Exam 5: Chromosomal Aberrations Flashcards Preview

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Flashcards in Exam 5: Chromosomal Aberrations Deck (32):
1

Chromosomal structural alterations occur in how many pregnancies

0.5%

2

Chromosomal structural alterations occur in how many live births

0.2%

3

2 main sources for mutations affecting chromosome structure

Healing of DNA double strand breaks
Unbalanced recombination

4

Most pregnancies involving aneuploid zygotes are

lost by spontaneous abortions

5

Only numerical aberrations observed in clinical practice are

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

6

Healing of DNA double strand breaks

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

7

Unbalanced recombination

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

8

balanced alteration

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

9

unbalanced alteration

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

10

Cri-du-Chat syndrome

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

11

Di George Syndrome

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

12

Insertion

moves fragment into middle of another chromosome

13

Translocation

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

14

Philadelphia Chromosome

translocation between chromosome 9 & 22
Bcr/Abl protein - dominant oncogene causing myelogenous leukemia

15

Robertsonian Translocation

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

16

Inversions

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

17

Abnormal chromosomes in pregnancies (at conception)

800/10,000 (.08%)

18

Abnormal chromosomes at live birth

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

19

Trisomy 21 occurance at birth

10/8,500 (0.001%)

20

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

15/8,500 (0.002%)

21

Unbalanced rearrangements at conception

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

22

Balanced rearrangements at conception and birth

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

23

karyotype

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

24

Karyotype should be used in cases of:

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

25

Process of Karyotype analysis

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)

26

Pedigrees of chromsomal aberration characteristics

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

27

Turner syndrome

monosomy of X (45,X) female

28

Klinefelter syndrome

47, XXY male

29

Bcr/Abl chimera

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

30

nonhomologous end joining (NHEJ)

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

31

structural aberrations

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

32

translocation Down syndrome

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