SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data

Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith–Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267–1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides

Detail-oriented cognitive style and social communicative deficits, within and beyond the autism spectrum: independent traits that grow into developmental interdependence

At the heart of debates over underlying causes of autism is the "Kanner hypothesis" that autistic deficits in social reciprocity, and a cognitive/perceptual 'style' favouring detail-oriented cognition, co-vary in autistic individuals. A separate line of work indicates these two domains are normally distributed throughout the population, with autism representing an extremity. This realisation brings the Kanner debate into the realm of normative co-variation, providing more ways to test the hypothesis, and insights into typical development; for instance, in the context of normative functioning, the Kanner hypothesis implies social costs to spatial/numerical prowess

Chemical Genetics Reveals an RGS/G-Protein Role in the Action of a Compound

We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-αq (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-αq signaling complex, and define new mutations in both RGS and G-αq, including a unique hypo-adapation allele of G-αq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation

The Australian Child Maltreatment Study (ACMS): protocol for a national survey of the prevalence of child abuse and neglect, associated mental disorders and physical health problems, and burden of disease

Introduction: Child maltreatment (physical abuse, sexual abuse, emotional abuse, neglect and exposure to domestic violence) is widely understood to be associated with multiple mental health disorders, physical health problems and health risk behaviours throughout life. However, Australia lacks fundamental evidence about the prevalence and characteristics of child maltreatment, its associations with mental disorders and physical health, and the associated burden of disease. These evidence gaps impede the development of public health strategies to better prevent and respond to child maltreatment. The aims of this research are to generate the first comprehensive population-based national data on the prevalence of child maltreatment in Australia, identify associations with mental disorders and physical health conditions and other adverse consequences, estimate attributable burden of disease and indicate targeted areas for future optimal public health prevention strategies. Methods and analysis: The Australian Child Maltreatment Study (ACMS) is a nationwide, cross-sectional study of Australia’s population aged 16 years and over. A survey of approximately 10 000 Australians will capture retrospective self-reported data on the experience in childhood of all five types of maltreatment (physical abuse, sexual abuse, emotional abuse, neglect and exposure to domestic violence). A customised, multimodule survey instrument has been designed to obtain information including: the prevalence and characteristics of these experiences; diagnostic screening of common mental health disorders; physical health; health risk behaviours and health service utilisation. The survey will be administered in March–November 2021 to a random sample of the nationwide population, recruited through mobile phone numbers. Participants will be surveyed using computer-assisted telephone interviews, conducted by trained interviewers from the Social Research Centre, an agency with extensive experience in studies of health and adversity. Rigorous protocols protect the safety of both participants and interviewers, and comply with all ethical and legal requirements. Analysis will include descriptive statistics reporting the prevalence of individual and multitype child maltreatment, multiple logistic and linear regression analyses to determine associations with mental disorders and physical health problems. We will calculate the population attributable fractions of these putative outcomes to enable an estimation of the disease burden attributable to child maltreatment. Ethics and dissemination: The study has been approved by the Queensland University of Technology Human Research Ethics Committee (#1900000477, 16 August 2019). Results will be published to the scientific community in peer-reviewed journals, scientific meetings and through targeted networks. Findings and recommendations will be shared with government policymakers and community and organisational stakeholders through diverse engagement activities, a dedicated Advisory Board and a systematic knowledge translation strategy. Results will be communicated to the public through an organised media strategy and the ACMS website

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

Emergence of a Small-World Functional Network in Cultured Neurons

The functional networks of cultured neurons exhibit complex network properties similar to those found in vivo. Starting from random seeding, cultures undergo significant reorganization during the initial period in vitro, yet despite providing an ideal platform for observing developmental changes in neuronal connectivity, little is known about how a complex functional network evolves from isolated neurons. In the present study, evolution of functional connectivity was estimated from correlations of spontaneous activity. Network properties were quantified using complex measures from graph theory and used to compare cultures at different stages of development during the first 5 weeks in vitro. Networks obtained from young cultures (14 days in vitro) exhibited a random topology, which evolved to a small-world topology during maturation. The topology change was accompanied by an increased presence of highly connected areas (hubs) and network efficiency increased with age. The small-world topology balances integration of network areas with segregation of specialized processing units. The emergence of such network structure in cultured neurons, despite a lack of external input, points to complex intrinsic biological mechanisms. Moreover, the functional network of cultures at mature ages is efficient and highly suited to complex processing tasks

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

The Kuramoto model in complex networks

181 pages, 48 figures. In Press, Accepted Manuscript, Physics Reports 2015 Acknowledgments We are indebted with B. Sonnenschein, E. R. dos Santos, P. Schultz, C. Grabow, M. Ha and C. Choi for insightful and helpful discussions. T.P. acknowledges FAPESP (No. 2012/22160-7 and No. 2015/02486-3) and IRTG 1740. P.J. thanks founding from the China Scholarship Council (CSC). F.A.R. acknowledges CNPq (Grant No. 305940/2010-4) and FAPESP (Grants No. 2011/50761-2 and No. 2013/26416-9) for financial support. J.K. would like to acknowledge IRTG 1740 (DFG and FAPESP).Peer reviewedPreprin

The Adult Repetitive Behaviours Questionnaire-2 (RBQ-2A): A Self-Report Measure of Restricted and Repetitive Behaviours

In two studies we developed and tested a new self-report measure of restricted and repetitive behaviours (RRB) suitable for adults. In Study 1, The Repetitive Behaviours Questionnaire-2 for adults (RBQ-2A) was completed by a sample of 163 neurotypical adults. Principal components analysis revealed two components: Repetitive Motor Behaviours and Insistence on Sameness. In Study 2, the mean RBQ-2A scores of a group of adults with autism spectrum disorder (ASD; N = 29) were compared to an adult neurotypical group (N = 37). The ASD sample had significantly higher total and subscale scores. These results indicate that the RBQ-2A has utility as a self-report questionnaire measure of RRBs suitable for adults, with potential clinical application