Human Genetic Testing Applications

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Human Genetic Testing Applications
It is important to understand that genetic
testing is quite different than other types of
laboratory tests. Testing your genetic material
is unique in that it can provide various kinds of
information about you, such as predicting the
risk of developing a particular disease before
symptoms even appear, determining whether you are
carrying a specific gene that could be passed on
to your children, and in some cases, informing
you as to whether some treatments will work
before you start therapy. In addition to
providing information about you, some genetic
tests may also provide results that can impact
the health and disease risks of your relatives.

• Medical Applications
• Your genetic material may be tested for a wide
  variety of medical reasons. Regardless of the
  reason, it is important to consider seeking help
  from a genetic counseling programs who can help
  you decide whether testing is right for you or to
  understand the meaning and implications of
  testing results. Examples of the different types
  of medical genetic testing include
• Diagnostic genetic testing is performed on people
  with symptoms suggesting a genetic disorder.
• Presymptomatic testing, or predictive testing,
  identifies the presence of variant genes that
  cause disease or increase disease risk, even if
  someone appears to be healthy.
• Carrier screening assesses whether individuals
  who wish to become parents have an increased risk
  for a child with an autosomal recessive or
  X-linked recessive disorder.
• Prenatal screening or diagnostic tests are used
  if a fetus may be at risk for health problems.
• Pharmacogenomics testing can predict the response
  to certain medications.
• Genetic testing to identify mutations that cause
  some cancers can provide information on an
• individuals prognosis and guide targeted
  therapy.
• Transplantation testing is used to tell whether
  an organ or tissue is a match for the transplant
  between a donor and recipient

Examples of Medical Applications Diagnostic
Testing
Diagnostic genetic testing is used to determine
if your symptoms are being caused by a specific
genetic condition. Genetic testing can also help
rule out a genetic condition as the cause of
symptoms. There are thousands of tests for
diagnosing inherited genetic disorders. Many look
at single genes such as those for cystic
fibrosis, sickle cell disease, or specific forms
of muscular dystrophy.
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Many inherited disorders are identified
indirectly by examining abnormalities in the
genetic end products (proteins or metabolites)
that are present in abnormal forms or quantities.
Genes code for the production of thousands of
proteins and, if there is a change in the code,
changes can occur in the production of those
proteins. So, rather than detecting the problem
in the gene, some types of testing look for
unusual findings related to the pertinent
proteins. An example is haemophilia, a bleeding
disorder. Screening may detect low levels of
specific clotting factors (proteins that regulate
blood clotting), which would suggest a bleeding
disorder. This would be followed by testing for
the genetic change that causes haemophilia when
there is a desire to know the specific variant
for testing of family members. Presymptomatic or
predictive testing Some genetic tests are used
to predict a disease that has not yet caused
symptoms. These tests are most commonly used for
individuals with a family history of genetic
diseases that do not cause signs and symptoms
until later in life, like Huntington disease and
hereditary hemochromatosis. Predictive genetic
tests can also help assess the risk of developing
a disease and allow individuals to take steps to
prevent or minimize risks for the disease. For
instance, women with a family history of breast
or ovarian cancer may wish to be tested for BRCA1
and BRCA2 mutations, which are associated with an
increased cancer risk. Genetic Carrier
Testing Carrier testing is done to determine if
someone carries a copy of a gene that could lead
to a genetic disorder in their child if combined
with a similar variant gene copy from their
partner. Carrier testing may be offered when
couples are planning a pregnancy or having their
first visit for prenatal care. Carrier testing
may also be done when an individual or a couple
has a family history of an autosomal recessive
disease. A carrier with only one copy of an
autosomal recessive variant usually will have no
noticeable symptoms or only mild symptoms. But if
their child inherits two copies, one from each
parent, that child will have the disease. With
each pregnancy, parents who carry a variant
causing the same autosomal recessive disease have
a one in four (25) chance of having a child with
that disease, and a 1 in 2 (50) chance that
their child will also carry the recessive gene
copy but not have symptoms. Theres also a 1 in 4
chance (25) that the child will not have the
disease or be a carrier. Common carrier tests
include those for Tay- Sachs disease, cystic
fibrosis, and sickle-cell anaemia. Carrier
testing may also be done to determine whether a
woman carries a variant gene on one of her two X
chromosomes that could lead to an X-linked
recessive disorder in a child. For more
information on this, see Patterns of Inheritance
in the Genetic Disorders section.
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Prenatal and newborn screening Prenatal genetic
testing provides expecting parents information
about a fetus potential genetic disorders. These
tests most commonly look for aneuploidies,
conditions in which there are extra or missing
chromosomes. Maternal blood tests to screen for
chromosomal disorders are typically offered
during the first and second trimesters. In
addition to these conventional screenings,
non-invasive cell- free fetal DNA screening may
be offered. These tests look at the DNA released
from the placenta that circulates in the womans
blood stream. This non-invasive blood test can
screen for Down syndrome, trisomy 13, trisomy 18,
and disorders with sex chromosomes, starting at
10 weeks of pregnancy. These tests are not
diagnostic and should only serve as a starting
point for further testing. If screening tests are
positive, diagnostic tests may be done on the
cells of the fetus or placenta. These are
collected by amniocentesis or chorionic villus
sampling. These tests do come with a small risk
of pregnancy loss. Every state requires newborn
screening to test for treatable conditions that
can cause serious developmental problems in
infancy and childhood. These tests are done on a
blood sample taken by pricking the childs heel
shortly after birth. While specific tests vary by
state, newborn screening can include tests for
congenital adrenal hyperplasia, a genetic disease
that causes the hormone cortisol to be decreased
in blood, phenylketonuria (PKU), an inherited
autosomal recessive metabolic disorder, and
hemoglobin disorders like sickle cell anemia.
These tests look for chemicals that indicate
genetic disorders, they do not test genes
directly. When appropriate, abnormal blood
screening tests in the newborn may be
supplemented by genetic testing (as with PKU, for
example). Predicting response to medications
Pharmacokinetics Some of us respond differently
than others to the same medications, or we may
experience different side effects from the same
drugs. The way we respond to medications can be
due to the gene variations we have inherited.
With respect to medications, our unique genetic
make-up and our individual response may mean that
a dose that is effective for one person may be
less effective for another or that a dose that is
safe for one person may be less safe for another
person. Looking for genetic variations that may
play a role in the over- or under- responsiveness
to a therapeutic drug is called pharmacogenomics
or pharmacokinetics. Most pharmacogenomics tests
currently look for variants in genes that code
for drug- metabolizing enzymes. There are many
enzymes in our bodies that metabolize or break
down specific drugs, allowing them to be
eliminated in urine or by other means. In some
cases, decrease activity in an enzyme that
metabolizes a medication may result in too much
drug staying in the body. In other cases,
individuals hyper metabolize drugs. This occurs
when there is increased activity of an enzyme
that breaks down the helpful drug too quickly,
leading to a lack of response to the drug.
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For more information on this subject, see the
article Pharmacokinetic Tests. Genetic testing
to guide cancer treatment Some genetic changes
are not inherited, but arise in an individuals
cells later in life and cannot be passed on to a
persons children. These are called somatic
mutations and they underlie many forms of cancer.
Somatic mutations can be caused by outside
factors like sun damage, or smoking tobacco, but
they often arise without a clear cause. Genetic
testing to identify somatic mutations can provide
information on an individuals prognosis and
guide treatment. These tests are usually
performed on a tumour sample, but may be
performed on a blood sample (called a liquid
biopsy). Treatments that disrupt a specific step
in cancer growth while causing minimal damage to
normal cells are called targeted therapies many
of these therapies have companion diagnostic
tests that demonstrate whether a tumor has the
necessary mutation for the targeted therapy to be
used. Cancers with certain somatic mutations may
have a more predictable response to chemotherapy
or targeted treatments than cancers without those
mutations. Breast cancer, chronic myelogenous
leukemia, lung cancer, and melanoma are a few
examples of cancers that may be tested for
specific mutations that predict a better response
to targeted therapies. Read the article on
Genetic Tests for Targeted Cancer Therapy for
additional details. Tissue typing for
transplantation Transplantation testing is used
to tell whether an organ or tissue, such as a
kidney, lung or bone marrow, is a match for the
transplant between a donor and recipient. If it
is not, a serious rejection reaction could occur
between the transplant recipient and the donated
organ or marrow. Basic laboratory testing for
tissue transplantation involves mixing the white
blood cells (leukocytes) from the donor (or the
donor tissue) and the recipient together and
observing whether an immune response occurs.
Although this technique is still commonly used,
analysis of the DNA in both the donor and the
recipient (tissue typing) is used to diminish the
likelihood of rejection in the case of tissue
transplantation. A very specific set of genes is
examined when DNA testing is used for tissue
typing a large set of genes called the Major
Histocompability Complex or MHC on chromosome 6.
These genes are highly variable between
individuals and they code for the production of
specific protein antigens located on the surface
of many cells. It is these antigens that
distinguish our own organs and tissues from
those of another individual. These antigens have
the ability to begin an immune system response
that results in organ or tissue rejection if the
tissue looks foreign.
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Non-medical Applications Forensic identity testing
Identity testing focuses on the identification of
an individual through the analysis of either
nuclear or mitochondrial DNA extracted from some
biologic material blood, tissue, hair, bone,
etc. Any material that contains cells with nuclei
can be used for nuclear DNA extraction and
eventual identity testing. Mitochondrial DNA,
which is extra-nuclear, is used when a sample
is severely degraded or if only hair shafts with
no attached cells are available. Increasingly,
identity testing is used to identify a suspect in
a criminal investigation by comparing the DNA
found at a crime scene to that of the suspected
individual. DNA sequences of individuals
convicted of crimes are put into a data bank
system that is accessible by law enforcement
officials. This system is referred to as CODIS or
Combined DNA Index System. This system has
helped to solve many crimes and also to clear
those wrongfully accused of a crime. Ancestry
testing Genetic testing to determine an
individuals ancestry has become increasingly
popular and more widely available. Several
companies market genetic ancestry testing, also
called genetic genealogy, directly to consumers
(DTC). By examining the variations in a persons
DNA, genetic testing can provide some information
on family history (genealogy) and where ancestors
might have come from years ago. Parentage
(paternity) testing The primary goal of
parentage testing is to identify the biological
parent of a given child. It is done to determine
an individuals parent or parents, for example,
in cases of adoption or alleged paternity. This
determination must be looked at very carefully
and must identify the alleged parent with at
least 99 certainty. The DNA testing techniques
used are similar to those used in identity
testing for a criminal investigation that is,
extracting DNA from cells and examining it in
such a way as to be able to determine what makes
it unique. If, after testing, the parent in
dispute is not excluded as a possible parent, a
mathematical estimate of the possibility that the
tested person could be the biological parent must
be calculated. This mathematical testing combines
the results of the genetic tests with other
non-genetic events (location of the alleged
parent at the time of conception, traits of the
parent and child, etc.) and results in a
parentage index. This index is a percentage of
the likelihood of parentage. Results of these
tests are admissible as evidence in court.