Direct-to-Consumer

Genetic Testing
An Overview of an Emerging
Technology and Its Dangers
present by
Neil Young
 To him who devotes his life to science,
nothing can give more happiness than
increasing the number of discoveries, but
his cup of joy is full when the results of his
studies immediately find practical
applications.

- Louis Pasteur
Overview
• Discuss:
– Single Nucleotide Polymorphisms (SNPs
–’snips’) and Their Importance
– Direct-to-Consumer (DTC) Genetic Tests
– Consumer Process
– Laboratory Process
– Identifiable Predispositions and Treatment
– Legal, Regulatory, and Ethical Concerns
– Future Prospects
Note
• Paternity and ancestry testing is also
included in the spectrum of DTC genetic
testing though they will not be discussed
during this presentation.
Scope
• Clinician (MD, NP, etc)

• Genetic counselor

• Biological scientist

• Everyday consumer
Single Nucleotide Polymorphisms
• Single changes that exist at a position in
the genome which can represent an allele

• SNPs in the past differentiated between

alleles as long as 1% or more of a
population has contains the same
sequence but databases contain some
that can be even rarer
Single Nucleotide Polymorphisms
Single Nucleotide Polymorphisms
• SNPs can occur inside a gene or outside

• Low rate of changes (10-8 base pairs)

• Human Genome Project and SNP

determination
How does this differ from
normal genetic testing?
• Offered directly to the consumer
• No defined clinical context
• No involvement of healthcare
professionals
• Not a single focused test but it examines
the entire genome including portions that
contain no information in today’s
perspective
The Consumer Process
• Why the internet?
– 9/2002: 6.6 million hits on NIH.gov and 5.3
million to WebMD.com
– 9/2004: 12.3 million and 11.1 million hits
respectively

– 2005: 70% of Internet savvy patients say their

healthcare decision was influenced by health
care websites
The Consumer Process
• Recent Google search

– www.genedx.com

– www.navigenics.com

– www.pathway.com
The Consumer Process
The Consumer Process
Note:

Navigenics does not provide medical advice,

diagnosis or treatment.
The Consumer Process
The Consumer Process
The Laboratory Process
• Based on basic Polymerase Chain
Reaction (PCR) and Southern blotting
techniques

• Actual procedures are protected by patent

and corporate secrecy
The Laboratory Process
The Laboratory Process
The Laboratory Process
The Laboratory Process
Predispositions and Treatment
• GeneDx.com

• Navigenics.com

• Pathway.com
 Predispositions and Treatment
• ------ B ------
• Bannayan-Riley-Ruvalcaba syndrome
------ A ------ • Basal cell nevus syndrome NEW: Now includes Deletion Testing!
• ADA Severe Combined Immunodeficiency NEW • Beta-Ketothiolase Deficiency NEW
• Adenosine Deaminase Deficiency NEW • Biotinidase Deficiency
• • Birt-Hogg-Dube Syndrome
Alagille Syndrome NEW: Includes Deletion Testing!
• Blackfan-Diamond Syndrome
• Alexander Disease
• Branchiootic SyndromeNEW!
• Allgrove syndrome; Achalasia-Addisonianism-Alacrima • Branchiootorenal SyndromeNEW!
• Alport Syndrome • Bruton type agammaglobulinemia NEW: Includes Deletion Testing!
• Amegakaryocytic Thromobocytopenia, congenital • Bullous ichthyosiform erythroderma
• Anauxetic Dysplasia ------ C ------
• Androgen Insensitivity Syndrome • Campomelic Dysplasia COMING SOON!
• Aniridia • Cardio-Facio-Cutaneous (CFC) Syndrome
• Carney Complex
• Anophthalmia
• Carnitine Palmitoyltransferase II (CPT2) DeficiencyNEW!
• Antley-Bixler Syndrome (ABS) COMING SOON! • Cartilage Hair Hypoplasia
• APECED • Chanarin-Dorfman Syndrome
• Aromatase Deficiency COMING SOON! • CHARGE Syndrome
• Atypical Rett syndrome • Cherubism
• Choroideremia
• Autism/Macrocephaly
• Chronic Granulomatous Disease
• Autoimmune Lymphoproliferative Syndrome (ALPS) • Clouston syndrome
• Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal • Coffin-Lowry Syndrome
DystrophySyndrome • Cohen syndrome
• Autosomal Recessive (ADA SCID) NEW • Collodion baby (lamellar ichthyosis)
• Autosomal Recessive Hypophosphatemic Rickets (ARHR)NEW! • Collodion baby (congenital ichthyosiform erythroderma)
• Cone Rod Dystrophy Autosomal DominantNEW!
• Autosomal Recessive Retinitis Pigmentosa (arRP)NEW!
• Cone Rod Dystrophy Autosomal RecessiveNEW!
• Autoimmune Polyglandular Syndrome • Congenital insensitivity to pain with anhidrosis (CIPA)
• Axenfeld-Rieger Syndrome • Congenital Neutropenia, recessive
• Congenital Recessive Ichthyosis (erythrodermic type)
• Costello syndrome (Facio-cutaneo-skeletal syndrome; FCS syndrome)
• Cowden Syndrome
• Craniofrontonasal syndrome (CFNS)NEW!
 Predispositions and Treatment
------ D ------ • ------ F ------
• Danon DiseaseNEW! • Fabry disease
• Familial Cold Urticaria syndrome
• Darier disease
• Familial Cutaneous Malignant Melanoma
• Dent disease • Familial Exudative Vitreoretinopathy (FEVR)NEW!
• Developmental Eye Disease • Familial Hypocalciuric Hypercalcemia
• Diamond-Blackfan Anemia • Familial Isolated Hyperparathyroidism (FIHP)
• Dilated CardiomyopathyNEW! • Familial Medullary Thyroid Carcinoma (FMTC)
• Familial Multiple Mole and Melanoma Syndrome
• Dopa-responsive Dystonia
• Familial Hibernian Fever (TRAPS)
• Duane-Radial Ray syndrome / Acro-Renal-Ocular syndrome
• Familial Mediterranean Fever
• Dyskeratosis Congenita (DKC) • Feingold syndrome
• Dystrophic Epidermolysis Bullosa • Focal Dermal Hypoplasia (FDH) / Goltz Syndrome NEW: Includes
Deletion Testing!
------ E ------ • Fumarase Hydratase Deficiency (FHD)
• Ectrodactyly - Ectodermal Dysplasia - Clefting Syndrome
------ G ------
• Epidermolysis Bullosa Dystrophica • GlaucomaNEW!
• Epidermolysis Bullosa, Junctional Type • Glutaric Aciduria Type I (GA1)
• Epidermolysis bullosa, junctional with Muscular Dystrophy • Glutaric Aciduria II (GAII)/ Multiple Acyl-Coa Dehydrogenase
Deficiency (MADD)
• Epidermolysis Bullosa, Junctional with Pyloric Atresia
• Glycogen Storage Disease Type II (GSDII) or Pompe Disease
• Epidermolysis Bullosa Simplex • Goltz Syndrome
• Epidermolytic hyperkeratosis • Gorlin
• Epidermolytic PPK Syndrome (Basal cell nevus syndrome, Nevoid basal cell carcinoma syndr
ome)
• Erythrokeratodermia variabilis NEW: Includes Deletion Testing!
• GTP Cyclohydrolase I Deficiency
 Predispositions and Treatment
• ------ I ------
• ------ H ------ • Ichthyosis bullosa of Siemens
• Hailey-Hailey disease (HHD; familial benign chronic pemphigus) • Ichthyosis linearis circumflexa
• Harlequin Ichthyosis (HI) • Ichthyosis vulgaris (IV), with or without associated atopic dermatitis
• Hay-Wells Syndrome • IL7R Severe Combined Immunodeficiency, Autosomal
• Hereditary Angioedema NEW: Includes Deletion Testing! Recessive (IL7R SCID)
• Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) • Immunodeficiency Syndrome with Hyper IgM, Type 2 NEW
• Hereditary Paraganglioma-Pheochromocytoma Syndrome (PGL/PCC)NEW!
• Inclusion Body Myopathy, Hereditary (HIBM)
• Herlitz Junctional Epidermolysis Bullosa
•
• Incontinentia Pigmenti (IP) / Hypohidrotic Ectodermal
Hermansky-Pudlak syndrome
•
Dysplasia with Immune Deficiency (HED-ID)NEW!
Hidrotic ectodermal dysplasia
• Hirschsprung Disease (HSCR) • Infantile Spasm Syndrome-2, X-linked
• HMG CoA Lyase Deficiency (3-Hydroxy-3-Methylglutaryl CoA Lyase • IRAK4 Deficiency, Invasive Pneumococcal Disease
Deficiency) • Isovaleric Acidemia
• Holocarboxylase Synthetase Deficiency (Multiple Carboxylase Deficiency)
• Holoprosencephaly NEW: Includes Deletion Testing! ------ J ------
• Holt-Oram Syndrome • JAK3 Severe Combined Immunodeficiency, Autosomal
• Hyper-IgD Syndrome (HIDS) Recessive (JAK3 SCID)
• Hyper-IgE Recurrent Infection Syndrome; Job's Syndrome; HIES • Job's Syndrome; HIES; Hyper-IgE Recurrent Infection Syndrome
• Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT)
• Junctional Epidermolysis Bullosa
• Hypertrophic CardiomyopathyNEW!
• Junctional Epidermolysis Bullosa with Pyloric Atresia
• Hypo-/Anhidrotic ectodermal dysplasia (X-linked)
• Hypocalcemia, Autosomal Dominant • Juvenile Retinoschisis
• Hypohidrotic Ectodermal Dypslasia (Autosomal Dominant)
• Hypohidrotic Ectodermal Dysplasia (Autosomal Recessive)
------ K ------
• Hypohidrotic Ectodermal Dysplasia with Immune Deficiency (HED-ID) / • Kallmann Syndrome
Incontinentia Pigmenti (IP)NEW! • Keratitis-Ichthyosis-Deafness Syndrome (KID Syndrome)
• Hypophosphatemic rickets (autosomal dominant form) • Ketothiolase Deficiency NEW
• Hypophosphatemic rickets (X-linked form) NEW: Includes Deletion Testing!
• Hypoparathyroidism, Familial Isolated
 Predispositions and Treatment
• ------ N ------
• ------ L ------ • Nemaline Myopathy
• Lamellar ichthyosis (type 1)
• Neutropenia, Congenital and Cyclic
• Lamellar ichthyosis (type 2)
• LEOPARD Syndrome • Neonatal Severe Primary Hyperparathyroidism
• Leber Congenital Amaurosis Autosomal Dominant NEW! • Netherton syndrome (NTS)
• Leber Congenital Amaurosis Autosomal RecessiveNEW!
• Leukocyte Adhesion Deficiency
• Neutral lipid storage disease with ichthyosis (NLSD)
• Lhermitte-Duclos disease • Nevoid basal cell carcinoma syndrome
• Limb-Mammary Syndrome • Niemann-Pick Disease, Types A and B
• Long-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase
(LCHAD) Deficiency / Mitochondrial Trifunctional Protein (MTP) Deficiency • Niemann-Pick Disease, Type C
• NOMID/CINCA Syndrome
------ M ------
• 3-Methylcrotonyl-CoA Carboxylase (3-MCC) Deficiency • Non-bullous congenital ichthyosiform erythroderma
• Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency (NBCIE)
• Metaphyseal Dysplasia without Hypotrichosis • Non-epidermolytic PPK
• Methylmalonic Acidemia
• Microphthalmia
• Non-Herlitz Junctional Epidermolysis Bullosa
• Methylmalonic Aciduria and Homocystinuria, Cobalamin C (cblC) Type • Noonan Syndrome
• Mucolipidosis Type IV • Noonan Syndrome - Prenatal Testing based on ultrasound
• Muckle-Wells syndrome findings
• Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)/ Glutaric Aciduria
II (GAII)<
• Multiple Endocrine Neoplasia type 1 • Non-syndromic Autism or Autism spectrum disorder
• Multiple Endocrine Neoplasia type 2A
• Multiple Endocrine Neoplasia type 2B ------ O ------
• Multiple Epiphyseal Dysplasia (MED)
• Omenn Syndrome, RAG or DCLRE1C types NEW:
• Multiple Exostoses, hereditary (HME) NEW: Includes Deletion Testing!
Includes Deletion Testing!
• Ornithine Transcarbamylase (OTC) Deficiency NEW:
Includes Deletion Testing!
 Predispositions and Treatment
• ------ S ------
• ------ P ------ • Severe Combined Immunodeficiency, DCLRE1C type
• Pachyonychia congenita, types I, II NEW: Includes Deletion Testing!
• Parathyroid Carcinoma • Severe Combined Immunodeficiency, JAK3 type
• Phenylketonuria (PKU)
• Severe Combined Immunodeficiency, RAG type
• Pneumothorax, Primary Spontaneous
• Pompe Disease or Glycogen Storage Disease Type II (GSDII) • Smith-Lemli-Opitz Syndrome
• Popliteal Pterygium Syndrome • Short-Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency
• POR Deficiency COMING SOON! • Shwachman-Diamond Syndrome
• Predisposition to Pyogenic Infections • Sjögren-Larsson syndrome
• Propionic Acidemia
• Smith-Magenis Syndrome NEW: Includes Deletion
• Pseudo-vitamin D deficiency rickets (autosomal recessive)
Testing!
• Pseudoachondroplasia (PSACH)
• Pseudohermaphroditism COMING SOON! • Spinal Muscular Atrophy with Respiratory Distress Type 1
•
(SMARD1)
Pseudoxanthoma Elasticum (PXE)
NEW!
• Peutz-Jeghers SyndromeNEW: Includes Deletion Testing!
• Pyogenic Sterile Arthritis, Pyoderma Gangrenosum • Split Hand - Split Foot Malformation
, and Acne (PAPA) Syndrome • Spondylometaepiphyseal Dysplasia, Menger type
------ R ------
• Stargardt DiseaseNEW!
• Retinitis pigmentosa • Steatocystoma multiplex
• Rett syndrome
• Rieger Syndrome ------ T ------
• Rubinstein-Taybi syndrome NEW: Includes Deletion Testing! • Testicular Feminization Syndrome
• Townes-Brocks syndrome
• Triple-A syndrome (Allgrove syndrome;
Achalasia-Addisonianism-Alacrima)
Predispositions and Treatment
• ------ U ------
• Unna-Thost disease

------ V ------
• Van der Woude Syndrome
• Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency
• Vohwinkel syndrome
• Von Hippel Lindau Syndrome NEW: Includes Deletion Testing!
• Vörner disease

------ W ------
• Wermer syndrome
• White sponge nevus
• Wolff-Parkinson-White (WPW) SyndromeNEW!

------ X ------
• X-linked Agammaglobulinemia
• X-linked Hydrocephalus / Congenital stenosis of the aqueduct of
Sylvius NEW: Includes Deletion Testing!
• X-linked recessive chondrodysplasia punctata NEW: Includes
Deletion Testing!
• X-linked recessive nephrolithiasis
• X-linked recessive retinoschisis
• X-linked Retinitis Pigmentosa NEW!
• XY Female Gonadal Dysgenesis
• XY Sex Reversal With or Without Adrenal Failure COMING SOON!
Predispositions and Treatment
Predispositions and Treatment
• Pathway Genomics
– Health Conditions
– Ancestry
– Carrier Status
– Drug Responses
Predispositions and Treatment
• Overall chance of breast or ovarian cancer
is 13.4% and 1.7% respectively
• BRCA1 and BRCA2
• With one of the genes the lifetime risk
becomes 36-85% and 16-60%
respectively
Predispositions and Treatment
• 30-50% call back from clients with positive
test results looking for in person genetic
counseling

• Problem of genetic penetrance

Legal, Regulatory, and Ethical
Concerns
• Regulations
– Clinical Laboratory Improvement
Amendments (CLIA) 1988
– Food and Drug Administration (FDA)
– Federal Trade Commission (FTC)
– Centers for Disease Control and Prevention
(CDC)
Legal, Regulatory, and Ethical
Concerns
• Effectiveness of genetic testing

• Risk ratios

• Results can be life changing

Legal, Regulatory, and Ethical
Concerns
• Scare tactics with advertising
• Metaphores in advertising

• Privacy
• Health Insurance Portability and
Accountability Act (HIPAA)
Legal, Regulatory, and Ethical
Concerns
• Who’s DNA is being tested?

• Who has access to that information?

• Future discoveries of SNP involvement

• Holt Vaughan, president of HealthCheckUSA
• "If it wasn't for a service like ours, people
wouldn't get this testing done.  In a perfect
world, everybody would get an hour with their
physician and the physician could run every
test known to man.  But that's just not the
way our healthcare system is evolving right
now"
Future of Regulation
• The Human Genetics Commission

• The American College of Medical Genetics

• Patented SNPs

• Future ethical questions

• Conclusion
Resources
American College of Medical Genetics, 2008, ACMG Statement on Direct-to-Consumer
Genetic Testing, Approved April 7. 
Applied Biosystems, 2003, Assays-by-design service for SNP assays: protocol, retrieved
Mar 24, 2009 from http://www.rockefeller.edu/genomics/pdf/
Applied_Biosystems_SNP_Assay-by-design.pdf.
Brooks, A., 1999, The essence of SNPs, Gene, 234: 177-186.
Ekman, A., P. Hall, and J. Litton, 2005, Can we trust cancer information on the internet?
A comparison of interactive cancer risk sites, Cancer Causes & Control, 16(6):765-
772.
Gollust, S. E., S. C. Hull, and B. S. Wilfond, 2002, Limitations of direct-to-consumer
advertising for clinical genetic testing, The Journal of the American Medical
Association, 288:1762-1767. Gurwitz, D. and Bregman-Eschet, Y., 2009, Personal
genomics services: whose genomes?, European Journal of Human Genetics, 3(4):1-
7.
Huang, A, 2008, FDA regulation of genetic tests, Genetics & Public Policy
Center, Retrieved on April 4, 2009 from www.dnapolicy.org.
Resources (cont’d)
Hudson, K., G. Javitt, W. Burke, and P. Byers, 2007, ASHG Statement on Direct-to-
Consumer Genetic Testing in the United States, The American Journal of Human
Genetics, 8:635-637.
Hunter, D. J., M. J. Khoury, and J. M. Drazen, 2008, Letting the genome out of the bottle -
will we get our wish?, The New England Journal of Medicine, 358:105-107.
Khoury, M., L. McCabe, and E. McCabe, 2003, Population screening in the age of
genomic medicine, The New England Journal of Medicine, 348(1):50-58.
Myers, M., M. Chang, C. Jorgensen, W. Whitworth, S. Kassim, J. Litch, L. Armstrong, B.
Bernhardt, A. Faucett, D. Irwin, J. Mouchawar, and L. Bradley, 2006, Genetic testing
for susceptibility to breast and ovarian cancer: Evaluating the impact of a direct-to-
consumer marketing campaign on physicians’ knowledge and practices, Genetics in
Medicine, 8(6):361-370.
Wollinsky, H., 2005, Do-it-yourself diagnosis, European Molecular Biology Organization,
6(9):805-807
Wood, F., D. Benson, E. LaCroix, E. Siegel, and S. Fariss, 2005, Use of internet
audience measurement data to gauge market share for online health information
services, Journal of Medical Internet Research, 7(3).
Questions