Whole genome sequencing identifies candidate genes and mutations that can explain diluted and other colour varieties of domestic canaries (Serinus canaria)

The domestic canary (Serinus canaria) is one of the most common pet birds and has been extensively selected and bred over the last few centuries to constitute many different varieties. Plumage pigmentation is one of the main phenotypic traits that distinguish canary breeds and lines. Feather colours in these birds, similarly to other avian species, are mainly depended on the presence of two major types of pigments: carotenoids and melanins. In this study, we exploited whole genome sequencing (WGS) datasets produced from five canary lines or populations (Black Frosted Yellow, Opal, Onyx, Opal × Onyx and Mogno, some of which carrying different putative dilute alleles), complemented with other WGS datasets retrieved from previous studies, to identify candidate genes that might explain pigmentation variability across canary breeds and varieties. Sequencing data were obtained using a DNA pool-seq approach and genomic data were compared using window-based FST analyses. We identified signatures of selection in genomic regions harbouring genes involved in carotenoid-derived pigmentation variants (CYP2J19, EDC, BCO2 and SCARB1), confirming the results reported by previous works, and identified several other signatures of selection in the correspondence of melanogenesis-related genes (AGRP, ASIP, DCT, EDNRB, KITLG, MITF, MLPH, SLC45A2, TYRP1 and ZEB2). Two putative causative mutations were identified in the MLPH gene that may explain the Opal and Onyx dilute mutant alleles. Other signatures of selection were also identified that might explain additional phenotypic differences between the investigated canary populations

Application of next generation semiconductor-based sequencing for the identification of apis mellifera complementary sex determiner (Csd) alleles from honey dna

The complementary sex determiner (csd) gene plays an essential role in the sex determination of Apis mellifera L. Females develop only if fertilized eggs have functional heterozygous genotypes at this gene whereas males, being haploids, are hemizygous. Two identical csd alleles produce non vital males. In light of the recent decline in honey bee populations, it is therefore important to monitor the allele variability at this gene. In this study, we tested the application of next generation semiconductor-based sequencing technology (Ion Torrent) coupled with environmental honey DNA as a source of honey bee genome information to retrieve massive sequencing data for the analysis of variability at the hypervariable region (HVR) of the csd gene. DNA was extracted from 12 honey samples collected from honeycombs directly retrieved from 12 different colonies. A specifically designed bioinformatic pipeline, applied to analyze a total of about 1.5 million reads, identified a total of 160 different csd alleles, 55% of which were novel. The average number of alleles per sample was compatible with the number of expected patrilines per colony, according to the mating behavior of the queens. Allele diversity at the csd could also provide information useful to reconstruct the history of the honey

BoBafit: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors’ profiles

Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit, able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations’ context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type

Fostering Functional Occupation and Mobility in People with Intellectual Disability and Visual Impairment Through Technology-Aided Support

Objectives: The study assessed a smartphone-based technology system, which was designed to support functional occupation and mobility in people with severe to profound intellectual disability and visual impairment. Methods: The technology system provided (a) verbal orientation cues to guide the participants to a desk with two containers (and two groups of 10 objects that were to be transported to two different destinations), (b) verbal instructions to take the objects (one at a time), (c) verbal orientation cues to reach the destinations where the objects taken had to be transported, (d) instructions to put away the objects at the destinations, and (e) praise and brief periods of preferred stimulation. Seven participants were involved in the study, which was carried out according to a nonconcurrent multiple baseline across participants design. Results: During the baseline (when the technology system was not available), the participants produced few or no correct responses (i.e., failed to collect, transport, and deposit objects at the right destinations). During the intervention phase (i.e., with the support of the technology system), their mean frequency of correct responses per session was between close to 19 and close to 20 (out of a maximum possible of 20) and their mean session duration varied between about 16 and 29 min. Conclusions: The data suggest that the technology system used in this study may be a viable resource to support activity and mobility in people with intellectual and visual disabilities

Pre-surgery supportive and goal-oriented strategies are associated with lower post-surgery perceived distress in women diagnosed with breast cancer

Background: Psycho-oncology literature pointed out that individual health outcomes may depend on patients’ propensity to adopt approach or, conversely, avoidant coping strategies. Nevertheless, coping factors associated with postoperative distress remain unclear, unfolding the lack of tailored procedures to help breast cancer patients manage the psychological burden of scheduled surgery. In view of this, the present study aimed at investigating: 1. pre-/post-surgery distress variations occurring among women diagnosed with breast cancer; 2. the predictivity of approach and avoidant coping strategies and factors in affecting post-surgery perceived distress. Methods: N = 150 patients (mean age = 59.37; SD = ± 13.23) scheduled for breast cancer surgery were administered a screening protocol consisting of the Distress Thermometer (DT) and the Brief-COPE. The DT was used to monitor patients’ distress levels before and after surgery (± 7 days), whereas the Brief-COPE was adopted only preoperatively to evaluate patients’ coping responses to the forthcoming surgical intervention. Non-parametric tests allowed for the detection of pre-/post-surgery variations in patients’ perceived distress. Factor analysis involved the extraction and rotation of principal components derived from the Brief-COPE strategies. The predictivity of such coping factors was investigated through multiple regression (Backward Elimination). Results: The Wilcoxon Signed-Rank Test yielded a significant variation in DT mean scores (TW = -5,68 < -zα/2 = -1,96; p <.001) indicative of lower perceived distress following surgery. The four coping factors extracted and Varimax-rotated were, respectively: 1. cognitive processing (i.e., planning + acceptance + active coping + positive reframing); 2. support provision (i.e., instrumental + emotional support); 3. emotion-oriented detachment (i.e., self-blame + behavioral disengagement + humor + denial); 4. goal-oriented detachment (i.e., self-distraction). Among these factors, support provision (B =.458; β = −.174; t = − 2.03; p =.045), encompassing two approach coping strategies, and goal-oriented detachment (B =.446; β = −.176; t = − 2.06; p =.042), consisting of one avoidant strategy, were strongly related to post-surgery distress reduction. Conclusion: The present investigation revealed that the pre-surgery adoption of supportive and goal-oriented strategies led to postoperative distress reduction among breast cancer patients. These findings highlight the importance of timely psychosocial screening and proactive interventions in order to improve patients’ recovery and prognosis

Lower Prevalence of Chronic Pain in Manifest Huntington’s Disease: A Pilot Observational Study

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of “no Pain” in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning.</jats:p

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways' genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells' differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells' phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val66Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes

Analysis of honey environmental DNA indicates that the honey bee (Apis mellifera L.) trypanosome parasite Lotmaria passim is widespread in the apiaries of the North of Italy

Lotmaria passim is a trypanosomatid that infects honey bees. In this study, we established an axenic culture of L. passim from Italian isolates and then used its DNA as a control in subsequent analyses that investigated environmental DNA (eDNA) to detect this trypasonosomatid. The source of eDNA was honey, which has been already demonstrated to be useful to detect honey bee parasites. DNA from a total of 164 honey samples collected in the North of Italy was amplified with three L. passim specific PCR primers and 78% of the analysed samples gave positive results. These results indicated a high prevalence rate of this trypanosomatid in the North of Italy, where it might be considered another threat to honey bee health