THE ERA OF INDIVIDUAL GENOMES. Sandra Viz Lasheras Advanced Genetics ( )

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1 THE ERA OF INDIVIDUAL GENOMES Sandra Viz Lasheras Advanced Genetics ( )

2 CONTENTS 1. INTRODUCTION - The genomic era - Sequencing techniques 2. PROJECTS genomes project - Individual genome (Watson genome) - Personal Genome Project (PGP) 3. GENOMIC MEDICINE - Personalized medicine 4. CONCLUSION

3 1. INTRODUCTION...FROM GENES TO GENOMES THE GENOMIC ERA WHY? Genetic variability Study of population migrations and speciations Animal and Plant breeding Molecular knowleage Personalized medicine HOW? First sequencing techniques (1977) 2001 Human genome

4 1. INTRODUCTION SEQUENCING TECHNIQUES AND THEIR ACHIEVEMENTS First generation: Sanger Method (1977/1990) Enabled sequencing of clonal DNA populations Second generation: 454 (2005) Massively increased throughput by parallelizing many reactions Illumina (2006) SOLiD (2007) Ion torrent (2010) Third generation: Illumina synthetic long read (2012), 10xGenomics (2015), Pac Bio (2011), Nanopore (2014) Allows direct sequencing of single DNA molecules

5 1. INTRODUCTION COST PER GENOME NIH. Web page. The Cost of Sequencing a Human Genome From 100 million $ to $ per genome!

6 2. PROJECTS 1000 GENOMES PROYECTS The goal of the 1000 Genomes Project was to find most genetic variants with frequencies of at least 1% in the populations studied. The relationship between genotype and phenotype and aid our understanding of the role of genetic variation in human history, evolution and disease Individuals from 26 human populations Catalog of 84,7 million variants 86% of these 84.7 million restricted to individuals from a single continent (Africa) 1000 Genomes Project Consortium. (2015). A global reference for human genetic variation. Nature, 526(7571),

7 2. PROJECTS JAMES WATSON WHOLE- GENOME SEQUENCING (2008) The objective was catalogue genetic variation in the subject's DNA using the Next Generation Sequencing (454/Roche-pyrosequencing) Single nucleotid polymorphisms (SNPs): 3,3 million SNPs Copy number variation (CNP): 23 CNVs (26-1,6mB) 9 dna GAINS 14 DNA loss Insertions and deletions (Indels): 222,718 65,67 insertios 157,04 deletios Polimorfism of Alu SINE elements Wheeler et al. Nature. 2008

8 2. PROJECTS JAMES WATSON WHOLE- GENOME SEQUENCING (2008) Comparation with other personal genome (C.Venter) Shared 1.68 million of the SNPs 5230 non-synonymous changues (58% of the Watson s non-synonymous SNPs) Different from each other by 7648 protein coding changues VS

9 2. PROJECTS PERSONAL GENOMES PROJECT Objective: to make a wide spectrum of data about humans accesible to increase biological literacy and improve human health. - Open-consent format for the collection of combined genomic and phenotypic information, allowing this data to be shared publicity volunteers to analyse genome, traits and enviroment - Goes beyong genome sequencinfg to create additional layers of information associated enviromental and trait profiling. The Genome-Enviroment-Trait Evidence (GET-evidence)

10 2. PROJECTS PERSONAL GENOMES PROJECT - Pilot study PGP-10: Whole genome sequencing, epigenetic profile, microbiome profiling Priorization of the variants with potential clinical relevance The pilot study revealed several rare variants that have been implicated in serious diseases but the voluntears didn t have these deseases. Risks of publishing Loos of privacity for you and your relatives. Infer paternity or other features of the participant's genealogy Reveal propensity for a disease currently lacking effective treatment options Claim statistical evidence that could affect employment or insurance or the ability to obtain financial services for the participant Benefices Prevention Moving towards personalized medicine

11 3. GENOMIC MEDICINE "An emerging medical discipline that involves using genomic information about an individual as part of their clinical care (e.g., for diagnostic or therapeutic decisionmaking) and the health outcomes and policy implications of that clinical use." Research programs generating the evidence base, and designing and testing the implementation of genome sequencing as part of an individual's clinical care.

12 3. GENOMIC MEDICINE PERSONALIZED MEDICINE DETECTION OF GENES CAUSING GENETIC DISEASES ( BIOMARKERS) 1. Whole exome sequencing 2. Genome sequencing Identify high-risk individuals Preventive intervention Personalized genetic diagnostic Personalized Treatment Pharmacogenomics

13 3. GENOMIC MEDICINE PHARMACOGENOMICS 38% to 75% of patients fail to respond to a treatment Targeting specific disease markers Enhancing drug safety Advancing therapies reducing cost Spear BB, et al. Trends Mol Med 2001;7:201-4

14 3. GENOMIC MEDICINE PERSONALIZED MEDICINE CYP2D6 alleles Dean, L. (2016). Tamoxifen therapy and CYP2D6 genotype.

15 4. CONCLUSIONS Individual genomes will become the approach of choice for understanding the complexity of human biology. High-quality clinical and therapeutic data, available from large-scale randomized controlled trials and databases are improving now. Link all these phenotype data to the genotyping data. Urgent innovation in the data analysis. + Decrease of the costs

16 REFERENCES 1000 Genomes Project Consortium. (2015). A global reference for human genetic variation. Nature, 526(7571), Wheeler, D. A., Srinivasan, M., Egholm, M., Shen, Y., Chen, L., McGuire, A.,... & Gomes, X. (2008). The complete genome of an individual by massively parallel DNA sequencing. Nature, 452(7189), Lunshof, J. E., Bobe, J., Aach, J., Angrist, M., Thakuria, J. V., Vorhaus, D. B.,... & Church, G. M. (2010). Personal genomes in progress: from the human genome project to the personal genome project. Dialogues in clinical neuroscience, 12(1), 47. Spear, B. B., Heath-Chiozzi, M., & Huff, J. (2001). Clinical application of pharmacogenetics. Trends in molecular medicine, 7(5), Cho, S. H., Jeon, J., & Kim, S. I. (2012). Personalized medicine in breast cancer: a systematic review. Journal of breast cancer, 15(3),