Exam #5: Chromosomal Aberrations Flashcards Preview

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Flashcards in Exam #5: Chromosomal Aberrations Deck (25):
1

Frequency of Chromosomal Aberrations

The majority of fetuses w/ chromosomal aberrations are spontaneously aborted i.e. chromosomal aberrations are much more frequent at conception than at birth

For 10,000 pregnancies:
- 800 w/ chromosomal aberrations, BUT only 50 live births
- 47, XXY, XXX, & XYY, and then Trisomy 21 had the most live births of the numerical aberrations (15 & 10)
- Balanced rearrangement has more live births than those two numerical aberrations
- Unbalanced rearrangements were spontaneously aborted 85% of the time

2

Two Sources of Mutation Affecting Chromosomes

1) Numerical Aberrations = Nondisjunction during meiosis
2) Structural Chromosomal Alterations = rearrangements, loss, & duplication of parts of a chromosome

3

Balanced Alteration

- Move a fragment of DNA from one chromosome to another i.e. Translocations & Insertions (Inversion too)
- No loss or gain of genetic material

4

Unbalanced Alteration

- Deletions & Duplications
- BOTH change the amount of DNA in the cell
- BOTH have an impact on the carrier
- Deletions are typically more severe

5

Cri-Du-Chat Syndrome

- Caused by a deletion on chromosome 5 (del5p)
- Face symptoms: Microcephaly, Hypertelorism, Micrognathia
- Brain/CNS: Severe mental retardation
- Cardiovascular: Heart Defects
- Other: "Cat-like cry"

6

Di George Syndrome

- Caused by a microdeletion on chromosome 22
- Autosomal dominant inheritance
- Symptoms: heart defects, immunodeficiency, hypoparathyoridism, mental retardation, cleft palate

7

Why do balanced chromosomal alterations cause infertility in otherwise healthy carriers?

- Unbalanced alterations affect the carrier b/c the gene dosage is changed
- Balanced typically DO NOT
- However, balanced alterations greatly reduce the success of meiosis & subsequent pregnancy

8

Philadelphia Chromosome

- Translocation between chromosomes 9 & 22
- Moves ABL tyrosine kinase gene from chromosome 9 next to the BCR region of chromosome 22
- BCR/ABL chimeric protein is the dominant oncogene in CML

9

Robertsonian Translocation

- Long & short arms of a chromosome are exchanged
- Result is one chromosome w/ both long arms & one chromosome w/ both short arms
- Most common with chromosomes 13 & 14 in humans

10

CML

- Chronic Myelogenous Leukemia
- BCR/ABL protein from translocation of chromosome 9 & 22

11

Inversion

- Chromosome suffers two breaks
- Broken-off fragment is reinserted in the wrong orientation/ upside-down
- Balanced alteration
- Often asymptomatic in carrier BUT problems arise in offspring

12

Karyotype

- Studying the chromosome composition under light microscopy
- From cultured living cells of the patient that are arrested in metaphase

13

Turner Syndrome Karyotype

- Monosomy of X (45,X)
- Patient is female

14

Klinefelter Karyotype

- 47, XXY
- Patient is male

15

Down Syndrome Karyotype

- Trisomy 21

16

Edwards Karyotype

- Trisomy 18

17

Patau Karyotype

- Trisomy 13

18

Aneuploid

Uneven number of chromosomes

19

What are the two sources of structural chromosomal aberrations?

1) Healing of ds-DNA breaks with nonhomologous end joining
2) Unbalanced recombination

20

Hypertelorism

Increased distance between two organs, typically the eyes

21

Micrognathia

A condition where the jaw is undersized

22

Insertion

Moves the DNA fragment into the middle of another chromosome

23

Translocation

Moves the DNA fragment to the end of the another chromosome

24

How do you make a Karyotype?

1) Obtain live cell culture
2) Arrest in metaphase
3) Lyse in hypotonic solution
4) Fix to microscope slide
5) Stain

25

What are the indications for a karyotype?

- Problems of early growth/development
- Stillbirth/ Neonatal death
- Fertility problems
- Pregnancy with advanced maternal age (>35)