PERSONAL GENOMICS

Maryam Nazir

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

Techniques SNP arrays Partial sequencing Whole genome sequencing

Can be used to evaluate:○ SNPs○ Indels○ Large SVs○ New sequences○ Haplotypes

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

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

Each participant:Full DNA sequenceExtensive phenotype information

○ Medical records○ MRI images○ Other measurements

Volunteer criteria:Permanent residents of the US, Canada, UKAble to submit tissue and/or genetic samplesInformed consent“no promise of anonymity and data return”

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

Gene signaturesGene expression pattern in a cell can be uniquely

characteristic of a conditionRisk assessment, diagnostic & prognostic applicationsMatch patients and treatments

Pharmacogenomics Field that analyzes how

genetic makeup affects an individual’s response to drugs

Want to tailor treatments for patients based on their genetics

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...)

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

Human Ancestry Looks at a person’s DNA at

specific locations compares results to defined groups

Mitochondrial DNATraces direct maternal line

Y-Chromosome DNATraces a male’s direct paternal line

Autosomal DNATests all ancestry, shows how

closely a person is related to others

Commercial Services Gentle

most comprehensive genetic test currently on the market

screens for >1700 genetic conditionspredicts 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 Sciencescommercializing full genome sequencingdo not provide any genetic analysis or counselling component

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

23andMe Mail order “spit kits” SNP genotyping (DNA array) Assessment of:

inherited traitsancestrygenetic risk for >240 diseases and common

conditions Information presented in user profile $99

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

Other Issues How relevant are the results of

commercial services? Clinical utility?

Education needed in interpreting results and communicating genetic informationFor the average person/patientFor doctorsFor the public & media

genetic counselling

Conclusions A fairly large number of loci that are known to

be predictive of disease have been identifiedMany of these can be clinically targeted

Immediate applications are limited at present The promise of personal genomics lies in the

futureMust 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

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.