Personal genomics

1. MaryamNazir Personal genomics

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.