Lecture 1 - Clinical Cytogenetics

Question 1

spontaneous abortions:
chromosome abnormalities account for 50% of ____ trimester miscarriages
most common autosomal trisomy?
most common single abnormalitiy

Answer 1

1st;
trisomy 16;
45, XO (Turner genotype)

Question 2

____ chromosomes have a stalk and a satellite portion. the _____ ____ region is found in the satellite region and contains ____ genes

Answer 2

acrocentric;
nucleolar organizer region (NOR);
ribosomal RNA

Question 3

submetacentric chromatids:
p = for the ___ arm;
q = for the ___ arm

Answer 3

short, long

Question 4

G-bandind (Giemsa stain):
stains ___ rich DNA;
G-light bands indicate ____;
G-dark bands indicate ____

Answer 4

AT;
euchromatin (active);
heterochromatin (inactive)

Question 5

C-banding stains ____ and ____

Answer 5

centromere, heterochromatin

Question 6

____ is the display of chromosomes, from the largest to the smallest.
_____ is the use of nomenclature to describe the chromosomal complement

Answer 6

karyogram;

karyotype (ie 46, XY)

Question 7

what is the most commonly used sample for chromosomal analysis?

Answer 7

nucleated white cells (From peripheral blood)

Question 8

to visual chromosomes, they are arrested in _____. to do this you use the ____ inhibitor colcemid

Answer 8

metaphase;

mitotic

Question 9

FISH:

used to localize segments of a chromosome by labeling the ___ Segment with a fluorescent tag and allowing it to…..

Answer 9

DNA;

anneal to its homologous region

Question 10

with _____, nucleic acid sequences are arranged in grids. DNA or RNA probes are hybridized and a scanner detects the relative amounts of _____

Answer 10

microarrays;

complementary binding

Question 11

comparative genomic hybridization:
analyzes ____ and ____ of genetic material;
ie ____ abnormalities only

Answer 11

gains, losses;

unbalanced

Question 12

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

Answer 12

SNP;

neutral (e.g. balanced translocation)

Question 13

_____ is failure of homologous chromosomes (meiosis ___) or chromatids (meiosis __) to properly segregate

Answer 13

non-disjunction;

1, 2

Question 14

nondisjunction:
if occurs in meiosis ___, isodisomy can occur;
if occurs in meiosis ___, heterodisomy can occur

Answer 14

2, 1

Question 15

consider UPD for…
____ disorder in an individual with only one documented carrier parent;
____ disorder transmitted from father to son

Answer 15

autosomal recessive;

X-linked

Question 16

polyploidy vs aneuploidy:
haploid change in chromosome number =
47, XXY would be an example of ____;
69, XXX would be an example of ____

Answer 16

polyploidy,
aneuploidy;
polyploidy

Question 17

most common cause of triploidy is a haploid ___ + 2 ____

Answer 17

egg, sperm

Question 18

____ is due to replication without meoitic division

Answer 18

tetraploidy

ie 92, XXYY

Question 19

what is the only viable monosomy?

Answer 19

45, XO (Turner)

all others = lethal

Question 20

turner syndrome:
___ stature, ovarian ____ causing ____ ovary;
____ neck or cystic ____

Answer 20

short, dysgenesis, streak;

webbed, hygroma

Question 21

turner syndrome:
2 heart defects associated with it =
_____ kidney;
____ in hands and feet at birth

Answer 21

coarctation of aorta, bicuspid aortic valve;
horseshoe;
lymphedema

Question 22

turner mosaics 45,X/46,XY are associated with increased risk of ____;
the 45, X genotype (most common) is usually due to ____ nondisjunction

Answer 22

gonadoblastomas;

paternal

Question 23

klinefelter:
classic chromosomal genotype = ____
clinically evident when?

Answer 23

47 XXY;

after puberty

Question 24

klinefelter:
___, firm testes, ____ extremities, ____, female hair distribution;
presence of _____ in cells;
increased risk of what kind of malignancy?

Answer 24

small, long;
gynecomastia;
barr body (inactivated X chrom);
germ cell tumors

Question 25

47 ____ = female; ___ stature; increased risk of ____ and ____ problems

Answer 25

XXX; tall; learning disabilities, psych

Question 26

47 ___ = male; due to ____ meiosis 2 error; ____ stature; increased incidence of _____ and severe ____

Answer 26

XYY; paternal; tall; learning disabilities, acne

Question 27

name the syndrome: trisomy 13 = trisomy 18 = trisomy 21 = which chromosome is the submetacentric one

Answer 27

patau; edwards; down 18 (others are acrocentric)

Question 28

patau syndrome: | 75% due to meiosis __ nondisjunction. maternal or paternal error?

Answer 28

1; | maternal

Question 29

``` patau: CNS effect = ____ or _____; facial effect = _____ limb effect = _____ and _____ do most live past 1? ```

Answer 29

microcephaly, holoprosencephaly; cleft lip/palate; polydactyly, rocker bottom feet; no :(

Question 30

edwards: 90% due to meiosis ____ nondisjunction. maternal or paternal? do most live past 1?

Answer 30

2; maternal; no :(

Question 31

``` edwards: facial effect: ____ and _____; limb effect: ____ and ____; ___Tonia short sternum, heart probs ```

Answer 31

micrognathia, prominent occiput; overlapping fingers, rocker-bottom feet; hyper

Question 32

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?

Answer 32

1, maternal; unbalanced; 21q22; yes :)

Question 33

with ____ trisomy 21, the kid has 2 cell lines: 47, XX+21 and 46,XX

Answer 33

mosaic

Question 34

down: ____ folds, ____ palpebral fissures; ____ spots on eyes. _____ which is curvature of fingers;

Answer 34

epicanthal, upslanted; brushfield; clinodactyly

Question 35

down: increased risk for what 2 kinds of cancer? CNS problem? 2 GI problems?

Answer 35

AML, ALL; alzhemiers; duodenal atresia, hirschsprung

Question 36

roberstonian translocations are translocations between the ____ arms of ____ chromosomes

Answer 36

long (q), acrocentric

Question 37

a deletion of the p16 region in chromosome 4 causes ____ syndrome. characteristic ____Telorism, ____ ____ facies, ____ nasal bridge, and microcephaly + heart probs

Answer 37

wolf-hirschhorn; hypertelorism; greek helmet; broad

Question 38

cru-du-chat syndrome: deletion of ___ on chromosome ____; ___cephaly, _____ folds, ____ cry; ____tonia in infants

Answer 38

p14 (short arm), 5; micro, epicanthal; high pitched/cat; hypo

Question 39

____ 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?

Answer 39

contiguous; | 22q11 deletion ie Digeorge

Question 40

CATCH-22 of digeorge:

Answer 40

``` Cleft palate Abnormal facies Thymic aplasia (T cell deficiency) Cardiac defects Hypocalcemia (parathyroid aplasia) ``` 22q11 deletion

Question 41

22q11 deletions causes ____ heart defects such as _____

Answer 41

conotruncal (outflow); | tetralogy of fallot

Question 42

velocardialfacial syndrome: ____, facial, and cardiac defects: ie ____ facies

Answer 42

palate; | long

Question 43

prader willi syndrome is usually due to a (paternal or maternal) deletion of what?

Answer 43

paternal; | 15q12

Question 44

a ____ duplication is a contiguous doubling of a segment

Answer 44

tandem

Question 45

duplication syndrome to know? | causes symptoms similar to ____, but milder

Answer 45

22q11.2; | 22q11 deletion

Question 46

rieciprocal translocations: ____ translocations = both translocated chromes plus 2 normal homologs; carriers are usually ____

Answer 46

balanced; | clinically normal

Question 47

translocations: "____" separation produces normal and balanced offspring; ____ or ____ separation produces unbalanced offspring. segregation occurs in _____ of meisos 1

Answer 47

alternate; adjacent 1, 2; metaphase 1

Question 48

adjacent ___: homolgous centromeres go to the same pole; adjacent __ = homolgous centromeres separate; which is the worst ie least viable?

Answer 48

adjacent 2; adjacent 1; adjacent 2 is THE worst

Question 49

one should suspect a patient to be a translocation ____ when there are multiple pregnancy losses

Answer 49

carrier

Question 50

in translocation nomenclature, the "derivative" chromosome is named based off of the chromosome's ____

Answer 50

centromere

Question 51

in ___ syndrome, a child has a balanced translocation and a supernumerary der(22); this occurs when the parent is a balanced carrier of a _____

Answer 51

emanuel; | t(11,22)

Question 52

``` emanuel syndrome: intellectual disability or no? ___Cephaly, ___gnathia; ____ abnormalities heart defects cleft palate ```

Answer 52

yes, severe; micro, micro; kidney

Question 53

____ _____ occurs when the long arms of 2 acrocentric chromes fuse at the centromeres and the 2 short arms are _____

Answer 53

robertsonian translocation; | lost

Question 54

acrocentric chromes = (5 of them)

Answer 54

13, 14, 15, 21, 22

Question 55

a ______ carrier of a robertsonion translocation has 45 chromes. a ____ carrier has 46 chromes. which is worse?

Answer 55

balanced; unbalanced; unbalanced

Question 56

robertsonion translocation segregation: in _____ segregation, the gametes are normal or balanced; in adjacent segregation, the gametes are ____, leading to ____ or ____

Answer 56

alternate; | unbalanced, miscarriage, down syndrome

Question 57

_____ inversions are inversions that include the centromere. what is the most common one?

Answer 57

PERIcentric; | 9 (typically benign)

Question 58

_____ inversions are inversions in one arm of the chrome (ie don't involve centromere)

Answer 58

PARAcentric

Question 59

inversions are typically benign, but increase the risk for _____

Answer 59

abortions (ie recurrent miscarriages)