Lecture 2b - Numerical Chromsome Aberrations

Question 1

Euploidy

Answer 1

-normal number of structurally normal chrs

euploid females have 46 chrs - 44 autosomes, 2 X

Question 2

Aneuploidy

Answer 2

• less or more than normal diploid number

- recognized as small deviation -> major deviations are not compatible with lfie

Question 3

Most common Aneuploidies

Answer 3

1) Monosomy:
- lack of one pair of chromosomes
- usually lethal (X monosomy quite common)

2) Trisomy:
- eg/ Downsyndrome (Trisomy 21)
- additional copy of a chromosome
- incidence of trisomy incr withmaternal age

Question 4

Pathways which generate Aneuploidy

Answer 4

1) Mitotic Checkpoint defect
2) Cohesion defect
3) Merotelic attachment
4) Multipolar mitotic division

Question 5

Common cause of Trisomy

Answer 5

Meiotic Non-Disjunction
1 = All zygotes are abnormal (2x monosomic, 2x trisomic)
2= 50% Euploid, 25% Monosomic, 25% trisomic

Question 6

Down syndrome

Answer 6

• 95% of cases = Trisomy 21 (47 XY + 21)-> cause meiotic non-disjnxn
• Parents have normal Karyotype
• Maternal age -> indic meiotic non dij in Ovum (95% of cases extra Chrs from mother)
• Paternal Age - no corell (but can in rar cases come from)

Question 7

Other causes of Downsyndrome

Answer 7

-4% - T(14,12) Robertsonian Trnaslocation -> long arm of Chrs not whole chrs

-1% MOSAICS:
> hve 46 and 47 in cells -> MITOTIC NON-Disjunction in early embryogenesis

Question 8

Other Trisomy

Answer 8

1) PATAU Syndrome: 13

2) EDWARDS SYNDROME: 18

Question 9

Triploidy

Answer 9

• three of every chromosomes
• 69 chrs (3 haploid sets of 23)
• rare and such individuals very abnormal –> survivors are mosaic (some cells 46 some 69)

Question 10

Cause of Triploidy

Answer 10

• Fertilization by 2 sperms

- Fertilization by Diploid Sperm/Ovum

Question 11

Sex Chromosome Abnormalities

Answer 11

• Xo = TUrners (45, X0)
• XXY: Klienfelter
• XXX: Super WOman
• XYY Jacobs (low inteligence - tall - criminals)

Question 12

Uni-parental Disomy (UPD)

Answer 12

-both chrs in a zygote come from a single parent

Question 13

Trisomic Rescue (Uniparental rescue)

Answer 13

• Fertilized egg = trisomy due non-disjunction

- a copy is lost from trisomy to form normal number –> if remaining copies from same parent = UPD

Question 14

Somatic Duplication (Monosomic Rescue)

Answer 14

• fertilized ovum has 1 chrs from normal parent + no chrom from other (NULLISOMY)
• monosomy overcome by -> somatic Duplication –> UPD

Question 15

UPD clinically

Answer 15

• Prader-willi + Angelmann
• involve 15q

other defects:
> Imprinting defects
> Microdeletion (15q)

Question 16

Mosaic

Answer 16

• individual with more than 1 cytogenetically distinct populations of cells with same origin
• usually people with turner syndrome -> are Mosaics

Question 17

X-chromosome Mosaicism

Answer 17

• X-inactivation occurs randomly

- half cells have paternal/maternal X inactive

Question 18

Chimera

Answer 18

-ptnt has more than one cytogenetically distinct population of cells with different origin

Question 19

Example of Chimera

Answer 19

-Pregnancy leads to Microchimerism:

> presence of small number of cells that originate from another individual