1,721,037 research outputs found
The Prenatal Microbiome: A New Player for Human Health
Full text linkThe last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance
New Insights into the Molecular Bases of Familial Alzheimer's Disease
No full textLike several neurodegenerative disorders, such as Prion and Parkinson diseases, Alzheimer’s disease (AD) is characterized by spreading mechanism of aggregated proteins in the brain in a typical “prion-like” manner. Recent genetic studies have identified in four genes associated with inherited AD (amyloid precursor protein-APP, Presenilin-1, Presenilin-2 and Apolipoprotein E), rare mutations which cause dysregulation of APP processing and alterations of folding of the derived amyloid beta peptide (Aβ). Accumulation and aggregation of Aβ in the brain can trigger a series of intracellular events, including hyperphosphorylation of tau protein, leading to the pathological features of AD. However, mutations in these four genes account for a small of the total genetic risk for familial AD (FAD). Genome-wide association studies have recently led to the identification of additional AD candidate genes. Here, we review an update of well-established, highly penetrant FAD-causing genes with correlation to the protein misfolding pathway, and novel emerging candidate FAD genes, as well as inherited risk factors. Knowledge of these genes and of their correlated biochemical cascade will provide several potential targets for treatment of AD and aging-related disorder
The role of the gut microbiome in the healthy adult status
No full textThe gut microbiome, which hosts up to 1000 bacterial species that encode about 5 million genes, performmany
of the functions required for host physiology and survival. Consequently, it is also known as “our forgotten
organ”. The recent development of next-generation sequencing technologies has greatly improved metagenomic
research. In particular, it has increased our knowledge about the microbiome and its mutually beneficial relationships
with the human host.Microbial colonization begins immediately at birth. Although influenced by a variety
of stimuli, namely, diet, physical activity, travel, illness, hormonal cycles and therapies, the microbiome is practically
stable in healthy adults. This suggests that the microbiome plays a role in themaintenance of a healthy state
in adulthood. Quantitative and qualitative alterations in the composition of the gut microbiome could lead to
pathological dysbiosis, and have been related to an increasing number of intestinal and extra-intestinal diseases.
With the increase in knowledge about gut microbiome functions, it is becoming increasingly more possible to
develop novel diagnostic, prognostic and, most important, therapeutic strategies based on microbiome
manipulation
The evolving role of genetic tests in reproductive medicine
Full text linkInfertility is considered a major public health issue, and approximately 1 out of 6 people worldwide suffer from infertility during their reproductive lifespans. Thanks to technological advances, genetic tests are becoming increasingly relevant in reproductive medicine. More genetic tests are required to identify the cause of male and/or female infertility, identify carriers of inherited diseases and plan antenatal testing. Furthermore, genetic tests provide direction toward the most appropriate assisted reproductive techniques. Nevertheless, the use of molecular analysis in this field is still fragmented and cumbersome. The aim of this review is to highlight the conditions in which a genetic evaluation (counselling and testing) plays a role in improving the reproductive outcomes of infertile couples. We conducted a review of the literature, and starting from the observation of specific signs and symptoms, we describe the available molecular tests. To conceive a child, both partners' reproductive systems need to function in a precisely choreographed manner. Hence to treat infertility, it is key to assess both partners. Our results highlight the increasing importance of molecular testing in reproductive medicine
Genetic Landscape of Familial Melanoma
No full textAbout 10% of all forms of melanoma occur in a familial context and may be due to germline predisposing mutations transmitted as autosomal dominant traits within the affected families. CDKN2A is a highly penetrant gene associated to familial melanomas, being responsible of up to 40% of the cases. Other high, moderate, and low penetrance genes are being discovered, even if their own contribution to melanoma risk is still under debate. Indeed, next generation sequencing-based strategies enable large genomic regions to be analyzed, thus identifying novel candidate genes. These strategies, in diagnostic settings, may also improve the identification of the hereditary cases between all melanomas. The identification of the at-risk subjects gives an important opportunity for cancer surveillance in order to reduce the risk of onset and/or make early diagnosis. In addition, the identification of molecular biomarkers may drive the future development of specific targeted therapies, as already done for other inherited cancer syndromes. Here, we summarize the state of the art regarding the molecular basis of the hereditary susceptibility to develop melanoma
La “whole genome amplification” su singola cellula.
No full textWhole genome amplification on single cell. The whole genome amplification (WGA) is a method for an entire genome amplification, starting with low amounts of DNA. Particularly, it allows downstream analysis, such as genomic screening [i.e., comparative genomic hybridization (CGH) array, next generation sequencing] and single gene mutation detection in single cells. Because WGA could introduce few bias, dependent on different methods, their selection should be related to the application. The first WGA method was based on amplification reaction and differently from a regular polymerase chain reaction (PCR), in which a single genetic locus is amplified, different locus were amplified simultaneously. Nowadays, several methods have been developed for WGA: degenerate oligonucleotide PCR and primer extension preamplification based on PCR, and multiple displacement amplification achieved with isothermal reaction setup. Each WGA approach has limitations, such as the genome coverage, chimeric DNA molecules, preferential allele amplification or allele drop-out and the guanine-cytosine (GC) richness (GC%). In this review, we detailed different WGA methods for single cell and their most important applications, such as cancer diagnosis and reproductive medicine
Comparative metagenomic analysis of human gut microbiome composition using two different bioinformatic pipelines
Full text linkTechnological advances in next-generation sequencing-based approaches have greatly impacted the analysis of microbial
community composition. In particular, 16S rRNA-based methods have been widely used to analyze the whole set of bacteria
present in a target environment. As a consequence, several specific bioinformatic pipelines have been developed to manage these
data.MetaGenome Rapid Annotation using Subsystem Technology (MG-RAST) and Quantitative Insights IntoMicrobial Ecology
(QIIME) are two freely available tools for metagenomic analyses that have been used in a wide range of studies. Here, we report
the comparative analysis of the same dataset with both QIIME and MG-RAST in order to evaluate their accuracy in taxonomic
assignment and in diversity analysis.We found that taxonomic assignment was more accurate with QIIME which, at family level,
assigned a significantly higher number of reads.Thus, QIIME generated a more accurate BIOM file, which in turn improved the
diversity analysis output. Finally, although informatics skills are needed to install QIIME, it offers a wide range of metrics that are
useful for downstream applications and, not less important, it is not dependent on server times
Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease
No full textGenetic studies support the amyloid cascade as the leading hypothesis for the pathogenesis of Alzheimer's disease (AD). Although significant efforts have been made in untangling the amyloid and other pathological events in AD, ongoing interventions for AD have not been revealed efficacious for slowing down disease progression. Recent advances in the field of genetics have shed light on the etiology of AD, identifying numerous risk genes associated with late-onset AD, including genes related to intracellular endosomal trafficking. Some of the bases for the development of AD may be explained by the recently emerging AD genetic "hubs," which include the processing pathway of amyloid precursor protein and the endocytic pathway. The endosomal genetic hub may represent a common pathway through which many pathological effects can be mediated and novel, alternative biological targets could be identified for therapeutic interventions. The aim of this review is to focus on the genetic and biological aspects of the endosomal compartments related to AD progression. We report recent studies which describe how changes in endosomal genetics impact on functional events, such as the amyloidogenic and non-amyloidogenic processing, degradative pathways, and the importance of receptors related to endocytic trafficking, including the 37/67 kDa laminin-1 receptor ribosomal protein SA, and their implications for neurodegenerative diseases
Current Updates on Expanded Carrier Screening: New Insights in the Omics Era
No full textGenetic carrier screening has been successfully used over the last decades to identify individuals at risk of transmitting specific DNA variants to their newborns, thus having an affected child. Traditional testing has been offered based on familial and/or ethnic backgrounds. The development of high-throughput technologies, such as next-generations sequencing, able to allow the study of large genomic regions in a time and cost-affordable way, has moved carrier screening toward a more comprehensive and extensive approach, i.e., expanded carrier screening (ECS). ECS simultaneously analyses several disease-related genes and better estimates individuals’ carrier status. Indeed, it is not influenced by ethnicity and is not limited to a subset of mutations that may arise from poor information in some populations. Moreover, if couples carry out ECS before conceiving a baby, it allows them to obtain a complete estimation of their genetic risk and the possibility to make an informed decision regarding their reproductive life. Despite these advantages, some weakness still exists regarding, for example, the number of genes and the kind of diseases to be analyzed and the interpretation and communication of the obtained results. Once these points are fixed, it is expectable that ECS will become an ever more frequent practice in clinical settings
Should a BRCA2 stop codon human variant, usually considered a polymorphism, be classified as a predisposing mutation?
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