Dhavendra Kumar, Institute of Cancer & genetics, University Hospital of Wales, Cardiff, UK; Genomic Policy Unit, The University Hospital of Wales, Pontypridd, UK and The Genomic Medicine Foundation (UK). 

The natural selection theory for evolution  put forward by Charles Darwin had clear overtones reflected in some of our present-day concepts of the genetic basis of biological life. Mendel’s laws of inheritance, and successive discoveries in various aspects of genetics, laid the foundation of Mendelian genetics, a major recognized field within the science of genetics. This subsequently became the cornerstone for human genetics. Several years later the science of genetics is rewarded with the genome era. The future now appears bright, opening up many opportunities on the horizon. Clinical genetics is now a recognized medical specialty among several disciplines comprising the current spectrum of modern medicine. The basis of clinical genetics is grounded in the sound knowledge and understanding of medical genetics which emerged as a spin-off of ‘Human Genetics’.

Fifty years after the discovery of the double-helix structure of the deoxyribonucleic acid [DNA] molecule (Watson and Crick, 1953), characterization of the complete sequence and organization of the human genome was successfully accomplished (Lander et al., 2001; Venter et al., 2001). This major scientific achievement laid the foundation of ‘human genomics’; that section of the biological sciences which studies variations, mutations and functions of genes and controlling regions, and their implications on human variation, health and disease. This is strengthened by developments in the other areas of genomics relating to bacteria, vectors, parasites, animals and plants.

The identification of all human genes and their regulatory regions provides the essential framework in our understanding of the molecular basis of disease. This advance has also provided a firm foundation for the future development of genomic technologies that can be applied to modern medical science. Rapid developments in global gene analysis, gene product analysis, medical bio-informatics, and targeted molecular genetic testing are destined to change the practice of modern medicine (Guttmacher and Collins, 2002). However, many practicing clinicians perceive developments in genomics as primarily confined to the research arena with little clinical applicability. DNA/RNA-based methods of disease susceptibility screening, molecular-based disease diagnosis and prognosis, and genomics-based therapeutic choices and prediction of treatment outcome are some of the key promising areas that have influenced and raised expectations for reforming the practice of modern clinical medicine.

Undoubtedly the science of genomics holds tremendous potential for improving human health. The expert working group convened by the World Health Organization [WHO] has made several recommendations on the scope and application of genomics on global health (WHO, 2002). It is acknowledged that the information generated by genomics will provide major benefits in the prevention, diagnosis and management of communicable and genetic diseases as well as other common medical diseases, including cardiovascular diseases, cancer, diabetes and mental illnesses (Cardon and Bell, 2001). Together these constitute the major health burden, as reflected in chronic ill-health and mortality. In addition, a number of infectious diseases are associated with genomic mutations manifesting in the form of increased susceptibility, clinical severity, desired therapeutic response to anti-microbial therapy and in conferring protection. It is possible that the protective effect of a microbial vaccine might be influenced by genomic variation.

The sequence of the entire human genome is nearly complete but this is not limited to one individual alone . Each person carries a distinct sequence. The variation among all humans is reflected in variation within the human genome. The genomic variation between individuals together with environmental factors probably determines the disease susceptibility, and is important in drug efficacy and side effects (Holden, 2000; Chakravati, 2000). The key to genomic variation lies in finding single nucleotide polymorphisms [SNPs] and its use in disease association studies (Stephens et al. 2001). The positional cloning (identifying the gene by location followed by functional analysis) of the disease susceptibility loci will depend upon the successful application of haplotype associations. In addition, these will be important in clinical studies to find individuals in whom a drug is likely to be efficacious. The use of SNPs in pharmacogenetics is currently restricted to studying genes for drug-metabolizing enzymes, such as P450s, and variations in genes that target drug receptors. The newly emerging dynamic field of pharmacogenomics is an exciting application of genomic variation in drug discovery and drug development.

The recent cloning of real disease susceptibility genes for multifactorial diseases is encouraging, for example, the identification of NOD2 as a susceptibility gene for Crohn’s disease (Hugot et al., 2001 and Ogura et al., 2001). This is a major development in understanding the pathophysiology of inflammatory bowel disease. Similar studies are likely to unravel the genetic mechanisms in other complex medical diseases. A comprehensive SNP map will allow the cloning of other susceptibility alleles. However, this will depend upon population sample and size, the method employed, linkage disequilibrium or association studies rather than the technology used (Cardon and Bell, 2001). Some of the best genetic studies of this kind include susceptibility to infectious disease, for example an association between chemokine receptors (CCR5) and HIV susceptibility, and between the bacterial transporter protein Nramp and resistance to macrophage-infecting bacteria such as Mycobacterium tuberculosis. Similarly, various alleles at the G6PDH locus determine malaria susceptibility (Tishkoff et al., 2001).

These kind of studies and clinical applications of the resulting outcomes are not without ethical concerns. Some of the questions and concerns are related to ownership of the genes and freedom to use collected DNA for such studies. These are complex and emotional issues, especially when dealing with populations who may have been exploited. These issues should always be dealt with carefully under the statutory requirements and rules.

There has been a tremendous surge in various sub-specialties and technologies with names ending in -omics. We are rapidly moving into the “omics” era. In addition to genomics, several new specialist fields with an ‘omics’ suffix have recently appeared, for example, pharmacogenomics, nutrigenomics, metabonomics, transcriptomics, proteomics, micribiomics, glycomics, toxicogenomics, and many more. Whatever the basis of distinction might be, the driver of all these terms is GENOMICS  – the study of genomes in its entirety.

Genomics is not just about genome sequencing. Apart from full-length cDNAs and their sequences, copies of mRNAs that actually exist and code for different proteins are probably more important. The study of proteins thus derived falls within the broad field of proteomics, a likely outcome of functional genomics and probably a true companion to genomics. It is likely that eventually proteomics will have more practical applications in clinical medicine. This is rapidly moving ahead with the completion of the HapMap project (Nature, 2005) and the future ‘functional-variant database’, a natural outcome of the HapMap project (Gibbs, 2005).

It is vital that existing gaps in our knowledge about various ‘omics’ disciplines are filled to ensure efficient use of the valuable information emerging from research. It is also important that the gap between ‘genetic professionals’ and the ‘primary-care community,  and as well as the ‘public health community’, is narrowed (Khoury et al., 2003). Integration of this knowledge in the medical education curriculum and the continued professional education programs is urgently required to ensure applications of genomics in the provision of healthcare.

During the last two decades, the practice of medical genetics or clinical genetics, has found its niche within the broad horizon of clinical medicine. Genetic services now constitute a small, but albeit important, component of modern medical practice and public health. Currently, genetic services focus on providing information on chromosomal and single-gene diseases with limited contribution to multifactorial/polygenic diseases. How would this then be different from genomics? Already there is tremendous enthusiasm for the recently introduced term of ‘genomic medicine’. In a primer on genomic medicine, Guttmacher and Collins (2002) viewed “genetics as the study of single genes and their effects” and genomics as “the study not just of single genes, but of the functions and interactions of all the genes in the genome.”  In simple terms, there is a quantitative difference between the two fields – the study of multiple genes as opposed to one gene. Thus genetics can be seen as part of genomics! However, there is a qualitative difference between genetics and genomics in medical and health applications ranging from the concept of disease in genetics to the concept of information in genomics (Khoury et al., 2003).

The practice of medical genetics has traditionally focused on those conditions that result from specific alterations or mutations in single genes (e.g., inborn errors of metabolism, Duchenne muscular dystrophy, and Huntington’s disease), whole or part of chromosomes (e.g., trisomy 21 in Down syndrome), or associated with congenital malformations and developmental disabilities. The existing model of medical genetic services for these conditions includes laboratory diagnosis, genetic counseling and management. This is supported by public health measures to ensure delivery of genetic services and genetic screening (e.g., new-born screening or screening the high-risk population). On the other hand, the practice of genomics in medicine and public health will focus on information resulting from variation at one or multiple loci and strong interactions with environmental factors, for example diet, drugs, infectious agents, chemicals, physical agents, and behavioral factors (Khoury et al., 2003).

What medical and public health applications could one foresee following the completion of human genome sequence in 2003? How could these be applied and delivered to the 95% of human diseases that do not fall under the rubric of genetic disorders? These are some of the likely questions related to genomic medicine. Medical and public health professionals urgently need to make the changes necessary to accommodate rapid identification and characterization of the numerous genomic variants at multiple loci which increase or decrease the risks for various diseases, singly or in combination with other genes, and with various chemical, physical, infectious, pharmacologic, and social factors (Khoury, 1999). This genetic and genomic information is crucial in assessing the disease susceptibility among healthy individuals, and in personalized primary and secondary prevention planning. Collins and McKusick (2001) stated that “By the year 2010, it is expected that predictive genetic tests will be available for as many as a dozen common conditions, allowing individuals who wish to know this information to learn their risks for which interventions are or will be available. Such interventions could take the form of medical surveillance, lifestyle modifications, diet, or drug therapy. Identification of persons at highest risk for colon cancer, for example, could lead to targeted efforts to provide colonoscopic screening to those individuals, with likelihood of preventing many premature deaths.”

Personalized medicine will encompass not only common medical diseases, but could include a wide range of preventable diseases [ ]. Genetic testing for future disease susceptibility using multiple genomic variants will be possible and affordable with the application of ‘high throughput’ microarrays-based genetic testing.

A wealth of information on genomics is rapidly being acquired with the potential for major impact on human health. However, this data and information is scattered throughout several scientific journals, reviews and state-sponsored reports and bulletins.  A clinician or health professional often has difficulty in accessing and assimilating this information for application in the medical and public health practice. More importantly, an inability to assimilate and interpret leads to frustration and avoidance of potentially useful information. This article sets out the subject from the historical progress to general aspects of genomics and the describing in some detail the medical and health applications.

Exciting new developments in biotechnology and bioinformatics have opened unimaginable horizons that were inconceivable only few years ago. The talk of the next generation sequencing (NGS) is not restricted to the bench of few interested post-doctoral level and young investigators. It is evident everywhere and is now firmly engrained in minds and souls of genetic and genomic researchers, clinicians and health professionals. A number of genetic diseases or group of rare disorders can now be investigated with confidence using multi-gene NGS panels reducing the time in making an accurate diagnosis and helping the clinician to plan focussed clinical investigations and management. Further, many undiagnosed or poorly defined conditions and complex clinical cases can now be investigated using powerful genome technologies, notably the comparative array genomic hybridisation (array CGH), whole exome sequencing (WES) and even whole genome sequencing (WGS), albeit with limited outcomes (Berg et al., 2011; Biesecker and Green, 2014). The focus has shifted from finding the pathogenic sequence variations to functional importance of genome level changes. Unravelling of the complexities of the RNA molecules has made a huge impact in molecular and experimental biology, the basis for transcriptomics (Xa et al., 2014). In addition, challenging and controversial stem cell genomic research has captured the headlines with promises and expectations of massive proportions, notably for neurodegenerative disorders (Lindvall, 2004). Targeting specific segments of the gene using the oligonucleotide skipping technique has raised expectations for treating a number of Mendelian genetic conditions (Goodchild, 2011). This is truly the beginning of the promising phase for applied and translational genomics.

The enormous genomic data and information generated by genome wide association studies (GWAS), deciphering the complex phenotypes by copy number variations and single nucleotide polymorphisms and applying knowledge gained from genetic and genomic analysis in rare Mendelian disorders have offered fine molecular understanding of the underlying pathogenic mechanisms. There is lot of enthusiasm for applying next generation sequencing methods (alongside the Sanger sequencing) in new gene discoveries, unravelling novel molecular mechanisms and identifying critical focal points in molecular pathways in designing and developing targeted molecular therapy models.

Several major global initiatives are being pursued to curate and annotate enormous genomic data and information from new genomic technological advances. The common theme is genotype-phenotype correlation. Leaders in this approach include the Human Variome Project (, Gen2Phen project ( and recently launched Human Phenome Project (Freimer and Sabbati, 2003). Successful outcomes of these projects might offer clarification and evidence that could be applied in medicine and health. However, there is sufficient evidence around supporting the argument for genomic applications for enhancing the diagnostic and probably the prognostic potential of genomic medicine and health. Promising new therapeutic developments have followed, particularly discovery and development of new drugs and pharmacogenetic / pharmacogenomics evidence necessary for personalised pharmacotherapy.

So how do genomics and all related genome technologies impact upon Medicine and Health? Do we have enough data, understanding and robust evidence to apply and translate in practising effective and efficient clinical medicine? We are probably safe to gently move in the next phase of the genomic and personalized medicine. Has genome sequencing done any good to human health? Francis Collins believes that I think there are people who’s lives have been saved because of the study of the genome.

Genomic medicine and health genomics is a global phenomenon. Prospects of this major revolution are enormous and unimaginable. Skeptics argue that this is all disproportionately overhyped. Nevertheless massive investments in all parameters are poured into this field globally with sky-high promises and huge expectations. A major global alliance has committed itself to bring all geneticists, genome scientists, genome technology experts, genetic clinicians and health genomic experts together for the benefit of global health (

Perhaps, it is most relevant at this juncture to remind us that the practice of Medicine is an art based on sound scientific principles. It would be appropriate to quote Sir William Osler’s remarks, “If there were no individual variability, medicine would have been science not an art.” Genomics in this context provides the basis of individual variability and the modern genomic era clinician will need to ensure that this continues to be applied as an art.


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Deploying whole genome sequencing in clinical practice and public health: Meeting the challenge one bin at a time. Genetics in Medicine (2011) 13, 499–504;

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Diagnostic Clinical Genome and Exome Sequencing. N Engl J Med 370:2418-2425

Cardon, LR and Bell, JI (2001) Association study designs for complex diseases. Nat. Rev.Genet. 2:91-99.

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Collins FS, McKusick VA (2001): Implications of the Human Genome Project for medical science. JAMA 285:540-544.

Freimer, Nelson & Sabatti, Chiara (2003).

The Human Phenome Project. Nature Genetics 34:15-21.

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Goodchild J (2011). Therapeutic oligonucleotides. Methods Mol Biol. 764:1-15.

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Hugot, JP et al. (2001): Association of NOD2 leucine-rich variants with susceptibility to Crohn’s disease. Nature 411:599-603.

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International Conference on Birth Defects 2014

“Genes, Genome and Human Malformations” 9 – 11 February 2014  & Symposium on Genetic Eye Diseases in Clinical Ophthalmology 11 February 2014 Waters Edge, Colombo, Sri Lanka

Ophthalmic Genetics and Genetic Counseling for Clinicians and Basic Scientists – Conference & Workshop Jointly Organize for the First Time in India by the Indo-UK Genetic Education Forum On 15th & 16th (Sat, Sun) February, 2014
Venue: Narayana Nethralaya – 1 Auditorium, Rajaji Nagar, Bangalore – 10

The Fourth Cardiff Cardiovascular Genetics Conference, 21-22 November 2013
Abstracts for invited speakers and spoken/ poster presentations:

Speakers’ Abstract Booklet
Cardiovascular Genetics Symposium Abstracts

Cardiff Spire Cardiff Hospital

  • Genetic diseases of the heart and blood vessels
  • Inherited bone and connective tissue diseases
  • Genetic muscle and nerve diseases
  • Inherited and Familial cancers
  • Congenital anomalies and malformation syndromes
  • Inherited metabolic disorders
  • Rare/Orphan genetic diseases
  • To book an appointment telephone 029 2073 5515



Genetic disorders among peoples from the Indian Subcontinent, Cardiff-2005

Challneges of genetic disorders in the Indian subcontinent, ICHG, Brisbaine-2006

Cardiovascula genetics in clinical practice, Bangalore, India-2010

Challenges of genetics & genomics in Medicine, Chennai, India-2011

Clinical Genetics & Genomic Medicine, New Delhi, India-2011

Genes and human malformations, Bangalore, India-2012

 Indian Cancer Genetics Conference, Mumbai, India-2013

 Current Trends in Genetic and Genomic Medicine, Lucknow, India-2013

 Next revolution in genetics & genomics, New Delhi, India-2013

Genomic news and Genome Mirror

Recently global genomics community moved a step forward by coming closer through the creation of a shared framework for distributing and analyzing massively complex genomic information to facilitate medical progress and innovations. The framework, appropriately called the Global Genomic Alliance, includes leading research institutions and organizations actively engaged in genomics research in healthcare. Leaders of the alliance are the US National Institutes of Health (, the Wellcome Trust Sanger Institute (Hinxton, Cambridgeshire, UK;, and the Beijing Genomics Institute ( The alliance aims to focus on standardizing and sharing genomic and clinical data. The white paper (click attached) announcing setting up of the global alliance states, “the cost of genome sequencing has fallen one-million fold in the past several years, fuelling an explosion of information about the genetic basis of human health and disease.”

The global genomic alliance is open for commercial and not- for-profit organizations to join forces with other leading data, health care, research, and disease advocacy organizations to establish an evidence base for genomic research and medicine that adheres to the highest standards of ethics and privacy. So far, nearly 70 organizations in Asia, Australia, Africa, Europe, North America and South America who are committed to creating a common framework that supports data analysis and protects the autonomy and privacy of participating individuals. Signatories of an accompanying Letter of Intent to create a not-for-profit, inclusive, public–private, international, non-governmental organization include healthcare providers, research institutions, disease advocacy groups, life science and information technology companies.

Quotes from several leading partner organizations advocate and emphasize the need for this global genomic initiative ( “This is an excellent initiative and we are very proud to be a part of it,” says Janet Thornton, Director of the EMBL-European Bioinformatics Institute in the UK. “As part of the Global Alliance and members of ELIXIR, we can help make this vision a reality. Sharing data and information is at the heart of our mission, and developing resources that enable innovation is a large part of what we do. The European Genome-phenome Archive, the Embassy Cloud, and BioMedBridges are just a few projects at EMBL-EBI that can support the alliance’s technical standards for interoperability as well as for data access and security.”

“The ability to collect and analyse large amounts of genomic and clinical data presents a tremendous opportunity to learn about the underlying causes of cancer, inherited and infectious diseases, and responses to drugs,” says David Altshuler, Deputy Director of the Broad Institute of Harvard and MIT in the US. “However, we will only realize this opportunity if we can establish effective and ethically responsible approaches to share data. We believe that by working together, and by committing to the principle that each individual has the right to decide whether and how broadly to share their personal health information, we can accelerate progress in life sciences and medicine.”

“The European Genome-phenome Archive (EGA) is just one example of what the Global Alliance is trying to achieve,” adds Paul Flicek of EMBL-EBI. “It matches up genome data with other features while protecting key information about patients, but applying for access can be complicated. Streamlining the process for a researcher to gain access to these datasets would have a dramatic, positive impact on research.”

A disease might occur in one in 1,000 or one in 100,000 babies, according to Dr. David Altshuller, deputy director and chief academic officer at the Broad Institute of Harvard University (Cambridge, MA, USA) and the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA; A medical center or even an experienced clinician might never see an affected child or might just see one, so no one ever learns.”

The Global Alliance will foster innovation in a number of ways, notably though the establishment of open standards supporting the development of interoperable information-technology platforms for biomedicine. These platforms will enable sharing and learning from data, wherever it may be stored.
To express an interest in joining the Global Genomic Alliance, please contact

Genomics and Health in Developing World

Genomics and Health in the Developing World provides detailed and comprehensive coverage of population structures, human genomics, and genome variation–with particular emphasis on medical and health issues–in the emerging economies and countries of the developing world. With sections dedicated to fundamtals of genetics and genomics, epidemiology of human disease, biomarkers, comparative genomics, developments in translational genomic medicine, current and future health strategies related to genetic disease, and pertinent legislative and social factors, this volume highlights the importance of utilizing genetics/genomics knowledge to promote and achieve optimal health in the developing world. Grouped by geographic region, the chapters in this volume address: – Inherited disorders in the developing world, including a thorough look at genetic disorders in minority groups of every continent – The progress of diagnostic laboratory genetic testing, prenatal screening, and genetic counseling worldwide – Rising ethical and legal concerns of medical genetics in the developing world – Social, cultural, and religious issues related to genetic diseases across continents Both timely and vastly informative, this book is a unique and comprehensive resource for genetists, clinicians, and public health professionals interested in the social, ethical, economic, and legal matters associated with medical genetics in the developing world.

Principles and Practice of Cardiovascular Genetics

Consisting of contributions from experts in all specialties of cardiovascular genetics and applied clinical cardiology, Principles and Practice of Clinical Cardiovascular Genetics serves as the comprehensive volume for any clinician or resident in cardiology and genetics. Each chapter provides a detailed and comprehensive account on the molecular genetics and clinical practice related to specific disorders or groups of disorders, including Marfan syndrome, thoracic and abdominal aortic aneurysms, hypertrophic, dilated and restrictive cardiomyopathies and Arrhythmogenic right ventricular cardiomyopathy, as well as many others. All sections comprehensively address cardiovasuclar genetic disorders, beginning with an introduction and including separate sections on the disease’s basic biological aspects, specific genetic mechanisms or issues, clinical aspects, genetic management (e.g., genetic diagnosis, risk assessment, genetic counseling, genetic testing), and clinical management issues. The final section exclusively addresses the management of cardiovascular genetic disorders, specifically considering stem cell therapy, genetic counseling, pharmacogenomics and the social and ethical issues surrounding disease treatment.