Transcript What is Genetic Testing?

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)
Uses of Genetic Testing:
• To detect disease-related genotypes,
mutations, phenotypes, or karyotypes for
clinical purposes
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
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
Genetic Tests for Constitutional Mutations
• Molecular Tests
• Cytogenetic Tests
• Biochemical Tests
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
Molecular Test: Muscular Dystrophy
• Obtain blood sample from child
• Read the DNA sequence of the DMD gene
• Identify the mutation that caused the
disease
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
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
Cytogenetic Test: Child with MCA
and autism
• Obtain a
blood sample
from baby
• Look at
chromosomes
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
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
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
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’s
blood
How is this information useful?
• Can diagnose the baby in time to
treat and avoid all clinical
consequences of the disease
Treatment: 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)
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
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
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
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
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.
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
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
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