1. Maryam Nazir

2. Personal Genomics:  Branch of genomics concerned with the sequencing and analysis of the genome of an individual  Once sequenced, it can be compared with published literature to determine likelihood of disease risk or trait expression  Main aim: to inform preventative action

3. Techniques  SNP arrays  Partial sequencing  Whole genome sequencing Can be used to evaluate: ○ SNPs ○ Indels ○ Large SVs ○ New sequences ○ Haplotypes

4. Cost of Sequencing  Continual development of new sequencing technologies, next-generation sequencing Increased speed and reduced cost of sequencing Now possible to offer genetic testing to consumers

5. Personal Genome Project  Large, long-term study  Aim: To sequence and publicize the complete genomes and medical records of 100,000 volunteers  All data will be available in the public domain  Purpose: To enable research in personal genomics and personalized medicine

6.  Each participant: Full DNA sequence Extensive phenotype information ○ Medical records ○ MRI images ○ Other measurements  Volunteer criteria: Permanent residents of the US, Canada, UK Able to submit tissue and/or genetic samples Informed consent “no promise of anonymity and data return”

7. Personalized Medicine  A model of medicine which proposes the customization of healthcare with medical decisions being tailored to the individual patient  Goal: To individualize prevention, diagnosis, and treatment--by use of genetic differences as markers  Disease risk >2500 diseases have predictive medical value ○ Can be recommended for genetic tests for single genes or whole genome sequencing

8.  Gene signatures Gene expression pattern in a cell can be uniquely characteristic of a condition Risk assessment, diagnostic & prognostic applications Match patients and treatments

10. Pharmacogenomics  Field that analyzes how genetic makeup affects an individual’s response to drugs  Want to tailor treatments for patients based on their genetics

11. Cancer genomics  Main goal: to identify genes, or gene signatures, that may provide insights into cancer diagnosis, predicting clinical outcomes or targets for cancer therapies  Tumour sequence is compared to a matched normal tissue  Personalized cancer treatments  Genetic profiles of tumours part of recommended evaluation for certain cancers (colon, breast, lung...)

12. Nutrigenomics  Study of how individual genetic variation affects a person’s response to nutrients and impacts their risk of nutrition-related chronic diseases  People respond differently to certain foods

13. Human Ancestry  Looks at a person’s DNA at specific locations  compares results to defined groups  Mitochondrial DNA Traces direct maternal line  Y-Chromosome DNA Traces a male’s direct paternal line  Autosomal DNA Tests all ancestry, shows how closely a person is related to others

14. Commercial Services  Gentle most comprehensive genetic test currently on the market screens for >1700 genetic conditions predicts response to certain medications  HelloGenome (Korea) genotyping (SNP chips) and full genome sequencing (Solexa machines)  Illumina, Sequenom, Oxford Nanopore Technologies, Pacific Biosciences, Complete Genomics, 454 Life Sciences commercializing full genome sequencing do not provide any genetic analysis or counselling component

15.  Positive Bioscience (Mumbai) Next-generation sequencing To determine most beneficial cancer treatment for patients  Nutrigenomix SNP genotyping Each gene tested is involved in the way the body processes a certain dietary component With information obtained, can tailor the diet to prevent chronic diseases (cancer, heart disease, type 2 diabetes) -ex. Caffeine Only available through registered dieticians $385

16. 23andMe  Mail order “spit kits”  SNP genotyping (DNA array)  Assessment of: inherited traits ancestry genetic risk for >240 diseases and common conditions  Information presented in user profile  $99

18. Ethical Issues  Personal privacy & misuse of information Whose responsibility? Who owns the genomic info?  Genetic discrimination Discrimination based on information obtained from an individual’s genome Genetic Information Nondiscrimination Act (U.S.) ○ Prevents discrimination by health insurers and employers, but does not apply to life insurance or long-term care insurance  Psychosocial stress Consequence of knowing one’s predisposition to disease Know risk, have no cure

19. Other Issues  How relevant are the results of commercial services? Clinical utility?  Education needed in interpreting results and communicating genetic information For the average person/patient For doctors For the public & media  genetic counselling

20. Conclusions  A fairly large number of loci that are known to be predictive of disease have been identified Many of these can be clinically targeted  Immediate applications are limited at present  The promise of personal genomics lies in the future Must first build a database of personal genomes  Many people envision a future where personal genomic information is one of the essential tools used to tailor one’s medical care

21. References  Offit, Kenneth. "Personalized medicine: new genomics, old lessons." Hum Genet. 130. (2011): 3-14.  Snyder, Michael, Jiang Du, and Mark Gerstein. "Personal genome sequencing: current approaches and challenges." Genes Dev. 24. (2010): 423-431.  Werner, Thomas. "Next generation sequencing in functional genomics." Briefings in Bioinformatics. 2.5 (2010): 499-511.  Cooper, David N., et al. "Genes, Mutations, and Human Inherited Disease at the Dawn of the Age of Personalized Genomics." Human Mutation. 31.6 (2010): 631–655.  Chin, Lynda, Jannick N Andersen1, and P Andrew Futreal. "Cancer genomics: from discovery science to personalized medicine." Nature Medicine. 17.3 (2011): 297-303.