Biology subjects

Reichert, J.

Publications and source records attributed to Reichert, J..

16 recordsLinked to original sources

bioRxiv2026

The builder's legacy: persistent reef structure creates a window for coral recovery after adult loss

Coral reef recovery depends on successful juvenile recruitment, yet which local factors govern early coral demography remains poorly resolved. Adult coral cover and reef structural complexity are widely hypothesized to regulate juvenile success, but their independent and interactive effects have not been mechanistically disentangled, nor has the relative role of living adult tissue versus persisting structural framework been clarified. Here, combining in situ coral size-structure surveys with high resolution photogrammetry across 405 reef segments spanning the main Hawaiian Islands, we quantify how adult cover and three-dimensional reef structure, measured as rugosity and fractal dimension, jointly shape juvenile coral densities. We reveal nonlinear relationships between juvenile density and adult cover, peaking at intermediate (~8%) coral cover, with fine-scale surface complexity and vertical relief exerting opposing influences across the cover gradient. Together, these reveal a structural legacy window in which reduced adult cover relaxes constraints on juvenile establishment while the three-dimensional habitat built by those adults persists. This decoupling of biological loss from structural loss creates a transient opportunity for population renewal, with intermediate-cover reefs supporting juveniles across the broadest range of structural configurations. More generally, our results show how the physical legacy of ecosystem engineers can continue to regulate population recovery after the organisms that create it have declined.

ecology↗

bioRxiv2026

Global integrators of light signalling and nutrient homeostasis safeguard symbiosis under light stress

Their large, protein-rich seeds render many legume plants like beans, peas or soy attractive food or fodder crops. This is thanks to nitrogen-fixing root nodulation symbiosis (RNS) with rhizobial bacteria, a mutualistic association enabling legumes to not only form storage seeds, but also thrive in nitrogen poor habitats. These benefits come at a cost: accommodating millions of bacteria that actively fix N2 requires substantial nutrient and energy input. Evolutionarily successful hosts employ a multi-layered regulatory system balancing endogenous nutrient status and interorganismal nutrient exchange with symbiosis establishment and progression. Root infection as well as nodule organogenesis and -lifespan are tightly regulated, ensuring a mutualistic status. Under adverse conditions, established nodules can be deactivated by induction of nodule senescence in a process involving the transcription factor genes NAM ATAF CUC (NAC) 094 (Wang et al., 2023) and FIXATION UNDER NITRATE (FUN) (Lin et al., 2024). The molecular basis and role of senescence induction in RNS regulation is still far from understood. Here, we demonstrate that in Lotus japonicus, the two photomorphogenesis genes ELONGATED HYPOCOTYL5 (HY5) and the B-Box-containing zinc finger transcription factor gene BBX21 are required and sufficient for maintaining nodule function under high light intensities. Loss of either HY5 or BBX21 results in a light-dependent increase of NAC094 transcript levels, nodule necrosis and early senescence, and enhanced nodule proliferation. Moreover, expression of dominant negative HY5 or BBX21 is sufficient to induce nodule necrosis and hypernodulation. Our data establish LjHY5 and LjBBX21 as a novel gene pair safeguarding nodule function and nitrogen fixation by preventing light induced senescence. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/741514v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@b16552org.highwire.dtl.DTLVardef@72f82eorg.highwire.dtl.DTLVardef@3cfbcorg.highwire.dtl.DTLVardef@3b542a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

plant biology↗

bioRxiv2026

Coral settlement module designs for scalable reef restoration

The global coral reef crisis has prompted restoration initiatives worldwide. Targeting the coral larval stage is among the most scalable approaches as recruitment operates over large spatial scales. It thus represents one of the best levers for coral population recovery. Active coral larval seeding has shown considerable success, and passive substrate engineering has emerged as a promising complementary strategy. Coral settlement modules featuring helix recesses have increased settlement and survival by up to 80-fold on small experimental units, but whether these results translate to tools deployable at the scale of thousands of units, remains yet an open question. Here, we transferred structural features from successful experimental coral settlement designs into production-ready concrete modules to (i) evaluate coral recruitment on five designs at four reef sites differing in flow regime and coral cover over one year; (ii) compare production-scale performance against experimental clay modules and natural reef substrate; and (iii) identify key parameters for large-scale production. The helix recess geometry of coral settlement modules outperformed the featureless control design approximately 20-fold and exceeded natural reef recruitment at least 3- to 32-fold. The helix features were successfully transferred from experimental clay to production-scale concrete modules, yielding comparable settlement densities when standardized to crevice length, which proved to be the biologically relevant unit of available habitat. Production feasibility was demonstrated by producing 690 modules for deployment on a hybrid reef on the west side of Oahu, Hawaii. The passive coral larval recruitment approach presented here could substantially improve the logistical and economic feasibility of large-scale coral reef restoration. This approach requires neither coral larval rearing, handling, nor coral fragmenting, and is compatible with active larval seeding where genetic diversity or larvae supply are limiting factors. The coral settlement modules can be cast in standardized concrete molds at precast facilities. Modules have demonstrated consistent coral recruitment enhancement across reef environments with contrasting flow and coral cover. Deploying mixed arrays of helix-recess structures with designs offering multi-level complexity and three-dimensional rugosity maximizes outcomes for coral, fish, and invertebrate communities simultaneously. Site selection is the most critical deployment decision and should consider larval supply, hydrodynamics, and substrate stability which drive recruitment outcomes more than design choice alone. The modules offer a range of application potential, ranging from integration into existing coastal infrastructure over stand-alone reef restoration approaches, to substrate-consolidating interconnected arrangements.

ecology↗

bioRxiv2025

Demographic insights for coral restoration

O_LICoral reef decline has prompted a global surge in reef restoration initiatives. The success of initiatives that aim to sustain coral populations or assemblages will depend on demographic principles. Restoration strategies generally follow two demographic pathways: supplemental approaches, which increase population numbers through the repeated addition of recruits, fragments, or adults, without fundamentally altering long-term population dynamics; and structural approaches, which enhance vital rates-growth, survival, or reproduction- through changes that modify the demographic processes governing population growth on a sustained basis, either extrinsically (e.g., herbivory, habitat protection) or intrinsically (e.g., assisted evolution). Some interventions, such as supplemental feeding, may temporarily improve vital rates but still function as supplemental approaches because benefits persist only while interventions continue. C_LIO_LIWe synthesized 28 coral matrix population models spanning morphologically diverse coral species from the Caribbean, Hawaii, and the Great Barrier Reef to quantify supplemental and structural changes needed to increase population growth. C_LIO_LIResults highlight two consistent demographic leverage points for which population growth was most sensitive: (1) survival of reproductive adults and (2) successful recruitment. Improving adult survival or recruitment by 20% through structural means produced a 5% increase in population growth rate across population on average, assuming the whole population was affected. By contrast through supplemental means, the same increase required [~]100 recruit outplants or 5-10 adult outplants per 1,000 individuals in a population annually. For large populations typical of restoration targets (105-107 individuals), this translates to 103 adult and 104 recruit outplants per year--levels rarely logistically or economically feasible. C_LIO_LIThese findings yield two key implications. First, supplemental interventions are inefficient for large populations and demand sustained, large-scale effort, even when they temporarily enhance growth or survival. Second, strategies enhancing vital rates across broad geographic areas represent the most effective means of boosting coral abundance, including habitat protection, alleviation of environmental stressors, and interventions which promote long-term survival and recruitment. Our demographic framework underscores that if the restoration goal is sustained increases in coral cover, success depends less on repeated supplements and more on interventions that produce lasting improvements in vital rates. C_LI

ecology↗

bioRxiv2025

Cylindrical, pylon-like structures with helix recesses enhance coral larval recruitment

The decline of coral reefs requires scalable restoration strategies to enhance natural recovery processes such as coral larval recruitment. Previous research has shown that conical structures with helix recesses substantially increase settlement and early survival. However, the applicability of this microhabitat design with helix recesses in broader engineering contexts has yet to be assessed. Hereby, we tested (1) whether helix recesses can be transferred from conical dome geometries to space-efficient cylindrical pylon-like geometries, and (2) whether they can be implemented with different materials. In a field experiment in K[a]neohe Bay, Hawaii, coral recruitment was monitored over six months on cylindrical and conical structures incorporating an optimized helix profile. Cylindrical modules supported recruitment densities similar to those on conical designs, demonstrating a successful transfer of the microhabitat design to compact geometries. Planar recruit densities were [~]300 times higher across all structures, compared to those observed on nearby natural reefs. These results show that the helix recess design is functionally robust across both module shapes and materials. Cylindrical structures with integrated helix recesses, therefore, represent a practical, low-cost design element that can be incorporated in coastal engineering and restoration projects to enhance coral settlement. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/680805v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@126b7cborg.highwire.dtl.DTLVardef@ec7c4corg.highwire.dtl.DTLVardef@1d49a78org.highwire.dtl.DTLVardef@e97189_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2025

Correlative MS Imaging for cellular identification and analysis of in situ cryo-ET

In situ cryo-electron tomography (cryo-ET) offers direct access to protein structures in their native state and environment. A central challenge for this technique is the identification and classification of imaged cells, as sample heterogeneity with respect to cell type and functional state can significantly impact the data. Currently, cells can be classified using subtomogram averaging or fluorescent labeling, which require sufficiently distinguishable macromolecules, genetic modifications, or the availability of suitable labels. In MALDI-MS Imaging (MSI) individual cells can be identified and classified reliably, making use of the distributions of phospholipid species, metabolites and small proteins with characteristic profiles for specific cell types. Here we present an integrated pipeline combining MSI and in situ cryo-ET for single-cell identification and classification. Our approach enables MSI data acquisition directly from EM grids and can be used on any eukaryotic single-cell cryo-ET sample without prior modification in less than 36 h. We apply this workflow to describe cell-to-cell heterogeneity in cultured HeLa cells, to distinguish between distantly related HeLa and Polytomella cells, and between primary cultured rat neurons and glial cells. Finally we present a data integration workflow combining cryo-ET, light microscopy and MSI aligned in the same coordinate system to facilitate efficient data visualization and interpretation. We anticipate that this approach will change the way that structural biologists can approach cellular heterogeneity in cryo-ET, as cells can be identified and classified reliably post acquisition.

biophysics↗

bioRxiv2025

Coral skeletal cores as windows into past Symbiodiniaceae community dynamics

The symbiosis between the dinoflagellate Symbiodiniaceae family and reef-building corals underpins the productivity of coral reefs. This relationship facilitates the deposition of calcium- carbonate skeletons that build the reef structure thanks to the energy derived from photosynthesis. The loss of Symbiodiniaceae from coral tissues--resulting in coral bleaching--impedes coral growth and can lead to mass mortality if the symbiosis fails to recover. Given that Symbiodiniaceae communities are dynamic and can shift in response to environmental stressors in the decades- to centuries-long lifespan of coral colonies, understanding these changes is crucial. Although the reconstruction of Symbiodiniaceae communities from coral skeleton records has recently been demonstrated as feasible, no studies have yet assessed reconstructions across different species and locations. Here, we present an approach to use coral skeletons for reconstructing the Symbiodiniaceae community on decadal and centennial scales and resolving dynamics related with coral species and environmental history of sampling locations. For this, we used dated coral skeleton cores from Porites Iobata and Diploastrea heliopora, species commonly used as climate archives, sampled in Palau and Papua New Guinea. We also examined the effect of various DNA extraction protocols on community reconstruction. Here we show that the reconstructed Symbiodiniaceae communities significantly varied across all cores and DNA extraction methods, with decalcification-based protocols enhancing the retrieval of skeletal-bound DNA. Moreover, we observed distinct community dynamics related to the specific coral host and sampling location. Notably, associations of Symbiodiniaceae dynamics with past heat stress events were apparent in cores of both species from Palau. Our findings enable a deeper understanding of the temporal and spatial variability in Symbiodiniaceae communities, offering insights that may refine the use of paleobiological proxies in climate studies and reveal broader ecological trends and microbially-aided adaptation pathways in corals.

systems biology↗

bioRxiv2025

YAbS: The Antibody Society's antibody therapeutics database

Therapeutic antibodies have gained prominence in recent years due to their precision in targeting specific diseases. As these molecules become increasingly essential in modern medicine, comprehensive data tracking and analysis are critical for advancing research and ensuring successful clinical outcomes. YAbS, The Antibody Societys Antibody Therapeutics Database, serves as a vital resource for monitoring the development and clinical progress of therapeutic antibodies. The database catalogues detailed information on over 2,900 commercially sponsored investigational antibody candidates that have entered clinical study since 2000, as well as all approved antibody therapeutics. Data for the late-stage clinical pipeline and antibody therapeutics in regulatory review or approved (over 450 molecules) are openly accessible (https://db.antibodysociety.org). Antibody-related information includes molecular format, targeted antigen, current development status, indications studied, and the clinical development timeline of the antibodies, as well as the geographical region of company sponsors. Furthermore, the database supports in-depth industry trends analysis, facilitating the identification of innovative developments and the assessment of success rates within the field. This resource is continually updated and refined, providing invaluable insights to researchers, clinicians, and industry professionals engaged in antibody therapeutics development.

scientific communication and education↗

bioRxiv2024

RGB color indices as proxy for symbiont cell density and chlorophyll content during coral bleaching

Coral bleaching, the breakdown of the symbiosis between the coral host and endosymbiotic microalgae, is the main cause of widespread coral reef degradation. Current methods for assessing coral health based on visual appearance, such as the use of color reference cards, are limited by subjective human color perception and low resolution. Digital photography with RGB (Red, Green, Blue) color channel analyses offers a fast, non-invasive, and standardized alternative to estimate physiological parameters. However, the link between coral color and physiological parameters during bleaching may vary depending on the type of stressor. While such approaches are extensively used in plant studies, their application in estimating Symbiodiniaceae cell density and chlorophyll content in corals requires further attention. In this study, we analyzed the correlation between Symbiodiniaceae cell density and chlorophyll content across three coral species (Acropora muricata, Pocillopora verrucosa, and Stylophora pistillata) with 19 color indices derived from the RGB channels currently established as predictors of chlorophyll content in plants. Corals were exposed to three bleaching conditions (acute short-term and chronic long-term heat stress and menthol bleaching) to identify the best color indices for assessing coral health through image analysis. We found that the Red index had the strongest linear correlation with symbiont cell density and chlorophyll content across species (R2 up to 0.97), so that relative changes in this color index can be directly interpreted as corresponding changes in tissue parameters. To train a model that predicts symbiont densities of a distinct sample set using the Red index, we found 10 to 12 samples to be sufficient to achieve an accuracy of > 95 % of the models trained on the full datasets. This research contributes to improved image analysis as a reliable and non-invasive tool for monitoring, by providing guidelines for a systematic use of RGB data to interpret coral health.

ecology↗

bioRxiv2024

Optimized recess design in artificial structures dramatically enhances coral settlement and survival

The worldwide decline of coral reefs, driven by climate change and local stressors, demands new, scalable restoration approaches. Coral larvae offer significant potential for reef recovery, as a single coral colony can release millions of offspring, with almost all larvae dying before finding a suitable habitat. Building upon an iterative design process, incorporating a gradient of sizes and angles based on larval settlement preferences observed in nature, we developed and tested seven 3D-printed settlement module designs, proposed to enhance coral larvae habitat. We studied the settlement and survival of coral larvae on the settlement modules integrating these designs and adjacent reef structures in K[a]neohe Bay over one year. Helix recesses dramatically outperformed other structural features, increasing settlement by [~]80-fold and post-settlement survival over a year by 20-50-fold compared to control modules. In contrast to natural reef substrates, settlement on modules with helix recesses increased by [~]70-fold. We identified the recess dimensions and light levels preferred as settlement habitat. In a parallel tank experiment, we explored the impacts of hydrodynamics on the settlement and survival of Montipora capitata larvae on modules with helix recesses. We found that settlement was more pronounced under high-flow conditions, suggesting a crucial role of micro-scale hydrodynamics in entraining settling corals. These findings highlight the potential of helix recesses to significantly improve early coral recruitment, a critical bottleneck in reef restoration. By integrating these structures into artificial reefs and coastal infrastructure, our approach offers an innovative, scalable, and cost-effective solution to enhance reef resilience and accelerate ecosystem recovery in a changing ocean.

ecology↗

bioRxiv2024

habtools: an R package to calculate 3D metrics for surfaces and objects

O_LITechnological advances in three-dimensional imaging techniques have opened the door to advanced morphological analyses and habitat mapping for biologists and ecologists. C_LIO_LIAt the same time, the challenge of translating complex 3D data into meaningful metrics that can be used in conjunction with biological data currently hinders progress and accessibility. C_LIO_LIWe introduce habtools, an R package that provides R functions to efficiently calculate complexity and shape metrics from DEMs, 3D meshes and 2D shapes as well as some helper functions to facilitate workflow. C_LIO_LIWe expect the functionality of habtools to continue to expand as new metrics and faster methods become available, and welcome new contributions and ideas. C_LI

ecology↗

bioRxiv2024

Species identity and composition shape productivity of stony corals

Coral biodiversity has an enhancing but saturating effect on community productivity, however, the direct effects of neighbouring coral colonies on productivity remain poorly understood due to the complex interplay of biotic and abiotic factors. We set up a fully controlled aquarium experiment, in which we quantified the effects of species identity and composition on the productivity of nine stony coral species from three families. Baseline productivity and the response to neighbouring organisms strongly differed between species. Regardless of whether species increased or decreased productivity, the responses were consistently more pronounced and positive towards conspecific than heterospecific neighbours, indicating kin selection effects between closely related species. Species productivity in monoculture and productivity in polyculture were inversely correlated, with inherently less productive species overperforming in polyculture and vice versa. Our results highlight that contact-free interactions in marine animals shape biodiversity-productivity effects otherwise known from plant communities.

ecology↗

bioRxiv2023

Common types of microdebris affect the physiology of reef-building corals

Marine debris, particularly microdebris (< 1 mm) poses a potential threat to marine life, including reef-building corals. While previous research has mainly focused on the impact of single polymer microplastics, the effects of natural microdebris, composed of a mixture of materials, have not been explored. Therefore, this study aimed to assess the effects of different microdebris, originating from major sources of pollution, on reef-building corals. For this, we exposed two scleractinian coral species, Pocillopora verrucosa and Stylophora pistillata, known to frequently ingest microplastics, to four types of microdebris in an 8-week laboratory experiment: fragmented environmental plastic debris, artificial fibers from clothing, residues from the automobile sector consisting of tire wear, brake abrasion, and varnish flakes, a single polymer microplastic treatment consisting of polyethylene particles, and a microdebris-free control treatment. Specifically, we (I) compared the effects of the different microdebris on coral growth, necrosis, and photosynthesis, (II) investigated the difference between the microdebris mixtures and the exposure to the single polymer treatment, and (III) identified potential mechanisms causing species-specific effects by contrasting the feeding responses of the two coral species on microdebris and natural food. We show that the fibers and tire wear had the strongest effects on coral physiology, with P. verrucosa being more affected than S. pistillata. Both species showed increased volume growth in response to the microdebris treatments, accompanied by decreased calcification in P. verrucosa. Photosynthetic efficiency of the symbionts was enhanced in both species. The species-specific physiological responses might be attributed to feeding reactions, with P. verrucosa responding significantly more often to microdebris than S. pistillata. These findings highlight the effect of different microdebris on coral physiology and the need for future studies to use particle mixtures to better mimic naturally occurring microdebris and assess its effect on corals in more detail. HighlightsO_LIThe effects of major sources of microdebris pollution on coral physiology were compared. C_LIO_LIOverall, microdebris had only minor impacts on coral physiology. C_LIO_LIArtificial fibers and tire wear caused the strongest effect on coral physiology. C_LIO_LISingle polymer and complex microdebris caused similar, yet species-specific effects. C_LIO_LISpecies-specific effects might be due to different feeding behaviors. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/569976v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1ba7ba8org.highwire.dtl.DTLVardef@c5795org.highwire.dtl.DTLVardef@4a10deorg.highwire.dtl.DTLVardef@9983e5_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2021

Interactive effects of microplastic pollution and heat stress on reef-building corals

Plastic pollution is an emerging stressor that increases pressure on ecosystems such as coral reefs that are already challenged by climate change. However, the effect of plastic pollution in combination with global warming is largely unknown. Thus, the goal of this study was to determine the cumulative effect of microplastic pollution with that of global warming on reef-building coral species and to compare the severity of both stressors. For this, we conducted a series of three controlled laboratory experiments and exposed a broad range of coral species (Acropora muricata, Montipora digitata, Porites lutea, Pocillopora verrucosa, and Stylophora pistillata) to microplastic particles in a range of concentrations (2.5-2,500 particles L-1) and mixtures (from different industrial sectors) at ambient temperatures and in combination with heat stress. We show that microplastic can occasionally have a negative effect on the corals thermal tolerance. In comparison to heat stress, however, microplastic constitutes a minor stressor. While heat stress led to decreased photosynthetic efficiency of algal symbionts, and increased bleaching, tissue necrosis, and mortality, treatment with microplastic particles had only minor effects on the physiology and health of the tested coral species at ambient temperatures. These findings underline that while efforts to reduce plastic pollution should continue, they should not replace more urgent efforts to halt global warming, which are immediately needed to preserve remaining coral reef ecosystems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/454458v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@c2eeb0org.highwire.dtl.DTLVardef@1c49ea6org.highwire.dtl.DTLVardef@18bab59org.highwire.dtl.DTLVardef@9e952b_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2018

Novel genes for autism implicate both excitatory and inhibitory cell lineages in risk

We present the largest exome sequencing study to date focused on rare variation in autism spectrum disorder (ASD) (n=35,584). Integrating de novo and case-control variation with an enhanced Bayesian framework incorporating evolutionary constraint against mutation, we implicate 99 genes in ASD risk at a false discovery rate (FDR) [≤] 0.1. Of these 99 risk genes, 46 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 50 show higher frequencies in individuals ascertained for ASD, and comparing ASD cases with disruptive mutations in the two groups shows differences in phenotypic presentation. Expressed early in brain development, most of the risk genes have roles in neuronal communication or regulation of gene expression, and 12 fall within recurrent copy number variant loci. In human cortex single-cell gene expression data, expression of the 99 risk genes is also enriched in both excitatory and inhibitory neuronal lineages, implying that disruption of these genes alters the development of both neuron types. Together, these insights broaden our understanding of the neurobiology of ASD.

genetics↗

bioRxiv2018

Identification of rare de novo epigenetic variations in congenital disorders

Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. With recent dramatic advances in genomic technologies, genome-wide surveys of cohorts of patients with ND/CAs for point mutations and structural variations have greatly advanced our understanding of their genetic etiologies1,2. However, even after whole genome sequencing (WGS), a substantial fraction of such disorders remain unexplained3. In contrast, the possibility that constitutive epigenetic variations (epivariations) might underlie such traits has not been well explored. We hypothesized that some cases of ND/CA are caused by aberrations of DNA methylation that lead to a dysregulation of normal genome function. By comparing DNA methylation profiles from 489 individuals with ND/CAs against 1,534 population controls, we identified epivariations as a frequent occurrence in the human genome. De novo epivariations were significantly enriched in cases when compared to controls. RNAseq data from population studies showed that epivariations often have an impact on gene expression comparable to loss-of-function mutations. Additionally, we detected and replicated an enrichment of rare sequence mutations overlapping CTCF binding sites close to epivariations. Thus, some epivariations occur secondary to cis-linked mutations in regulatory regions, providing a rationale for interpreting non-coding genetic variation. We propose that epivariations likely represent the causative genomic defect in 5-10% of patients with unexplained ND/CAs. This constitutes a yield comparable to CNV microarrays, and as such has significant diagnostic relevance.

genomics↗