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What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

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Page 1: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

What is Genetic Testing?And what is its value?

Sherri J. Bale, Ph.D., FACMG

President and Clinical Director

GeneDx

Page 2: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Definition of Genetic Testing:

• The analysis of human DNA in any of its forms or related products (chromosomes, RNA, proteins)

• To detect disease-related genotypes, mutations, phenotypes, or karyotypes for clinical purposes

Uses of Genetic Testing:

Page 3: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

More definitions

• Genotype vs. Phenotype– The genetic make-up, as distinguished from

the physical appearance

• Mutation– A genetic change, usually one that is

associated with a disease

• Karyotype– A visual presentation of chromosomes

Page 4: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Two Main Types of Genetic Tests

• Constitutional– Tests for mutations that affect ALL CELLS in

the body, and have been there since conception

• Acquired– Tests for changes that affect only certain cells

or cell types in the body, and that occurred later in life

Page 5: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Genetic Tests for Constitutional Mutations

• Molecular Tests

• Cytogenetic Tests

• Biochemical Tests

Page 6: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Molecular Test: Example

• Analysis of DNA sequence in patient with a rare inherited disease– Muscular Dystrophy – Gene: DMD– Clinical Picture

• 1 in 3500 male births• progressive muscle weakness

starting in early childhood• wheelchair by age 12• death in 20s

Page 7: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Molecular Test: Muscular Dystrophy

• Obtain blood sample from child

• Read the DNA sequence of the DMD gene

• Identify the mutation that caused the disease

Page 8: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

How is this information useful?

• Can test Mom – Is she an unaffected carrier of the mutation? Is she at risk to have more children with this disease?

• Can test siblings of affected child• Can offer prenatal diagnosis in Mom’s next

pregnancy OR• Can offer pre-implantation genetic

diagnosis• Can provide information about prognosis

Page 9: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Cytogenetic Test: Example

• Karyotype – to examine the chromosomal complement of an individual including number, form, and size of the chromosomes.

• Frequently used for children who present with multiple anomalies, developmental delay, autism

Page 10: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Cytogenetic Test: Child with MCA and autism

• Obtain a blood sample from baby

• Look at chromosomes

Page 11: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

New type of Cytogenetic Test

• Cross between a molecular and Cytogenetic test – arrayCGH- tests for presence/absence of genes at 1000s of positions on each chromosome. Much more sensitive than a karyotype

Page 12: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

How is this information useful?

• Can determine exactly which genes are involved

• Can test parents and siblings of affected child to see if they carry the abnormality

• Can offer prenatal diagnosis in next pregnancy OR

• Can offer pre-implantation genetic diagnosis

• Can provide information about prognosis

Page 13: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Biochemical Test

• Analyzes the quantity of a downstream product of a gene (e.g. not looking directly at the gene, or the chromosome).

• Example: Newborn Screening– Mandated in all 50 states– Twenty primary targets that all states do– Over 4 million newborns tested each year

Page 14: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Biochemical Test: PKU

• Phenylketonuria– Inherited metabolic disorder – If untreated, leads to mental retardation, seizures– Affects 1 in 20,000 newborns

Missing enzyme:Phenylalanine Hydroxylase

Measure amount of Phenylalanine in baby’sblood

Page 15: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

How is this information useful?

• Can diagnose the baby in time to treat and avoid all clinical consequences of the diseaseTreatment: Restrict phenylalanine in

the diet

• Can test siblings of affected child to see if they are carriers for the disease (1 in 70 in the general population are carriers)

Page 16: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Genetic Tests for Acquired Mutations

• Molecular Tests

• Cytogenetic Tests

Tests for changes that affect only certain cells

or cell types in the body, and that occurred later in life

Page 17: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Molecular Test for Acquired Disease

• KRAS gene test on tumor tissue from patients with colorectal cancer– Obtain tumor from patient– Extract DNA; treat with enzyme that allows

visualization of the mutation

Page 18: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

How is this information useful?

• Patients who’s colon tumors do not have a KRAS mutation are much more likely to respond to Cetuximab therapy

• Identifies patients most likely to benefit from specific therapies

• Allows choice of alternative therapies (and saves time and money) for patients unlikely to respond

Page 19: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Cytogenetic Test for Acquired Disease: Example

• Her-2/neu gene amplification in Breast Cancer– Occurs early in oncogenesis– Seen in up to 1/3 of breast cancers– Associated with poor prognosis– Responds to Herceptin (trastuzumab)

treatment– Does not respond to Tamoxifen treatment

Page 20: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Cytogenetic Test for Acquired Disease

• FISH (Fluorescent In Situ Hybridization) for HER-2/neu is a gene-based test that allows one to count the number of HER-2 genes in a cell.

 

Page 21: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

How is this information useful?

• Assists in selection of patients for chemotherapy, and which therapy to use

• Predicts response to adjuvant therapy

• Increases survival

• Allows choice of alternative therapies (and saves time and money) for patients unlikely to respond

Page 22: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Genetic Testing in the News Today

Recreational Genetics– 23andMe, KnowMe, Navigenics

Nutrigenomics– Sciona, Genelex, Market America, Suracell

Ancestry Testing– African Ancestry,GeneTree,DNAPrint

Skin and Hair Care– HairDx, Dermagenetics

Canine Breed Analysis Ready for clinical use

Not ready for prim

e time

Page 23: What is Genetic Testing? And what is its value? Sherri J. Bale, Ph.D., FACMG President and Clinical Director GeneDx

Summary

• Constitutional genetic tests impact patients with inherited disorders and their families, by providing information about diagnosis, prognosis, treatment, and informing reproductive decisions

• Genetic tests for acquired diseases impact patients with diseases like cancer, provide information about diagnosis and prognosis, and inform treatment decisions

• Genetics and genetic testing impacts many phases of our lives, and will do so even more in the future