White Gene Research Articles

Ghrelin deficiency sex-dependently alters food intake, locomotor activity, and white adipose tissue gene expression in a binge-eating mouse model

Ghrelin deficiency sex-dependently alters food intake, locomotor activity, and white adipose tissue gene expression in a binge-eating mouse model

Platelet to white blood cell ratio was an independent prognostic predictor in acute myeloid leukemia

ABSTRACT Background Recently, platelet to white blood cell ratio (PWR) was reported as an independent prognostic predictor in acute promyelocytic leukemia. Acute myeloid leukemia (AML) often presents with abnormal platelet counts and white blood cell counts (WBC) at disease diagnosis. However, the clinical impact of PWR on cytogenetically normal AML (CN-AML) is still unclear. Therefore, we evaluate its prognostic impact on CN-AML patients. Methods We recorded the clinical information at the time of disease diagnosis, and calculated the ratio of platelet counts to WBC in 338 patients with CN-AML. To assess the prognostic value of PWR, we divided patients into low, intermediate and high group based on the values of PWR. The independent prognostic value of PWR was investigated in the context of the well-established predictors including white blood cell counts, age, and genes of NPM1, FLT3-ITD, CEBPA, and DNMT3A mutations. Receiver operating characteristic (ROC) curve was used to assess the performance of its prognostic prediction. Results Higher PWR have the higher levels of platelet counts, but lower levels of white blood cell counts, percentage of bone marrow blasts, FLT3-ITD and NPM1 mutations. The performance of survival prediction was comparable between PWR alone and combined molecular biomarkers. Moreover, PWR had the additional prognostic information to the molecular biomarkers. Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. Conclusion We found PWR was an independent prognostic predictor in CN-AML.

Involvement of VIVID in white light-responsive pigmentation, sexual development and sterigmatocystin biosynthesis in the filamentous fungus Podospora anserina.

Light serves as a source of information and regulates diverse physiological processes in living organisms. Fungi perceive and respond to light through a complex photosensory system. Fungi have evolved the desensitization mechanism to adapt to the changing light signal in a natural environment. White light exerts multiple essential impacts on the model filamentous fungus Podospora anserina. However, the light sensing and response in this species has not been investigated. In this study, we demonstrated that the loss of function of the light desensitization protein VIVID (VVD) in P. anserina triggered exacerbated light responses and therefore led to drastic morphological and physiological changes. The white light-sensitive mutant Δvvd showed growth reduction, spermatia overproduction, enhanced hyphae pigmentation and reduced oxidative stress tolerance. We observed the decreased expression level of sterigmatocystin gene cluster by transcriptome analysis and finally detected the reduced production of sterigmatocystin in Δvvd in response to white light. Our data indicate that VVD acts as a repressor of white collar complex. This study exhibits a vital role of VVD in governing white light-responsive gene expression and secondary metabolite production and contributes to a better understanding of the photoreceptor VVD in P. anserina.

Identification and expression analysis of phosphate transporter (PHT) gene family in Lupinus albus cluster root under phosphorus stress.

According to global estimation, 5.7 billion hectares of agricultural land contain limited phosphorus (P) availability leading to insufficient plant growth and productivity. Internal phosphate transporters play an essential role in mediating P mobilization and uptake from the soil. White lupin (Lupinus albus) is a cluster root (CR) forming crop with great potential to survive under P limited soil. However, it is imperative to identify and characterize the phosphate transporter (PHT) gene family in plants to validate their involvement in solving P deficiency problems. The recent availability of white lupin high-quality genome allowed us an exhaustive searches in the whole genome and identified five phosphates transporters subfamilies, including 35 putative genes that are unevenly distributed on 16 chromosomes. The LaPHT1 subfamily contained eight genes, LaPHT2 subfamily have three, LaPHT3 subfamily have eight, LaPHT4 subfamily have nine, and LaPHO subfamily has seven. Gene structure and duplication were also examined in detail. Syntenic analysis revealed that white lupin PHT family members had maximum the collinear relationship with those in L. angustifolius followed by Phaseolus vulgaris but showed the least collinear relationship with those in Arabidopsis. Gene ontology (GO) analysis revealed that the in white lupin PHT genes were enriched in functions regulated P uptake, transport, and recycling mechanisms. RT-qPCR was performed to evaluate the transcript levels of LaPHT genes in different parts of CR under P deficient hydroponic culture. Our study would provide better understanding the genetic evolution and expression phosphate of phosphate transporters in L. albus CR under P deficiency. It will also be helpful for further functional-based studies to solve P deficiency-related issues and mitigate P stress responses.

Brown adipose tissue involution associated with progressive restriction in progenitor competence.

Human brown adipose tissue (BAT) undergoes progressive involution. This involution process is not recapitulated in rodents, and the underlying mechanisms are poorly understood. Here we show that the interscapular BAT (iBAT) of rabbits whitens rapidly during early adulthood. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied by loss of brown adipogenic competence of progenitors. Single-cell RNA sequencing reveals that rabbit and human iBAT progenitors highly express the FSTL1 gene. When iBAT involutes in rabbits, adipocyte progenitors reduce FSTL1 expression and are refractory to brown adipogenic recruitment. Conversely, FSTL1 is constitutively expressed in mouse iBAT to sustain WNT signaling and prevent involution. Progenitor incompetence and iBAT paucity can be induced in mice by genetic deletion of the Fstl1 gene or ablation of Fstl1+ progenitors. Our results highlight the hierarchy and dynamics of the BAT progenitor compartment and implicate the functional incompetence of FSTL1-expressing progenitors in BAT involution.

Development of linkage InDel markers of the white petal gene based on whole-genome re-sequencing data in <italic>Brassica napus</italic> L.

<p id="C3">InDel is widely distributed across the genome and occurs in a high density and large numbers in a genome. To date, the researches about linkage InDel markers of the white petal gene in <italic>B. napus</italic> L are very less yet. In this study, we constructed the F₂ mapping population from the cross between DH Y05 (yellow petal) and DH W01 (white petal). Two bulks with 30 yellow petal lines and 30 white petal lines of F₂ population were constructed by mixing an equal amount of DNA. Then two bulks and parents were performed 30× whole-genome re-sequencing. Darmor-bzh as the reference genome was aligned to sequence data from the two bulks and parents. QTL-seq and PoPoolation2 workflow were applied to identify the candidate region of the white petal gene. A major candidate region was identified on chromosome C03 (52-54 Mb) of Darmor-bzh. The insertion-deletion (InDel) sites can be visualized in candidate interval by Integrative Genomics Viewer (IGV). Based on these Indel variations, we used Vector and Blast to design InDel primers. Eight InDel markers closely linked to the white petal gene were screened by Polyacrylamide gel electrophoresis (PAGE). In summary, these results provide a basis for fine mapping white petal gene and InDel molecular marker located on functional genes as well as molecular marker assisted selection breeding.

Mapping and CRISPR homology-directed repair of a recessive white eye mutation in Plodia moths

SummaryThe pantry moth Plodia interpunctella is a worldwide pest of stored food products and a promising laboratory model system for lepidopteran functional genomics. Here we describe efficient methods for precise genome editing in this insect. A spontaneous recessive white-eyed phenotype maps to a frameshift deletion (c.737delC) in the white gene. CRISPR NHEJ mutagenesis of white replicates this phenotype with high rates of somatic biallelic knockout. G0 individuals with mutant clones on both eyes produced 100% mutant progeny, making white an ideal marker for co-conversion when targeting other genes. CRISPR HDR experiments corrected c.737delC and reverted white eyes to a pigmented state in 37% of G0 mosaic adults. These repaired alleles showed practical rates of germline transmission in backcrosses, demonstrating the potential of the technique for precise genome editing. Plodia offers a promising avenue for research in this taxon because of its lab-ready features, egg injectability, and editability.

Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons.

The social environment is a major determinant of morbidity, mortality and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune-stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, while we observe pronounced rank-related differences in baseline immune gene activity, only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

Genome-wide association study reveals white lupin candidate gene involved in anthracnose resistance

Key messageGWAS identifies candidate gene controlling resistance to anthracnose disease in white lupin.White lupin (Lupinus albus L.) is a promising grain legume to meet the growing demand for plant-based protein. Its cultivation, however, is severely threatened by anthracnose disease caused by the fungal pathogen Colletotrichum lupini. To dissect the genetic architecture for anthracnose resistance, genotyping by sequencing was performed on white lupin accessions collected from the center of domestication and traditional cultivation regions. GBS resulted in 4611 high-quality single-nucleotide polymorphisms (SNPs) for 181 accessions, which were combined with resistance data observed under controlled conditions to perform a genome-wide association study (GWAS). Obtained disease phenotypes were shown to highly correlate with overall three-year disease assessments under Swiss field conditions (r > 0.8). GWAS results identified two significant SNPs associated with anthracnose resistance on gene Lalb_Chr05_g0216161 encoding a RING zinc-finger E3 ubiquitin ligase which is potentially involved in plant immunity. Population analysis showed a remarkably fast linkage disequilibrium decay, weak population structure and grouping of commercial varieties with landraces, corresponding to the slow domestication history and scarcity of modern breeding efforts in white lupin. Together with 15 highly resistant accessions identified in the resistance assay, our findings show promise for further crop improvement. This study provides the basis for marker-assisted selection, genomic prediction and studies aimed at understanding anthracnose resistance mechanisms in white lupin and contributes to improving breeding programs worldwide.

Serglycin Is Involved in Adipose Tissue Inflammation in Obesity

Abstract Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

Identification of bZIP transcription factors and their responses to brown spot in pear.

Basic leucine zipper (bZIP) is a conserved transcription factor (TF) widely present in eukaryotes, and it plays an important role in regulating plant growth and stress responses. To better understand the white pear bZIP gene family, comprehensive bioinformatics analysis of the pear genome was performed. A total of 84 PbbZIP genes were identified, which were divided into 13 subfamilies by phylogenetic analysis. The 84 PbbZIP genes were all located in the nucleus, and 77 of those genes were unevenly distributed across the 17 chromosomes of white pear. The other 7 PbbZIP genes were located on the scaffold. Subsequent expression profile analysis showed that PbbZIP genes in exocarp were significantly upregulated or downregulated in ‘Huangguan’ pear with brown spot (BS) compared with healthy pear and in response to hormonal treatment with gibberellin A3 (GA3). These results provide helpful insights into the characteristics of PbbZIP genes and their responses to BS in ‘Huangguan’ pear.

Abstract CC06-01: Identifying therapeutic options for patients with advanced prostate cancer through genes in liquid biopsies

Abstract Prostate cancer (PCa) is curable in most men but becomes lethal for patients with metastases at diagnosis and those who experience biochemical recurrence (BCR) after curative therapies. Androgen deprivation therapy is given upon BCR, but patients inevitably fail and become castration resistant (CRPC), dying from metastatic (m)CRPC despite receiving 2nd and 3rd line therapies (androgen receptor inhibitors/ARIs and/or taxanes). Drugs targeting other pathways have been tested in clinical trials. Few are implemented in practice due to low response rates, although some show a significant benefit in subsets of unselected patients. This clinical heterogeneity underscores the cellular and functional heterogeneity of malignant cells, highlighting the need for biomarkers of response to therapies. In line with the growing interest in using non-invasive liquid biopsies to monitor disease progression, we hypothesized that genes encoding proteins representative of prostate epithelial cell-subtypes may be detectable in blood as predictive biomarkers. Our objective was to identify such representative genes and test them in the blood of patients to determine whether they can stratify patients for optimal disease management. 14 genes pertaining to cell subtypes were chosen based on a thorough literature review. The panel was validated in transcriptomic datasets showing their predominant overexpression in metastases of mCRPC cases compared to primary tumours and benign prostate from diverse cohorts of patients. TaqMan assays were designed and optimized in serial dilutions of RNA from five prostate cancer cell lines. The panel was tested in the blood of healthy controls (n=9) and patients prior to prostatectomy (n=8), post-curative therapies (n=7), or mCRPC (n=19). In control men with no prostatic disease in their lifetime, we see low or no expression of most genes, with no correlation with age (29-71 years old). No association was seen between the proportions of different white blood cells and genes of interest expressed at varying levels in the blood of mCRPC patients. The threshold for overexpression in patients was defined as 2.58 standard deviation above the mean expression from controls (99.5% confidence interval). Phenotypic and functional diversity was seen in all categories of patients. Changes in genes patterns were significant in mCRPC cases based on current treatments (at time of blood draw) and the choice of initial curative therapy. For example, neuroendocrine genes were predominantly overexpressed in patients who underwent curative radiation therapy, whereas stem cell genes arose in cases under AR-Is at blood draw. In conclusion, we identified circulating genes that may be clinically meaningful to stratify and follow patients and predict response to therapies. Genes encoding drug targets may allow patient-tailored clinical trials for personalized treatments to impact on this unpredictable and lethal disease. Citation Format: Seta Derderian, Edouard Jarry, Arynne Santos, Mohanachary Amaravadi, Quentin Vesval, Lucie Hamel, Nathalie Cote, Marie Vanhuyse, Armen Aprikian, Simone Chevalier. Identifying therapeutic options for patients with advanced prostate cancer through genes in liquid biopsies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr CC06-01.

Regulatory modules of human thermogenic adipocytes: functional genomics of large cohort and Meta-analysis derived marker-genes

BackgroundRecently, ProFAT and BATLAS studies identified brown and white adipocytes marker genes based on analysis of large databases. They offered scores to determine the thermogenic status of adipocytes using the gene-expression data of these markers. In this work, we investigated the functional context of these genes.ResultsGene Set Enrichment Analyses (KEGG, Reactome) of the BATLAS and ProFAT marker-genes identified pathways deterministic in the formation of brown and white adipocytes. The collection of the annotated proteins of the defined pathways resulted in expanded white and brown characteristic protein-sets, which theoretically contain all functional proteins that could be involved in the formation of adipocytes. Based on our previously obtained RNA-seq data, we visualized the expression profile of these proteins coding genes and found patterns consistent with the two adipocyte phenotypes. The trajectory of the regulatory processes could be outlined by the transcriptional profile of progenitor and differentiated adipocytes, highlighting the importance of suppression processes in browning. Protein interaction network-based functional genomics by STRING, Cytoscape and R-Igraph platforms revealed that different biological processes shape the brown and white adipocytes and highlighted key regulatory elements and modules including GAPDH-CS, DECR1, SOD2, IL6, HRAS, MTOR, INS-AKT, ERBB2 and 4-NFKB, and SLIT-ROBO-MAPK. To assess the potential role of a particular protein in shaping adipocytes, we assigned interaction network location-based scores (betweenness centrality, number of bridges) to them and created a freely accessible platform, the AdipoNET (https//adiponet.com), to conveniently use these data. The Eukaryote Promoter Database predicted the response elements in the UCP1 promoter for the identified, potentially important transcription factors (HIF1A, MYC, REL, PPARG, TP53, AR, RUNX, and FoxO1).ConclusionOur integrative approach-based results allowed us to investigate potential regulatory elements of thermogenesis in adipose tissue. The analyses revealed that some unique biological processes form the brown and white adipocyte phenotypes, which presumes the existence of the transitional states. The data also suggests that the two phenotypes are not mutually exclusive, and differentiation of thermogenic adipocyte requires induction of browning as well as repressions of whitening. The recognition of these simultaneous actions and the identified regulatory modules can open new direction in obesity research.

Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis.

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Genome-Wide DNA Polymorphism Analysis and Molecular Marker Development for the Setaria italica Variety "SSR41" and Positional Cloning of the Setaria White Leaf Sheath Gene SiWLS1.

Genome-wide DNA polymorphism analysis and molecular marker development are important for forward genetics research and DNA marker-assisted breeding. As an ideal model system for Panicoideae grasses and an important minor crop in East Asia, foxtail millet (Setaria italica) has a high-quality reference genome as well as large mutant libraries based on the “Yugu1” variety. However, there is still a lack of genetic and mutation mapping tools available for forward genetics research on S. italica. Here, we screened another S. italica genotype, “SSR41”, which is morphologically similar to, and readily cross-pollinates with, “Yugu1”. High-throughput resequencing of “SSR41” identified 1,102,064 reliable single nucleotide polymorphisms (SNPs) and 196,782 insertions/deletions (InDels) between the two genotypes, indicating that these two genotypes have high genetic diversity. Of the 8,361 high-quality InDels longer than 20 bp that were developed as molecular markers, 180 were validated with 91.5% accuracy. We used “SSR41” and these developed molecular markers to map the white leaf sheath gene SiWLS1. Further analyses showed that SiWLS1 encodes a chloroplast-localized protein that is involved in the regulation of chloroplast development in bundle sheath cells in the leaf sheath in S. italica and is related to sensitivity to heavy metals. Our study provides the methodology and an important resource for forward genetics research on Setaria.

White adipocyte-targeted dual gene silencing of FABP4/5 for anti-obesity, anti-inflammation and reversal of insulin resistance: Efficacy and comparison of administration routes

Obesity is a serious health problem with tremendous economic and social consequences, which is associated with metabolic diseases and cancer. Currently available anti-obesity drugs acting in the gastrointestinal tract, or the central nervous system have shown limited efficacy in the reduction of obesity, accompanied by severe side effects. Therefore, a novel therapeutic delivery targeting adipocytes and normalizing excess fat transport and accumulation is necessary to maximize efficacy and reduce side effects for long-term treatment. Fatty acid binding protein 4 (FABP4) is an adipokine that coordinates lipid transport in mature adipocyte and its inhibition in obesity model showed weight loss and normalized insulin response. Reduction of FABP4 level in adipocytes was compensated by fatty acid binding protein 5 (FABP5), which resulted in reduction of recovery of obesity and co-morbidities related to obesity by FABP4 knock-down alone. In this study, we developed a non-viral gene delivery system, sh (FABP4/5)/ATS9R, that silences FABP4 and FABP5 simultaneously with oligopeptide (ATS9R) that can selectively target mature adipocyte. For future clinical application to increase patient compliance, sh (FABP4/5)/ATS9R was administered subcutaneously and intraperitoneally to obese animal model and both routes demonstrated startling dual gene efficacy in visceral adipose tissues. Furthermore, dual gene silencing efficiently alleviated obesity, improved insulin sensitivity and restored hepatic metabolism in high fat diet-induced type 2 diabetes mouse model. Targeted-dual gene silencing of sh (FABP4/5)/ATS9R in adipose tissues demonstrated synergistic effects to overcome obesity and obesity-induced metabolic diseases and beneficial effects against liraglutide, providing a great potential for future translational research.

Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene (hTERT) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients (N = 244) was statistically significant (p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant (p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant (p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient’s clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.

Genetically Encoded CRISPR Components Yield Efficient Gene Editing in the Invasive Pest Drosophila suzukii.

Originally from Asia, Drosophila suzukii Matsumura is a global pest of economically important soft-skinned fruits. Also commonly known as spotted wing drosophila, it is largely controlled through repeated applications of broad-spectrum insecticides by which resistance has been observed in the field. There is a pressing need for a better understanding of D. suzukii biology and for developing alternative environmentally friendly methods of control. The RNA-guided Cas9 nuclease has revolutionized functional genomics and is an integral component of several recently developed genetic strategies for population control of insects. Here, we describe genetically modified strains that encode three different terminators and four different promoters to express Cas9 robustly in both the soma and/or germline of D. suzukii. The Cas9 strains were rigorously evaluated through genetic crossing to transgenic strains that encode single-guide RNAs targeting the conserved X-linked yellow body and white eye genes. We find that several Cas9/gRNA strains display remarkably high editing capacity. Going forward, these tools will be instrumental for evaluating gene function in D. suzukii and may even provide tools useful for the development of new genetic strategies for control of this invasive species.

Evaluation of CSF1R-related adult onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria.

Diagnostic criteria for adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation have recently been proposed. Our objective was to assess their accuracy in an independent multicenter cohort. We evaluated the sensitivity and specificity of the diagnostic criteria for ALSP (including the "probable" and "possible" definitions) in a national cohort of 22 patients with CSF1R mutation, and 59 patients with an alternative diagnosis of adult onset inherited leukoencephalopathy. Overall, the sensitivity of the diagnostic criteria for ALSP was 82%, including nine of 22 patients diagnosed as probable and nine of 22 diagnosed as possible. Twenty of the 59 CSF1R mutation-negative leukoencephalopathies fulfilled the diagnostic criteria, leading to a specificity of 66%. Diagnostic criteria for ALSP have an overall limited sensitivity along with a modest specificity. We suggest that in patients suspected of genetic leukoencephalopathy, a comprehensive magnetic resonance imaging pattern-based approach is warranted, together with white matter gene panel or whole exome sequencing.

Association and epistatic analysis of white matter related genes across the continuum schizophrenia and autism spectrum disorders: The joint effect of NRG1-ErbB genes

Background Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. Methods We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. Results Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. Discussion Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.