Expanding deep phenotypic spectrum associated with atypical pathogenic structural variations overlapping 15q11-q13 imprinting region.

BACKGROUND: The 15q11-q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader-Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11-q13 duplication syndrome (resulting from the two common forms of duplications-either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. METHODS: Conducted a genomic study to identify the frequency of pathogenic variants impacting the 15q11-q13 region in an ethnically homogenous population from Bangladesh. Screened all known disorders from the DECIPHER database and identified variant enrichment within this cohort. Using the Horizon analysis platform, performed enrichment analysis, requiring at least >60% overlap between a copy number variation and a disorder breakpoint. Deep clinical phenotyping was carried out through multiple examination sessions to evaluate a range of clinical symptoms. RESULTS: This study included eight individuals with clinically suspected PWS/AS, all previously confirmed through chromosomal microarray analysis, which revealed chromosomal breakpoints within the 15q11-q13 region. Among this cohort, six cases (75%) exhibited variable lengths of deletions, whereas two cases (25%) showed duplications. These included one type 2 duplication, one larger atypical duplication, one shorter type 2 deletion, one larger type 1 deletion, and four cases with atypical deletions. Furthermore, thorough clinical assessments led to the diagnosis of four PWS patients, two AS patients, and two individuals with 15q11-q13 duplication syndrome. CONCLUSION: Our deep phenotypic observations identified a spectrum of clinical features that overlap and are unique to PWS, AS, and Dup15q syndromes. Our findings establish genotype-phenotype correlation for patients impacted by variable structural variations within the 15q11-q13 region.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Endophytic Fungal Consortia Enhance Basal Drought-Tolerance in Moringa oleifera by Upregulating the Antioxidant Enzyme (APX) through Heat Shock Factors.

Global climate change has imposed harsh environmental conditions such as drought. Naturally, the most compatible fungal consortia operate synergistically to enhance plant growth and ecophysiological responses against abiotic strains. Yet, little is known about the interactions between phytohormone-producing endophytic fungal symbionts and plant growth under drought stress. The existing research was rationalized to recognize the role of newly isolated drought-resistant, antioxidant-rich endophytic fungal consortia hosting a xerophytic plant, Carthamus oxycantha L., inoculated to Moringa oleifera L. grown under drought stress of 8% PEG (polyethylene glycol-8000). Under drought stress, the combined inoculation of endophytic strain Microdochium majus (WA), Meyerozyma guilliermondi (TG), and Aspergillus aculeatus (TL3) exhibited a significant improvement in growth attributes such as shoot fresh weight (1.71-fold), shoot length (0.86-fold), root length (0.65-fold), dry weight (2.18-fold), total chlorophyll (0.46-fold), and carotenoids (0.87-fold) in comparison to control (8% PEG). Primary and secondary metabolites were also increased in M. oleifera inoculated with endophytic consortia, under drought stress, such as proteins (1.3-fold), sugars (0.58-fold), lipids (0.41-fold), phenols (0.36-fold), flavonoids (0.52-fold), proline (0.6-fold), indole acetic acid (IAA) (4.5-fold), gibberellic acid (GA) (0.7-fold), salicylic acid (SA) (0.8-fold), ascorbic acid (ASA) (1.85-fold), while abscisic acid (ABA) level was decreased (-0.61-fold) in comparison to the control (8% PEG). Under drought stress, combined inoculation (WA, TG, TL3) also promoted the antioxidant activities of enzymes such as ascorbate peroxidase (APX) (3.5-fold), catalase (CAT) activity (1.7-fold), and increased the total antioxidant capacity (TAC) (0.78-fold) with reduced reactive oxygen species (ROS) such as H2O2 production (-0.4-fold), compared to control (8% PEG), and stomatal aperture was larger (3.5-fold) with a lesser decrease (-0.02-fold) in water potential. Moreover, combined inoculation (WA, TG, TL3) up regulated the expression of MolHSF3, MolHSF19, and MolAPX genes in M. oleifera under drought stress, compared to the control (8% PEG), is suggestive of an important regulatory role for drought stress tolerance governed by fungal endophytes. The current research supports the exploitation of the compatible endophytic fungi for establishing the tripartite mutualistic symbiosis in M. oleifera to alleviate the adverse effects of drought stress through strong antioxidant activities.

Seaweeds for the sustainable blue economy development: A study from the south east coast of Bangladesh.

Bangladesh is a maritime country with an area of 118000 km2 which supports a large number of commercially important species. Currently seaweeds are considered as important component of blue economy development in Bangladesh and farming is practiced at small scale level (Hypnea spp, Caulerpha reacemosa, Gelidium sp. are cultured). For the expansion of the seaweed farming in Bangladesh, a complete understanding of social and economic status of current farmers is important. However, information on socio-economic status of seaweed industry in Bangladesh is very limited. Therefore, this study aimed to understand existing culture methods and their cost, marketing channel and problems with seaweed farming in south east coast of Bangladesh. We used questionnaire survey and focus group discussions to collect data from seaweed farmers, researchers, local community and entrepreneurs. The study found that farmers are currently practicing long-line and horizontal net methods for the seaweed farming in the south east coastal region. The study also found that these culture methods are economically profitable. Seaweeds are currently sold locally and a proper value chain for seaweed marketing is still missing. Existing seaweed farmers are facing the problems related to insufficient credits for starting seaweed farming, lack of proper guidelines for farming and processing of harvested seaweed. This study suggests that for industrial level expansion of seaweed production in Bangladesh a proper value chain, development of seaweed derived products, farm monitoring systems, smooth seed supply and information hubs are required.

Molecular Mechanisms of the 1-Aminocyclopropane-1-Carboxylic Acid (ACC) Deaminase Producing Trichoderma asperellum MAP1 in Enhancing Wheat Tolerance to Waterlogging Stress.

Waterlogging stress (WS) induces ethylene (ET) and polyamine (spermine, putrescine, and spermidine) production in plants, but their reprogramming is a decisive element for determining the fate of the plant upon waterlogging-induced stress. WS can be challenged by exploring symbiotic microbes that improve the plant's ability to grow better and resist WS. The present study deals with identification and application of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-producing fungal endophyte Trichoderma asperellum (strain MAP1), isolated from the roots of Canna indica L., on wheat growth under WS. MAP1 positively affected wheat growth by secreting phytohormones/secondary metabolites, strengthening the plant's antioxidant system and influencing the physiology through polyamine production and modulating gene expression. MAP1 inoculation promoted yield in comparison to non-endophyte inoculated waterlogged seedlings. Exogenously applied ethephon (ET synthesis inducer) and 1-aminocyclopropane carboxylic acid (ACC; ET precursor) showed a reduction in growth, compared to MAP1-inoculated waterlogged seedlings, while amino-oxyacetic acid (AOA; ET inhibitor) application reversed the negative effect imposed by ET and ACC, upon waterlogging treatment. A significant reduction in plant growth rate, chlorophyll content, and stomatal conductance was noticed, while H2O2, MDA production, and electrolyte leakage were increased in non-inoculated waterlogged seedlings. Moreover, in comparison to non-inoculated waterlogged wheat seedlings, MAP1-inoculated waterlogged wheat exhibited antioxidant-enzyme activities. In agreement with the physiological results, genes associated with the free polyamine (PA) biosynthesis were highly induced and PA content was abundant in MAP1-inoculated seedlings. Furthermore, ET biosynthesis/signaling gene expression was reduced upon MAP1 inoculation under WS. Briefly, MAP1 mitigated the adverse effect of WS in wheat, by reprogramming the PAs and ET biosynthesis, which leads to optimal stomatal conductance, increased photosynthesis, and membrane stability as well as reduced ET-induced leaf senescence.

An ANKRD26 nonsense somatic mutation in a female with epidermodysplasia verruciformis (Tree Man Syndrome).

Epidermodysplasia verruciformis (EV) is an extremely rare hereditary skin disease characterized by an abnormal susceptibility to the human papilloma virus (HPV) with an increased risk of cutaneous malignancy. Here we report the first female severe EV case in Bangladesh, a 10-year-old girl with a nonsense somatic mutation impacting ANKRD26 gene.