Introduction
The practice of Medicine and Healthcare delivery are dynamic and interdependent horizons that are subject to change in the light of scientific and technological advances. However, few core values and expectations remain on board. These include the Medicine and Healthcare directed at very personal level and focused to the needs of those who might most benefit. In order to deliver and meet these objectives, all medical and healthcare professionals require to be equipped with most up to date knowledge and evidence to sustain quality and effective healthcare delivery. Thus the approach for delivering the ‘evidence-based medical and healthcare’ remains at the center for personalized medicine. The personalized medicine is part of the dogma that includes other parameters notably the medicine to be precise, preemptive, participatory, predictive and preventive. There is no doubt that the scientific and clinical precision is the core requirement for the ‘6 Ps’ driven clinical medicine practice and healthcare delivery.
Recent advances in genome sciences and technologies offer great hope for meeting high aspirations and expectations of the precision medicine. There is great hype and lot of expectations from genomic application and translation in clinical medicine and healthcare. The term genomic medicine literally emerged as the human genome project became a reality. This movement has gained momentum and strength as new sequencing methods and related supportive elements became firm and deliverable. Most people now agree and are committed to harness gains of genomics for delivering effective and efficient practice and delivery of the precision and personalized medicine. In this context, the hybrid term of ‘Genomic and Precision Medicine’ is widely accepted by most professionals and the public.
There is now huge amount of data and massive information available now on genomic and precision medicine. Some of this is available as multiple isolated reviews or contained within books. However, most of this either out of date or extremely truncated and thus does not meet the standard required for structuring and delivering the evidence-based, precision and personalized medicine. The current proposal aims to collate, prepare and publish on-line a series of classified and high caliber volumes that embody the Genomic and Precision Medicine. Each volume is written and carefully edited to meet high expectations and demands of scientific, medical and healthcare professionals. The series has the technical edge over other competitive resources by having the benefit of regular digital updates and thus keeping abreast with new developments and advances.
Proposer’s experience
This e-book series is proposed and edited by Professor Dhavendra Kumar who has established experience and committed to the genomics led precision and personalized medicine.
Professor Kumar’s special interests in clinical genetics include clinical cardiovascular genetics (inherited conditions of heart and blood vessels), genomic medicine and genomic applications in global healthcare. Heis a practicingConsultant in Clinical Genetics with special interests in cardiovascular genetics and genomic medicine. Currently, he serves as the Honorary Clinical Professor, William Harvey Research Institute, Queen Mary University of London, UK. In addition, he is affiliated with many other academic institutions in the UK, China and India.
He has authored/edited ‘Genetic disorders of the Indian Subcontinent’, 2004; ‘Genomics and Clinical Medicine’, Oxford, 2008; ‘Principles and Practice of Clinical Cardiovascular Genetics’, Oxford, 2010, ‘Oxford Specialist Handbook on Inherited Cardiac Disease’, 2011, ‘Genomics and Health in the Developing World’, Oxford, 2012; ‘Genomic Medicine- Principles & Practice’, Oxford, 2014; ‘Genomics and Society’, Cambridge (USA), 2015, ‘Medical Health Genomics’, Cambridge (USA), 2016, ‘Cardiovascular Genetics and Genomics- Principles and Clinical Practice’, Springer-Nature 2018 and ‘Clinical Molecular Medicine-Principles and Practice’, Academic Press Elsevier, 2019.
He is the founding editor in chief for the new genomics publications- Applied and Translational Genomics, Genomic and Molecular Medicine, Current Trends in Genomic Medicine and Cardiovascular Genetics & Genomics. In addition, he founded 2 genetic/genomics journals (Genomic Medicine & Applied and Translational Genomics) and serves on the editorial board of many other bio-medical journals. He is the Associate Editor(s) of Human Genomics, the official journal for HUGO; Journal of Genetics of the Institute of Science, Bangalore, India and Journal of Translational Medicine of Springer-Nature.
He founded and leads the Genomic Medicine Foundation (UK) for promoting fellowship and scholarship in genomic medicine and healthcare. In collaboration with other international genetic & genomic organizations, the Foundation has launched the Global Familial Heart Challenge (GFHC) and the Global Consortium for Genomic Education (GC4GE).
He is passionate for genetics and genomics education and set up the new ‘Diploma in Genomic Medicine and Healthcare’ course at the University of South Wales. He is the Founder/Lead for the ‘Indo-UK Genetic Education Forum promoting genetics/genomics across the Indian subcontinent. He continues to work and engage in discussion and collaboration for raising awareness and promoting genetics/ genomics for improved healthcare and socio-economic benefits in the emerging economies of the developing world.
Aims:
‘To collate and publish a series of online volumes on key titles illustrating the new advances and expanding scientific and technical knowledge in clinical applications of the genomic and precision medicine.”
Objectives:
- To identify key scientific and clinical areas in the practice of genomic and precision medicine.
- To prepare proposals for individual titles relevant to the series.
- To select and recruit lead authors for individual titles.
- To design and structure each volume as part of a large volume online series.
- To plan and prepare a binding and concluding volume on generic, ethical and legal aspects of the genomic and precision medicine.
Proposed series volumes
1. The Human genome
This volume covers basic scientific and biological aspects of the human genome in its entire structure and function.
2. Genome sequencing and variation
This volume covers all laboratory methods of genome sequencing, an essential component of the genomic and precision medicine. Description and interpretation of the genome sequence changes and variation are central to the applied and translational genomics.
3. Systemic genomics and Bioinformatics
This volume covers the computational and hypothetical systemic aspects of genomics. It extends to include bioinformatic approaches to genome sequencing variation and interpretation. In this chapter a number of the computational model of systemic biology is explored for the genomic and precision medicine practice.
4. Metabolomics
The functional part of the genome determines a number of interacting complex genes and molecules that continuously evolve and create an adaptive metabolic environment congenial to multiple functions of different body organs and extending to defined systems. In Charles Darwin’s evolutionary terms, the metabolic make up of an organ or body systems is vital for the survival of the organism. This volume sets out the broader spectrum of the clinical practice of genomic and precision medicine.
5. Metagenomics
Practically all body surface and parts with external and internal links harbor several millions to trillions of microbial single and multiple cellular organisms and many living creatures. The genomic make up of these microbial agents is collectively described as the metagenomic profile distributed in terms of the organ (for example eye, ears and skin etc.) or body part (for example mouth, vagina or anus etc.). This volume covers the expanding knowledge of metagenomics, considered to be important for a number of commensals and opportunistic bacteria and other microbes inhabiting the human body.
6. Microbial genomics and Pathogenomics
This volume covers genomic structure of major categories of microbial organisms with emphasis on all major pathogens underpinning infectious diseases. It also includes a section on genome based drugs and vaccines discovery and development.
7. Clinical genomics and genetic counseling
This important volume sets out principles and practice of clinical genomics and genetic counseling that are established specialist medical disciplines. Genetic & Genomic physicians, genetic/ genomic specialist nurses and genetic counselors are skilled professionals dealing with a number of common and rare genetic diseases with the focus on genetic/genomic diagnosis. In addition, other tasks include assessing the genetic risks and impact on close and extended family members, assisting and delivering the diagnostic and predictive genetic/ genomic testing, actively contributing to the management and treatment of a number of inherited/ genetic diseases as a key member of the multi-disciplinary team and actively contributing to the genetic/ genomic education and training of fellow clinical and healthcare professionals.
8. Genomics of rare diseases
This volume deals with heterogeneous rare diseases of diverse aetiology and pathophysiology. Most, by definition, are rare assessed by the incidence and prevalence. Genetic and genomic factors are heterogeneous and variable in these disorders. Apart from a number of physical congenital anomalies, many such diseases manifest with complex, life threatening functional morbidity. In this volume emphasis is given on mutations & variants in specific genes and the impact and pathological significance of genomic structural changes (single nucleotide polymorphisms, copy number variations, genomic microdeletions and genomic microduplications).
9. Genomics of complex disorders
There are many common medical multi-system disorders with complex aetiology and pathophysiology. In most cases, the precise causation is unknown. Examples include obesity, type 2 diabetes mellitus, age-related macular degeneration, Alzheimer’s dementia, epilepsy, schizophrenia, bipolar depression, coronary artery disease, bronchial asthma, essential hypertension and some common skin conditions such as eczema and psoriasis. Conventionally most of these conditions are described as multi-factorial determined by the complex interactions of underlying several hundreds and thousands of genetic/ genomic factors with a range of environmental factors and challenges, commonly referred to as the polygenic inheritance pattern. The advent and increasing use of the genome sequencing have led to much better understanding and appreciation of the heritability in many complex diseases.
10. Cancer genomics
The cancer is a genetic disease involving a number of genes, molecules and cellular structures. In most cases, these pathological changes result from life-long exposure to toxic, infectious and immunological factors. There is increasing evidence for underlying pre-existing, inherited or acquired, mutations and variants in a number of genes and their regulatory elements. The seminal ‘two hit’ theory explains the fundamental genetic and genomic basis of cancer aetiology and pathogenesis. This volume covers all major aspects of genetics and genomic aspects of cancer development, diagnosis, management including the fast emerging stratified targeted molecular therapy in a number of common cancers.
11. Cardiovascular genomics
Cardiovascular diseases are collectively a huge challenge and one of the major causes of high level of morbidity and mortality in the developed world and the fast emerging economies of developing nations, like Barzil, China and India. Practically, every single cardiovascular disease is identified with complex aetiology and pathogenesis. Genetic and genomic factors are now established underlying the causation of congenital heart disease, cardiomyopathies, arrhythmias, atrial & ventricular fibrillation, cardiac conduction disease, inflammatory and immunological diseases of the heart & blood vessels, inherited/ acquired connective tissue diseases involving the heart and blood vessels, coronary artery disease and hypertension of both systemic and pulmonary arterial/ venous circulation. This volume provides in detail the current understanding and evidence for genetic and genomic bases of the cardiovascular disease.
12. Reproductive and fetal genomics
One of the major outcomes of the genetic and genomic medicine is the primary prevention of the genetic risks through informed choices and making decisions on reproductive options. In addition, diagnosis and interventions for male factor infertility and female infertility help the aspiring couple to consider appropriate route for achieving a successful pregnancy. Many procedures are available backed up by genetic and genomic testing including maternal serum screening for chromosomal aneuploidies, non-invasive prenatal diagnosis, conventional prenatal diagnosis by chorionic villous biopsy and amniocentesis and fetal blood sampling. Newer genomics led methods include pre-implantation genetic screening (PGS) and testing (PGD). This volume is dedicated to focus on all genomic aspects of reproductive and fetal medicine.
13. Ophthalmic genomics
Blindness at all ages is a global health problem with huge socio-economic impact. Apart from infections, vitamin A nutritional deficiency, immunologic eye conditions, toxic exposures, accidents and occupational hazards, genetic and genomic factors are implicated in a number of congenital and later onset medical conditions manifesting with progressive vision loss. This volume covers common Mendelian and complex eye genetic disorders with discussion on genomic variation and links with age-related degenerative eye conditions.
14. Neurology and Neuropsychiatric genomics
Genetic ad genomic factors are abundant in the pathogenesis of a number of early and late onset neurological and neuropsychiatric disorders. In addition to classic single gene neuro-muscular diseases, there are many complex diseases of polygenic/ multi-factorial nature where recent whole genome exome and full sequencing have revealed single nucleotide polymorphisms, copy number variation and novel specific gene changes. This approach has led to many critical genomic regions aetiologically important for a range of neuro-psychiatric conditions. This volume provides critical and balanced review on the clinical status of genomic neurology and neuro-psychiatry.
15. Mitochondrial genomics
In addition to the nuclear genome, the mitochondrial genome is a major component of the human genome. The nuclear DNA (nDNA) is distinct from the mitochondrial DNA (mtDNA) where intervening non-coding sequences (introns) are absent and coding sequences are critical for the assembly of a number of transfer RNAs (tRNA) and ribosomal RNAs (rRNA). The mtDNA molecule is compact and arranged in circular manner. Most mtDNA is confined to energy rich tissues and organs, like brain, eyes, heart and muscles. Specific mutations and variants in the mtDNA are known for a number of complex multi-organ disorders. These are matrilineal and could not be passed on by an affected male. Moreover, the distribution of mtDNA wild and mutated copies may differ within different organs and tissues, termed as heteroplasmy. However, often similar clinical picture could result from nDNA sequence changes that impact on the mitochondrial function. This volume presents the whole field of mitochondrial genomics with clinical examples encountered in contemporary medical practice. Discussion on preventive and therapeutic aspects of mitochondrial disorders is also highlighted.
16. Immunogenomics
This volume deals with genetic and genomic aspects of the structure and function of the whole immune system. Apart from few rare immune deficiency disorders, majority conditions result from complex antigen and antibody interactions that are to large extent depend on many genes and polymorphic variants underpinning the T-cell dependent immunologic function. In addition to many auto-immune and iso-immune diseases, genetic and genomic factors play a significant role in the monoclonal antibody production that are central to targeted therapy for few cancers.
17. Therapeutic genomics- Gene therapy (including genome editing) and Cell therapy (stem cell and somatic cell)
This volume deals with many treatment modalities for genetic diseases and circumventing or correcting the genetic or genomic aberrations that underpin complex medical conditions or adverse and unwanted outcomes of the drug therapy, particularly for neoplasia. Most gene therapy trials have failed to yield satisfactory or even any promising outcomes. Now the emphasis is laid on gene/ genome editing using the Cas9/CRISP-R approach. However, these are mostly in very stages of development. Genomic basis of the cell therapy, using stem cells derived from either embryonic or somatic cells, has gained momentum and currently explored in many clinical trials. These novel approaches feature in this volume.
18. Epigenomics- epigenome structure, function and human diseases
Within the genome, a number of regions, in close proximity to the promoter areas of genes, make an important part of the genome system identified as the epigenome. This region, through complex molecular mechanisms, regulates switching on and turning off genes confined to most somatic cells. Such molecular mechanisms include methylation and histone modifications. Some of these mechanisms are specific to ‘parent of origin’, the basis of ‘genetic imprinting’. Some inherited disorders are determined through parental genetic imprinting and are important for phenotypic variation. The field of epigenomics has gained importance and applications in ‘transgenerational transmission’ of certain physical and behavioural phenotypes and outcomes of therapy. This volume covers some of these important aspects of epigenetics and epigenomics.
19. Toxicogenomics and Ecogenomics
Adverse physical and functional outcomes of exposure to toxins (including poisonous substances) largely depend up on the nature, duration, pattern, dosage and adjuvant factors. To some extent, this might also depend on the stage of development, age, gender and probably the genetic or genomic make up of the individual. Increasingly, importance of the individual’s genomic variation is agreed crucial for the outcome, for example anti-convulsant teratogenic effects, fetal anomalies born to diabetic mothers, risks of neonatal onset neoplasia argued with parental occupational exposures to hydrocarbons and many other examples. Increasingly, there is concern attached to environmental pollution, global warming, deforestation and many other ecological changes. Individual genomic variation is believed to be central to adverse outcomes. This volume features the genomic basis of adverse physical and behavioral outcomes to toxins and ecological changes.
20. Clinical Nutrigenomics
This volume is dedicated to genetic and genomic aspects of nutritional factors underpinning optimal physical fitness and health. Individual’s genetic and genomic make up and functionality determines how a particular nutrient is digested, assimilated and metabolized by the body. The ultimate point of any nutrient lies in the final utilization by the target tissue or organ of very specific biochemical ingredient harvested from the metabolic pool. Many aspects of the genome determine the nutritional value of a given nutrient, for example the glycemic index of carbohydrates, bio-availability of nitrogenous compounds from protein rich foods, lipid absorption and transport from the gut and transport of iron and other trace metals important for cellular functions.
21. Genomic Education and Training
Many aspects of genomic applications in science, biotechnology, clinical medicine and healthcare require core and specialist knowledge, skills development and competencies for carrying out a number of tasks. There are now several knowledge-based courses and opportunities for skills and competencies development and assessment. This volume convers all major aspects of genetic and genomic education training that are currently offered and evaluated targeted at researchers, physicians, nurses, genetic counselors, bioinformatics technicians and other professionals.
22. Population and Forensic genomics
One of the major powers of genetics and genomics lies in deciphering genetic and genomic variation at individual, ethnic and population levels. Since the near completion of the human genome sequencing, most ethnic and major populations have been genotyped for its origin, evolution, geographic movements, population admixture, founder mutations and variants and monitoring the genetic drift. An important and promising use of individual and population genetic/ genomic variation is evident from its forensic applications. Apart from crime scene genetic analysis, population level genomic variation is used in disaster management through victims’ identification, such as following tsunami, earthquake, major air/ train accidents and terrorist attacks. This volume features most of these aspects of population genomics.
23. Genomics and Bioeconomy
Most scientific and technological advances follow a period of reflection and then a phase of commercial applications. This is followed by significant socio-economic enthusiasm indicated by new investment and occupational opportunities. Examples include automotive industry, air transport, information technology, digital appliances and novel recreational avenues. Recent scientific and technological advances in the field of genomics and related ‘omics’ disciplines have opened doors to several new commercial and bio-economic opportunities. Massive investments and venture capital expenditures are made in genomic driven infra structure development, new scientific instruments manufacturing, new drugs and vaccines development, enhanced food and animal food products and bio-fuel generation. Some of these new collateral economic developments feature in this dedicated volume.
24. Ethical, Social and Legal aspects of Genomics
This volume deals with contentious and sensitive ethical, moral and social issues surrounding the scientific, clinical and healthcare delivery of genetics and genomics for the benefit of individual, family, community and the population at large. There are many institutional, organizational and professional good practice guidelines that are important for both professionals and the public. Some of the issues involve ownership of the data, patents, intellectual property, consent and confidentiality. Many governments and collective national organizations, for example European Union, have designed regulatory and statutory instruments to safeguard peoples and the public from potential harm of genomic technology applications.
25. Pharmacogenomics and Targeted Pharmacotherapy
In this volume, basic and applied aspects of pharmacogenetics and pharmacogenomics are discussed. This field has gained major importance in genomic and precision medicine that aims to deliver personalized evidence-based pharmacotherapy. There is now abundant genomic variants data and evidence on many drugs for both positive (safe and effective benefits) and negative (adverse drug reactions and unwanted side effects) outcomes. Recent applications of specific and highly expensive anti-cancer and other medications have established importance of genetic/ genomic testing for efficient and effective targeted molecular therapy. This approach is also discussed under the broad remit of stratified and personalized medicine.
Series Advisors
The series is supported and supervised by a pane of eminent genetic/ genomic scientists, clinicians and allied healthcare professionals. These people are all voluntary who share and support aims and objectives of the Genomic Medicine Foundation (UK):
1. Professor Sir Munir Primohamed, The Patron of the Genomic Medicine Foundation (UK), University of Liverpool, UK
2. Professor Sir Mark Caulfield, Chief Scientist, Genomics England Ltd. and Director of the William Harvey Research Institute, Queen Mary University of London, UK
3. Professor Charles Lee, Director of the Genomic Medicine Laboratory, Jackson Laboratory, Yale University, Connecticut, USA and President of the Human Genome Organization International (HUGO).
4. Professor William Newman, Consultant Clinical Geneticist and the Director, Centre for Genomic Medicine, The University of Manchester, UK.
5. Professor Sian Ellard, Head of Molecular Genetics, Royal Devon and Exeter Hospital, University of Exeter, UK.
6. Dr. Ewan Burney, Director of the European BioInformartics Institute, The Sanger Genome Campus, Hixton, Cambridge, UK; Chair of the Genomic Alliance for Global Health (GA4GH)
7. Dr. Teri Monolio, Deputy Director, National Human Genome Research Institute, NIH, Bethesda, USA.
8. Professor Geoffrey Ginsburg, Director- Center for Genomic Medicine, Duke University School of Medicine, North Carolina, USA
9. Professor Bruce Korf, Director- Human Genetics, University of Alabama Medical School, Birmingham, USA.
10. Professor John Mattick, Principal Investigator, The Garvan Institute, Sydney, NSW, Australia.
Draft prepared and presented by
Dhavendra Kumar
Cardiff/ London, 1 September 2019