scholarly journals Precision Autism: Genomic Stratification of Disorders Making Up the Broad Spectrum May Demystify Its “Epidemic Rates”

2021 ◽  
Vol 11 (11) ◽  
pp. 1119
Author(s):  
Elizabeth B. Torres
Keyword(s):  
Neurological Disorders ◽  
Genetic Information ◽  
Self Regulation ◽  
Compact Set ◽  
Human Tissues ◽  
Brain Disorders ◽  
Overlapping Genes ◽  
Genomic Information ◽  
Genes Expression ◽  
Exponential Rates

In the last decade, Autism has broadened and often shifted its diagnostics criteria, allowing several neuropsychiatric and neurological disorders of known etiology. This has resulted in a highly heterogeneous spectrum with apparent exponential rates in prevalence. I ask if it is possible to leverage existing genetic information about those disorders making up Autism today and use it to stratify this spectrum. To that end, I combine genes linked to Autism in the SFARI database and genomic information from the DisGeNET portal on 25 diseases, inclusive of non-neurological ones. I use the GTEx data on genes’ expression on 54 human tissues and ask if there are overlapping genes across those associated to these diseases and those from SFARI-Autism. I find a compact set of genes across all brain-disorders which express highly in tissues fundamental for somatic-sensory-motor function, self-regulation, memory, and cognition. Then, I offer a new stratification that provides a distance-based orderly clustering into possible Autism subtypes, amenable to design personalized targeted therapies within the framework of Precision Medicine. I conclude that viewing Autism through this physiological (Precision) lens, rather than viewing it exclusively from a psychological behavioral construct, may make it a more manageable condition and dispel the Autism epidemic myth.

scholarly journals Precision Autism: Genomic Stratification of Disorders Making Up the Broad Spectrum May Demystify its "Epidemic Rates"

2021 ◽  
Author(s):  
Elizabeth B Torres
Keyword(s):  
Neurological Disorders ◽  
Genetic Information ◽  
Self Regulation ◽  
Compact Set ◽  
Human Tissues ◽  
Brain Disorders ◽  
Overlapping Genes ◽  
Genomic Information ◽  
Genes Expression ◽  
Exponential Rates

In the last decade, Autism has broadened and often shifted its diagnostics criteria, allowing several neuropsychiatric and neurological disorders of known etiology. This has resulted in a highly heterogeneous spectrum with apparent exponential rates in prevalence. We ask if it is possible to leverage existing genetic information about those disorders making up Autism today and use it to stratify this spectrum. To that end, we combine genes linked to Autism in the SFARI database and genomic information from the DisGeNet portal on 25 diseases, inclusive of non-neurological ones. We use the GTEx data on genes' expression on 54 human tissues and ask if there are overlapping genes across those associated to these diseases and those from Autism-SFARI. We find a compact set of genes across all brain-disorders which express highly in tissues fundamental for somatic-sensory-motor function, self-regulation, memory, and cognition. Then, we offer a new stratification that provides a distance-based orderly clustering into possible Autism subtypes, amenable to design personalized targeted therapies within the framework of Precision Medicine. We conclude that viewing Autism through this physiological (Precision) lens, rather than from a psychological behavioral construct, may make it a more manageable condition and dispel the Autism epidemic myth.

scholarly journals The gut-microbiota-brain axis in autism: what Drosophila models can offer?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Safa Salim ◽  
Ayesha Banu ◽  
Amira Alwa ◽  
Swetha B. M. Gowda ◽  
Farhan Mohammad
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Autism Spectrum ◽  
Brain Disorders ◽  
Mediated Communication ◽  
The Impact ◽  
Insight Into ◽  
Drosophila Models

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Cost of Brain Disorders in Italy – A Review

2009 ◽  
Vol 4 (2) ◽  
pp. 120
Author(s):  
Maura Pugliatti ◽  
Paola Cossu ◽  
Patrik Sobocki ◽  
Ettore Beghi ◽  
◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Disease Burden ◽  
Psychotic Disorders ◽  
Ad Hoc ◽  
Cost Model ◽  
Adult Mortality ◽  
Brain Disorders ◽  
European Brain ◽  
Socioeconomic Burden ◽  
The Brain

Brain disorders represent 35% of the total disease burden in Europe and 37% of the total disease burden in European regions with very low child mortality and low adult mortality; the latter group includes Italy. The negative socioeconomic impact of this burden is reflected in two fundamental issues: consumption of resources and state of health. In recent years, the European Brain Council (EBC), a co-ordinating council formed by European organisations and patient associations in neurological disorders, has encouraged and supported projects aimed at analysing the socioeconomic burden of brain disorders in Europe. Within the EBC, the pan-European study on Cost of Disorders of the Brain in Europe (CDBE) aimed at reporting the best possible estimates of the societal cost of 12 brain disorders (addiction, affective disorders, anxiety disorders, tumours, dementia, epilepsy, migraine and other headaches, multiple sclerosis, Parkinson's disease, psychotic disorders, stroke and trauma) based on the existing literature, using an ad hoc cost model. The aggregated results for Italy from the CDBE study are reviewed in this paper.

scholarly journals Analysis of shared heritability in common disorders of the brain

Science ◽  
2018 ◽  
Vol 360 (6395) ◽  
pp. eaap8757 ◽  
Author(s):  
◽  
Verneri Anttila ◽  
Brendan Bulik-Sullivan ◽  
Hilary K. Finucane ◽  
Raymond K. Walters ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Neurological Disorders ◽  
Statistical Power ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
Brain Disorders ◽  
Cognitive Measures ◽  
Genome Wide ◽  
The Brain

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

scholarly journals CURRENT ISSUES OF LEGAL REGULATION OF HUMAN GENOME DATABASES CREATING AND FUNCTIONING

2020 ◽  
Vol 16 (2) ◽  
pp. 134-144
Author(s):  
Алексей Чемерис ◽  
Владимир Анисимов ◽  
Фарит Аминев
Keyword(s):  
Human Genome ◽  
Genetic Information ◽  
Large Scale ◽  
Legal Regulation ◽  
National Standards ◽  
Genomic Research ◽  
Genomic Information ◽  
Federal Law ◽  
Genome Databases ◽  
State Organizations

The relevance of the article is due, on the one hand, to the active introduction of genomic research technologies into everyday life and the accumulation of a significant amount of genetic information while providing medical care and other genome screening and sequencing services by private and state organizations. On the other hand, it is relevant due to the beginning of the implementation of large-scale government projects to create an information-analytical system for storing and processing genetic data. In these circumstances, the issues of developing an effective legal regulation of creating and functioning of human genome databases are of particular importance. Aim: to study the requirements of international and national standards for statutory regulation of relations connected to genomic researches, as well as to collecting, processing, storing and using genetic information. Methods: in the study formal logical and general scientific methods of scientific knowledge are used; private scientific (comparative legal, formal dogmatic) methods are used. Results: Based on these requirements, the current national legislation is assessed, an urgent need is defined to adopt a special federal law on the protection of genomic information, which enshrines the necessary rules on procedures for forming relevant databases, the procedure for storing and using the resulting genomic information, as well as the legal regime of the information contained in the database.

Synthetic sequence entanglement augments stability and containment of genetic information in cells

Science ◽  
2019 ◽  
Vol 365 (6453) ◽  
pp. 595-598 ◽  
Author(s):  
Tomasz Blazejewski ◽  
Hsing-I Ho ◽  
Harris H. Wang
Keyword(s):  
Genetic Information ◽  
Recombinant Dna ◽  
Fitness Landscape ◽  
Essential Gene ◽  
Computational Design ◽  
Genetically Engineered ◽  
Toxin Gene ◽  
Overlapping Genes ◽  
Synonymous Mutations ◽  
Natural Mutation

In synthetic biology, methods for stabilizing genetically engineered functions and confining recombinant DNA to intended hosts are necessary to cope with natural mutation accumulation and pervasive lateral gene flow. We present a generalizable strategy to preserve and constrain genetic information through the computational design of overlapping genes. Overlapping a sequence with an essential gene altered its fitness landscape and produced a constrained evolutionary path, even for synonymous mutations. Embedding a toxin gene in a gene of interest restricted its horizontal propagation. We further demonstrated a multiplex and scalable approach to build and test >7500 overlapping sequence designs, yielding functional yet highly divergent variants from natural homologs. This work enables deeper exploration of natural and engineered overlapping genes and facilitates enhanced genetic stability and biocontainment in emerging applications.

scholarly journals N-Acetylaspartate Is an Important Brain Osmolyte

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 286 ◽  
Author(s):  
Marina Warepam ◽  
Khurshid Ahmad ◽  
Safikur Rahman ◽  
Hamidur Rahaman ◽  
Kritika Kumari ◽  
...  
Keyword(s):  
Human Brain ◽  
Protein Stability ◽  
Neurological Disorders ◽  
Thermal Denaturation ◽  
Dependent Manner ◽  
Brain Disorders ◽  
Ph Values ◽  
Neurological Conditions ◽  
The Brain ◽  
Insight Into

Most of the human diseases related to various proteopathies are confined to the brain, which leads to the development of various forms of neurological disorders. The human brain consists of several osmolytic compounds, such as N-Acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), glutamine (Gln), creatine (Cr), and choline-containing compounds (Cho). Among these osmolytes, the level of NAA drastically decreases under neurological conditions, and, hence, NAA is considered to be one of the most widely accepted neuronal biomarkers in several human brain disorders. To date, no data are available regarding the effect of NAA on protein stability, and, therefore, the possible effect of NAA under proteopathic conditions has not been fully uncovered. To gain an insight into the effect of NAA on protein stability, thermal denaturation and structural measurements were carried out using two model proteins at different pH values. The results indicate that NAA increases the protein stability with an enhancement of structure formation. We also observed that the stabilizing ability of NAA decreases in a pH-dependent manner. Our study indicates that NAA is an efficient protein stabilizer at a physiological pH.

Self-Regulation of Autophagy Genes Expression by Atg8a and Its Interacting Partners YL-1, Sequoia and Sir2 In  Drosophila

2019 ◽  
Author(s):  
Anne-Claire Jacomin ◽  
Stavroula Petridi ◽  
Marisa Di Monaco ◽  
Zambarlal Bhujabal ◽  
Ashish Jain ◽  
...  
Keyword(s):  
Self Regulation ◽  
Genes Expression

scholarly journals CSER and eMERGE: current and potential state of the display of genetic information in the electronic health record

2015 ◽  
Vol 22 (6) ◽  
pp. 1231-1242 ◽  
Author(s):  
Brian H Shirts ◽  
Joseph S Salama ◽  
Samuel J Aronson ◽  
Wendy K Chung ◽  
Stacy W Gray ◽  
...  
Keyword(s):  
Decision Support ◽  
Genetic Information ◽  
Clinical Care ◽  
Clinical Decision ◽  
Exploratory Research ◽  
Genomic Information ◽  
Group Discussions ◽  
Working Groups ◽  
Electronic Health ◽  
To Receive

Abstract Objective Clinicians’ ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). Materials and Methods The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. Results There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. Conclusion Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended.

Sign in / Sign up

Export Citation Format

Share Document