Genetic Testing

Three Types of Genetic Testing

Screening tests

Diagnostic tests

Predictive tests

(1) Screening Tests

Aimed at a population in whom more specific diagnostic tests should be performed.

Effective

inexpensive
useful for large populations
selects subjects for further study
amenable to treatment
medical genetics
individuals with disease.
Individuals who can transmit disease (carrier).

Useful

high sensitivity

i.e. likelihood someone with the disease tests positive.

high specificity

i.e. likelihood someone without the disease tests negative.

ability to discriminate between affected and unaffected individuals.

Positive Predictive Value (PPV): if you test positive, what’s the likelihood you have the disease.
Ex: 7 positive, 5 have the disease, PPV=5/7 = TP / (TP+FP)

want high sensitivity so willing to sacrifice specificity a bit…

Example:

sensitivity = 24/25 = pos result / # with disease = 96%
specificity = 9875/9975 = neg result / # without disease = 99%
PPV = 24/124 = TP/(TP+FP) = 19%

General population:

Sensitivity = 99%
Specificity = 99%
PPV = 1%

PPV is Ý in 1^st population because the frequency of the disorders in the population is increased!

Types of screening tests:

Newborn screening (24-72 hrs of life)

Congenital hypothyrodism
PKU
Can be treated…

Maternal Serum Screening (pregnancy)

Neural tube defects
Chromosomal abnormalities
Results can be confirmed by diagnostic testing

Maternal Serum – Triple Screen

3 analytes (test for neural tube defects and chromosome abnormalities)

a fetoprotein

unconjugated estriol

human chorionic gonadotropin

15-20 weeks gestation

sensitivity: 85-100% (NTD)
specificity: 62-85% (Chrom. Abn.)

Carrier Screening

Used only in specific situations (Tay-Sachs Þ Ashkenazi Jews, Sickle cell Þ African ancestry, etc.)

Can be more precise (diagnostic?)

Molecular testing

(2) Diagnostic Tests

Confirm the presence of a genetic disease in an individual already suspected of having the disease.

Process: if the screening test turns up positive Þ follow up with diagnostic test.

(3) Predictive or Pre-symptomatic Testing

Performed on healthy individuals who may have a risk factor.

positive family history for a disease.
Parent with a mutant gene.

2 scenarios

(1) individual will be affected (Huntington Disease)
(2) individual at risk (BRCA1 mutation)

Prenatal Testing

genetic screening and diagnostic testing

variety of procedures and tests

biomedical ethics of genetic counseling – ethical principles:

autonomy – patient coice
nonmaleficence – do no harm
beneficence – actively "do good"
justice – be fair and equal
veracity – tell the truth
fidelity – fulfilled duties

types:

(1) maternal serum screening

(2) amniocentesis

removal of amniotic fluid Þ cells grown in culture

11^th week of pregnancy (mesonephros does not produce amniotic fluid prior to 10^th week)

for cytogenetic studies

very accurate

(3) chorionic villus sampling

emoval of fetal portion of placenta Þ cells grown in culture

9^th –12^th week of pregnancy

for cytogenetic studies

high accuracy

higher risk than amniocentesis

(4) PUBS

(5) Ultrasonography

(6) Pre-implantation diagnosis

Why?

advanced maternal age
abnormal triple screen (see above)
family history of chromosomal abnormalities
mendelian disease at risk – diagnosable
abnormal ultrasound

prenatal tests

cytogenic analysis

mutation analysis (DNA)

biochemical analysis

a -fetoprotein

linkage analysis

Amniocentesis