structural abnormalities

Question 1

Chromosomal rearrangements require

Answer 1

two DNA double strand breaks (DSBs) and can be induced by a variety of DNA damaging agents

Question 2

Structural rearrangements can be

Answer 2

inherited and can also lead to further rearrangement during meiosis.

Question 3

two types of structural rearrangements

Answer 3

1. balanced

2. unbalanced

Question 4

Balanced:

Answer 4

Individuals with balanced rearrangements have normal complements of chromosomal material, meaning there is no loss of genetic material. However, these rearrangements have varying stabilities during meiosis and mitosis.

Question 5

examples of balanced

Answer 5

1. paracentric inversion (exclude centromere)
2. pericentric inversion (include centromere)
3. reciprocal translocation
4. robertsonian translocation

Question 6

Chromosomes with inversions can have normal genetic complements, and therefore may produce no phenotypes in carriers of the rearrangement. However,

Answer 6

inversions may generate abnormal gametes during meiosis

Question 7

During the pairing of homologs in meiosis, a loop is introduced in the homolog containing the

Answer 7

the inversion, which maximizes the association of homologous sequences

Question 8

If a crossover occurs within the inverted region of a paracentric inversion,

Answer 8

both dicentric (two centromeres) chromosomes and acentric chromosomes can be generated, leading to chromosome breakage or loss.

Question 9

In pericentric inversions,

Answer 9

crossovers within the inverted region can produce duplications and deletions.

Question 10

46,XX,inv(9)(p13q13),

Answer 10

a female with an inversion of the sequences between band 13 on the short arm and band 13 on the long arm of chromosome 9.

Question 11

Reciprocal translocation: results from

Answer 11

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

Question 12

As with inversions, carriers of reciprocal translocations have an increased _______; _______are often found in couples that have had two or more spontaneous abortions, and also in infertile males. When the chromosomes of a carrier of a balanced reciprocal translocation pair at meiosis, a ______ is formed.

Answer 12

risk of producing unbalanced gametes

balanced translocations

quadrivalent figure

Question 13

At anaphase, these chromosomes are segregated in one of three ways,

Answer 13

1. alternate,
2. adjacent-1,
3. adjacent-2 segregation.

Question 14

Alternate segregation,

Answer 14

the most frequent meiotic segregation pattern, produces gametes that have either the normal chromosome complement or two reciprocal translocation chromosomes, both of which are balanced with respect to chromosome complement

Question 15

However, adjacent-1 and –2 segregation mechanisms lead to

Answer 15

unbalanced gametes.
The risks to offspring depend on the specific translocation in question, but the general empirical risk is 5-10% lethality

Question 16

46,XX,t(9;22)(q34;q11.2),

Answer 16

a female with a translocation involving chromosomes 9 and 22, which has been shown to cause chronic myelogenous leukemia.

Question 17

Robertsonian translocation:

Answer 17

the fusion of two acrocentric chromosomes within their centromeric regions, resulting in the loss of both short arms (containing rDNA repeats).

Question 18

Robertsonian translocations result in the

Answer 18

reduction of chromosome number, but are considered balanced rearrangements because the loss of some rDNA repeats is not deleterious.

Question 19

Carriers of Robertsonian translocations are

Answer 19

phenotypically normal, but these rearrangements may lead to unbalanced karyotypes for their offspring, resulting in monosomies and trisomies.

Question 20

Robertsonian translocations involves

Answer 20

chromosome 14 are by far the most frequent, constituting ~85% of all Robertsonian translocations. Common examples include a translocation involving chromosomes 14 and 21, karyotype

Question 21

Unbalanced:

Answer 21

the chromosome set has additional or missing material. Phenotypes of these individuals are likely to be abnormal. Duplication of genetic material in gametes can lead to partial trisomy after fertilization with a normal gamete, while deletions lead to partial monosomy

Question 22

examples of unbalanced:

Answer 22

1. deletion
   a. terminal deletion
   b. interstitial deletion
2. duplication
3. ring chromosome
4. isochromosome

Question 23

Deletion:

Answer 23

loss of genetic information that can arise by simple chromosome breakage and rejoining, unequal crossing over between misaligned homologous chromosomes or sister chromatids, or by abnormal segregation of a balanced translocation or inversion.

Question 24

The clinical consequences of deletions reflect

Answer 24

haploinsufficiency, where the contribution of the remaining normal allele is unable to prevent disease

Question 25

the severity of the phenotype of deletion depends on

Answer 25

the size of the deletion and the number of genes affected.

Question 26

Duplication:

Answer 26

gain of genetic information, which is generally less harmful than deletion, but can lead to abnormalities (i.e. partial trisomy 21).
Duplications can also result from unequal crossing-over or by abnormal segregation during meiosis in a carrier of a translocation or inversion

Question 27

Ring Chromosome:

Answer 27

a chromosome fragment that circularizes and acquires kinetochore activity for stable transmission to daughter cells (also called a marker chromosome). Sample karyotype: 46,XY,r(13)(p11q34), which is a male with a supernumary ring chromosome derived from the p11 to q34 region of chromosome 13

Question 28

Isochromosome:

Answer 28

a chromosome in which one arm is missing and the other duplicated in a mirror-image fashion, possibly occurring through an exchange involving one arm of a chromosome and its homolog at the proximal edge of the arm, adjacent to the centromere.

Question 29

most common isochromsome is

Answer 29

on long arm of X chrome

but can also occur on autosomes

Question 30

A small percentage of Down syndrome patients

Answer 30

have the 21q21q isochromosome e.g. 46,XX, i(21)(21q21q).

Question 31

Contiguous gene syndromes

Answer 31

are defined as abnormal phenotypes caused by over-expression or loss (haploinsufficiency) of neighboring genes.

Question 32

Angelman syndrome

clinical

Answer 32

seizures

intellectual disabilities

Question 33

Prader-Willi syndrome

clinical

Answer 33

hypotonia,
hypopigmentation
hypogenitalism,
obesity

Question 34

DiGeorge syndrome clinical

Answer 34

absent or hypoplastic thymus and
parathyroids, 
congenital heart  disease
Velo-Cardio-Facial syndrome
cleft palate, 
lateral nasal buildup
cardiac septal defects

Question 35

digeorge chrom

Answer 35

del(22q11.2)

Question 36

prader willi chrom

Answer 36

del(15q11-q13) (paternal)

Question 37

angelman chrom

Answer 37

del(15q11-q13) (maternal)

Question 38

examples of contiguous

Answer 38

1. velovardiafacial

2. digeorge

Question 39

velocardialfacial chrom

Answer 39

del 22q11