Chromosomal Aberrations

Question 1

Give the frequency of chromosomal aberrations at conception and birth.

Answer 1

Conception: 0.5%

Live birth: 0.2% (structural < numerical)

Question 2

Numerical aberrations

Answer 2

Nondisjunction event in meiosis leading to gametes with missing or surplus chromosomes

Question 3

Numerical aberrations of the autosomes

Answer 3

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

Question 4

Numerical aberrations of the sex chromosomes

Answer 4

• -Monosomy of X (Turner) – female
• -XXY (Klinefelter) – male
• -XYY (male) and XXX (female) are very subtle

Question 5

2 main sources for mutations affecting chromosome structure

Answer 5

1. Aberrant healing of DNA strand breaks (such as by nonhomologous end-joining)
2. Unbalanced recombination (causes deletions and duplications)

Question 6

Balanced alterations

Answer 6

Do not typically change the amount of genetic material; include translocations and insertions

Question 7

Unbalanced alterations

Answer 7

Change the amount of DNA i the cell; include deletions (more severe) and duplications; cause of cri-du-chat and Di George syndromes

Question 8

Cri-du-chat syndrome

Answer 8

Prevalence: 1/25,000 (very rare)
Chromosomal defect: deletion on chromosome 5 (del5p)
Symptoms: microcephaly, hypertelorism, micrognathia, severe mental retardation, heart defects, specific cry

Question 9

Di George syndrome

Answer 9

Prevalence: 1/4000 (relatively rare)
Chromosomal defect: microdeletion on chromosome 22 (usually new)
Symptoms: congenital heart defect, immunodeficiency, hypoparathyroidism, mental retardation, cleft palate

Question 10

Why do balanced chromosomal alterations often cause infertility of otherwise healthy carriers?

Answer 10

Carriers of balanced alterations are typically unaware of their condition because they have all of their chromosomes (just in the wrong places), but meiosis produces unbalanced gametes that form inviable zygotes due to deletions and duplications that occur when recombined

Question 11

Inheritance of balanced alterations

Answer 11

Caused by translocations (exchange of long and short arms of chromosomes) or inversions (chromosome inserts broken fragment in the wrong orientation)

Question 12

Philadelphia chromosome

Answer 12

Translocation between chromosomes 9 and 22 causing chimeric Bcr/Acl protein to function as dominant oncogene and causing chronic myelogenous leukemia

Question 13

Philadelphia chromosome’s effect on health of carrier

Answer 13

Causes chronic myelogenous leukemia due to overactive receptor (creates oncogene)

Question 14

Robertsonian translocation

Answer 14

A type of translocation in which the long and short arms of two chromosomes are exchanged; two aberrant chrosomes are created (one with two long arms, one with two shorts arms); shorter typically gets lost

Question 15

Robertsonian translocation’s effect on health of carrier

Answer 15

Typically involves 13q and 14q (1/1,300) and causes no health problems

Question 16

Meiotic problems arising from inversion

Answer 16

Chromosome with inverted region formed inversion loop during meiosis to pair with normal homolog; if crossover occurs in inverted region, chromosomal material will be translocated and gametes will be inviable (see p. 542)

Question 17

Uses of karyotyping

Answer 17

Used to detect chromosomal anormalities under following circumstances:

1. Problems with early growth/development
2. Stillbirth/neonatal death
3. Fertility problems
4. Pregnancy with advanced maternal age (35+)
5. Sometimes cancer or family history of chromosomal aberrations

Question 18

Procedure of karyotyping

Answer 18

• -Culture live cells from patient (typically lymphocytes)
• -Arrest cells in metaphase
• -Lyse cells in hypotonic solution
• -Fix and spread chromosomes on microscope slides
• -Stain chromosomes

Question 19

Characteristics of pedigree of family with chromosomal aberration

Answer 19

• -Grandparents unaffected
• -Parents include some affected, some affected with early deaths/miscarries, and some unaffected
• -All children of parents are affected

Question 20

Abnormal chromosome statistics

Answer 20

• -Account for 800/10,000 live births

- -94% are spontaneously aborted

Question 21

Trisomy 21 statistics

Answer 21

10/45 live births (22%)

Question 22

Sex chromosome triploidy statistics

Answer 22

15/19 live births (79%)

Question 23

Unbalanced rearrangement statistics

Answer 23

27/10,000 pregnancies

Question 24

Balanced rearrangement statistics

Answer 24

• -19/10,000 pregnancies

- -16/19 live births (84%)