What Do We Know About the Genetic Architecture of Psychopathology?

In the second half of the twentieth century, twin and family studies established beyond a reasonable doubt that all forms of psychopathology are substantially heritable and highly polygenic. These conclusions were simultaneously an important theoretical advance and a difficult methodological obstacle, as it became clear that heritability is universal and undifferentiated across forms of psychopathology, and the radical polygenicity of genetic effects limits the biological insight provided by genetically informed studies at the phenotypic level. The paradigm-shifting revolution brought on by the Human Genome Project has recapitulated the great methodological promise and the profound theoretical difficulties of the twin study era. We review these issues using the rubric of genetic architecture, which we define as a search for specific genetic insight that adds to the general conclusion that psychopathology is heritable and polygenic. Although significant problems remain, we see many promising avenues for progress. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 18 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The journey from next-generation sequencing to personalized medicine?

Following the completion of the Human Genome Project in 2003, sequencing has become one of the most influential tools in biomedical research. Sequencing took off in earnest with the development of next-generation sequencing techniques in the early 2000s, making sequencing high throughput, faster, more affordable and commercially available to individual laboratories. With the improved understanding of the role of genetics in human disease, coupled with rapid advancement in sequencing technology, we are progressively unlocking the secrets of how our genes control the development of diseases. This has the potential to revolutionize medicine and healthcare, providing a significant step towards personalized medicine. How did we arrive here? What are the major achievements of sequencing technologies of the past two decades and how does it help us to piece the clues together towards personalized treatments and diagnosis?

In Search of a Unifying Concept in Human Diseases

Throughout the history of biological/medicine sciences, there has been opposing strategies to find solutions to complex human disease problems. Both empirical and deductive approaches have led to major insights and concepts that have led to practical preventive and therapeutic benefits for the human population. The classic definitions of “science” (to know) has been paired with the classic definition of technology (to do). One knew more as the technology developed, and that development was often based on science. In other words, one could do more if science could improve the technology. In turn, this made possible to know more science with improved technology. However, with the development of new technologies of today in biology and medicine, major advances have been made, such as the information from the Human Genome Project, genetic engineering techniques and the use of bioinformatic uses of sophisticated computer analyses. This has led to the renewed idea that Precision Medicine, while raising some serious ethical concerns, also raises the expectation of improved potential of risk predictions for prevention and treatment of various genetically and environmentally influenced human diseases. This new field Artificial Intelligence, as a major handmaiden to Precision Medicine, is significantly altering the fundamental means of biological discovery. However, can today’s fundamental premise of “Artificial Intelligence”, based on identifying DNA, as the primary nexus of human health and disease, provide the practical solutions to complex human diseases that involve the interaction of those genes with the broad spectrum of “environmental factors”? Will it be “precise” enough to provide practical solutions for prevention and treatments of diseases? In this “Commentary”, with the example of human carcinogenesis, it will be challenged that, without the integration of mechanistic and hypothesis-driven approaches with the “unbiased” empirical analyses of large numbers of data, the Artificial Intelligence approach with fall short.

Genomic and Epigenetic Foundations of Neocentromere Formation

Centromeres are essential to genome inheritance, serving as the site of kinetochore assembly and coordinating chromosome segregation during cell division. Abnormal centromere function is associated with birth defects, infertility, and cancer. Normally, centromeres are assembled and maintained at the same chromosomal location. However, ectopic centromeres form spontaneously at new genomic locations and contribute to genome instability and developmental defects as well as to acquired and congenital human disease. Studies in model organisms have suggested that certain regions of the genome, including pericentromeres, heterochromatin, and regions of open chromatin or active transcription, support neocentromere activation. However, there is no universal mechanism that explains neocentromere formation. This review focuses on recent technological and intellectual advances in neocentromere research and proposes future areas of study. Understanding neocentromere biology will provide a better perspective on chromosome and genome organization and functional context for information generated from the Human Genome Project, ENCODE, and other large genomic consortia. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A COMPREHENSIVE REVIEW ON GENETICS AND ITS IMPACT ON HUMAN DISEASES

In 1866, when Mendel was carrying out his pea plant experiments in the monastery, nobody could predict what was to come. A genius whose ideas were appreciated after 34 years of their discovery, quite literally planted the seeds for the genetics that we’re familiar with, today. The important breakthrough was the completion of The Human Genome Project in 2003, which meant that scientists now had the genetic dictionary in their hands for an in-depth review of DNA and associated mutations. Eventually, the picture started to become clearer and our earlier speculation about the role of family history and environment in genetic disorders, now had concrete proof. The modern-day geneticist aims to identify, diagnose, and treat gene related conditions more efficiently than ever. This article surveys the different ways in which genetic disorders manifest themselves, their causative mutations, as well as early detection and treatment

Decoding ‘Unnecessary Complexity’: A Law of Complexity and a Concept of Hidden Variation Behind “Missing Heritability” in Precision Medicine

The high hopes for the Human Genome Project and personalized medicine were not met because the relationship between genotypes and phenotypes turned out to be more complex than expected. In a previous study we laid the foundation of a theory of complexity and showed that because of the blind nature of evolution, and molecular and historical contingency, cells have accumulated unnecessary complexity, complexity beyond what is necessary and sufficient to describe an organism. Here we provide empirical evidence and show that unnecessary complexity has become integrated into the genome in the form of redundancy and is relevant to molecular evolution of phenotypic complexity. Unnecessary complexity creates uncertainty between molecular and phenotypic complexity, such that phenotypic complexity (CP) is higher than molecular complexity (CM), which is higher than DNA complexity (CD). The qualitative inequality in complexity is based on the following hierarchy: CP > CM > CD. This law-like relationship holds true for all complex traits, including complex diseases. We present a hypothesis of two types of variation, namely open and closed (hidden) systems, show that hidden variation provides a hitherto undiscovered “third source” of phenotypic variation, beside genotype and environment, and argue that “missing heritability” for some complex diseases is likely to be a case of “diluted heritability”. There is a need for radically new ways of thinking about the principles of genotype–phenotype relationship. Understanding how cells use hidden, pathway variation to respond to stress can shed light on why two individuals who share the same risk factors may not develop the same disease, or how cancer cells escape death.

BIOINFORMATICS APPROACHES TO UNDERSTAND GENE LOOPING IN THE HUMAN GENOME

This paper reviews up to date Bioinformatics Approaches to Understand Gene Looping in the Human Genome. Bioinformatics is used to study the sequences of biological molecules. It generally points out to genes, DNA, RNA, or protein, and is especially functional in analogizing genes and other protein sequences. You can believe in bioinformatics. Basically, the linguistics Bioinformatics uses computer programs for various applications, involving deliberate gene and protein functions. The beginning of the human genome project in 1990 and was completed in 2003. The Human Genome Project gave a prime improvement for the progress of bioinformatics. The (HGP) was organized by the National Institutes of Health and the U.S. Department of Energy. Without the interpretation given via bioinformatics, the information obtained from the HGP is not very functional. This page describes HGP bioinformatics research. Informatics is the formation, exploration, and function of databases. Main aim was to find the total set of human genes and make them available for more biological study and discover the total sequence of DNA bases in the human genome. A total and the correct sequence of the 3 billion DNA base pairs create the human genome and search all approximate 20,000 to 25,000 human genes. The genomes sequence of organisms that are main to medical research. To begin new tools to apply and inspect the data and to assemble this information broadly obtainable. DNA sequencing manufactures a sequence that is particularly a hundred bases long. Gene sequences manufacture thousands of bases. To study genes, small intersecting sequences set up long DNA sequences. Loops can clump associated genes into separate transcriptional axis chromatin from neighboring domains. Gene loops in yeast juxtapose promoter-terminator regions. Here we outline gene loops’ finding, the looping need proteins, and transcription by RNA polymerase II is by gen looping

BIJA, BIJABHAGA AND BIJABHAGA-AVAYAVA ASSOCIATED WITH ANUVANSHIKI

Ayurveda is one of the most ancient life sciences it is mentioned by acharyas that it is more ancient than man because it came earlier to earth. Being a life science there is description of how life came to origin, how to live life along with the description of various diseases under various disciplines. Here by Acharya Charak and Vriddha Vagbhatta- Bija, Bijabhaga and Bijabhaga-avayava is mention as three basic components of genetics, which are responsible for inheritance of various characteristics as well as for various diseases. The human genome project started in 1990 had aimed to identified human genetic coding of DNA, so that disease associated with genetic mutation or deletion can be prevented in their acute stage like cancer, leprosy, thalassemia, etc. In the same manner Acharyas also mention various diseases associated with bija, bijabhaga, bijabhaga-avayava dusti and transferred to next progeny. In this article we highlighted over the genetic defect of Secondary sexual development. Keywords: Bija, Bijabhaga, Bijabhaga-avayava, dusti, Shukra, Shonita, etc.