Genomic Dark Matter Implications For Understanding Human Disease Mechanisms Diagnostics And Cures

The vast majority of the human genome has been historically ignored from the point of view of molecular mechanisms of disease, diagnostics and potential therapeutic targets. The predominant focus of disease research has traditionally been placed on the protein-coding regions of the human genome, which account for only ~4-5% of its total sequence complexity. This bias has an obvious underlying reason: protein-coding regions encode a crucial class of molecules in a cell, whose function and importance are well established. Furthermore, proteins are the predominant class of cellular molecules against which effective therapeutics can be designed. This bias pervades the design of analytical tools made to measure DNA, DNA-protein interactions, as well as procedures used to measure and annotate transcriptome expression. Microarrays for example, are often biased to the regions of genome known to encode exons or promoters of protein-coding mRNAs. Other aspects of our approach towards measuring expression of RNAs such as the typical choice of polyA+ RNA selection, enriched in mRNAs, for next generation sequencing also reinforces this bias. In summary, the 2-3% of the genome and RNAs made from it has dominated the conceptual thinking of academic and medical communities as well as industries that make devices that measure nucleic acids for research or diagnostic purposes and the pharmaceutical industry. However, during the last decade a tide of data has gained sufficient momentum to suggest that the cell actually uses the remaining 97-98% of the genome to produce stable RNAs – the so-called “dark matter” RNA. The first reports to suggest this were based on tiling array technology and sequencing of ESTs, which while powerful, had their limitations: tiling arrays could not estimate the relative mass of the RNAs produced from the non-protein coding regions in a cell and the EST sequencing methods were not deep enough. The advent of next-generation sequencing, in particular, single-molecule sequencing has allowed us not only confirm the previous observations but also for the first time to estimate not only from where, but also how much non-exonic RNA is produced. Its fraction of the total transcriptome is quite significant, up to 2/3 of all RNA made in a human cell (http://www.biomedcentral.com/1741-7007/8/149 ). Moreover, the non-exonic RNAs are differentially expressed in disease: for example, between the primary tumors and metastatic derivatives. We believe that the logical next step from these observations is to ask three questions, perhaps some of the most important questions of our time in biomedical science: (1) do “dark matter” RNAs underlie mechanisms of human disease?; (2) Can they be used for diagnostics?; and (3) Can they be used as targets for therapeutics?. We thus would like to propose a Research Topic in the Frontiers in Genetics/Frontiers in Non-Coding RNAs that is specifically dedicated to publishing manuscripts addressing these three questions.

This book presents 15 selected contributions to the 22nd Evolutionary Biology Meeting, which took place in September 2018 in Marseille. They are grouped under the following major themes: · Origin of Life · Concepts and Methods · Genome and Phenotype Evolution The aims of these annual meetings in Marseille are to bring together leading evolutionary biologists and other scientists who employ evolutionary biology concepts, e.g. for medical research, and to promote the exchange of ideas and encourage interdisciplinary collaborations. Offering an up-to-date overview of recent advances in the field of evolutionary biology, this book represents an invaluable source of information for scientists, teachers and advanced students.

There is growing enthusiasm in the scientific community about the prospect of mapping and sequencing the human genome, a monumental project that will have far-reaching consequences for medicine, biology, technology, and other fields. But how will such an effort be organized and funded? How will we develop the new technologies that are needed? What new legal, social, and ethical questions will be raised? Mapping and Sequencing the Human Genome is a blueprint for this proposed project. The authors offer a highly readable explanation of the technical aspects of genetic mapping and sequencing, and they recommend specific interim and long-range research goals, organizational strategies, and funding levels. They also outline some of the legal and social questions that might arise and urge their early consideration by policymakers.

This foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates discoveries of specific genes and genomic regions associated with these conditions, the genetic and anatomic architecture of these syndromes, and addresses how recent advances in genomics are leading to a reappraisal of the biology underlying clinical neuroscience. In doing so, it critically examines the promise and limitations of these discoveries toward treatment, and to the interdisciplinary nature of understanding brain and behavior. Coverage includes new discoveries regarding autism, epilepsy, intellectual disability, dementias, movement disorders, language impairment, disorders of attention, schizophrenia, and bipolar disorder. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry focuses on key concepts, challenges, findings, and methods in genetics, genomics, molecular pathways, brain circuitry, and related neurobiology of neurologic and psychiatric disorders. Provides interdisciplinary appeal in psychiatry, neurology, neuroscience, and genetics Identifies key concepts, methods, and findings Includes coverage of multiple disorders from autism to schizophrenia Reviews specific genes associated with disorders Discusses the genetic architecture of these syndromes Explains how recent findings are influencing the understanding of biology Clarifies the promise of these findings for future treatment

Epigenetic Biomarkers and Diagnostics comprises 31 chapters contributed by leading active researchers in basic and clinical epigenetics. The book begins with the basis of epigenetic mechanisms and descriptions of epigenetic biomarkers that can be used in clinical diagnostics and prognostics. It goes on to discuss classical methods and next generation sequencing-based technologies to discover and analyze epigenetic biomarkers. The book concludes with an account of DNA methylation, post-translational modifications and noncoding RNAs as the most promising biomarkers for cancer (i.e. breast, lung, colon, etc.), metabolic disorders (i.e. diabetes and obesity), autoimmune diseases, infertility, allergy, infectious diseases, and neurological disorders. The book describes the challenging aspects of research in epigenetics, and current findings regarding new epigenetic elements and modifiers, providing guidance for researchers interested in the most advanced technologies and tested biomarkers to be used in the clinical diagnosis or prognosis of disease. Focuses on recent progress in several areas of epigenetics, general concepts regarding epigenetics, and the future prospects of this discipline in clinical diagnostics and prognostics Describes the importance of the quality of samples and clinical associated data, and also the ethical issues for epigenetic diagnostics Discusses the advances in epigenomics technologies, including next-generation sequencing based tools and applications Expounds on the utility of epigenetic biomarkers for diagnosis and prognosis of several diseases, highlighting the study of these biomarkers in cancer, cardiovascular and metabolic diseases, infertility, and infectious diseases Includes a special section that discusses the relevance of biobanks in the maintenance of high quality biosamples and clinical-associated data, and the relevance of the ethical aspects in epigenetic studies

A rapid development in diverse areas of molecular biology and genetic engineering resulted in emergence of variety of tools. These tools are not only applicable to basic researches being carried out world over, but also exploited for precise detection of abnormal conditions in plants, animals and human body. Although a basic researcher is well versed with few techniques used by him/her in the laboratory, they may not be well acquainted with methodologies, which can be used to work out some of their own research problems. The picture is more blurred when the molecular diagnostic tools are to be used by physicians, scientists and technicians working in diagnostic laboratories in hospitals, industry and academic institutions. Since many of them are not trained in basics of these methods, they come across several gray areas in understanding of these tools. The accurate application of molecular diagnostic tools demands in depth understanding of the methodology for precise detection of the abnormal condition of living body. To meet the requirements of a good book on molecular diagnostics of students, physicians, scientists working in agricultural, veterinary, medical and pharmaceutical sciences, it needs to expose the reader lucidly to: Give basic science behind commonly used tools in diagnostics Expose the readers to detailed applications of these tools and Make them aware the availability of such diagnostic tools The book will attract additional audience of pathologists, medical microbiologists, pharmaceutical sciences, agricultural scientists and veterinary doctors if the following topics are incorporated at appropriate places in Unit II or separately as a part of Unit-III in the book. Molecular diagnosis of diseases in agricultural crops Molecular diagnosis of veterinary diseases. Molecular epidemiology, which helps to differentiate various epidemic strains and sources of disease outbreaks. Even in different units of the same hospital, the infections could be by different strains of the same species and the information becomes valuable for infection control strategies. Drug resistance is a growing problem for bacterial, fungal and parasitic microbes and the molecular biology tools can help to detect the drug resistance genes without the cultivation and in vitro sensitivity testing. Molecular diagnostics offers faster help in the selection of the proper antibiotic for the treatment of tuberculosis, which is a major problem of the in the developing world. The conventional culture and drug sensitivity testing of tuberculosis bacilli is laborious and time consuming, whereas molecular diagnosis offers rapid drug resistant gene detection even from direct clinical samples. The same approach for HIV, malaria and many more diseases needs to be considered. Molecular diagnostics in the detection of diseases during foetal life is an upcoming area in the foetal medicine in case of genetic abnormalities and infectious like TORCH complex etc. The book will be equally useful to students, scientists and professionals working in the field of molecular diagnostics.

Readership: Geneticists and clinicians worldwide in addition to graduate students and researchers interested in populations and genomics