Genomics and Proteomics. DNA sequencing: dideoxy chain termination.
DNA Testing: Living Longer Via Personal Genomics
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Transcript of DNA Testing: Living Longer Via Personal Genomics
DNA Testing: Living Longer Via Personal Genomics
Melanie Swan+1-650-681-9482
@DIYgenomics www.DIYgenomics.org
October 10, 2010
Slides: http://slideshare.net/LaBlogga
2October 10, 2010DIYgenomics.org
Numerous useful applications of genomics
Ancestry
Pregnancy screening
Identity (paternity, forensics)
Health conditions
Pharmaceutical response
Athletic performance
Aging profile
Image credit: http://www.uchsc.edu/vivat/2006/September2006/images/DNA_strand.jpg
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Example: what to do with your data
Check if you have the risk allele for the BDNF gene Determine related SNP/rsID#, rs6265 (neuroplasticity) Search genomic data for rs6265 genotype (e.g., CC) Determine the risk allele (which letter?) (e.g.; G1) Opportunity: genomic database with three minimal fields:
gene, rsid# and risk allele Current genomics search resources
PharmGKB, dbSNP, GWAS catalog, SNPedia
Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving1Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in
Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.
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Finding your BDNF data, variant rs6265
Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser
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Conflicting consumer genomic test results
Source: http://dnasnips.com/dnaSnips/Heart.html
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DIYgenomics: genomic service comparison
Companies use Different genes/variants Different population averages Different quantitative scoring methodologies
Risk for top 20 Health Conditions
Response to 250 Drugs
Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, May;12(5):279-8. http://www.diygenomics.org/webapp/gen_data.php
Private data upload: Marat Nepomnyashy; https://addons.mozilla.org/en-US/firefox/addon/156946/
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DIYgenomics app - Android
Side-by-side comparison of consumer genomic services by loci and variants for top 20 conditions
Application developed by: Michael Kolb, Lawrence S. Wong, Melanie Swan
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DIYgenomics app - iPhone
Side-by-side comparison of consumer genomic services by loci and variants for top 20 conditions
Application developed by: Ted Odet, Greg Smith (ManyFriends.com)
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Drug response
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Athletic performance
Power/endurance (sprinter or marathoner) ACTN3 rs1815739 CC (power), TT
(endurance); ACE rs1799752 DD (power), II (endurance)
Ligament injury Favorable genotype: COL5A1 rs12722 CC
and GDF5 rs143383 GG Head injury
Two copies of ApoE ε4 (rs429358, rs7412) suggest slower recovery from head injuries
Strength Favorable genotype: H1F1A rs11549465 TT,
HFE rs1799945 GG, and HFE rs1800562 AA
Increased HDL in response to exercise Favorable genotype: IL-6 rs1800795 GG
http://www.genome.duke.edu/education/seminars/journal-club/documents/Assael_2009.pdf
More information: DIYgenomics.org Athletic Performance
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DIYgenomics study #1: MTHFR
Do common mutations in the MTHFR gene prevent vitamin B from working correctly?
Test whether 2 variations in the MTHFR gene (methylenetetrahydrofolate reductase) keep vitamin B9 (folic acid) from being metabolized into its active form (folate) rs1801133/C677T rs1801131/A1298C
Without this form of vitamin B, homocysteine may accumulate Risk: nutritional deficiencies and symptoms associated with diabetes
complications, including vascular damage and nerve damage 50% or more of the population may have some form of MTHFR
polymorphism
Source: http://diygenomics.pbworks.com/MTHFR
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MTHFR pathway diagram
Aaron Vollrath; http://bit.ly/cHRzS8
Legend: where interventions impact the pathway1 = Regular B-vitamin2 = Active form of B9 (folate)
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DIYgenomics MTHFR study protocol
1. Genotype
MTHFR gene SNPs:
rs1801133 (A/G)
rs1801131 (A/G)
2. Phenotype
Blood tests:
B-12 and
Homocysteine
3. Intervention
(2 week periods)
1. B-complex
2. L-methylfolate
3. B-complex + L-methylfolate
Investigate genotype-phenotype linkage and apply interventions to improve phenotypic outcomes
Protocol confirmed with two separate experts in the field
Source: http://diygenomics.pbworks.com/MTHFR
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MTHFR pilot study results
Average drug store vitamin (Centrum multivitamin) reduced homocysteine levels for 4/5 participants
Blood Test #
2. Homocysteine levels
DIYgenomics MTHFR citizen science study1
1. Genotype profiles
Baseline LMF
Source: http://diygenomics.pbworks.com/MTHFR_Results
1Results are not statistically significant and are intended as a pilot demonstration of citizen science as a model
Baseline+ LMF
Centrum
Homocysteine umol/l
Centrum
15October 10, 2010DIYgenomics.org
Boston University: Genetic Signatures of Exceptional Longevity in Humans
Source: Sebastiani P et al. Genetic Signatures of Exceptional Longevity in Humans. Science. 2010 Jul 21. http://diygenomics.org/citizengenomics/bu_longevity.php
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DIYgenomics aging study
Genomics + physical biomarkers + intervention Top twenty genomic mechanisms of aging
1. Aging-specific genetics
2. Diabetes and metabolic disease
3. Catabolism (waste removal) and other
4. Heart disease and blood operations
5. Cancer
Top twenty phenotypic biomarkers of aging Interventions
Traditional Novel
More information: http://diygenomics.pbworks.com/Aging
Image credit: http://www-nmr.cabm.rutgers.edu
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DNA sequencing: 10x/yr improvement
April 1, 2010 Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif Dec. 14, 2009
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Direct-to-Consumer genomics landscape
Single/few condition Multiple condition Whole genome
Cost
1Medical condition $9,500 Service Breadth
Public studies MatchmakingScientificMatch $1,995GenePartner $10-$99
PaternityGenelex $200-$475Identigene $149-$399
Pregnancy ScreeningCounsyl $349
NutrigenomicsAPO E Gene Diet $389Inherent Health $99
Coriell15 conditions
Scripps (Navigenics)28 conditions
Pers. Genome Proj.Conditions undisclosed
Harvard Med. Sch.
Genetic disorders,
PredispositionDNA Direct $200-$3,500Matrix Genomics $199-$799
Drug sensitivity,
$
Exome
23andme174 conditions
Navigenics*40 conditions
deCODEme49 conditions
$1,000
$429$299
Genomics71 conditions
Pathway*
$2,500
$999 $2,000
$985 *Must be physician-ordered
Knome
EdgeBio$6,000
$19,500
Knome
Illumina$48,000
$350,000
$99,500
$68,500
$20,0001
$39,500
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Genomics comparison scorecard
Consumer genomic service
# Cond-itions
Cost Report Data access
Visible research quality1
Updates
deCODEme 49 $2,000 + + +23andme 174 $429 Navigenics 40 $999 Pathway Genomics 71 $299 Coriell 7-15 public
study
PGP (Personal Genome Project)
n/a public study
1Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website
Which service to buy?
Melanie Swan+1-650-681-9482
@DIYgenomicswww.DIYgenomics.org
Slides: http://slideshare.net/LaBlogga
Creative Commons 3.0 license
Thank you! Questions?