Exam 5: Chromosomal Aberrations

Question 1

Chromosomal structural alterations occur in how many pregnancies

Answer 1

0.5%

Question 2

Chromosomal structural alterations occur in how many live births

Answer 2

0.2%

Question 3

2 main sources for mutations affecting chromosome structure

Answer 3

Healing of DNA double strand breaks

Unbalanced recombination

Question 4

Most pregnancies involving aneuploid zygotes are

Answer 4

lost by spontaneous abortions

Question 5

Only numerical aberrations observed in clinical practice are

Answer 5

Trisomy 21 (Down syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)

Question 6

Healing of DNA double strand breaks

Answer 6

Must be healed for cell to survive - happens by nonhomologous end joining
can create chimeric chromosomes
sometimes fixes chromosome in wrong place - cause structural aberrations

Question 7

Unbalanced recombination

Answer 7

can occur at almost any loci that share a certain degree of sequence homology
causes mostly deletions and duplications

Question 8

balanced alteration

Answer 8

chromosomal rearrangement that does not change the amount of DNA in the affected cell - often has no impact on carrier
often shows at reproduction - reduces success of meiosis and pregnancy
Meiosis can produce unbalanced (inviable) gametes from balanced precursors
Translocations, inversions

Question 9

unbalanced alteration

Answer 9

change that reduces or increases the amount of DNA per cell - impact on carrier often severe
Deletions or duplications

Question 10

Cri-du-Chat syndrome

Answer 10

rare (1/25,000)
deletion on chromosome 5
Microcephaly, Micrognathia, severe mental retardation, heart defects, cat-like cry

Question 11

Di George Syndrome

Answer 11

velocardiofacial syndrome, relatively frequent abnormality (1/4,000)
microdeletion on chromosome 22 - autosomal dominant
congenital heart defect; immunodeficiency, hypoparathyroidism, mental retardation, cleft palate

Question 12

Insertion

Answer 12

moves fragment into middle of another chromosome

Question 13

Translocation

Answer 13

move fragment from one chromosome to the end of another - can be reciprocal (swapping chromosome arms)

Question 14

Philadelphia Chromosome

Answer 14

translocation between chromosome 9 & 22

Bcr/Abl protein - dominant oncogene causing myelogenous leukemia

Question 15

Robertsonian Translocation

Answer 15

long and short arms of two chromosome are exchanged
Chromosome with two short arms often get lost during cell division if they do not contain essential genetic information
Most frequent chromosomal rearrangement is this translocation between chromosomes 13q and 14q

Question 16

Inversions

Answer 16

chromosome suffers two breaks ad broken-off fragment is re-inserted in wrong orientation
Balanced alteration - asymptomatic
Can lead to translocation of chromosomal material during crossover of meiosis (forms inversion loop to pair with normal homolog) = inviable gametes

Question 17

Abnormal chromosomes in pregnancies (at conception)

Answer 17

800/10,000 (.08%)

Question 18

Abnormal chromosomes at live birth

Answer 18

50/8,500 (0.006%) - far less than at conception

Question 19

Trisomy 21 occurance at birth

Answer 19

10/8,500 (0.001%)

Question 20

47,XXY, 47 XXX, 47 XYY occurance at birth

Answer 20

15/8,500 (0.002%)

Question 21

Unbalanced rearrangements at conception

Answer 21

27/10,000 (0.0027%) - only 4 actually born

Question 22

Balanced rearrangements at conception and birth

Answer 22

conception: 19/10,000 (0.0019%)
birth: 16/8,500 (0.0019%) - far better off than unbalanced rearrangements

Question 23

karyotype

Answer 23

study of chromosome composition in human cells - use of cytogenetic techniques to detect chromosomal abnormalities with light microscope

Question 24

Karyotype should be used in cases of:

Answer 24

problems of early growth/development (developmental delay, multiple malformations, dysmorphic facies, and mental retardation)
Stillbirth/neonatal death (diagnosis and data for genetic counseling)
Fertility problems (chromosomal abnormality in one parent cause for 3-6% of recurrent miscarriages or infertility)
Pregnancy with advanced maternal age
Cancer (detect chromosmal aberrations in tumor cells)
Family history of chromosomal aberrations

Question 25

Process of Karyotype analysis

Answer 25

culture live cells from patient (usually lymphocytes in blood)
arrest cells in metaphase (condensed and paired)
lysing cells in hypotonic solution
fixing chromosomes on microscope slides
stain chromosomes with different procedures (simple Giemsa stain reveals AT-rich bands; fluorescence in-situ hybridization)

Question 26

Pedigrees of chromsomal aberration characteristics

Answer 26

cause multiple abnormalities - presence of several individuals with multiple abnormalities
cause spontaneous abortions - multiple miscarriages
cause infertility

Question 27

Turner syndrome

Answer 27

monosomy of X (45,X) female

Question 28

Klinefelter syndrome

Answer 28

47, XXY male

Question 29

Bcr/Abl chimera

Answer 29

translocation of Abl tyrosine kinase gene from chromosome 9 to BCR region on chromosome 22 - Philadelphia chromosome
Bcr/Abl protein functions as dominant oncogene - active all time

Question 30

nonhomologous end joining (NHEJ)

Answer 30

process that attaches loose chromosome fragment to another chromosome regardless of sequence homology
way of fixing double strand break damage, random, sometimes placed wrong

Question 31

structural aberrations

Answer 31

chromosomal structural abnormalities - rearrangements, loss, and duplications of parts of a chromosome
less frequent than numerical aberrations

Question 32

translocation Down syndrome

Answer 32

translocation of a terminal fragment of chromosome 21 to short arm of chromosome 8
partial trisomy 21 due to the translocation