Structural Chromosomal Abnormalities

Question 1

what is the cause of chromosomal rearrangements?

Answer 1

double stranded DNA breaks

Question 2

when are DNA double stranded breaks normal?

Answer 2

during recombination

Question 3

where do DNA double strand breaks occur the most?

Answer 3

regions in chromosomes where repeated sequences are prevalent

Question 4

what are the 5 rearrangements of chromosomes?

Answer 4

1. deletion
2. insertion
3. inversion
4. translocation
5. duplication

Question 5

what are the 3 types of balanced rearrangements?

Answer 5

1. inversions
2. reciprocal translocation
3. robertsonian translocation

Question 6

what is considered a balanced structural rearrangement?

Answer 6

normal complement of chromosome material (no loss of genetic material)

Question 7

what is an inversion?

Answer 7

two double strand breaks, intervening sequence is inverted and the broken ends are rejoined

Question 8

what is a paracentric inversion?

Answer 8

an inversion that excludes the centromere

Question 9

what is a pericentric inversion?

Answer 9

an inversion that includes the centromere

Question 10

what can occur if recombination occurs with a paracentric inversion chromosome?

Answer 10

dicentric chromosomes (two centromeres) and acentric chromosomes (no centromere) can be formed which can lead to breakage or loss

Question 11

what can occur if recombination occurs with a pericentric inversion chromosome?

Answer 11

duplications and deletions

Question 12

with inverted chromosomes, what is a likely structure that will form to facilitate recombination?

Answer 12

a loop to match up homologs

Question 13

what is a reciprocal translocation?

Answer 13

breaking and rejoining of non-homologous chromosomes, with a reciprocal exchange of the broken segments

Question 14

where are balanced translocations usually found?

Answer 14

in couples that have had 2 or more spontaneous abortions, also in infertile males

Question 15

what is formed when reciprocal translocations come together prior to segregation during meiosis?

Answer 15

quadrivalent figure

Question 16

what are the 3 ways that the quadrivalent figure can be segregated?

Answer 16

1. alternate
2. adjacent-1
3. adjacent-2

Question 17

what does the alternate segregation pattern of reciprocal translocations form?

Answer 17

normal or balanced gametes

normal chromosome complement or 2 reciprocal translocation chromosomes

Question 18

what is the most common segregation of reciprocal translocations?

Answer 18

alternate segregation

Question 19

what does the adjacent-1 segregation of reciprocal translocations form?

Answer 19

unbalanced gametes

Question 20

what does the adjacent-2 segregation of reciprocal translocations form?

Answer 20

unbalanced gametes

Question 21

what is the lethality of reciprocal translocations?

Answer 21

5-10%

Question 22

what does a translocation between chromosome 9 and 22 usually result in?
46, XX t(9;22)(q32;q11.2)

Answer 22

chronic myelogenous leukemia

Question 23

what does this karyotype mean?

46, XX inv(9) (p13q13)

Answer 23

female with inversion of sequences between band 13 on short arm and band 3 on long arm of chromosome 9

Question 24

what is a robertsonian translocation?

Answer 24

fusion of two acrocentric chromosomes within centromeric regions resulting in loss of both short arms

Question 25

what do short arms of acrocentric chromosomes usually contain

Answer 25

rDNA repeats

Question 26

what is the most common chromosome rearragement in our species?

Answer 26

translocation of 13q and 14q | 1 in 1300 people

Question 27

what is the most important clinical aspect of robertsonian translocations?

Answer 27

robertsonian translocation involving chromosome 21 can lead to translocation down syndrome

Question 28

what happens to the karyotype of a robertsonian translocation?

Answer 28

reduction in number of chromosomes (most commonly to 45 but sometimes to 44

Question 29

True or False | Robertsonian translocations are considered unbalanced rearrangements and lead to abnormal phenotypes

Answer 29

False | Robertsonian translocations are considered BALANCED and lead to NORMAL phenotypes

Question 30

what happens to the offspring of robertsonian translocation patients?

Answer 30

unbalanced karyotypes resulting in monosomies and trisomies

Question 31

what are 2 common robertsonian translocations?

Answer 31

13q and 14q | 14q and 21q

Question 32

how is a robertsonian translocation abbreviated?

Answer 32

"der" or "rob"

Question 33

what is an unbalanced structural rearrangement?

Answer 33

chromosome has additional or deleted material and is unbalanced leading to abnormal phenotype

Question 34

what are the 4 types of unbalanced structural arrangements?

Answer 34

1. deletion 2. duplication 3. ring chromosome 4. isochromosome

Question 35

what are the 2 types of deletions?

Answer 35

1. terminal (at end) | 2. interstitial (on inside)

Question 36

what is the clinical consequence of deletions?

Answer 36

haploinsufficiency

Question 37

what is haploinsufficiency?

Answer 37

contributions of the remaining gene is not enough to prevent disease or express the normal phenotype

Question 38

what determines the severity of a phenotype in a deletion?

Answer 38

the size of the deletion and the number of genes affected

Question 39

what is the abbreviation used to express a deletion?

Answer 39

del

Question 40

what does this karyotype mean? | 46, XY del (5)(p15)

Answer 40

male with deletion on short arm at one-five on the 5th chromosome results in Cri-du-chat syndrome

Question 41

what is a duplication?

Answer 41

gain of genetic material, less harmful than deletion

Question 42

what is a partial trisomy a result of?

Answer 42

duplication

Question 43

what are the 2 ways that duplications can occur?

Answer 43

1. unequal crossing over | 2. abnormal segregation in meiosis

Question 44

what is a ring chromosome?

Answer 44

centromere joins itself and gain kinetochore activity

Question 45

what is another name for a ring chromosome?

Answer 45

marker chromosome

Question 46

how is a ring chromosome abbreviated?

Answer 46

r

Question 47

what is an isochromosome?

Answer 47

chromosome that has a missing arm and the other arm is duplicated in a mirror image fashion

Question 48

how is an isochromosome abbreviated?

Answer 48

i

Question 49

what is the most common isochromosome observed?

Answer 49

long arm of X chromosome i(Xq)

Question 50

how can an isochrome cause down syndrome?

Answer 50

there is an isochromosome with 21q21q and then there is a normal 21 chromosome. This is 3 21 chromosomes which leads to DS

Question 51

what disease would this karyotype lead to? | 46, XX (21) (21q21q)

Answer 51

Down syndrome

Question 52

in general, what is the chance of recurrence with a family that had a baby with abnormal karyotype?

Answer 52

very low, chromosomal structural abnormalities are very rare and due to a random event, unlikely to occur again. plus if one occurred, recurrence could be diagnosed during utero of the next baby

Question 53

what is a contiguous gene syndrome?

Answer 53

abnormal phenotypes caused by over-expression or loss of neighboring gene

Question 54

what are the 2 contiguous gene syndromes that occur from deletions on the long arm of chromosome 22?

Answer 54

velocardiofacial syndrome | digeorge syndrome

Question 55

what is the phenotype of velocardiofacial syndrom?

Answer 55

cleft palate | septal defects

Question 56

what is the phenotype of digeorge syndrome?

Answer 56

neural crest, branchial pouches, great vessels | outflow tract defects in the heart

Question 57

what do most chromosomal disorders result in?

Answer 57

miscarriage