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SCREENING
GROUP 1
HUMAN GENETICS
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What is Genetic Testing
Genetic testing can bedefined as the analysis of
chromosomes, DNA,RNA or proteinsto detect abnormalities that maycause a genetic disease.
Examples of genetic testing includeprenatal diagnosis, heterozygote
carrier detection and
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What is Screening
Screeningis the testing of
apparently healthy populations to identify
previously undiagnosed diseases or people at
high risk of developing a disease.
Screening aims to detect early disease before
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Screening
POPULATIONSCREENING
The pre-sumptiveidentification of anunrecognized diseaseor defect by theapplication of tests,examinations, or other
procedures which canbe applied rapidly tosort out apparentlywell persons whoprobably have adisease from those
who probably do not.
GENETICSCREENING
Search in a populationfor personspossessing certaingenotypes that:
1) are already
associated withdisease orpredisposition todisease
2) May lead todisease in their
descendants
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PRINCIPLESOF
SCREENING
DISEASECHARACTERIS
TICS
Condition shouldbe serious and
relatively common Natural history of
disease should beclearly understood
An acceptable andeffectivetreatment
Prenatal diagnosisshould be
available
TestCharacteristic
s
Acceptable tothe population
Easy to perform Relatively
inexpensive Valid and
SystemCharacteristics
Resources for diagnosisand treatment of the
disorder must beaccessible
A strategy forcommunicating resultsefficiently andeffectively must be in
place
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VALIDITY
Ability to correctly identifythose with the disease. It is
measured as the proportionof affected individuals inwhom the test is positive.
SENSITIVITY
Ability of a test to separateindividuals who have the
disease from those who do
not
SPECIFICITY
Ability to correctly identify
those without the disease. Itis measured as the
proportion of affectedindividuals in whom the test
is negative.
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Outcomes of a
Screening TestTrue Disease Status
ScreeningTest
Positive Negative
Positive True Positives
(a)
False Positives
(b)
Negative False Negatives(c)
True Negatives
(d)
a, b, c and d represent the number of individuals in a population who
were found to have the disease and test result combinations shown.
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Yield from the
Screening Test:Predictive ValuePOSITIVE
PREDICTEDVALUE
Likelihood that aperson with a
positive test hasthe disease
NEGATIVEPREDICTED
VALUE
Likelihood that aperson with a
negative test doesnot have the
disease
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Second Outline LevelThird Outline Level
Fourth Outline LevelFifth Outline Level
Newborn screening
Programsrepresent an ideal
opportunity forpresymptomaticdetection and
prevention ofgenetic disease.
Characteristic ofselected newborn
screeningprograms
Eg:Phenylketonuria(PKU),Duchenne
musculardystrophy
An effective publichealth strategy fortreatable disorder
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Disease Inheritance Prevalance Screening
test
Treatment
PKU Auto.recessive
1/10,000-1/15,000
Guthrie test Dieatarydistriction of
phenylalanin
e
Galactosemi
a
Auto.
Recessive
1/50,000-
1/100,000
Transferase
assay
Dietary
restriction of
galactose
Congenital
hypothyroidi
sm
Sporadic
(usually)
1/5000 Measuremen
t of thyroxine
or TSH
Hormone
replacement
Sickle cell Auto. 1/400-1/600 Isoelectric Prophylactic
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Heterozygote Screening
Intervention consist ofpresentation of risk
figures and option suchas prenatal diagnosis
Eg: Tay-Sachs disease,major -Thalessemia,
Cystic fibrosis
Consist of testing atarget population toidentify unaffectedcarriers of disease
gene.
Selected examples ofheterozygote
screening programs inspecific ethnic group.
The carrier can then begiven information
about risk andreproductive option
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Disease Ethnic
group
Carrier
frequency
At risk
couple
frequency
Disease
incidence
in
newborns
Tay-Sachs Ashkenazi
Jews
1/30 1/900 1/3,600
-
Thalessemia
Greeks,Italia
n
1/30 1/900 1/3,600
Cystic
Fibrosis
Northern
European
1/25 1/625 1/ 2,500
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Fourth
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Fourth Outline LevelFifth Outline Level
Guthrie Test
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A drop of blood is usually obtained by pricking theheel of a newborn infant on the sixth or seventh dayof life.
The blood is collected on a piece of filter paper andsent to a central laboratory. A small disk of the filterpaper is punched out and placed on an agargel plate containing Bacillus subtilis and B-2-thienylalanine. The agar gel is able to support
bacterial growth but the B-2-thienylalanine inhibitsbacterial growth.
In the presence of extra phenylalanine leached fromthe impregnated filter paper disk, the inhibition is
overcome and the bacteria grow. Within a day thebacterial growth surrounding the paper disk is visibleto the eye. The amount of growth, measured as thediameter of the colony, is roughly proportional to theamount of phenylalanine in the serum.
The result is read b com arin the diameter of each
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PRESYMPTOMATICDIAGNOSIS
DEFINITION
Genetic testing can sometimes be performed
to identify individuals who have inherited a
disease- causing gene before they develop
symptom.
IMPORTANCE
Help in making reproductive decision
Provide reassurance
Improve health supervision
RECOMMENDED
To individuals who are known be at risk
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Psychosocial implications
Anxiety CostPotential
Stigmatization
Carrierdetection ledto cancellationof healthinsurance oremployer
discrimination Right to
choose not tobe tested andpotential forinvasion of
privacy
The issue of privacyand confidentialityand the need for
accuratecommunication ofrisk information
Expensiveprocedure liketesting typicallyconsists ofsequencing all
exons of bothgenes as well assome intronicnucleotides neareach exons