Cardiovascular diseases are the leading cause of global deaths, and many risk factors contribute to their pathogenesis. In this context, prostanoids, which derive from arachidonic acid, have ...attracted attention for their involvement in cardiovascular homeostasis and inflammatory processes. Prostanoids are the target of several drugs, but it has been shown that some of them increase the risk of thrombosis. Overall, many studies have shown that prostanoids are tightly associated with cardiovascular diseases and that several polymorphisms in genes involved in their synthesis and function increase the risk of developing these pathologies. In this review, we focus on molecular mechanisms linking prostanoids to cardiovascular diseases and we provide an overview of genetic polymorphisms that increase the risk for cardiovascular disease.
Genetic markers (especially short tandem repeats or STRs) located on the X chromosome are a valuable resource to solve complex kinship cases in forensic genetics in addition or alternatively to ...autosomal STRs. Groups of tightly linked markers are combined into haplotypes, thus increasing the discriminating power of tests. However, this approach requires precise knowledge of the recombination rates between adjacent markers. The International Society of Forensic Genetics recommends that recombination rate estimation on the X chromosome is performed from pedigree genetic data while taking into account the confounding effect of mutations. However, implementations that satisfy these requirements have several drawbacks: they were never publicly released, they are very slow and/or need cluster-level hardware and strong computational expertise to use. In order to address these key concerns we developed Recombulator-X, a new open-source Python tool. The most challenging issue, namely the running time, was addressed with dynamic programming techniques to greatly reduce the computational complexity of the algorithm. Compared to the previous methods, Recombulator-X reduces the estimation times from weeks or months to less than one hour for typical datasets. Moreover, the estimation process, including preprocessing, has been streamlined and packaged into a simple command-line tool that can be run on a normal PC. Where previous approaches were limited to small panels of STR markers (up to 15), our tool can handle greater numbers (up to 100) of mixed STR and non-STR markers. In conclusion, Recombulator-X makes the estimation process much simpler, faster and accessible to researchers without a computational background, hopefully spurring increased adoption of best practices.
Sudden cardiac death (SCD) is an unexpected natural death due to cardiac causes, usually happening within one hour of symptom manifestation or in individuals in good health up to 24 h before the ...event. Genomic screening has been increasingly applied as a useful approach to detecting the genetic variants that potentially contribute to SCD and helping the evaluation of SCD cases in the post-mortem setting. Our aim was to identify the genetic markers associated with SCD, which might enable its target screening and prevention. In this scope, a case-control analysis through the post-mortem genome-wide screening of 30 autopsy cases was performed. We identified a high number of novel genetic variants associated with SCD, of which 25 polymorphisms were consistent with a previous link to cardiovascular diseases. We ascertained that many genes have been already linked to cardiovascular system functioning and diseases and that the metabolisms most implicated in SCD are the lipid, cholesterol, arachidonic acid, and drug metabolisms, suggesting their roles as potential risk factors. Overall, the genetic variants pinpointed herein might be useful markers of SCD, but the novelty of these results requires further investigations.
Rapidly Mutating Y-STRs (RM Y-STRs) were recently introduced in forensics in order to increase the differentiation of Y-chromosomal profiles even in case of close relatives. We estimate RM Y-STRs ...mutation rates and their power to discriminate between related individuals by using samples extracted from a wide set of paternal pedigrees and by comparing RM Y-STRs results with those obtained from the Y-filer set. In addition, we tested the ability of RM Y-STRs to discriminate between unrelated individuals carrying the same Y-filer haplotype, using the haplogroup R-M269 (reportedly characterised by a strong resemblance in Y-STR profiles) as a case study. Our results, despite confirming the high mutability of RM Y-STRs, show significantly lower mutation rates than reference germline ones. Consequently, their power to discriminate between related individuals, despite being higher than the one of Y-filer, does not seem to improve significantly the performance of the latter. On the contrary, when considering R-M269 unrelated individuals, RM Y-STRs reveal significant discriminatory power and retain some phylogenetic signal, allowing the correct classification of individuals for some R-M269-derived sub-lineages. These results have important implications not only for forensics, but also for molecular anthropology, suggesting that RM Y-STRs are useful tools for exploring subtle genetic variability within Y-chromosomal haplogroups.
Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly ...relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few studies have evaluated the efficacy of vaginal mRNA markers in women of different ages. In this multicentric study, a 19-plex mRNA profiling assay including vaginal-specific markers (CYP2B7P1, MUC4, MYOZ1) was tested in a collection of 6–20-month-old vaginal swabs obtained from pre- (n = 84) and postmenopausal (n = 55) female volunteer donors. Overall, participating laboratories were able to correctly identify ~85% of samples as vaginal mucosa by mRNA profiling. The assay’s success rate did not differ between the two age groups and was not affected by the time interval between swab collection and RNA analysis. MYOZ1 resulted a less sensitive vaginal marker compared to MUC4 and CYP2B7P1. A significant relative increase in the contribution to the total amplification signal was observed for MUC4, compared to CYP2B7P1 and MYOZ1, in postmenopausal women. Observation of other body fluids and tissues different from vaginal mucosa was also evaluated in connection to information on previous sexual activity and menstrual cycle phase at the time of sampling.
Forensic DNA phenotyping (FDP) provides the ability to predict the human external traits from unknown sample donors, directly from minute amounts of DNA found at the crime scene. We developed a MPS ...multiplex assay, with the aim of genotyping all 41 DNA markers included in the HIrisPlex-S system for simultaneous prediction of eye, hair and skin colours. Forensic samples such as blood, skeletal remains, touch DNA, saliva swab, artificially degraded samples together with individuals with known phenotypes and a set of 2800 M control DNA were sequenced on the Ion Torrent platform in order to evaluate the concordance testing results and the forensic suitability of the 41-plex MPS assay. The panel was evaluated by testing a different number of PCR cycles and the volume of reagents for library preparation. The study demonstrated that full and reliable profiles were obtained with 0.1–5 ng, even with high degraded DNA. The increment of the number of PCR cycles results in an improvement of correctly genotyping and phenotyping for samples with low amounts of degraded DNA but higher frequencies of artefacts were found. The high DNA degradation level did not influence the correct genotyping and phenotyping and the critical parameter affecting the result is the quantity of input DNA. Eye and hair colour was predicted in 92.60% of individuals and skin colour in 85.15% of individuals. The results suggest that this MPS assay is robust, highly sensitive and useful for human pigmentation prediction in the forensic genetic field.
Roccapelago (MO) is a small village located in the Northern Central Apennines, with a population of 31 inhabitants (2014). In 2010, more than 400 individuals dated between the end of the 16th and the ...18th century, many of which partially mummified, were discovered in the crypt of the church. This small village, because of its geographical location and surrounding environment, seems to possess the characteristics of a genetic isolate, useful for population genetics and genealogical analyses. Thus, a diachronic study of DNA aimed at investigating the structure and dynamics of the population of Roccapelago over the about 4 centuries, was conducted by analyzing ancient and modern inhabitants of the village. The 14 modern samples were selected by considering both the founder surnames of the village, identified thanks to the study of parish registers, and the grandparent’s criterion. From 25 ancient mummies, morphologically assigned to male individuals, the petrous bone, that harbors high DNA amounts, was selected for the DNA extraction. The quantification and qualitative assessment of total human male DNA were evaluated by a real-time PCR assay using the Quantifiler Trio DNA Quantification Kit and multiplex PCR of 27 Y-chromosome short tandem repeat (Y-STR) markers included in the Yfiler Plus PCR Amplification Kit, with seven rapidly mutating Y-STR loci for improving discrimination of male lineages, was performed to genotype the samples. Y-STRs were analyzed according to the criteria of ancient DNA (aDNA) analysis to ensure that authentic DNA typing results were obtained from these ancient samples. The molecular analysis showed the usefulness of the Y chromosome to identify historically relevant remains and discover patterns of relatedness in communities moving from anthropology to genetic genealogy and forensics.
In toxicogenetics, an integrative approach including the prediction of phenotype based on post-mortem genotyping of drug-metabolising enzymes might help explain the cause of death (CoD) and manner of ...death (MoD). The use of concomitant drugs, however, might lead to phenoconversion, a mismatch between the phenotype based on the genotype and the metabolic profile actually observed after phenoconversion. The aim of our study was to evaluate the phenoconversion of
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drug-metabolising enzymes in a series of autopsy cases tested positive for drugs that are substrates, inducers, or inhibitors of these enzymes. Our results showed a high rate of phenoconversion for all enzymes and a statistically significant higher frequency of poor and intermediate metabolisers for
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after phenoconversion. No association was found between phenotypes and CoD or MoD, suggesting that, although phenoconversion might be useful for a forensic toxicogenetics approach, more research is needed to overcome the challenges arising from the post-mortem setting.
Innovative technological approaches are crucial to enhance naturalistic museum collections and develop information repositories of relevant interest to science, such as threatened animal taxa. In ...this context, museomics is an emerging discipline that provides a novel approach to the enhancement and exploitation of these collections. In the present study, the discovery of a neglected lion skeleton in the Museum of Zoology “Pietro Doderlein” of the University of Palermo (Italy) offered the opportunity to undertake a multidisciplinary project. The aims of the study consisted of the following: (i) adding useful information for museographic strategies, (ii) obtaining a new genetic data repository from a vulnerable species, (iii) strengthening public awareness of wildlife conservation, and (iv) sharing new learning material. The remains of the lion were examined with a preliminary osteological survey, then they were restored by means of 3D printing of missing skeletal fragments. Phylogenetic analyses based on cytochrome b sequence clearly indicate that the specimen belongs to the Central Africa mitochondrial clade. At the end of the study, the complete and restored skeleton was exhibited, along with all of the information and data available from this project. This study shows a useful approach for the restoration and enhancement of a museum specimen, with important opportunities for preserving biodiversity and driving specific conservation policies, but also for providing Life Science learning material.
The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, ...the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.
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