SCREENIN G GROUP 1 HUMAN GENETICS

What is Genetic Testing

can be defined as the analysis of chromosomes, DNA,RNA or proteins to detect abnormalities that may cause a genetic disease.

Genetic testing

Examples of genetic testing include prenatal diagnosis, heterozygote carrier detection and

What is Screening

Screening

is 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

Screening
POPULATION SCREENING The pre-sumptive identification of an unrecognized disease or defect by the application of tests, examinations, or other procedures which can be applied rapidly to sort out apparently well persons who probably have a disease from those who probably do not. GENETIC SCREENING Search in a population for persons possessing certain genotypes that:
1)

2)

are already associated with disease or predisposition to disease May lead to disease in their descendants

PRINCIPLES OF SCREENING
DISEASE CHARACTERIS TICS

System Characteristics

Condition should be serious and relatively common Natural history of disease should be clearly understood An acceptable and effective treatment Prenatal diagnosis should be available

Test Characteristic s

Resources for diagnosis and treatment of the disorder must be accessible A strategy for communicating results efficiently and effectively must be in place

Acceptable to the population Easy to perform Relatively inexpensive Valid and

VALIDITY

Ability of a test to separate individuals who have the disease from those who do not

SENSITIVITY

Ability to correctly identify those with the disease. It is measured as the proportion of affected individuals in whom the test is positive.

SPECIFICITY

Ability to correctly identify those without the disease. It is measured as the proportion of affected individuals in whom the test is negative.

Outcomes of a True Disease Status Screening Test Screening Positive Negative

Test Positive Negative
True Positives (a) False Negatives (c) False Positives (b) 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.

POSITIVE PREDICTED VALUE

Yield from the Screening Test: Predictive Value

Likelihood that a person with a positive test has the disease

NEGATIVE PREDICTED VALUE Likelihood that a person with a negative test does not have the disease

Newborn screening
Programs represent an ideal opportunity for presymptomatic detection and prevention of genetic disease.

An effective public health strategy for treatable disorder

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Eg: Phenylketonuria (PKU),Duchenne muscular dystrophy

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selected newborn screening programs

Disease PKU

Inheritance Prevalance Screening test Auto.recessiv 1/10,000 e -1/15,000

Treatment

Guthrie test Dieatary distriction of phenylalanin e Transferase Dietary assay restriction of galactose Measuremen Hormone t of thyroxine replacement or TSH Prophylactic

Galactosemi Auto. a Recessive Congenital Sporadic hypothyroidi (usually) sm Sickle cell Auto.

1/50,0001/100,000 1/5000

1/400-1/600 Isoelectric

Heterozygote Screening
Intervention consist of presentation of risk figures and option such as prenatal diagnosis Consist of testing a target population to identify unaffected carriers of disease gene.

Click to edit the outline text format Second Outline LevelSelected examples of heterozygote Third Outline Level Fourth Outline Level Fifth Outline Level
screening programs in specific ethnic group.

The carrier can then be given information about risk and reproductive option

Eg: Tay-Sachs disease, major -Thalessemia, Cystic fibrosis

Disease

Ethnic group

Carrier frequency

At risk couple frequency

Disease incidence in newborns 1/3,600

Tay-Sachs

Ashkenazi Jews

1/30

1/900

Greeks,Italia 1/30 Thalessemia n Cystic Fibrosis Northern European 1/25

1/900

1/3,600

1/625

1/ 2,500

Guthrie Test

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Second Outline Level Click to edit the outline text format Third Second Outline Level Outline Third Outline Level Level Fourth Outline Level Fourth Fifth Outline Level

A drop of blood is usually obtained by pricking the heel of a newborn infanton the sixth or seventh day of life. The blood is collected on a piece offilter paperand sent to a central laboratory. A small disk of the filter paper is punched out and placed on anagar gelplate containingBacillus subtilis and B-2thienylalanine. The agar gel is able to support bacterial growth but the B-2-thienylalanine inhibits bacterial growth. In the presence of extra phenylalanine leached from the impregnated filter paper disk, the inhibition is overcome and the bacteria grow. Within a day the bacterial growth surrounding the paper disk is visible to the eye. The amount of growth, measured as the diameter of the colony, is roughly proportional to the amount of phenylalanine in the serum. The result is read by comparing the diameter of each

PRESYMPTOMATIC DIAGNOSIS
DEFINITIO N Genetic testing can sometimes be performed to identify individuals who have inherited a disease- causing gene before they develop symptom. Help in making reproductive decision IMPORTA NCE Provide reassurance Improve health supervision

RECOMMEND ED

To individuals who are known be at risk

Psychosocial implications
Anxiety Cost Potential Stigmatization

Carrier detection led to cancellation of health insurance or employer discrimination Right to choose not to be tested and potential for invasion of privacy

Expensive procedure like testing typically consists of sequencing all exons of both genes as well as some intronic nucleotides near each exons

The issue of privacy and confidentiality and the need for accurate communication of risk information