Search Results (25)

Autosomal trisomy, a genetic disorder characterized by the presence of an extra autosome, is a rare but important chromosomal abnormality in horses, often associated with infertility, developmental abnormalities, and reduced life expectancy. This study represents the largest population-level screening for autosomal trisomy in horses; the analysis used single nucleotide polymorphism (SNP) panel genotype intensity data from 17,078 horses, 6601 of which were juveniles (i.e., ≤12 months of age) when genotyped. Using methodologies adapted from similar screening studies in cattle, the only aneuploidy detected was trisomy 27 in two juvenile male Irish Sport Horses (ISH) (0.03% prevalence among juveniles or 0.01% prevalence in the overall population). One ISH colt was cytogenetically confirmed and displayed no overt external phenotypic abnormalities, while cytogenetics was not undertaken on the other ISH colt, nor was it phenotypically assessed. Parentage analysis revealed that one ISH colt inherited two different copies of chr27 from the sire, demonstrating heterodisomy, likely due to a nondisjunction event during meiosis I in the sire. The other ISH colt inherited two different copies of chr27 from the dam, also indicating heterodisomy; the dam was 23 years of age when the colt was born. Based on the observed prevalence of autosomal trisomy, it can be estimated that at least 3 foals per 10,000 live births are likely to have autosomal trisomy. Though, given that only 74 (i.e., 0.004%) of horses were genotyped within a month of birth, this is likely an underestimate. The economic consequence of undiagnosed trisomy in high-value breeding horses that are potentially infertile could be substantial. As horse genotyping for parentage verification and discovery is transitioning to medium-density single nucleotide polymorphism panels, routine genomic screening for autosomal aneuploidy could be readily undertaken and potentially should form a standard screening prerequisite along with other genetic defects at horse sales. Currently, thoroughbred horses registered for racing are not genotyped, and only a limited number of sport horse studbooks are using SNP genotyping. This highlights an opportunity for those already genotyping to expand their support for breeders through low-cost, high-value chromosomal screening at the time of registration rather than incurring additional costs over the horse’s life cycle to determine the root cause of certain phenotypes owing to the undiagnosed trisomy. Full article

Studying the cell cycle is essential for understanding the molecular mechanisms that regulate cell division, growth, and differentiation in living organisms. However, mitosis constitutes only a brief phase of the overall cell cycle, making its analysis challenging in asynchronous cell populations due to its transient and dynamic nature. Cell synchronization methods help to enrich populations at specific cell cycle stages, including mitosis, typically by using chemical inhibitors to arrest cells at defined checkpoints. However, many existing protocols rely on combinations of inhibitors that interfere with normal mitotic progression, disrupting dynamics and causing side effects such as chromosome non-disjunction or lagging chromosomes, which limit their applicability. In this study, we present an RO3306 block-and-release strategy to selectively enrich cell populations at defined mitotic stages without compromising cell viability or disrupting their progression to mitotic exit. This approach provides a reliable method for studying mitotic events with high temporal resolution. Furthermore, by preserving mitotic integrity, it offers a valuable framework for investigating the molecular mechanisms of cell division and the processes driving genomic instability in human cells. Full article

Turner syndrome (TS) is an X monosomy-related disorder caused by X chromosome nondisjunction during embryonic development. Patients with TS have only one intact X chromosome, with the other either completely or partially lost. TS affects various tissues, including the liver, kidneys, brain, cardiovascular system, and ovaries. These abnormalities are suggested to involve an altered dosage of escape genes that evade X chromosome inactivation. However, the mechanisms and roles of these escape genes in the TS phenotype remain unclear. We hypothesized that the expression levels of escape genes differ between wild-type (WT) and TS cell lines. In this study, we generated induced pluripotent stem cell (iPSC) lines from WT and TS fibroblasts and examined the expression levels of escape genes in both undifferentiated fibroblasts and reprogrammed iPSCs from WT and TS samples. The reprogrammed WT and TS iPSCs exhibited general characteristics of pluripotency, including the expression of pluripotency markers and the potential to differentiate into all three germ layers. Forty-five escape genes were differentially expressed between the WT and TS cell lines. Among these, five genes (ATP7A, PHKA1, EBP, ZFX, and SMC1A) were suggested to be implicated in the TS phenotype. However, further studies using additional cell lines are necessary to clarify the correlation between TS and escape genes. Full article

Supernumerary B chromosomes (Bs) have been documented in over 2000 species across the plant, animal, and fungal kingdoms, representing one of the most intriguing components of the genome that have consistently garnered significant attention in the past. These Bs form a distinct category of chromosomes that are not deemed essential. While coexisting with the standard set of chromosomes in an organism, the copy numbers of Bs can vary among individuals within a population or even among cells within a single organism. Multiple processes, including chromosomal rearrangement, uneven segregation, chromatid non-disjunction, and deletion in specific regions, lead to the formation of the Bs from the A chromosome. These dispensable Bs possess their own genetic content and do not undergo recombination with A chromosomes. Although various roles of Bs in breeding have been explored in the literature, their specific role in wheat improvement remains unclear. The understanding of their origins, composition, and evolutionary history in wheat is still incomplete. Therefore, this review discusses the current knowledge of the genetic makeup of Bs, their functions, their relationship with A chromosomes, and the morphogenetic consequences in the context of wheat. Full article

Down syndrome arises from chromosomal non-disjunction during gametogenesis, resulting in an additional chromosome. This anomaly presents with intellectual impairment, growth limitations, and distinct facial features. Positive correlation exists between maternal age, particularly in advanced cases, and the global annual incidence is over 200,000 cases. Early interventions, including first and second-trimester screenings, have improved DS diagnosis and care. The manifestations of Down syndrome result from complex interactions between genetic factors linked to various health concerns. To explore recent advancements in Down syndrome research, we focus on the integration of artificial intelligence (AI) and machine learning (ML) technologies for improved diagnosis and management. Recent developments leverage AI and ML algorithms to detect subtle Down syndrome indicators across various data sources, including biological markers, facial traits, and medical images. These technologies offer potential enhancements in accuracy, particularly in cases complicated by cognitive impairments. Integration of AI and ML in Down syndrome diagnosis signifies a significant advancement in medical science. These tools hold promise for early detection, personalized treatment, and a deeper comprehension of the complex interplay between genetics and environmental factors. This review provides a comprehensive overview of neurodevelopmental and cognitive profiles, comorbidities, diagnosis, and management within the Down syndrome context. The utilization of AI and ML represents a transformative step toward enhancing early identification and tailored interventions for individuals with Down syndrome, ultimately improving their quality of life. Full article

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997–2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS. Full article

Neural Architecture Search (NAS) has been widely applied across various fields, revealing intriguing patterns in the resulting optimized topologies. In this paper, we compare the topologies generated by NAS across two different experiments: linguistic grammaticality judgment and the MNIST task. Our analysis reveals a distinctive fork-like structure that consistently emerges in both experiments. Interestingly, this structure is highly effective despite not being typically designed by human experts. The emergence of this fork-like structure sheds new light on the potential of NAS to provide alternative designs that go beyond incremental improvements. Our paper offers a fresh perspective on automated architecture design, highlighting the potential of NAS to enable innovative approaches that can be applied across multiple domains. Full article

It is a well-known fact that the reproductive organs in women, especially oocytes, are exposed to numerous regulatory pathways and environmental stimuli. The maternal age is one cornerstone that influences the process of oocyte fertilization. More precisely, the longer a given oocyte is in the waiting-line to be ovulated from menarche to menopause, the longer the duration from oogenesis to fertilization, and therefore, the lower the chances of success to form a viable embryo. The age of menarche in girls ranges from 10 to 16 years, and the age of menopause in women ranges from approximately 45 to 55 years. Researchers are paying attention to the regulatory pathways that are impacting the oocyte at the very beginning during oogenesis in fetal life to discover genes and proteins that could be crucial for the oocyte’s lifespan. Due to the general trend in industrialized countries in the last three decades, women are giving birth to their first child in their thirties. Therefore, maternal age has become an important factor impacting oocytes developmental competence, since the higher a woman’s age, the higher the chances of miscarriage due to several causes, such as aneuploidy. Meiotic failures during oogenesis, such as, for instance, chromosome segregation failures or chromosomal non-disjunction, are influencing the latter-mentioned aging-related phenomenon too. These errors early in life of women can lead to sub- or infertility. It cannot be neglected that oogenesis is a precisely orchestrated process, during which the oogonia and primary oocytes are formed, and RNA synthesis takes place. These RNAs are crucial for oocyte growth and maturation. In this review, we intend to describe the relevance of regulatory pathways during the oogenesis in women. Furthermore, we focus on molecular pathways of oocyte developmental competence with regard to maternal effects during embryogenesis. On the background of transcriptional mechanisms that enable the transition from a silenced oocyte to a transcriptionally active embryo, we will briefly discuss the potential of induced pluripotent stem cells. Full article

The application of polyploidy in sustainable agriculture has already brought much appreciation among researchers. Polyploidy may occur naturally or can be induced in the laboratory using chemical or gaseous agents and results in complete chromosome nondisjunction. This comprehensive review described the potential of polyploidization on plants, especially its role in crop improvement for enhanced production and host-plant resistance development against pests and diseases. An in-depth investigation on techniques used in the induction of polyploidy, cytogenetic evaluation methods of different ploidy levels, application, and current research trends is also presented. Ongoing research has mainly aimed to bring the recurrence in polyploidy, which is usually detected by flow cytometry, chromosome counting, and cytogenetic techniques such as fluorescent in situ hybridization (FISH) and genomic in situ hybridization (GISH). Polyploidy can bring about positive consequences in the growth and yield attributes of crops, making them more tolerant to abiotic and biotic stresses. However, the unexpected change in chromosome set and lack of knowledge on the mechanism of stress alleviation is hindering the application of polyploidy on a large scale. Moreover, a lack of cost–benefit analysis and knowledge gaps on the socio-economic implication are predominant. Further research on polyploidy coupling with modern genomic technologies will help to bring real-world market prospects in the era of changing climate. This review on polyploidy provides a solid foundation to do next-generation research on crop improvement. Full article

Acrylamide (AA), is a chemical with multiple industrial applications, however, it can be found in foods that are rich in carbohydrates. Due to its genotoxic and cytotoxic effects, AA has been classified as a potential carcinogen. With the use of spectrophotometry, ICP-OES, fluorescence spectroscopy, and microscopy cell growth, metabolic activity, apoptosis, ROS production, MDA formation, CAT and SOD activity, ionome balance, and chromosome segregation were determined in Schizosaccharomyces pombe. AA caused growth and metabolic activity retardation, enhanced ROS and MDA production, and modulated antioxidant enzyme activity. This led to damage to the cell homeostasis due to ionome balance disruption. Moreover, AA-induced oxidative stress caused alterations in the cell cycle regulation resulting in chromosome segregation errors, as 4.07% of cells displayed sister chromatid non-disjunction during mitosis. Ascorbic acid (AsA, Vitamin C), a strong natural antioxidant, was used to alleviate the negative impact of AA. Cell pre-treatment with AsA significantly improved AA impaired growth, and antioxidant capacity, and supported ionome balance maintenance mainly due to the promotion of calcium uptake. Chromosome missegregation was reduced to 1.79% (44% improvement) by AsA pre-incubation. Results of our multiapproach analyses suggest that AA-induced oxidative stress is the major cause of alteration to cell homeostasis and cell cycle regulation. Full article

Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX) and is probably due to a nondisjunction during the meiosis. So far, only five cases prenatally diagnosed were described. The main features in 49,XXXXX karyotype include severe intellectual disability with delayed speech development, short stature, facial dysmorphisms, osseous and articular abnormalities, congenital heart malformations, and skeletal and limb abnormalities. Prenatal diagnosis is often difficult due to the lack of a clear echographic sign like nuchal translucency (NT), and mostly cases were postnatally described. We report the first case of a 49,XXXXX female that was detected by non-invasive prenatal screening (NIPS), quantitative fluorescence polymerase chain reaction (QF-PCR) and a fetal karyotype. Full article

With the advances in genomic sequencing, many organisms with novel biological properties are ripe for use as emerging model organisms. However, to make full use of them, transformation methods need to be developed to permit genome editing. Here, we present the development of transformation for the fungus fly Bradysia (Sciara) coprophila; this may serve as a paradigm for the development of transformation for other emerging systems, especially insects. Bradysia (Sciara) has a variety of unique biological features, including locus-specific developmentally regulated DNA amplification, chromosome imprinting, a monopolar spindle in male meiosis I, non-disjunction of the X chromosome in male meiosis II, X chromosome elimination in early embryogenesis, germ-line-limited (L) chromosomes and high resistance to radiation. Mining the unique biology of Bradysia (Sciara) requires a transformation system to test mutations of DNA sequences that may play roles for these features. We describe a Bradysia (Sciara) transformation system using a modified piggyBac transformation vector and detailed protocols we have developed to accommodate Bradysia (Sciara) specific requirements. This advance will provide a platform for us and others in the growing Bradysia (Sciara) community to take advantage of this unique biological system. In addition, the versatile piggyBac vectors described here and transformation methods will be useful for other emerging model systems. Full article

Drosophila has been a model system for meiosis since the discovery of nondisjunction. Subsequent studies have determined that crossing over is required for chromosome segregation, and identified proteins required for the pairing of chromosomes, initiating meiotic recombination, producing crossover events, and building a spindle to segregate the chromosomes. With a variety of genetic and cytological tools, Drosophila remains a model organism for the study of meiosis. This review focusses on meiosis in females because in male meiosis, the use of chiasmata to link homologous chromosomes has been replaced by a recombination-independent mechanism. Drosophila oocytes are also a good model for mammalian meiosis because of biological similarities such as long pauses between meiotic stages and the absence of centrosomes during the meiotic divisions. Full article

Human female fertility and reproductive lifespan decrease significantly with age, resulting in an extended post-reproductive period. The central dogma in human female reproduction contains two important aspects. One is the pool of oocytes in the human ovary (the ovarian reserve; approximately 10⁶ at birth), which diminishes throughout life until menopause around the age of 50 (approximately 10³ oocytes) in women. The second is the quality of oocytes, including the correctness of meiotic divisions, among other factors. Notably, the increased rate of sub- and infertility, aneuploidy, miscarriages, and birth defects are associated with advanced maternal age, especially in women above 35 years of age. This postponement is also relevant for human evolution; decades ago, the female aging-related fertility drop was not as important as it is today because women were having their children at a younger age. Spindle assembly is crucial for chromosome segregation during each cell division and oocyte maturation, making it an important event for euploidy. Consequently, aberrations in this segregation process, especially during the first meiotic division in human eggs, can lead to implantation failure or spontaneous abortion. Today, human reproductive medicine is also facing a high prevalence of aneuploidy, even in young females. However, the shift in the reproductive phase of humans and the strong increase in errors make the problem much more dramatic at later stages of the female reproductive phase. Aneuploidy in human eggs could be the result of the non-disjunction of entire chromosomes or sister chromatids during oocyte meiosis, but partial or segmental aneuploidies are also relevant. In this review, we intend to describe the relevance of the spindle apparatus during oocyte maturation for proper chromosome segregation in the context of maternal aging and the female reproductive lifespan. Full article

This paper proposes a deep neural network structuring methodology through a genetic algorithm (GA) using chromosome non-disjunction. The proposed model includes methods for generating and tuning the neural network architecture without the aid of human experts. Since the original neural architecture search (henceforth, NAS) was announced, NAS techniques, such as NASBot, NASGBO and CoDeepNEAT, have been widely adopted in order to improve cost- and/or time-effectiveness for human experts. In these models, evolutionary algorithms (EAs) are employed to effectively enhance the accuracy of the neural network architecture. In particular, CoDeepNEAT uses a constructive GA starting from minimal architecture. This will only work quickly if the solution architecture is small. On the other hand, the proposed methodology utilizes chromosome non-disjunction as a new genetic operation. Our approach differs from previous methodologies in that it includes a destructive approach as well as a constructive approach, and is similar to pruning methodologies, which realizes tuning of the previous neural network architecture. A case study applied to the sentence word ordering problem and AlexNet for CIFAR-10 illustrates the applicability of the proposed methodology. We show from the simulation studies that the accuracy of the model was improved by 0.7% compared to the conventional model without human expert. Full article