Rare Case of de Novo 2p15 Microdeletion Syndrome with Deletion Covering XPO1 and USP34 Genes Diagnosed in a Child - A Case Report.

Introduction: 2p15p16.1 microdeletion syndrome was described for the first time in 2007. The size of the microdeletion is variable and encompasses several genes, like XPO1, USP34, BCL11A, REL, PAPOLG, PEX13, COMMD1, B3GNT2, and EHBP1. Features of the syndrome include short stature, microcephaly, hypotonia, psychomotor developmental delay, anomalies of the fingers of the upper and lower limbs, dysmorphic features like receding forehead, broad nasal bridge, telecanthus, ptosis, flat philtrum, small mouth with a high, narrow palate and everted lower lip. The precise genotype-phenotype correlation in 2p15 deletion syndrome is not understood. The aim of the study is to present the patient's medical history and the diagnostic process. Case Presentation: A boy aged 9 was admitted to the Genetic Outpatient Clinic due to dysmorphic features and mild mental retardation. Full lips, broad nasal root, very light hair, excessively developed subcutaneous tissue, joint laxity, postural defect, flat-valgus foot with sandal gap, brachydactyly, and problems with concentration, memory, and counting were found. Diagnosis was based on microarray testing, and copy-number variation analysis was performed using CytoScan 750K array. Genetic imbalance in the form of a deletion within the short arm of chromosome 2 in the 2p15 region (containing 50 kbp) was shown. The microdeletion covers 2 genes: USP34 and XPO1. Parents were not carriers of that mutation. Conclusion: The phenotypic features presented by the patient were reflected in the genetic test. 2p15 microdeletion syndrome is genetically heterogeneous with possible de novo occurrence, as in the presented case. The precise genotype-phenotype correlation in 2p15 deletion syndrome should be widely studied because in the literature there is mainly mentioned 2p15p16.1 syndrome. Even though 2p15 microdeletion syndrome is a rare discovery and its features are mainly mild, it is necessary to pay special attention to them to refer patients to genetic counseling to make an accurate diagnosis.

Allergen Microarrays and New Physical Approaches to More Sensitive and Specific Detection of Allergen-Specific Antibodies.

The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Associated With Recurrence and Survival of Resectable Non-Small Cell Lung Cancer (NSCLC): A Retrospective Study.

INTRODUCTION: Curative lung resection remains the key therapeutic strategy for early-stage non-small cell lung cancer (NSCLC). However, a proportion of patients still experience variable outcomes and eventually develop recurrence or die from their disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as a deleterious factor that inhibits tumor cells apoptosis and leads to reduction of lymphocyte infiltration. However, there has been no research on the predicted role of PCSK9 as an immunohistochemical biomarker with survival in resectable NSCLC. METHODS: One hundred sixty-three patients with resectable NSCLC were retrospectively reviewed, and PCSK9 expression of resected NSCLC was analyzed by immunohistochemistry using tissue microarrays. RESULTS: PCSK9 was associated with recurrence (42.1% relapsed in the PCSK9lo group versus 57.9% relapsed in the PCSK9hi group, P = 0.006) and survival status (39.6% dead in PCSK9lo group versus 60.4% dead in PCSK9hi group, P = 0.004) in patients with resectable NSCLC. Moreover, resectable NSCLC patients with higher PCSK9 expression in tumor tissue experienced poorer disease-free survival (median disease-free survival: 10.5 versus 25.2 mo, hazard ratio = 1.620, 95% confidence interval: 1.124-2.334) and overall suvrival (median overall suvrival: 20.0 versus 54.1 mo, hazard ratio = 1.646, 95% confidence interval: 1.101-2.461) compared to those with lower PCSK9 expression. CONCLUSIONS: High PCSK9 expression of tumor was correlated with recurrence and worse survival status of resectable NSCLC in our retrospective study, which indicated that PCSK9 in NSCLC may be an immunohistochemical biomarker of poor prognosis for patients with resectable NSCLC. Further large-scale prospective studies are warranted to establish these results.

The study of galactomannans with different molecular weights and their ability to form microparticles suitable for pulmonary delivery.

The influence of locust bean gum (LBG) galactomannans (GMs) molecular weight (Mw) to assemble microparticulate systems was evaluated, and carriers for deep lung delivery were developed. A commercial batch of LBG with a mannose/galactose (M/G) ratio of 2.4 (batch 1) was used to study the influence of different microwave partial acid hydrolysis conditions on carbohydrate composition, glycosidic linkages, and aqueous solutions viscosity. The microwave treatment did not affect the composition, presenting 4-Man (36-42 %), 4,6-Man (27-35 %), and T-Gal (24-25 %) as the main glycosidic linkages. Depolymerization led to a viscosity reduction (≤0.005 Pa·s) with no major impact on polysaccharide debranching. The structural composition of the LBG galactomannans were further elucidated with sequence-specific proteins using carbohydrate microarray technologies. A second batch of LBG (M/G 3.3) was used to study the impact of GMs with different Mw on microparticle assembling, characteristics, and insulin release kinetics. The low-Mw GMs microparticles led to a faster release (20 min) than the higher-Mw (40 min) ones, impacting the release kinetics. All microparticles exhibited a safety profile to cells of the respiratory tract. However, only the higher-Mw GMs allowed the assembly of microparticles with sizes suitable for this type of administration.

Comparative Analysis of Shapley Values Enhances Transcriptomics Insights across Some Common Uterine Pathologies.

Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Microglial proliferation and astrocytic protein alterations in the human Huntington's disease cortex.

Huntington's disease (HD) is a neurodegenerative disorder that severely affects the basal ganglia and regions of the cerebral cortex. While astrocytosis and microgliosis both contribute to basal ganglia pathology, the contribution of gliosis and potential factors driving glial activity in the human HD cerebral cortex is less understood. Our study aims to identify nuanced indicators of gliosis in HD which is challenging to identify in the severely degenerated basal ganglia, by investigating the middle temporal gyrus (MTG), a cortical region previously documented to demonstrate milder neuronal loss. Immunohistochemistry was conducted on MTG paraffin-embedded tissue microarrays (TMAs) comprising 29 HD and 35 neurologically normal cases to compare the immunoreactivity patterns of key astrocytic proteins (glial fibrillary acidic protein, GFAP; inwardly rectifying potassium channel 4.1, Kir4.1; glutamate transporter-1, GLT-1; aquaporin-4, AQP4), key microglial proteins (ionised calcium-binding adapter molecule-1, IBA-1; human leukocyte antigen (HLA)-DR; transmembrane protein 119, TMEM119; purinergic receptor P2RY12, P2RY12), and indicators of proliferation (Ki-67; proliferative cell nuclear antigen, PCNA). Our findings demonstrate an upregulation of GFAP+ protein expression attributed to the presence of more GFAP+ expressing cells in HD, which correlated with greater cortical mutant huntingtin (mHTT) deposition. In contrast, Kir4.1, GLT-1, and AQP4 immunoreactivity levels were unchanged in HD. We also demonstrate an increased number of IBA-1+ and TMEM119+ microglia with somal enlargement. IBA-1+, TMEM119+, and P2RY12+ reactive microglia immunophenotypes were also identified in HD, evidenced by the presence of rod-shaped, hypertrophic, and dystrophic microglia. In HD cases, IBA-1+ cells contained either Ki-67 or PCNA, whereas GFAP+ astrocytes were devoid of proliferative nuclei. These findings suggest cortical microgliosis may be driven by proliferation in HD, supporting the hypothesis of microglial proliferation as a feature of HD pathophysiology. In contrast, astrocytes in HD demonstrate an altered GFAP expression profile that is associated with the degree of mHTT deposition.

Topographic analysis of pancreatic cancer by TMA and digital spatial profiling reveals biological complexity with potential therapeutic implications.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human malignancies. Tissue microarrays (TMA) are an established method of high throughput biomarker interrogation in tissues but may not capture histological features of cancer with potential biological relevance. Topographic TMAs (T-TMAs) representing pathophysiological hallmarks of cancer were constructed from representative, retrospective PDAC diagnostic material, including 72 individual core tissue samples. The T-TMA was interrogated with tissue hybridization-based experiments to confirm the accuracy of the topographic sampling, expression of pro-tumourigenic and immune mediators of cancer, totalling more than 750 individual biomarker analyses. A custom designed Next Generation Sequencing (NGS) panel and a spatial distribution-specific transcriptomic evaluation were also employed. The morphological choice of the pathophysiological hallmarks of cancer was confirmed by protein-specific expression. Quantitative analysis identified topography-specific patterns of expression in the IDO/TGF-ß axis; with a heterogeneous relationship of inflammation and desmoplasia across hallmark areas and a general but variable protein and gene expression of c-MET. NGS results highlighted underlying genetic heterogeneity within samples, which may have a confounding influence on the expression of a particular biomarker. T-TMAs, integrated with quantitative biomarker digital scoring, are useful tools to identify hallmark specific expression of biomarkers in pancreatic cancer.

Towards an Analytical Biology.

This article draws a perspective on the increasingly unavoidable question of whether steps can be taken in genomics and biology at large to move them more rapidly towards more analytical and deductive biology, akin to similar developments that occurred in other natural sciences, such as physics and chemistry, centuries ago. It provides a summary of recent advances in other relevant sciences in the last 3 decades that are likely to pull it in that direction in the next decade or so, as well as what methods and tools will make it possible.

DExplore: An Online Tool for Detecting Differentially Expressed Genes from mRNA Microarray Experiments.

Microarray experiments, a mainstay in gene expression analysis for nearly two decades, pose challenges due to their complexity. To address this, we introduce DExplore, a user-friendly web application enabling researchers to detect differentially expressed genes using data from NCBI's GEO. Developed with R, Shiny, and Bioconductor, DExplore integrates WebGestalt for functional enrichment analysis. It also provides visualization plots for enhanced result interpretation. With a Docker image for local execution, DExplore accommodates unpublished data. To illustrate its utility, we showcase two case studies on cancer cells treated with chemotherapeutic drugs. DExplore streamlines microarray data analysis, empowering molecular biologists to focus on genes of biological significance.

An Active Strategy Based on Different Droplet Removal Modes on Polydimethylsiloxane Magnetic Microstructures.

The efficient removal of droplets on solid surfaces holds significant importance in the field of fog collection, condensation heat transfer, and so on. However, on current typical surfaces, droplets are characterized by a passive and single removal mode, contingent on the traction force (e.g., capillary force, Laplace pressure, etc.) generated by the surface's physics and chemistry design, posing challenges for enhancing the efficiency of droplet removal. In this paper, an effective active strategy based on different removal modes is demonstrated on magnetic responsive polydimethylsiloxane (PDMS) superhydrophobic microplates (RM-MPSM). By regulating the parameters of microplates and droplet volume, different effective departure modes (top jumping and side departure) can be induced to facilitate the removal of droplets. Moreover, the removal volume of droplets through the side departure mode exhibits a significant reduction compared to that observed in the top jumping mode. The exceptional removal ability of RM-MPSM demonstrates adaptability to diverse functional applications: efficient fog collection, removal of condensation droplets and micro-particles. The efficient modes of droplet removal demonstrated in this work hold significant implications for broadening its application in many fields, such as droplet collection, heat transfer, and anti-icing.

Revisiting the antigen markers of vector-borne parasitic diseases identified by immunomics: identification and application to disease control.

INTRODUCTION: Protein microarray is a promising immunomic approach for identifying biomarkers. Based on our previous study that reviewed parasite antigens and recent parasitic omics research, this article expands to include information on vector-borne parasitic diseases (VBPDs), namely, malaria, schistosomiasis, leishmaniasis, babesiosis, trypanosomiasis, lymphatic filariasis, and onchocerciasis. AREAS COVERED: We revisit and systematically summarize antigen markers of vector-borne parasites identified by the immunomic approach and discuss the latest advances in identifying antigens for the rational development of diagnostics and vaccines. The applications and challenges of this approach for VBPD control are also discussed. EXPERT OPINION: The immunomic approach has enabled the identification and/or validation of antigen markers for vaccine development, diagnosis, disease surveillance, and treatment. However, this approach presents several challenges, including limited sample size, variability in antigen expression, false-positive results, complexity of omics data, validation and reproducibility, and heterogeneity of diseases. In addition, antigen involvement in host immune evasion and antigen sensitivity/specificity are major issues in its application. Despite these limitations, this approach remains promising for controlling VBPD. Advances in technology and data analysis methods should continue to improve candidate antigen identification, as well as the use of a multiantigen approach in diagnostic and vaccine development for VBPD control.

Ensemble Classifier Based on Interval Modeling for Microarray Datasets.

The purpose of the study is to propose a multi-class ensemble classifier using interval modeling dedicated to microarray datasets. An approach of creating the uncertainty intervals for the single prediction values of constituent classifiers and then aggregating the obtained intervals with the use of interval-valued aggregation functions is used. The proposed heterogeneous classification employs Random Forest, Support Vector Machines, and Multilayer Perceptron as component classifiers, utilizing cross-entropy to select the optimal classifier. Moreover, orders for intervals are applied to determine the decision class of an object. The applied interval-valued aggregation functions are tested in terms of optimizing the performance of the considered ensemble classifier. The proposed model's quality, superior to other well-known and component classifiers, is validated through comparison, demonstrating the efficacy of cross-entropy in ensemble model construction.

Multilevel assessment of carbamazepine effects: An integrative approach using zebrafish early-life stages.

Carbamazepine (CBZ) is the most commonly used drug in epilepsy treatment, and its metabolites are commonly detected among persistent pharmaceuticals in the aquatic environment. This study aimed to investigate CBZ effects on early-life-stage zebrafish (Danio rerio) (from 2 to 168 hpf) by employing of an integrative approach linking endpoints from molecular to individual level: (i) development; (ii) locomotor activity; (iii) biochemical markers (lactate dehydrogenase, glutathione-S-transferase, acetylcholinesterase and catalase) and (iv) transcriptome analysis using microarray. A 168 h - LC50 of 73.4 mg L-1 and a 72 h - EC50 of 66.8 mg L-1 for hatching were calculated while developmental effects (oedemas and tail deformities) were observed at CBZ concentrations above 37.3 mg L-1. At the biochemical level, AChE activity proved to be the most sensitive parameter, as evidenced by its decrease across all concentrations tested (∼25% maximum reduction, LOEC (lowest observed effect concentration) < 0.6 µg L-1). Locomotor behaviour seemed to be depressed by CBZ although this effect was only evident at the highest concentration tested (50 mg L-1). Molecular analysis revealed a dose-dependent effect of CBZ on gene expression. Although only 25 genes were deregulated in organisms exposed to CBZ when compared to controls, both 0.6 and 2812 µg L-1 treatments impaired gene expression related to development (e.g. crygmxl1, org, klf2a, otos, stx16 and tob2) and the nervous system (e.g. Rtn3, Gdf10, Rtn3), while activated genes were associated with behavioural response (e.g. prlbr and taar). Altogether, our results indicate that environmentally relevant CBZ concentrations might affect biochemical and genetic traits of fish. Thus, the environmental risk of CBZ cannot be neglected, especially in a realistic scenario of constant input of domestic effluents into aquatic systems.

N-Glycan Profiles of Neuraminidase from Avian Influenza Viruses.

The cleavage of sialic acids by neuraminidase (NA) facilitates the spread of influenza A virus (IV) descendants. Understanding the enzymatic activity of NA aids research into the transmission of IVs. An effective method for purifying NA was developed using p-aminophenyloxamic acid-modified functionalized hydroxylated magnetic particles (AAMPs), and from 0.299 to 0.401 mg of NA from eight IV strains was isolated by 1 mg AAMP. A combination of lectin microarrays and MALDI-TOF/TOF-MS was employed to investigate the N-glycans of isolated NAs. We found that more than 20 N-glycans were identified, and 16 glycan peaks were identical in the strains derived from chicken embryo cultivation. Multi-antennae, bisected, or core-fucosylated N-glycans are common in all the NAs. The terminal residues of N-glycans are predominantly composed of galactose and N-acetylglucosamine residues. Meanwhile, sialic acid residue was uncommon in these N-glycans. Further computational docking analysis predicted the interaction mechanism between NA and p-aminophenyloxamic acid.

Deep Learning Glioma Grading with the Tumor Microenvironment Analysis Protocol for Comprehensive Learning, Discovering, and Quantifying Microenvironmental Features.

Gliomas are primary brain tumors that arise from neural stem cells, or glial precursors. Diagnosis of glioma is based on histological evaluation of pathological cell features and molecular markers. Gliomas are infiltrated by myeloid cells that accumulate preferentially in malignant tumors, and their abundance inversely correlates with survival, which is of interest for cancer immunotherapies. To avoid time-consuming and laborious manual examination of images, a deep learning approach for automatic multiclass classification of tumor grades was proposed. As an alternative way of investigating characteristics of brain tumor grades, we implemented a protocol for learning, discovering, and quantifying tumor microenvironment elements on our glioma dataset. Using only single-stained biopsies we derived characteristic differentiating tumor microenvironment phenotypic neighborhoods. The study was complicated by the small size of the available human leukocyte antigen stained on glioma tissue microarray dataset - 206 images of 5 classes - as well as imbalanced data distribution. This challenge was addressed by image augmentation for underrepresented classes. In practice, we considered two scenarios, a whole slide supervised learning classification, and an unsupervised cell-to-cell analysis looking for patterns of the microenvironment. In the supervised learning investigation, we evaluated 6 distinct model architectures. Experiments revealed that a DenseNet121 architecture surpasses the baseline's accuracy by a significant margin of 9% for the test set, achieving a score of 69%, increasing accuracy in discerning challenging WHO grade 2 and 3 cases. All experiments have been carried out in a cross-validation manner. The tumor microenvironment analysis suggested an important role for myeloid cells and their accumulation in the context of characterizing glioma grades. Those promising approaches can be used as an additional diagnostic tool to improve assessment during intraoperative examination or subtyping tissues for treatment selection, potentially easing the workflow of pathologists and oncologists.

Aldo-keto reductase 1B10 as a Carcinogenic but Not a Prognostic Factor in Colorectal Cancer.

Colorectal cancer (CRC) is the leading cause of cancer death, but little is known about its etiopathology. Aldo-keto reductase 1B10 (AKR1B10) protein is primarily expressed in intestinal epithelial cells, but lost in colorectal cancer tissues. This study revealed that AKR1B10 may not be a prognostic but an etiological factor in colorectal tumorigenesis. Using a tissue microarray, we investigated the expression of AKR1B10 in tumor tissues of 592 colorectal cancer patients with a mean follow-up of 25 years. Results exhibited that AKR1B10 protein was undetectable in 374 (63.13%), weakly positive in 146 (24.66%), and positive 72 (12.16%) of 592 tumor tissues. Kaplan-Meier analysis showed that AKR1B10 expression was not correlated with overall survival or disease-free survival. Similar results were obtained in various survival analyses stratified by clinicopathological parameters. AKR1B10 was not correlated with tumor T-pathology, N-pathology, TNM stages, cell differentiation and lymph node/regional/distant metastasis either. However, AKR1B10 silencing in culture cells enhanced carbonyl induced protein and DNA damage; and in ulcerative colitis tissues, AKR1B10 deficiency was associated acrolein-protein lesions. Together this study suggests that AKR1B10 downregulation may not be a prognostic but a carcinogenic factor of colorectal cancer.

High expression of SHP2 predicts a promising prognosis in colorectal cancer.

Background: Src homology 2 domain-containing phosphatase 2 (SHP2) is hyper-activated in some solid tumors. Previous findings suggest that the expression of SHP2 in colorectal cancer (CRC) may be associated with prognosis. However, validation with large sample data is lacking. Materials and Methods: Tissue microarrays containing 860 CRCs and 197 mucosal tissues adjacent to the tumors were constructed. Immunohistochemistry was used to evaluate the expression of SHP2. Differences between SHP2 expression and clinicopathological parameters were evaluated. Kaplan-Meier survival curves and log-rank tests were used to analyze the relationships between SHP2 expression and the overall survival of patients. A Cox proportional hazard regression model was used for univariate and multivariate analyses of prognostic factors. Results: SHP2 expression in CRCs tissues was significantly higher than those in adjacent mucosal tissues (P < 0.001). SHP2 expression was related to tumor differentiation, depth of invasion, distant metastasis, vascular tumor thrombus, lymph node metastasis, and TNM classification (P < 0.05). The prognosis of the high-expression group of SHP2 was significantly better than that of the low-expression group (P = 0.008). Univariate analysis showed that the expression of SHP2 was a prognostic factor for CRC (P = 0.008). Multivariate analysis demonstrated that SHP2 remained an independent prognostic factor for CRC (P = 0.033). Conclusion: The expression of SHP2 was significantly higher in CRC tissues than in adjacent normal tissues. High expression of SHP2 was associated with a promising outcome, suggesting that SHP2 may be a favorable prognostic indicator of CRC.

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD.

Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3-4% of the world's population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8-21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for "isolated" ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

A 25-year odyssey of genomic technology advances and structural variant discovery.

This perspective focuses on advances in genome technology over the last 25 years and their impact on germline variant discovery within the field of human genetics. The field has witnessed tremendous technological advances from microarrays to short-read sequencing and now long-read sequencing. Each technology has provided genome-wide access to different classes of human genetic variation. We are now on the verge of comprehensive variant detection of all forms of variation for the first time with a single assay. We predict that this transition will further transform our understanding of human health and biology and, more importantly, provide novel insights into the dynamic mutational processes shaping our genomes.