Bale Slides

8/14/2019 Bale Slides

1/23

What is Genet ic Tes t ing?

And what is i ts value?

Sherri J . Bale, Ph.D., FACMG

President and Clinical Directo rGeneDx


2/23

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

clinicalpurposes

Uses of Genetic Testing:


3/23

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


4/23

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 occurredlater in life


5/23

Genetic Tests for ConstitutionalMutations

Molecular Tests

Cytogenetic Tests

Biochemical Tests


6/23

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 weaknessstarting in early childhood

wheelchair by age 12

death in 20s


7/23

Molecular Test: Muscular Dystrophy

Obtain blood sample from child

Read the DNA sequence of the DMD gene

Identify the mutation that caused thedisease


8/23

How is this information useful?

Can test MomIs she an unaffectedcarrier of the mutation? Is she at risk tohave more children with this disease?

Can test siblings of affected child Can offer prenatal diagnosis in Moms next

pregnancy OR

Can offer pre-implantation geneticdiagnosis

Can provide information about prognosis


9/23

Cytogenetic Test: Example

Karyotypeto 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


10/23

Cytogenetic Test: Child with MCA

and autism

Obtain a

blood sample

from baby

Look at

chromosomes


11/23

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


12/23


Can determine exactly which genes areinvolved

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 geneticdiagnosis

Can provide information about prognosis


13/23

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


14/23

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 babysblood


15/23


Can diagnose the baby in time totreatand avoid all clinicalconsequences of the disease

Treatment: Restrict phenylalanine inthe diet

Can test siblings of affected childto see if they are carriers for thedisease (1 in 70 in the generalpopulation are carriers)


16/23

Genetic Tests forAcquiredMutations

Molecular Tests

Cytogenetic Tests

Tests for changes that affect only certain cells

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


17/23

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


18/23


Patients whos 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


19/23

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


20/23


21/23


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 patientsunlikely to respond


22/23

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


23/23

Summary

Constitutional genetic tests impact patients withinherited disorders and their families, byproviding information about diagnosis,prognosis, treatment, and informing reproductivedecisions

Genetic tests for acquired diseases impactpatients with diseases like cancer, provideinformation about diagnosis and prognosis, andinform treatment decisions

Genetics and genetic testing impacts manyphases of our lives, and will do so even more inthe future

Bale Slides

Documents

Transcript of Bale Slides