Structural Chromosomal Aberrations

Question 1

structural aberrations occur due to ?
two types

Answer 1

Results from abnormalities from chromosome breakage w subsequent reunion in diff configuration=balanced or imbalanced

Balanced: complete, w no loss of genetic material
- Usually harmless, exception: where one of the breakpoints damages an important functional gene
- Carriers of balanced rearrangements at risk of making children w unbalanced chromosomal complement
- translocation, inversion and insertion

Unbalanced: incomplete amount of chromosomal material w serious clinical effects
- deletion+duplication, which compose isochromosome, ring chromosome, dicentric chromosome. marker chromosome

Question 2

translocations

Answer 2

Translocations- Transfer of genetic mat from one chromosome to another (2 types)

1. Reciprocal translocation breakage from at least two fragments from at least two chromosomes (non homo) w segments exchanged to form= 2 new derivative chromosomes

Number of chromosomes the same= 46
Common between 11 and 22 (switch) and others
Can be identified by detailed chromosomal banding studies=FISH
Overall incidence is 1:500

2. Robertsonian translocation a type of reciprocal translocation where breakage close to (or at) the centromeres of two acrocentric chromosomes (13-15, 21-22).

Total chromosome number reduces to 45
Results in fusion of long arms otherwise fusion called= centric fusion.
Short arms = lost fragments w no clinical relevance (only have genes for rRNA
Overall incidence is 1:1000

Question 3

segregation at meiosis of translocation chromosomes

Answer 3

Balanced reciprocal translocation generate significantly chromosome imbalance leading to pregnancy loss or birth of infant w abnormalities

• problems arise bc chromosomes in translocation cannot pair normally to form bivalents; instead form clusters=pachytene quadrivalent

2:2 segregation
Alternate segregation: gametes w complete genetic info
Adjacent chromosomes segregate together=unbalanced haploid

• Normal 11 (A)+ derivative 22 (C)= trisomy for distal long arm of 11 and monosomy for distal long arm of 22

3:1= three chromosomes segregate tone gamete resulting in tertiary trisomic

Question 4

insertion

Answer 4

Segment of one chromosome inserts to another. If inserted material has moved from somewhere in another chromosome, karyotype is balanced (translocation). Otherwise, insertion causes unbalanced chromosome

Carrier of balanced deletions-insertions have 50% of making unbalanced gametes bc random chromosome segregation causes 50% change of gametes inheriting deletion or insertion but not both

Question 5

inversion

Answer 5

Two break arrangement involving a single chromosome which a segment is inverted (reversed in position). If the inversion: (chromosome 9? As polymorphism)
- involves centromere= pericentric reversion.
- Involves one arm= paracentric inversion

Inversion=balanced (only cause problem if disrupt important gene).
- Unbalanced gametes produced when crossover is within inversion segment during M1. An inversion loop forms as chromosome attempt to maintain homologous pairing at synapsis
: Forms two recombinant chromosomes : one is a duplication of a distal non-inverted seg and one the opposite

Question 6

dicentric chromosomes

Answer 6

part of unbalanced:
Has two centromeres, formed through fusion of two chromosomes segments (that have centromere)
- The parts that don’t are discarded

Also Formed by: translocation or Robertsonian translocation specifically

Question 7

Deletion

Answer 7

Partial monosomy : Involves loss of chromosome =monosomy for that segment of chromosome

Very large deletion=not survive
More than 2%=lethal outcome

Divided in 3 groups:

1. interstitial- within the inside part of chromosome
   Cri Du Chat (4p) and Wolf-Hirschhorn (5p)
2. terminal towards the end
3. microdeletions (more recently found)
   Prader Willi (overeating+hypogenitailism) and Angelman syndromes (paroxynms, epipeltic regions,apoxia)
   identified w help of FISH

Question 8

Cri Du Chat

Answer 8

Name from Cat cry or affected neonates= development of larynx

Both conditions (also Wolf-Hirschhorn) rare 1:50,000

Severe mental retardation, microcephaly, motor disorders, growth retardation, congenital heart disease

Question 9

Wolf-Hirschhorn

Answer 9

Retarded, cleft lip+ palate microcephaly, cardiac malformations and hypospadias (opening of urethra on the underside of penis instead of at tip

Question 10

ring chromosome

Answer 10

When break occurs on each arm leaving two “sticky ends” on central position that reunite as ring.
- When two distal fragments are lost= serious effects

Unstable in mitosis so only found in a proportion of cells
Usually cells are monosomic due to absence of ring chromosome

Question 11

isochromosome

Answer 11

Show loss of one arm w duplication w other
- Instead of p and q: (p+ p) and (q + q)

due to Centromere divided transversely rather than longitudinally

Most common is two long arms of X chromosome: 15% of turner syndrome cases