Doug Brutlag 2011 The impact of genomics on the future of medicine and health Muhammad Faisal 2015-Arid-3638 PhD(scholar) Biochemistry

Doug Brutlag 2011 What is genomic medicine?  Genomic medicine or healthcare involves the use of many pieces of genetic information in order to help to:  Assess a person’s risk of developing a disease  Refine the diagnosis of disease, and predict prognosis Individualise treatment  Predict the effects of drugs, and prevent adverse effects  Develop new treatments  Diagnose infections and track epidemics.

Doug Brutlag 2011 Leveraging Genomic Information Novel Diagnostics Microchips & Microarrays - DNA Gene Expression - RNA Proteomics - Protein Understanding Metabolism Understanding Disease Inherited Diseases - OMIM Infectious Diseases Pathogenic Bacteria Viruses Novel Therapeutics Drug Target Discovery Rational Drug Design Molecular Docking Gene Therapy Stem Cell Therapy

Doug Brutlag 2011 Impact of Genomics on Medicine I.Diagnostics II.Therapeutics III.Ethical, Legal and Social Issues IV.Strategic V.Preventive

Doug Brutlag 2011 Impact of Genomics on Medicine I. Diagnostics Genomics: Identifying all known human genes Functional Genomics: Functional analysis of genes –In what tissues are they important? –When in development are the genes used? –How are they regulated? Novel diagnostics –Linking genes to diseases and to traits –Predisposition to diseases –Expression of genes and disease Personal Genomics –Understanding the link between genomics and environment –Improving health care

Doug Brutlag 2011

Whole genome sequencing  Whole genome sequencing (WGS) determines the sequence of nucleotide bases throughout the entire genome, rather than only the protein coding regions.  whole genome sequencing is mainly used in research studies.  It appears to be useful for identifying variation in regulatory sequences, as well as in coding genes.

Doug Brutlag 2011 Whole Exome sequencing  The exome is the part of the genome which codes for proteins, and represents around 2% of the total DNA.  Clinically, some of the most promising applications of this technique are in disease diagnosis.  It is particularly useful where family history suggests an inherited Mendelian disorder.

Doug Brutlag 2011 Genome wide association studies  Genome wide association studies are especially useful for finding genetic variations which contribute to the development of common and complex diseases.  Examples include bipolar disorder, coronary artery disease, rheumatoid arthritis, and types I and II diabetes.

Doug Brutlag 2011 Microarray comparative genomic hybridisation  This technique is used to detect copy number variations above a certain size.  Microarray comparative genomic hybridisation has become an essential diagnostic tool, particularly for geneticists and paediatricians  To detect microdeletion and microduplications, or larger chromosomal disorders.

Doug Brutlag 2011 Molecular Pathology’s network view of a sample of tests and diseases  A total of 45 nodes and 96 edges are depicted in the figure.  The nodes are the most common tests and diseases in the directory and edges are drawn from tests to disease if the test is used commonly for disease characterization.  The extent of genetic testing suggests that next generation sequencing and whole genomic analysis approaches have the potential to replace 85% of the tests found in this directory.

Doug Brutlag 2011

Electro Health Recorded Databases(EHR)  A major role of the international Human Variome Project ( is to ensure that genetic variation information generated during routine diagnostic and predictive testing is collected and shared in the course of routine clinical practice.  Several countries have formed the Global Alliance for Genomics and Health to develop a framework for data sharing.  Linking large population datasets to a personally controlled EHR system add significant value to the health care system.

Doug Brutlag 2011

Impact of Genomics on Medicine II. Therapeutics Novel Drug Development  Identifying novel drug targets  Validating drug targets  Predicting toxicity and adverse reactions  Improving clinical trials and testing Gene therapy  Replacing the gene rather than the gene product Stem cells therapies  Replacing the entire cell type or tissue to cure a disease

Doug Brutlag 2011 Pharmacogenomics What is pharmacogenomics?  It deals with the influence of genetic variation on drug response. What is the aim of pharmacogenomics?  Personalized medicine  Adjusting drug, amounts and delivery to suit patients  Maximize efficacy and minimize side effects  Identify genetics of adverse reactions  Identify patients who respond optimally

Doug Brutlag 2011 Applications of pharmacogenomics

Doug Brutlag 2011 Impact of Genomics on Medicine III. Ethical, Legal and Social Issues Personal Privacy Insurability Employability Discrimination Genetic selection versus eugenics Cosmetic genetics Patentability of genes, proteins and other natural products

Doug Brutlag 2011

Impact of Genomics on Medicine IV. Strategic Genomics can discover disease associated genes Genomics can discover disease causing genes. Genomics provides understanding of disease Genomics and bioinformatics provides basis for novel drug development Genomics provides basis for novel genetic and stem cell therapies Genomics provides the basis for preventive medicine.

Doug Brutlag 2011 v) Preventive Medicine

Doug Brutlag 2011 Founder of Preventive Medicine: Louis Pasteur When thinking about diseases, I never think about how to cure them, but instead I think about how to prevent them.

Doug Brutlag 2011 Preventive Medicine The goal is to prevent disease from occurring. First one must identify the cause of the disease. Treat the cause of the disease rather than the symptoms Genomics identifies genetic causes of inherited disease. When Paul Wise (a Stanford pediatrician) heard that we may soon sequence every child’s genome at birth, he stated: –“… all medicine may soon become pediatrics!” Infectious disease, auto immune disease and aging: environmental or acquired diseases

Doug Brutlag 2011 Health Care Policy  Current health care treats disease rather than maintaining health (Illness care?)  Future health care prevent disease  Reduce need for expensive interventions  Need social pressures to control behavior and increase vigilance.

Doug Brutlag 2011 Future Prospective  build the infrastructure for EHR databases that integrate patients' genomic and medical information for clinical and research applications  establish national and international knowledge- sharing platforms  develop well designed and integrated public and professional education efforts nationwide

Doug Brutlag 2011 Conclusion Genomic analysis provides opportunities for new approaches to therapeutic development, health care delivery and population health management to seize the transformative opportunities that personalised, precision genomic medicine offers.

Doug Brutlag 2011 References Anneke Lucassen and Richard S. Houlston The impact of genomics on the future of medicine and health. Genes: 5,

Doug Brutlag 2011