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SEMINAR ON GENETIC TESTING, ETHICAL ,LEGAL AND PSYCHOSOCIAL ISSUES

By:-Ms. Shalini joshim.sc.nsg ist years.c.o.n. dehradun

CONTENT Definition of genetic testing Purpose of genetic testing Types of genetic testing Basis of genetic testing Prenatal diagnosis and screening Common diagnostic test Techniques for pathological

examination Ethical legal and psychosocial issue in

genetic testing

REASON FOR GENETIC TESTING

Finding genetic disease in unborn child Finding out if people carry genes for a

disease and might pass it on to their children.

Screening embryos for disease. Testing for genetic disease in adult before

they cause symptoms. Making a diagnosis in a person who has

disease symptoms Figuring out the type or dose of a medicine

that is best for a certain person.

DEFINITION

Genetic testing is defined as “examining a sample of blood or other body fluids or tissue

for bio-chemical chromosomal, or genetic markers that indicate the presence or absence

of genetic disease.

A genetic testing is analyzing a DNA to look for genetic alteration that may indicate an

increased risk for developing a specific disease or disorder.

Or

It is also defined as type of medical test, identifies changes in chromosomes, genes or

proteins.

Carrier screening which involves identifying unaffected individuals who carry one copy for the disease to be expressed.

Pre implantation genetic diagnosis.

Pre natal diagnostic testing.

New born screening

Pre symptomatic testing for estimating the risk of adult onset cancer and alziemer’s disease

Conformational diagnosis of a symptomatic individual.

Forensic or identity testing. Pre symptomatic testing for predicting adult onset

disorders such as Huntington’s chorea. It allows the genetic disorder of vulnerabilities to

inherited diseases. It can be used to determine a child potentiality or

person ancestry.

TYPES OF GENETIC TESTING

BASIS OF GENETIC TESTING Quantitative genetic research has built a strong

case for the importance of genetic factor in many complex behavioural disorder and dimensions in the domains of psychopathology, personality and cognitive abilities.

The genetic basis of behavioural disorder has largely relied on a reductionist one gene one disorder (ONOD) approach in which a single gene is necessary and sufficient to develop a disorder.

In contrast a quantitative trait loci approach involves the search for multiple genes.

PRENATAL DIAGNOSIS

Managing the remaining weeks of the pregnancy

Determining the outcome of the pregnancy Planning for possible complications with the

birth process Planning for problems that may occur in the

newborn infant Deciding whether to continue the pregnancy Finding conditions that may affect future

pregnancies.

COMMON DIAGNOSTIC TEST

ULTRASONOGRAPHY

This is a non-invasive procedure that is harmless to both the fetus and the mother.

The developing embryo can first be visualized at about 6 weeks gestation.

Recognition of the major internal organs and extremities to determine if any abnormality can best be accomplished between 16 to 20 weeks gestation.

USEFUL IN DETERMINATION OF the size and position of the fetus,

the size and position of the placenta,

the amount of amniotic fluid,

the appearance of fetal anatomy,

LIMITATION OF USG

Abnormalities may not be detected until later in pregnancy, or may not be detected at all.

A good example of this is Down syndrome (trisomy 21) where the morphologic abnormalities are often not marked,

AMNIOCENTESIS This is an invasive procedure . Amniocenteses are performed between 14 and 20

weeks gestation. An ultrasound examination always precedes

amniocentesis In the third trimester of pregnancy, the amniotic

fluid can be analyzed for determination of fetal lung maturity

amniotic fluid can be analyzed for lecithin:sphingomyelin (LS) ratio, and/or for phosphatidyl glycerol (PG).

fetal loss (0.5%) maternal Rh sensitization. If oligohydramnios is present, then amniotic

fluidcannot be obtained.

CHORIONIC VILLI SAMPLING: CVS can be safely performed between 9.5 and 12.5

weeks gestation.

In this procedure, a catheter is passed via the vagina through the cervix and into the uterus to the developing placenta under ultrasound guidance

The introduction of the catheter allows sampling of cells from the placental chorionic villi.

These cells can then be analyzed by variety of techniques. The most common test employed on cells obtained by CVS is chromosome analysis to determine the karyotype of the fetus.

MATERNAL BLOOD SAMPLING FOR FETAL CELLS

This is a new technique that makes use of the phenomenon of fetal blood cells gaining access to maternal circulation through the placental villi.

The fetal cells can be sorted out and analyzed by a variety of techniques to look for particular DNA sequences

Fluorescence in-situ hybridization (FISH) is one technique that can be applied to identify particular chromosomes of the fetal cells recovered from maternal blood and diagnose aneuploid condition such as the trisomies and monosomy X.

PROBLEMS It is difficult to get many fetal blood cells. There may not be enough to reliably determine

anomalies of the fetal karyotype or assay for other abnormalities.

MATERNAL SERUM ALPHA FETO PROTEIN

The developing fetus has two major blood proteins-albumin and alpha-fetoprotein (AFP).

The MSAFP test can be utilized to determine the levels of AFP from the fetus

Ordinarily, only a small amount of AFP gains access to the amniotic fluid and crosses the placenta to mother's blood.

When there is a neural tube defect in the fetus,

Then there is a means for escape of more AFP into the amniotic fluid.

The AFP from the fetus will end up in maternal blood in higher amounts.

Neural tube defects include anencephaly and spina bifida .

MATERNAL SERUM BETA-HCG:

This test is most commonly used as a test for pregnancy.

The beta-HCG can also be quantified in serum from maternal blood, and this can be useful early in pregnancy when threatened abortion or ectopic pregnancy suspected

because the amount of beta-HCG will be lower than expected.

An elevated beta-HCG coupled with a decreased MSAFP suggests Down syndrome.

Very high levels of HCG suggest trophoblastic disease (molar pregnancy).

The absence of a fetus on ultrasonography along with an elevated HCG suggests a hydatidiform mole

The HCG level can be used to follow up treatment for molar pregnancy to make sure that no trophoblastic disease, such as a choriocarcinoma, persists.

MATERNAL SERUM ESTRIOL:The amount of estriol in maternal serum is dependent upon a viable fetus, a properly

functioning placenta, and maternal well-being.

substrate for estriol begins as dehydroepiandrosterone (DHEA) made by the

fetal adrenal glands

This is further metabolized in the placenta to estriol.

The measurement of serial estriol levels in the third trimester will give an indication of general well-being of the fetus

If the estriol level drops, then the fetus is threatened and delivery may be necessary emergently

Estriol tends to be lower when Down syndrome is present and when there is adrenal hypoplasia with anencephaly.

The estriol crosses to the maternal circulation and is excreted by the maternal kidney in urine or by the maternal liver in the bile

INHIBIN-A Inhibin is secreted by the placenta and the corpus

luteum.

Inhibin –A is associated with an increased risk of trisomy 21,

A high inhibin –A may be associated with a risk for preterm delivery.

PREGNANCY-ASSOCIATED PLASMA PROTEIN A (PAPP-A)

Low levels of PAPP-A as measured in maternal serum during the first trimester may be associated with fetal chromosomal anomalies including trisomies 13, 18, and 21

Low PAPP-A levels in the first trimester may predict an adverse pregnancy outcome, including a small for gestational age (SGA) baby or stillbirth.

A high PAPP-A level may predict a large for gestational age (LGA) baby.

"TRIPLE" OR "QUADRUPLE" SCREEN

Combining the maternal serum assays may aid in increasing the sensitivity and specificity of detection for fetal abnormalities.

The classic test is the triple screen for alpha-fetoprotein (MSAFP), beta-HCG, and estriol (uE3). The "quadruple screen" adds inhibin-A.

TECHNIQUES FOR

PATHOLOGIC EXAMINATION

GROSS EXAMINATION:

It is useful in detecting gross fetal parts.

The pattern of gross abnormalities can often suggest a possible chromosomal abnormality or a syndrome.

Consultations are obtained with clinical geneticists to review the findings

Examination of the placenta is very important, because the reason for the fetal loss may be a placental problem

MICROSCOPIC EXAMINATION

Microscopic examination of the placenta is important

Microscopy can aid in determination of gestational age (lung, kidney maturity), presence of infection, presence of neoplasia, or presence of "dysplasia" (abnormal organogenesis).

RADIOGRAPHY:- Radiographic views are essential for analysis

ofthe fetal skeleton.

Radiographs are useful for comparison with prenatal ultrasound, and help define anomalies when autopsy consent is limited

To determine sites to be examined microscopically.

Conditions diagnosed by postmortem radiography may include:

Skeletal anomalies (dwarfism, dysplasia, etc.)

Neural tube defects (anencephaly, spina bifida, etc.)

Osteogenesis imperfecta

Soft tissue changes (hydrops, hygroma, etc.)

Teratomas or other neoplasms

Growth retardation

Orientation and audit of fetal parts

Assessment of catheter or therapeutic device placement

MICROBIOLOGIC CULTURE Culture can aid in diagnosis or confirmation of

congenital infections:- T - toxoplasmosis O - other, such as Listeria monocytogenes,

group B streptococcus, syphilis R - rubella C - cytomegalovirus H - herpes simplex or human

immunodeficiency virus (HIV)

KARYOTYPING

Tissues must be obtained as fresh as possible for culture and without contamination.

A useful procedure is to wash the tissue samples in sterile saline prior to placing them into cell culture media.

Tissues with the best culture for growth are those with the least maceration: placenta, lung, and diaphragm.

Obtaining tissue from more than one site can increase the yield by avoiding contamination or by detection of mosaicism.

ETHICAL ,LEGAL AND PSYCHOSOCIAL ISSUES

CONSENT TO BEING SCREENED:-

Patient need to sufficiently informed about the implication of genetic screening before they can provide informed consent.

The public view genetic with a sense of inevitability. However, a genetic condition alone may modify risks from environmental or life style factor.

The voluntary nature of the screening process must be emphasized.

COUNSELING To reduce potential psychological distress,

counseling should be available to provide information about genetic risk and explain choices regarding genetic testing and further management.

Support is needed for individuals who need to consider issue such as stigma disclosure to family members and confidentiality.

Couple known to carry a recessive or dominance single gene defect or sex linked condition need counseling about their reproductive option. This may include prenatal diagnosis and possible pregnancy termination in the case of an affected fetus and pre-implantation genetic diagnosis.

THE RISK OF STIGMA:-

The public’s understanding of genetic may be limited and can lead to sigma.

Misunderstanding of the genetic risk of developing disease can increase stigmatization. This may be around life expectancy, lifestyle choices, or decision about having children.

Identification of a genetic condition before birth raises issue of whether the parents wish to terminate the pregnancy. Some commentators have argues that the ability to only select perfect babies is a form of eugenesis.

Confidentiality

Like other medical information, result from genetic testing are considered confidential, under normal practice, the doctor patient relationship protect against disclosure of genetic information.

However there is less clarity where relative wish to know the result of a family member’s genetic test, as it may have direct relevance for them.

Another particular dilemma is the case of a pregnant woman wanting to know the result of a test taken by the baby’s father.

The storage of genetic screening data and registries of patients creates particular concern, given that the results may impact

negatively on family members.

DISCLOSURE TO FAMILY MEMBERS:-

Doctors face a dilemma when reporting the results of genetic screening. Standard medical practice is based on the principles that doctor’s should focus on their patient and that medical information should remain confidential.

It is unclear if doctors are ethically permitted to inform relatives in cases when the result of genetic test indicates real risk to their health.

Doctors may also be faced with a decision about whether to persuade patient about the need to disclose their test result to relatives.

Although most professional bodies that disclosure should not be against the right of relatives have won priorities.

The primary concerns among the public is the use of genetic information to delay access to health insurance or medical treatment.

Conversely health insurance claim right to access such data where it exist to avoid the moral hazards of patient with known condition taking out an insurance policy without disclosing this information.

SUMMARY

B

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