Chromosomes and Cytogenetics- Lectures 41-42

Question 1

_____ is the study of chromosomes and the mechanisms of chromosome disorders.

Answer 1

Cytogenetics

Question 2

____ of spontaneous abortions that occur in the first trimester will have a chromosomal abnormality.

Answer 2

65%

Question 3

When can karyotyping be performed?

Answer 3

mitotic phase of the cell cycle

Question 4

Describe how karyotyping is performed.

Answer 4

blood sample is taken and G-banding procedure allows for discrimination of banding per chromosome, allowing for them to be lined up into 22 pairs of autosomes and one pair of sex chromosomes

Question 5

What are the sections of chromosomes.

Answer 5

p-arm (short arm)
q-arm (long arm)
telomere (cap at the ends of chromosomes)
centromere (central condensed region essential for mitotic spindle attachment)

Question 6

____ chromosomes are those that have very similar lengths of p and q arms, whereas ______ chromosomes are those that have visually shorter p arm compared to the q arm and ____ which have very short p arms and contain only repetitive information and ribosomal RNA genes.

Answer 6

Metacentric
sub-metacentric
acrocentric

Question 7

What chromosomes are considered to be acrocentric?

Answer 7

13, 14, 15, 21, and 22

Question 8

What are the possible changes in chromosomal copy numbers and what are general changes in number called?

Answer 8

monosomy/ deletion (1 copy)
trisomy (three copies)
aneuploidy

Question 9

How do anuploidys occur?

Answer 9

failure to properly segregate chromosomes during the division steps of meiosis

Question 10

Are aneuploidies compatible with life?

Answer 10

since most chromosomes have large gene dose involvement, most non-sex linked are not viable, however trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) can lead to a live birth

Question 11

Describe Down Syndrome.

Answer 11

trisomy 21
most common trisomy seen in live births (1:800)`
95% due to non-disjunction
highly correlated with AMA
Results in intellectual disability, short stature, hearing loss, seizures, heart malformations, digestive tract malformations, increased disease risk, typical facial features
life expectancy ~60 years

Question 12

Describe Edward syndrome.

Answer 12

trisomy 18
1:6,000 live births
Results in rocker bottom feet, overlapping fingers, multiple congenital organ anomalies, restricted growth, microcephaly, short palpebral fissures, small chin and mouth, low-set ears, and cutis aplasia
95% result in spontaneous abortion or miscarriage
poor survival rates (4 days)

Question 13

Describe Patau syndrome.

Answer 13

trisomy 13
1:10,000 live births
Results in distinctive midline defect (cleft lip/palate), multiple congenital organ anomalies, hypotelorism and holoprosencephaly, midline cleft palate, and polydactyly
life expectancy ~130 days

Question 14

Clinical features of trisomies can be attenuated if the non-disjunction of the chromosome occurs _____, creating a ____ state.

Answer 14

after fertilization

mosaic

Question 15

Describe Turner syndrome.

Answer 15

monosomy X
1:5,000 live female births
loss of PAR region likely results in webbed neck, lymphedema in early ages, short stature, coarctation of aorta, structural kidney defects, ovarian dysgenesis
99% of embryos spontaneously aborted

Question 16

What is PAR?

Answer 16

pseudoautosomal regions

repeat sequences at both ends of sex chromosomes that act as autosomal genes and escape X-inactivation

Question 17

Describe Klinefelter syndrome.

Answer 17

47,XXY
one X chromosome will be inactive, but will still express three pairs of PARs
1:1,000 live male births
half maternal and half paternal in origin
results in small testes, low testosterone, gynecomastia, no spermatogenesis, taller and thinner, learning issues and ADHD

Question 18

Describe Super female syndrome.

Answer 18

47, XXX
1:1,000 female births
mostly maternal in origin
one X is active, but still three pairs of PARs
results in tall stature, balance problems, generally fertile, risk of speech delay and learning issues

Question 19

Describe Jacob syndrome.

Answer 19

47, XYY
1:1,000 live male births
paternal in origin
only X is active, but three pairs of PARs present
tall but normally proportioned, so most will be completely asymptomatic

Question 20

What screenings can be used to detect risk of an anuploidy in the first trimester?

Answer 20

NT (nucal translusency)
PAPP-A (pregnancy associated plasma protein-)
f-bhCG

Question 21

Anuploidy accounts for ____ of first trimester pregnancy loss ____ of second trimester pregnancy loss.

Answer 21

66%

20%

Question 22

What results of a triple screen would indicate increased risk for Down syndrome?

Answer 22

increased NT
low PAPP-A
high f-bhCG

Question 23

What triple screen results would indicate an increased risk of Edward syndrome?

Answer 23

increased NT
low PAPP-A
low f-bhCG

Question 24

What screenings can be used to detect risk of an anuploidy in the second trimester?

Answer 24

AFP (alpha fetoprotein)
estriol
hCG
Inhibin A

Question 25

What results on quad screening would indicate increased risk of Down syndrome?

Answer 25

low AFP and estriol
high hCG
high Inhibin

Question 26

What results on a quad screening would indicated increased risk of Turner syndrome?

Answer 26

decreased AFP and Estriol

very high hCG and Inhibin

Question 27

What results on a quad screening would indicate an increased risk of Edward syndrome?

Answer 27

low estriol

very low hCG

Question 28

What results on a quad screening would indicate an increased risk for Patau syndrome?

Answer 28

increased AFP

Question 29

How would you confirm the results of a triple or quad screening?

Answer 29

amniocentesis
CVS (chorionic villi sampling)
NIPS (non-invasive prenatal screening)

Question 30

What is uniparental diploidy?

Answer 30

normal number of chromosomes but all from mother or father

pathogenic (mostly clinically significant with chromosomes containing imprinted regions – 6,7,11,14,15,16)

Question 31

What is the result of paternal origin uniparental diploidy?

Answer 31

complete hydatidiform mole (no fetal tissue, only trophoblast hyperplasia, leading to choriocarcinoma)
results from an egg that lacks a nucleus and is fertilized by one normal sperm

Question 32

What is the result of maternal origin uniparental diploidy?

Answer 32

ovarian teratoma (disorganized embryonic material)
results from an activated unovulated oocyte

Question 33

What is triploidy?

Answer 33

23 x 3 = 69 chromosomes

caused by polyspermy (fertilization of a normal egg with two sperm resulting in a partial mole containing fetal tissue)

Question 34

What is tetraploidy?

Answer 34

23 x 4 = 92 chromosomes

caused by failure of the first zygotic division (usually does not contain fetal tissue and is spontaneously aborted)

Question 35

Partial segments of chromosomes can be deleted, resulting in ______, or duplicated, resulting in ______. This can involve either end of the chromosome (______) or an internal region (______).

Answer 35

partial monosomy
partial trisomy
terminal
interstitial

Question 36

Provide examples of deletion syndromes that can be visualized on karyotyping.

Answer 36

Wolf-Hirshhorn syndrome (4p16 terminal deletion)

Question 37

What are translocations and inversions?

Answer 37

abnormalities in which genetic material is not gained or lost, but is relocated

Question 38

What is a balanced translocation?

Answer 38

a translocation where no genes are disrupted
occurs when there is a reciprocal interchange of genetic material between two non-homologous chromosomes
carriers typically have no phenotype, but risk recurrent miscarraige or phenotypically abnormal offspring because gametes will be unbalanced

Question 39

What are unbalanced translocations?

Answer 39

partial monosomy of one chromosome in conjunction with a partial trisomy of another chromosome

Question 40

What is a Robertsonian translocation?

Answer 40

a special class of translocation involved homologous (same chromosome) or non-homologous exchange of the long arm and loss of the short arms of acrosomal chromosomes (13, 14, 15, 21, 22) –> fusion containing all of the genetic materials of the long arms of involved chromosomes while repetitive ribosomal RNA genes present on the short arms are lost

Question 41

What is a pericentric inversion?

Answer 41

two breaks in one chromosome where the area in between the breaks inverts and rejoins including the centromere

Question 42

What is paracentric inversion?

Answer 42

two breaks in one chromosome where the area in between the breaks inverts and rejoins confined to only one arm of the chromosome

Question 43

Rarely, homologous recombination can occur with an inversion, involving _______.

Answer 43

an elaborate looped pairing during meiosis.

Question 44

What does the loop pairing during meiosis cause?

Answer 44

unbalanced chromosomal abnormality in the conceptus with a partial duplication of one end of the inverted region in conjunction with a partial deletion of the other end of the inverted region

Question 45

Describe the formation and results of ring chromosomes.

Answer 45

tip of p arm is fused with the q arm on the same chromosome
genetic material at the tip can be lost, creating a terminal deletion
easily lost during mitosis