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Valle, D.

Publications and source records attributed to Valle, D..

8 recordsLinked to original sources

Population structure of Phytophthora infestans collected from potatoes in Ecuador, Colombia, Peru, Bolivia and Uruguay

Late blight, a destructive disease affecting potatoes, is caused by the oomycete Phytophthora infestans and remains a major threat to potato production worldwide. Understanding the population structure of this pathogen is essential for effective disease management. We examined the genetic structure of South American P. infestans populations using 182 isolates: 97 from Bolivia and southern Peru, 14 from Colombia, 57 from Ecuador (1993-2022), and 14 from Uruguay. The isolates were characterized by clonal lineage, mitochondrial haplotype, and mating type using multilocus genotypes based on microsatellite (SSR) markers. In Bolivia, only the lineage/haplotype 2A1/Ia was identified, whereas Peru exhibited both 2A1/Ia and EC1/IIa, all of which were mating type A1. Puno was the sole department where both lineages were present. In historical Ecuadorian populations, we found US1/Ib and EC1/IIa (P. infestans), as well as EC2/Ic and EC3/Ia (Phytophthora andina), while recent populations showed only US1. In Colombia, EC1/IIa and a distinct clonal lineage (CO4/Ia) were identified within the present dataset. In Uruguay, 2A1/Ia was predominant. These results provide updated insights into the genetic diversity and geographic distribution of P. infestans across South America and highlight the importance of continued regional surveillance for improved late blight management.

plant biology↗

Bridging the gap between movement data and connectivity analysis using the time-explicit Step Selection Function (tSSF)

BackgroundUnderstanding how to connect habitat remnants to facilitate the movement of species is a critical task in an increasingly fragmented world impacted by human activities. The identification of dispersal routes and corridors through connectivity analysis requires measures of landscape resistance but there has been no consensus on how to calculate resistance from habitat characteristics, potentially leading to very different connectivity outcomes. MethodsWe propose a new model called the time-explicit step selection function (tSSF) that can be directly used for connectivity analysis in the context of the spatial absorbing Markov chain (SAMC) framework without requiring arbitrary transformations. The tSSF model combines a time model with a standard selection function and can provide complementary information regarding how animals use landscapes by separately assessing the drivers of time to traverse the landscape and the drivers of habitat selection. These models are illustrated using GPS-tracking data from giant anteaters (Myrmecophaga tridactyla) in the Pantanal wetlands of Brazil. ResultsThe time model revealed that the fastest movements tended to occur between 8 pm and 5 am, suggesting a crepuscular/nocturnal behavior. Giant anteaters moved faster over wetlands while moving much slower over forests and savannas, in comparison to grasslands. We found that wetlands were consistently avoided whereas forest and savannas tended to be selected. Importantly, this model revealed that selection for forest increased with temperature, suggesting that forests may act as important thermal shelters when temperatures are high. Finally, the tSSF results can be used to simulate movement and connectivity within a fragmented landscape, revealing that giant anteaters will often not use the shortest-distance path to the destination patch (because that would require traversing a wetland, an avoided habitat) and that approximately 90% of the individuals will have reached the destination patch after 49 days. ConclusionsThe approach proposed here can be used to gain a better understanding of how landscape features are perceived by individuals through the decomposition of movement patterns into a time and a habitat selection component. This approach can also help bridge the gap between movement-based models and connectivity analysis, enabling the generation of time-explicit results.

animal behavior and cognition↗

Identifying latent behavioral states in animal movement with non-parametric Bayesian methods

O_LIUnderstanding animal movement often relies upon telemetry and biologging devices. These data are frequently used to estimate latent behavioral states to help understand why animals move across the landscape. While there are a variety of methods that make behavioral inferences from biotelemetry data, some features of these methods (e.g., analysis of a single data stream, use of parametric distributions) may limit their generality to reliably discriminate among behavioral states. C_LIO_LITo address some of the limitations of existing behavioral state estimation models, we introduce a non-parametric Bayesian framework called the mixed-membership method for movement (M4), which is available within the open-source bayesmove R package. This framework can analyze multiple data streams (e.g., step length, turning angle, acceleration) without relying on parametric distributions, which may capture complex behaviors more successfully than current methods. We tested our Bayesian framework using simulated trajectories and compared model performance against two segmentation methods (behavioral change point analysis (BCPA) and segclust2d), one machine learning method (expectation-maximization binary clustering (EMbC)), and one type of state-space model (hidden Markov model (HMM)). We also illustrated this Bayesian framework using movements of juvenile snail kites (Rostrhamus sociabilis) in Florida, USA. C_LIO_LIThe Bayesian framework estimated breakpoints more accurately than the other segmentation methods for tracks of different lengths. Likewise, the Bayesian framework provided more accurate estimates of behavior than the other state estimation methods when simulations were generated from less frequently considered distributions (e.g., truncated normal, beta, uniform). Three behavioral states were estimated from snail kite movements, which were labeled as encamped, area-restricted search, and transit. Changes in these behaviors over time were associated with known dispersal events from the nest site, as well as movements to and from possible breeding locations. C_LIO_LIOur non-parametric Bayesian framework estimated behavioral states with comparable or superior accuracy compared to the other methods when step lengths and turning angles of simulations were generated from less frequently considered distributions. Since the most appropriate parametric distributions may not be obvious a priori, methods (such as M4) that are agnostic to the underlying distributions can provide powerful alternatives to address questions in movement ecology. C_LI

ecology↗

De novo mutation in ancestral generations evolves haplotypes contributing to disease

PurposeThe variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated deeply for its potential impact on the genomic architecture of disease traits. MethodsWe generated and analyzed a database of variants derived from exome sequencing (ES) data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits, and 643 unaffected relatives. ResultsUsing uniform manifold approximation and projection (UMAP), we showed that the TK genomes are more similar to those of Europeans and consist of two main subpopulations: clusters 1 and 2 (N=235 and 1,181) that differ in admixture proportion and variome (https://turkishvariomedb.shinyapps.io/tvdb/). Furthermore, the higher inbreeding coefficient (F) values observed in the TK affected compared to unaffected individuals correlated with a larger median span of long-sized (>2.64 Mb) runs of homozygosity (ROH) regions (p-value=2.09e-18). We show that long-sized ROHs are more likely to be formed on recently configured haplotypes enriched for rare homozygous deleterious variants in the TK-affected compared to TK-unaffected individuals (p-value= 3.35e-11). Analysis of genotype-phenotype correlations reveals that genes with rare homozygous deleterious variants in long-sized ROHs provide the most comprehensive set of molecular diagnoses for the observed disease traits with a systematic quantitative analysis of HPO (Human Phenotype Ontology) terms. ConclusionOur findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.

genomics↗

Loss of function variants in PCYT1A causing spondylometaphyseal dysplasia with cone/rod dystrophy have broad consequences on lipid metabolism, chondrocyte differentiation, and lipid droplet formation.

AbstractSpondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) is a rare autosomal recessive disorder of the skeleton and the retina caused by biallelic variants in PCYT1A, encoding the nuclear enzyme CTP:phosphocholine cytidylyltransferase (CCT), which catalyzes the rate-limiting step in phosphatidylcholine (PC) biosynthesis by the Kennedy pathway. As a first step in understanding the consequences of PCYT1A variants on SMD-CRD pathophysiology, we generated and characterized a series of cellular models for SMD-CRD, including CRISPR-edited PCYT1A-null HEK293 and ATDC5 cell lines. Immunoblot and PC synthesis assays of cultured skin fibroblasts from SMD-CRD patient cell lines revealed patient genotype-specific reductions in CCT steady state levels (10-75% of wild-type) and choline incorporation into PC (22-54% of wild-type). While PCYT1A-null HEK293 cells exhibited fewer and larger lipid droplets in response to oleate loading than their wild-type counterparts, SMD-CRD patient fibroblasts (p.Ser323Argfs*38 homozygotes) failed to show significant differences in lipid droplet numbers or sizes as compared to controls. Lipid droplet phenotypes in PCYT1A-null HEK293 cells were rescued by transfection with wild-type, p.Ala99Val, and p.Tyr240His human PCYT1A cDNAs. While both edited cellular models had normal morphology and proliferation rates compared to unedited controls, Pcyt1a-null ATDC5 cells demonstrated accelerated rates of chondrocyte differentiation as compared to their wild-type counterparts. Lipidomics revealed changes in 75-200 lipid levels in PCYT1A-null HEK293 and ATDC5 cells or in SMD-CRD patient fibroblasts as compared to wild-type controls. The specific lipids altered and extent of change varied by cell type. Importantly, both PCYT1A-null HEK293 cells and SMD-CRD patient fibroblast cell lines had decreased phosphatidylcholine:phosphatidylethanolamine (PC:PE) ratios and decreased levels of several lysophosphatidylcholine (LPC) species as compared to wild-type controls, suggesting compensatory PC production through increased LPC remodeling by LPCAT or decreased conversion of PC to LPC by phospholipase A2. Our results show that all tested PCYT1A alleles associated with SMD-CRD are hypomorphic and suggest involvement of PCYT1A in chondrocyte differentiation, PC:PE ratio maintenance and LPC metabolism, and lipid droplet formation. Author SummaryRare genetic disorders can reveal the function of genes on an organismal scale. When normal gene activity is lost, patients can experience a range of symptoms, often dependent on the residual activity of the encoded protein. Rare variants in the gene PCYT1A can cause multiple inherited disorders, including a disorder of the skeleton and the retina characterized by short stature, bone abnormalities, and blindness. PCYT1A is required for normal cellular function, particularly lipid metabolism, but the role of this gene in human disease is still poorly understood. To determine consequences of genetic variants in patients with this disorder, we made and studied a series of cellular models, including cells cultured from patients and CRISPR-edited cell lines lacking normal copies of PCYT1A. Here we show that patient variants lead to reduced PCYT1A expression and/or function and have adverse consequences on cell biology and lipid metabolism that are often cell-type specific. This work advances understanding of the role of lipid metabolism in skeletal and eye development.

genetics↗

Comparison of National Level Spatial and Spatio-temporal Models of Malaria

Geospatial statistical models play an important role in malaria control and prevention; they are widely used to produce malaria risk maps, which are essential to guide efficient resource allocation for intervention. Although many models are available for spatial mapping, the most commonly used model in the literature is the Bayesian geostatistical model (BGM), which is based on an underlying Gaussian process. To our knowledge, methods such as splines and decision trees ensemble methods have not been compared relative to their predictive skill for country level malaria prevalence mapping. Moreover, as more countries now have multiple datasets collected throughout the past decade, it is critical to evaluate if the inclusion of past datasets and the use of spatio-temporal models improve the prediction accuracy of present spatial distribution of malaria. Here we compare the prediction accuracy of five models under spatial and spatio-temporal settings in five African countries. The five models are stepwise logistic regression, generalized additive model (GAM), gradient boosted trees (GBM), Bayesian additive regression trees (BART) and the BGM. There is not a single best model to predict malaria prevalence on a national scale. The model performances varied from country to country, and from spatial to spatio-temporal setting. In general, BGM, GAM and BART models performed well, with BGM being the most consistent. The inclusion of past data is not always beneficial: the predictive performance of GAM and GBM increased under spatio-temporal setting, but BGMs performance decreased in most of the countries. An accurate depiction of malaria risk is important and statistical assumptions that are suitable for a country does not always fit other countries and a wide range of models and settings should be used. It ensures that we find the best modeling approach possible and can provide additional insight to the spatial distribution of malaria risk.\n\nAuthor summaryMalaria is still affecting hundreds of millions of people every year, and killing hundreds of thousands. As the majority of malaria intervention and control policies are developed at the national level, accurate spatial prediction of malaria risk is important. Choosing the best modeling approach for prediction is not straightforward. Here we compare the predictive performance of five models in five countries, with and without dataset from multiple surveys, to provide empirical evidence on whether there is a single best model for national level malaria prediction, and whether inclusion of past dataset may be beneficial in predicting current distribution of malaria risk. We find that models performances vary from country to country and there is no single best model. Although Bayesian geostatistical model is widely and commonly used in the literatures, its performance is not necessarily superior to other simpler-to-fit methods such as general additive model (splines) and Bayesian additive regression tree. Importantly, we also show that the incorporation of past data does not always improve spatial predictions of current disease risk. Together, this demonstrate the importance of fitting wide range of models as part of the prediction mapping process, instead of relying on a one-size-fit-all model.

epidemiology↗

Validation of new tools to identify expanded repeats: an intronic pentamer expansion in RFC1 causes CANVAS

Genomic technologies such as Next Generation Sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS families and identified a core ancestral haplotype, estimated to have arisen in Europe over twenty-five thousand years ago. WGS of the four RFC1 negative CANVAS families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.

genetics↗

Darker eggs resist more to desiccation: the case of melanin in Aedes, Anopheles and Culex mosquito vectors

Mosquito vectors lay their eggs in the aquatic milieu. During early embryogenesis water passes freely through the transparent eggshell, composed of exochorion and endochorion. Within two hours the endochorion darkens via melanization but even so eggs shrink and perish if removed from moisture. However, during mid-embryogenesis, cells of the extraembryonic serosa secretes the serosal cuticle, localized right below the endochorion, which greatly reduces water flow and allows the egg to survive outside the water. The degree of egg resistance to desiccation (ERD) at late embryogenesis varies among different species: Aedes aegypti, Anopheles aquasalis and Culex quinquefasciatus eggs can survive in a dry environment for [≥] 72, 24 and 5 hours, respectively. In some adult insects, darker-body individuals show greater resistance to desiccation than lighter ones. We asked if melanization enhances serosal cuticle-dependent ERD. Species with higher ERD at late embryogenesis exhibit more melanized eggshells. The melanization-ERD hypothesis was confirmed employing two Anopheles quadrimaculatus strains, the wild type and the mutant GORO, with a dark-brown and a golden eggshell, respectively. In all cases, serosal cuticle formation is fundamental for the establishment of an efficient ERD but egg viability outside the water is much higher in mosquitoes with darker eggshells than in those with lighter ones. The finding that pigmentation influences egg water balance is relevant to understand the evolutionary history of insect coloration. Since eggshell and adult cuticle pigmentation ensure insect survivorship in some cases, they should be considered regarding species fitness and novel approaches for vector or pest insects control.

evolutionary biology↗