Lecture 1 - Clinical Cytogenetics Flashcards
spontaneous abortions:
chromosome abnormalities account for 50% of ____ trimester miscarriages
most common autosomal trisomy?
most common single abnormalitiy
1st;
trisomy 16;
45, XO (Turner genotype)
____ chromosomes have a stalk and a satellite portion. the _____ ____ region is found in the satellite region and contains ____ genes
acrocentric;
nucleolar organizer region (NOR);
ribosomal RNA
submetacentric chromatids:
p = for the ___ arm;
q = for the ___ arm
short, long
G-bandind (Giemsa stain):
stains ___ rich DNA;
G-light bands indicate ____;
G-dark bands indicate ____
AT;
euchromatin (active);
heterochromatin (inactive)
C-banding stains ____ and ____
centromere, heterochromatin
____ is the display of chromosomes, from the largest to the smallest.
_____ is the use of nomenclature to describe the chromosomal complement
karyogram;
karyotype (ie 46, XY)
what is the most commonly used sample for chromosomal analysis?
nucleated white cells (From peripheral blood)
to visual chromosomes, they are arrested in _____. to do this you use the ____ inhibitor colcemid
metaphase;
mitotic
FISH:
used to localize segments of a chromosome by labeling the ___ Segment with a fluorescent tag and allowing it to…..
DNA;
anneal to its homologous region
with _____, nucleic acid sequences are arranged in grids. DNA or RNA probes are hybridized and a scanner detects the relative amounts of _____
microarrays;
complementary binding
comparative genomic hybridization:
analyzes ____ and ____ of genetic material;
ie ____ abnormalities only
gains, losses;
unbalanced
as opposed to comparative genomic hybridization arrays, ____ arrays can determine things such as loss of heterozygosity and UPD. ie, able to detect allelic copy ____ changes
SNP;
neutral (e.g. balanced translocation)
_____ is failure of homologous chromosomes (meiosis ___) or chromatids (meiosis __) to properly segregate
non-disjunction;
1, 2
nondisjunction:
if occurs in meiosis ___, isodisomy can occur;
if occurs in meiosis ___, heterodisomy can occur
2, 1
consider UPD for…
____ disorder in an individual with only one documented carrier parent;
____ disorder transmitted from father to son
autosomal recessive;
X-linked
polyploidy vs aneuploidy:
haploid change in chromosome number =
47, XXY would be an example of ____;
69, XXX would be an example of ____
polyploidy,
aneuploidy;
polyploidy
most common cause of triploidy is a haploid ___ + 2 ____
egg, sperm
____ is due to replication without meoitic division
tetraploidy
ie 92, XXYY
what is the only viable monosomy?
45, XO (Turner)
all others = lethal
turner syndrome:
___ stature, ovarian ____ causing ____ ovary;
____ neck or cystic ____
short, dysgenesis, streak;
webbed, hygroma
turner syndrome:
2 heart defects associated with it =
_____ kidney;
____ in hands and feet at birth
coarctation of aorta, bicuspid aortic valve;
horseshoe;
lymphedema
turner mosaics 45,X/46,XY are associated with increased risk of ____;
the 45, X genotype (most common) is usually due to ____ nondisjunction
gonadoblastomas;
paternal
klinefelter:
classic chromosomal genotype = ____
clinically evident when?
47 XXY;
after puberty
klinefelter:
___, firm testes, ____ extremities, ____, female hair distribution;
presence of _____ in cells;
increased risk of what kind of malignancy?
small, long;
gynecomastia;
barr body (inactivated X chrom);
germ cell tumors
47 ____ = female;
___ stature;
increased risk of ____ and ____ problems
XXX;
tall;
learning disabilities, psych
47 ___ = male;
due to ____ meiosis 2 error;
____ stature;
increased incidence of _____ and severe ____
XYY;
paternal;
tall;
learning disabilities, acne
name the syndrome:
trisomy 13 =
trisomy 18 =
trisomy 21 =
which chromosome is the submetacentric one
patau;
edwards;
down
18 (others are acrocentric)
patau syndrome:
75% due to meiosis __ nondisjunction. maternal or paternal error?
1;
maternal
patau: CNS effect = \_\_\_\_ or \_\_\_\_\_; facial effect = \_\_\_\_\_ limb effect = \_\_\_\_\_ and \_\_\_\_\_ do most live past 1?
microcephaly, holoprosencephaly;
cleft lip/palate;
polydactyly, rocker bottom feet;
no :(
edwards:
90% due to meiosis ____ nondisjunction. maternal or paternal?
do most live past 1?
2;
maternal;
no :(
edwards: facial effect: \_\_\_\_ and \_\_\_\_\_; limb effect: \_\_\_\_ and \_\_\_\_; \_\_\_Tonia short sternum, heart probs
micrognathia, prominent occiput;
overlapping fingers, rocker-bottom feet;
hyper
down:
90% due to meiotic ___ nondisjunction. paternal or maternal?
can also be due to balanced or unbalanced robertsonian translocation?
duplication of down syndrome critical region which is ____;
do most live past 1?
1, maternal;
unbalanced;
21q22;
yes :)
with ____ trisomy 21, the kid has 2 cell lines: 47, XX+21 and 46,XX
mosaic
down:
____ folds, ____ palpebral fissures;
____ spots on eyes. _____ which is curvature of fingers;
epicanthal, upslanted;
brushfield;
clinodactyly
down:
increased risk for what 2 kinds of cancer?
CNS problem?
2 GI problems?
AML, ALL;
alzhemiers;
duodenal atresia, hirschsprung
roberstonian translocations are translocations between the ____ arms of ____ chromosomes
long (q), acrocentric
a deletion of the p16 region in chromosome 4 causes ____ syndrome. characteristic ____Telorism, ____ ____ facies, ____ nasal bridge, and microcephaly + heart probs
wolf-hirschhorn;
hypertelorism;
greek helmet;
broad
cru-du-chat syndrome:
deletion of ___ on chromosome ____;
___cephaly, _____ folds, ____ cry;
____tonia in infants
p14 (short arm), 5;
micro, epicanthal;
high pitched/cat;
hypo
____ gene syndromes occur with deletion of submicroscopic segments that contain 2 or more closely linked genes that impact multiple organ symptoms. what is an example?
contiguous;
22q11 deletion ie Digeorge
CATCH-22 of digeorge:
Cleft palate Abnormal facies Thymic aplasia (T cell deficiency) Cardiac defects Hypocalcemia (parathyroid aplasia)
22q11 deletion
22q11 deletions causes ____ heart defects such as _____
conotruncal (outflow);
tetralogy of fallot
velocardialfacial syndrome:
____, facial, and cardiac defects:
ie ____ facies
palate;
long
prader willi syndrome is usually due to a (paternal or maternal) deletion of what?
paternal;
15q12
a ____ duplication is a contiguous doubling of a segment
tandem
duplication syndrome to know?
causes symptoms similar to ____, but milder
22q11.2;
22q11 deletion
rieciprocal translocations:
____ translocations = both translocated chromes plus 2 normal homologs;
carriers are usually ____
balanced;
clinically normal
translocations:
“____” separation produces normal and balanced offspring;
____ or ____ separation produces unbalanced offspring.
segregation occurs in _____ of meisos 1
alternate;
adjacent 1, 2;
metaphase 1
adjacent ___: homolgous centromeres go to the same pole;
adjacent __ = homolgous centromeres separate;
which is the worst ie least viable?
adjacent 2;
adjacent 1;
adjacent 2 is THE worst
one should suspect a patient to be a translocation ____ when there are multiple pregnancy losses
carrier
in translocation nomenclature, the “derivative” chromosome is named based off of the chromosome’s ____
centromere
in ___ syndrome, a child has a balanced translocation and a supernumerary der(22);
this occurs when the parent is a balanced carrier of a _____
emanuel;
t(11,22)
emanuel syndrome: intellectual disability or no? \_\_\_Cephaly, \_\_\_gnathia; \_\_\_\_ abnormalities heart defects cleft palate
yes, severe;
micro, micro;
kidney
____ _____ occurs when the long arms of 2 acrocentric chromes fuse at the centromeres and the 2 short arms are _____
robertsonian translocation;
lost
acrocentric chromes = (5 of them)
13, 14, 15, 21, 22
a ______ carrier of a robertsonion translocation has 45 chromes. a ____ carrier has 46 chromes. which is worse?
balanced;
unbalanced;
unbalanced
robertsonion translocation segregation:
in _____ segregation, the gametes are normal or balanced;
in adjacent segregation, the gametes are ____, leading to ____ or ____
alternate;
unbalanced, miscarriage, down syndrome
_____ inversions are inversions that include the centromere. what is the most common one?
PERIcentric;
9 (typically benign)
_____ inversions are inversions in one arm of the chrome (ie don’t involve centromere)
PARAcentric
inversions are typically benign, but increase the risk for _____
abortions (ie recurrent miscarriages)
