CLINICAL APPLICATIONS Flashcards
It is the application of cytogenetics to clinical settings
Clinical Cytogenetics
True or False:
Cytogenetics abnormalities may be found in normal individuals (who looks normal phenotypically)
True
True or False:
Cytogenetic abnormalities may be found on patients with phenotypic anomalies (e.g., cleft palate)
True
True or False:
Cytogenetic abnormalities may be found on patients with diagnosed genetic disorders
True
True or False:
Diagnosis of cytogenetic disorders may be made at any stage of life
True
It is a stage wherein genetic abnormalities are diagnosed before birth.
Prenatal cytogenetics
True or False:
In prenatal cytogenetics, baby in the womb of the mother can be diagnosed with cytogenetics abnormalities
True
In this stage the baby is born and you may seek evidence for cytogenetic abnormalities
Postnatal cytogenetics
At this stage, babies are born seemingly normal but later in life they would manifest some genetic abnormalities; developmental, physical, or mental disabilities will manifest during adulthood
Childhood and adult cytogenetics
It is established if the same set of features are seen in several unrelated individuals; assumed to
have a common basis of specific chromosomal abnormalities but may occur in different degrees
Syndrome
These are usually caused by a common/single-specific chromosomal abnormality
Syndrome
In this stage, 50% - 60% of spontaneous abortions during early months of pregnancy have a demonstrable chromosomal abnormality and 52% of which are autosomal trisomies.
Prenatal cytogenetics
1:3 conceptuses (embryo in the uterus) have chromosomal abnormality but seen only in 6:1000
live births due to biological elimination of recognized errors
Prenatal cytogenetics
Rate of biological elimination of Monosomy X (Turner’s Syndrome)
95%
Rate of biological elimination of Trisomy 13 (Patau Syndrome)
90%
Rate of biological elimination of Trisomy 18 (Edwards Syndrome)
80%
Rate of biological elimination of Trisomy 21 (Down Syndrome)
65%
True or False:
As the number of chromosomes
goes higher the chances of being born alive is greater.
True
It is the most common chromosomal error in spontaneous losses
45, X (Monosomy X - Turner’s Syndrome)
It is the most common trisomy seen in abortus
Trisomy 16
This analysis should be done if a woman is suspected to be at an increased risk of having an abnormal child
Prenatal chromosome analysis
3 methods to obtain cells from prenatal chromosomal analysis
- Amniocentesis
- On chorionic villus biopsy
- On umbilical cord blood
True or False:
Screening for maternal age-related risk is an indications for prenatal cytogenetics
True
True or False:
Family history of or previous child with chromosomal abnormality might be an indication for prenatal cytogenetics
True
True or False:
Abnormal levels of AFP (alpha fetoprotein) in a screening test is an indication for prenatal cytogenetics
True
It is a fetal protein that is usually associated with neural tube defect
Alpha fetoprotein
True or False:
Fetal abnormality detected on ultrasound is an indication of prenatal cytogenetics
True
A parent who is a carrier of unbalanced gametes and A parent who is a carrier of X-linked genetic
disorder is an indication of prenatal cytogenetics
True
It is a type of neural tube defects that is completely open brain and spinal cord
Craniorachischisis
It is a type of neural tube defects that is open brain and lack of skull vault
Anencephaly
It is a type of neural tube defects that has herniation of the meninges and brain
Encephalocele
It is a type of neural tube defects that has occipital skull and spine defects with extreme retroflexion of the head
Iniencephaly
It is a type of neural tube defects that has closed asymptomatic neural tube defect in which some of the vertebrae are not completely close
Spina bifida occulata
It is a type of neural tube defects that has deficiency of at least two vertebral arches
Closed spinal dysraphism
It is a type of neural tube defects that has protrusion of the meninges filled with CSF, through a defect in the skull or spine
Meningocele
It is a type of neural tube defects that has open spinal cord with a meningeal cysts
Myelomeningocele
This analysis is used on both biological parents to differentiate between an inherited rearrangement and a “de novo” anomaly in the child
Karyotype analysis
In this stage, Approximately 0.6% - 1.0% of all newborns have a
gross chromosomal abnormality
Postnatal cytogenetics
If a newborn infant presents with manifestations of a syndrome, a karyotype analysis is needed to?
- Confirm diagnosis
- Substantiate a diagnosis
- Provide information related to clinical findings
True or False
Presence of multiple congenital anomalies is an indication of postnatal cytogenetics
True
True or False
Suspected aneuploidy and childhood and adult cytogenetics are indications of postnatal cytogenetics
True
Indications for adults and childhood cytogenetics in postnatal
a. Unexplained mental retardation or developmental delay
b. Suspected aneuploidy
c. Presence of multiple congenital anomalies
a. Unexplained mental retardation or developmental delay
True or False:
- Suspected unbalanced autosome - Suspected sex chromosomal abnormality
- Suspected fragile X syndrome
are indication of postnatal cytogenetics for adults and childhood
True
True or False:
Multiple spontaneous abortions is an indication of postnatal cytogenetics for adults and childhood
True
This syndrome has an insatiable appetite caused by a defect in the hypothalamus that causes the person to never actually feel full
Prader-Willi Syndrome
It is a direct correlation between the presence of various chromosomal abnormalities and patient’s response to treatment
Cancer genetics
These are usually caused by genetic mutations
Cancer genetics
is directly associated with certain
chromosomal abnormalities, and are usually best appreciated in patients with leukemia
Tumorigenesis
Indications for cancer cytogenetics
- Confirm a clinical diagnosis
- Monitor disease progression - relapse and disease progression
- Monitor patients’ response to therapy
It is a valuable tool in clinical oncology wherein we label the antibodies that is used against the antigen with fluorescent dye
FISH (fluorescent in situ hybridization)
It is wherein a patient no longer has
evidence of cells with the chromosomal abnormalities
Cytogenetic remission
It is a translocation wherein you have two chromosomes that has one break on each arm where exchange of genetic information happens
Balanced-reciprocal translocation
It is a translocation wherein the two long arms broke with the centromere, and then joined together, the two long arms joined
together and the two short arm also joined together
Robertsonian translocation
signals occur if the translocation
results in separation of two probes generating two-different colored signals in place of the original single-color signal
Splitting
signals occur in the translocation
results in relocation of two different probes into proximity causing generation of a new color
Fusion
Translocation are seen in?
- chronic myeloid leukemia
- acute myeloid leukemia
- acute lymphoblastic leukemia
This method is used for the ABL locus on chromosome 9
red
this method is used for the BC locus on chromosome 22
green
This signal will be formed with fusion of green and red signals
yellow signal
Probe: Chromosome 7
Chromosomal Abnormality: ?
Use/ Disease: ?
Chromosomal Abnormality: Trisomy 7
Use/ Disease: MDS and AML
Probe: Chromosome 8
Chromosomal Abnormality: ?
Use/ Disease: ?
Chromosomal Abnormality: Trisomy 8
Use/ Disease: acute & chronic disorders
Probe: Chromosome 12 - specific centromere
Chromosomal Abnormality: ?
Use/ Disease: ?
Chromosomal Abnormality: Trisomy 12
Use/ Disease: CLL
Probe: X and Y probes
Chromosomal Abnormality: ?
Use/ Disease: ?
Chromosomal Abnormality: For BM (Bone Marrow) transplantation of
M from F
Patient: male
Donor: female
Use/ Disease: Monitor Success, monitor treatment
patient who undergoes this transplantation usually first undergo BM radiation in order to destroy malignant cells that are
present in the bone marrow
BM transplantation
How will you know if the BM transplantation is syccessful?
There is no XY chromosome
It detects all nucleated cells both normal and abnormal, thus provide a more accurate estimate of disease involvement within the total population
FISH (Fluorescent in situ hybridization)
This can be used to monitor
response to treatment with decreasing disease cell population
Testing sequential sample
This can only be performed on dividing cells, since cancer cells are continuously dividing, analysis will usually show 100% abnormal cells
Karyotyping
True or False:
The karyotype will identify the
chromosomal abnormalities while the FISH will establish the baseline
frequency of leukemic clones which can be used as reference point for all of the patients’ future testing
True
Which of the following is true of a syndrome?
a) Consist of the same group of chromosomal abnormalities
b) Abnormalities present in the same degree
c) Observed in the same group of people
d) Arise from different forms of chromosomal abnormalities
A
Genetic abnormalities is NOT seen in which of the following individuals?
a) Seemingly normal
b) With gross deformities
c) With confirmed genetic disorder
d) None of these
D
Although chromosomal abnormalities are present in 1:3 conceptus, only 6:1000 livebirths
manifest the disorder. Which of the following explains this low incidence at birth?
a) Repair mechanism of recognized errors
b) Biologic elimination of recognized errors
c) Poor identification of genetic abnormalities
d) Low interest on genetic abnormalities
B
Which of the following is the most common chromosomal abnormalities seen in spontaneous abortion?
a) 47, XY, +13
b) 47, XY, +18
c) 47, XY, +21
d) 45, X
D
Which of the following specimens is not used for prenatal cytogenetic testing?
a) Umbilical cord blood
b) Chorionic villi
c) Amniotic fluid
d) Fetal bladder aspirate
D
The incidence of fetal loss among patients with genetic abnormalities is greatest during which of the following phase of pregnancy?
a) 1st trimester
b) 2nd trimester
c) 3rd trimester
d) Newborns
A
Which of the following groups of mothers have the highest tendency to have cytogenetically abnormal progeny?
a) Less than 25 yrs old
b) 26-30 yrs old
c) 31-35 yrs old
d) More than 35 yrs old
D
Which of the following is an indication for prenatal cytogenetics?
a) Presence of multiples congenital anomalies
b) Unexplained mental retardation
c) An abnormal level of alpha-fetoprotein (AFP)
d) Suspected aneuploidy
C
Which of the following relationships has not been established between cancer and genetics?
a) Specific chromosomal rearrangements are directly associated with tumor formation
b) Direct correlation exists between presence of various chromosomal abnormalities and therapeutic response
c) Genetic findings are now required in the diagnosis of most hematopoietic cancers
d) None of these
D
Philadelphia chromosome or abl-bcr fusion gene is a diagnostic of which of the following hematopoietic malignancy?
a) Acute myelogenous leukemia
b) Acute lymphoblastic leukemia
c) Chronic myelogenous leukemia
d) Chronic lymphocytic leukemia
C
