1.Pg.278 284_human Gene Group 1

8/3/2019 1.Pg.278 284_human Gene Group 1

1/17

SCREENING

GROUP 1

HUMAN GENETICS


2/17

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


3/17

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


4/17

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


5/17

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


6/17

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.


7/17

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.


8/17


9/17

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


10/17

Click to edit the outline text forma

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


11/17

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


12/17

Click to edit the outline text forma



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


13/17

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


14/17

Cl ck to ed t theoutline textformat

SecondOutline Level

ThirdOutlineLevel

Fourth

Click to edit the outline text format



Guthrie Test


15/17

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


16/17

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


17/17

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

Documents

1.Pg.278 284_human Gene Group 1