing this regrowth morphology were partially \"rescued\" by exogenous GA application, demonstrating the influence of GA during regrowth. Our findings provide insights into the physiological and genetic processes of mowing red clover, to serve as a base for red clover yield improvement.

plant biology↗

bioRxiv2019

The Genome of the Zebra Mussel, Dreissena polymorpha: A Resource for Invasive Species Research

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves, with nearly 450 million years of divergence between zebra mussels and its closest sequenced relative. Although the D. polymorpha genome is highly repetitive, we have used a combination of long-read sequencing and Hi-C-based scaffolding to generate the highest quality molluscan assembly to date. Through comparative analysis and transcriptomics experiments we have gained insights into processes that likely control the invasive success of zebra mussels, including shell formation, synthesis of byssal threads, and thermal tolerance. We identified multiple intact Steamer-Like Elements, a retrotransposon that has been linked to transmissible cancer in marine clams. We also found that D. polymorpha have an unusual 67 kb mitochondrial genome containing numerous tandem repeats, making it the largest observed in Eumetazoa. Together these findings create a rich resource for invasive species research and control efforts.

genomics↗

bioRxiv2019

Histone methyltransferase MMSET/NSD2 is essential for generation of B1 cell compartment in mice

Humoral immunity in mice and man relies on the function of two developmentally and functionally distinct B cell subsets - B1 and B2 cells. While B2 cells are responsible for most of the adaptive response to environmental antigens, B1 cells, which are comprised of phenotypically distinct B1a and B1b cells, are carriers of the innate humoral immunity that relies on production of poly-reactive and low affinity antibodies. The molecular mechanism of B cell specification into different subsets is not well established. Here we identified lysine methyltransferase MMSET/NSD2 as a critical regulator of the B1 cell population. We show that NSD2 deficiency in B cell precursors prevents generation of the B1 cell compartment, while having a minor impact on B2 cells. Our data revealed MMSET/NSD2, which catalyzes histone H3 lysine 36 di-methylation, as the first in class epigenetic master regulator of a major B cell lineage in mice.

immunology↗

bioRxiv2019

Blood-brain barrier dysfunction in aging induces hyper-activation of TGF-beta signaling and chronic yet reversible neural dysfunction

Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the mechanisms underlying the transition from a young-and-healthy to aged-and-dysfunctional brain are not well understood. Here, we report breakdown of the vascular blood-brain barrier (BBB) in aging humans and rodents, which begins as early as middle age and progresses to the end of the lifespan. Gain-of-function and loss-of-function manipulations show that this BBB dysfunction triggers hyperactivation of transforming growth factor {beta} (TGF{beta}) signaling in astrocytes, which is necessary and sufficient to cause neural dysfunction and age-related pathology. Specifically, infusion of the serum protein albumin into the young brain (mimicking BBB leakiness) induced astrocytic TGF{beta} signaling and an aged brain phenotype including aberrant electrocorticographic activity, vulnerability to seizures, and cognitive impairment. Furthermore, conditional genetic knockdown of astrocytic TGF{beta} receptors, or pharmacological inhibition of TGF{beta} signaling, reversed these symptomatic outcomes in aged mice. Finally, we found that this same signaling pathway is activated in aging human subjects with BBB dysfunction. Our study identifies dysfunction in the neurovascular unit as one of the earliest triggers of neurological aging, and demonstrates that the aging brain may retain considerable latent capacity which can be revitalized by therapeutic inhibition of TGF{beta} signaling.

neuroscience↗

bioRxiv2018

Measuring Illumina Size Bias Using REcount: A Novel Method for Highly Accurate Quantification of Engineered Genetic Constructs

Quantification of DNA sequence tags associated with engineered genetic constructs underlies many genomics measurements. Typically, such measurements are done using PCR to enrich sequence tags and add adapters, followed by next-generation sequencing (NGS). However, PCR amplification can introduce significant quantitative error into these measurements. Here we describe REcount, a novel PCR-free direct counting method for NGS-based quantification of engineered genetic constructs. By comparing measurements of defined plasmid pools to droplet digital PCR data, we demonstrate that this method is highly accurate and reproducible. We further demonstrate that the REcount approach is amenable to multiplexing through the use of orthogonal restriction enzymes. Finally, we use REcount to provide new insights into clustering biases due to molecule length across different Illumina sequencing platforms.

genomics↗

bioRxiv2017

The circadian hippocampus and its reprogramming in epilepsy: impact for chronotherapeutics

Gene and protein expression displays circadian oscillations in numerous body organs. These oscillations can be disrupted in diseases, thus contributing to the disease pathology. Whether the molecular architecture of cortical brain regions oscillates daily and whether these oscillations are modified in brain disorders is less understood. We identified 1200 daily oscillating transcripts in the hippocampus of control mice. More transcripts (1600) were oscillating in experimental epilepsy, with only one fourth oscillating in both conditions. Proteomics confirmed these results. Metabolic activity and targets of antiepileptic drugs displayed different circadian regulation in control and epilepsy. Hence, the hippocampus, and perhaps other cortical regions, shows a daily remapping of its molecular landscape, which would enable different functioning modes during the night/day cycle. The impact of this remapping in brain pathologies needs to be taken into account not only to study their mechanisms, but also to design drug treatments and time their delivery.

neuroscience↗

bioRxiv2017

Red wood-ant nests are traps for fault-related CH4 micro-seepage

Methane (CH4) is common on Earth, forms the major commercial natural gas reservoirs, and is a key component of the global carbon cycle, but its natural sources are not well-characterized. We present a geochemical dataset acquired from a red wood-ant (RWA; Formica polyctena) nest in the Neuwied Basin, a part of the East Eifel Volcanic Field (EEVF), focusing on methane (CH4), stable carbon isotope of methane ({delta}13C-CH4), RWA activity patterns, earthquakes, and earth tides. Nest gas and ambient air were continuously sampled in-situ and analyzed to detect microbial, thermogenic, and abiotic fault-related micro-seepage. Methane degassing was not synchronized with earth tides. Elevated CH4 concentrations in nest gas appear to result from a combination of microbial activity and fault-related emissions moving via through fault networks through the RWA nest. Two {delta}13C-CH4 signatures were identified in nest gas: -69{per thousand} and -37{per thousand}. The -69{per thousand} signature of {delta}13C-CH4 within the RWA nest is attributed to microbial decomposition of organic matter. This finding supports previous findings that RWA nests are hot-spots of microbial CH4. Additionally, the -37% {delta}13C-CH4 signature is the first evidence that RWA nests also serve as traps for fault-related emissions of CH4. The -37{per thousand} {delta}13C-CH4 signature can be attributed either to thermogenic/fault-related or to abiotic/fault-related CH4 formation originating from e.g. low-temperature gas-water-rock reactions in a continental setting at shallow depths (microseepage). Sources of these micro-seeps could be Devonian schists (\"Sphaerosiderith Schiefer\") with iron concretions (\"Eisengallen\"), sandstones, or the iron-bearing \"Klerf Schichten\". We cannot exclude overlapping micro-seepage of magmatic CH4 from the Eifel plume. Given the abundance of RWA nests on the landscape, their role as sources of microbial CH4 and traps for abiotically-derived CH4 should be included in estimation of methane emissions that are contributing to climatic change.

ecology↗

bioRxiv2017

A dead gene walking: convergent degeneration of a clade of MADS-box genes in Brassicaceae

Genes are born, and eventually they die. In contrast to gene birth, however, gene death has found only limited scientific interest, even though it is of considerable evolutionary importance. Here we use Bsister genes, a subfamily of MIKC-type MADS-box genes, as a model to investigate gene death in unprecedented detail. Typical MIKC-type genes encode conserved transcription factors controlling plant development. We show that ABS-like genes, a clade of Bsister genes, are indeed highly conserved in Brassicaceae maintaining the ancestral function of Bsister genes in ovule and seed development. In contrast, their closest paralogs, the GOA-like genes, have been undergoing convergent gene death in Brassicaceae. Intriguingly, erosion of GOA-like genes occurred after millions of years of co-existence with ABS-like genes. We thus describe Delayed Convergent Asymmetric Degeneration (DCAD), a so far neglected but possibly frequent pattern of duplicate gene evolution that does not fit classical scenarios. DCAD of GOA-like genes may have been initiated by a reduction in the expression of an ancestral GOA-like gene in the stem group of Brassicaceae and driven by dosage subfunctionalization. Our findings have profound implications for gene annotations in genomics, interpreting patterns of gene evolution and using genes in phylogeny reconstructions of species.

evolutionary biology↗

bioRxiv2017

Heterogeneous Contribution of Microdeletions in the Development of Common Generalized and Focal epilepsies

BackgroundMicrodeletions are known to confer risk to epilepsy, particularly at genomic rearrangement \"hotspot\" loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.\n\nMethodsWe assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.\n\nResultsWhen hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00x10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22x10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78x10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.\n\nConclusionsOur results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.

genetics↗