By:Ms. Shalini joshi
m.sc.nsg ist year
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
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
Making a diagnosis in a person who has disease
Figuring out the type or dose of a medicine that is
best for a certain person.
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.
It is also defined as type of medical test, identifies
changes in chromosomes, genes or proteins.
screening which involves identifying unaffected
individuals who carry one copy for the disease to be
implantation genetic diagnosis.
natal diagnostic testing.
symptomatic testing for estimating the risk of adult
onset cancer and alziemer’s disease
diagnosis of a symptomatic
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
It can be used to determine a child potentiality or
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.
Managing the remaining weeks of the pregnancy
Determining the outcome of the pregnancy
Planning for possible complications with the birth
Planning for problems that may occur in the newborn
Deciding whether to continue the pregnancy
Finding conditions that may affect future pregnancies.
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
Recognition of the major internal organs and extremities
to determine if any abnormality can best be accomplished
between 16 to 20 weeks gestation.
the size and position of the fetus,
the size and position of the placenta,
the amount of amniotic fluid,
the appearance of fetal anatomy,
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
This is an invasive procedure .
Amniocenteses are performed between 14 and 20
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 fluid
cannot be obtained.
CVS can be safely performed between 9.5 and 12.5 weeks
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
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.
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
The developing fetus has two major blood proteinsalbumin 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
The AFP from the fetus will end up in maternal blood in
Neural tube defects include anencephaly and spina bifida .
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
because the amount of beta-HCG will be lower than
An elevated beta-HCG coupled with a decreased MSAFP
suggests Down syndrome.
Very high levels of HCG suggest trophoblastic disease
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.
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
This is further metabolized in the placenta to
The estriol crosses to the maternal circulation and is
excreted by the maternal kidney in urine or by the
maternal liver in the bile
The measurement of serial estriol levels in the third
trimester will give an indication of general well-being of
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
Inhibin is secreted by the placenta and the corpus luteum.
Inhibin –A is associated with an increased risk of trisomy
A high inhibin –A may be associated with a risk for preterm
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
PAPP-A levels in the first trimester may
predict an adverse pregnancy outcome, including a
small for gestational age (SGA) baby or stillbirth.
high PAPP-A level may predict a large for
gestational age (LGA) baby.
Combining the maternal serum assays may aid in
increasing the sensitivity and specificity of detection for
The classic test is the triple screen for alpha-fetoprotein
(MSAFP), beta-HCG, and estriol (uE3). The "quadruple
screen" adds inhibin-A.
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 of the placenta is
Microscopy can aid in determination of
gestational age (lung, kidney
maturity), presence of infection, presence of
neoplasia, or presence of "dysplasia"
Radiographic views are essential for analysis of
the 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.
Skeletal anomalies (dwarfism, dysplasia, etc.)
Neural tube defects (anencephaly, spina bifida, etc.)
Soft tissue changes (hydrops, hygroma, etc.)
Teratomas or other neoplasms
Orientation and audit of fetal parts
Assessment of catheter or therapeutic device placement
Culture can aid in diagnosis or confirmation of congenital
infections: T - toxoplasmosis
O - other, such as Listeria monocytogenes,
B streptococcus, syphilis
R - rubella
C - cytomegalovirus
H - herpes simplex or human immunodeficiency virus
Tissues must be obtained as fresh as possible for culture and
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.
Patient need to sufficiently informed about the implication of
genetic screening before they can provide informed
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
To reduce potential psychological distress, counseling
should be available to provide information about genetic
risk and explain choices regarding genetic testing and
Support is needed for individuals who need to consider
issue such as stigma disclosure to family members and
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
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
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.
Like other medical information, result from genetic testing
are considered confidential, under normal practice, the
doctor patient relationship protect against disclosure of
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
The storage of genetic screening data and registries of
patients creates particular concern, given that the results
negatively on family
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
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.
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Gangane S. D. “human genetics” 3rd edition, Elsevier publishers, 2010.
Mandal Sanjay “ fundamentals of human genetics” 2nd edition, New Central
Book agency, Page no. 209-212.
Perry, Lsowdermilk, “Maternity and women’s health care” 8th edition, mosby
by Elsevier page no. 67-69.
Sharma, Kumar Suresh, “human genetics in nursing, 2nd edition, Jaypee
Oxford essential dictionary. For learners of English, oxford university press.