Lecture 2a - Structural Chromosome Aberrations

Question 1

Cytogenetics

Answer 1

• study of chromosome number/structure/function

- allows us to study chromosome inheritance (but not monogenic)

Question 2

Deletion

Answer 2

• when chromosome breaks a a piece is lost -> results in Partial Monosomy for that chromosome
• either INTRAGENIC (affect sequence w/i gene)
• or MUTLIGENIC (affecting many genes)

Question 3

types of Deletion

Answer 3

1) Terminal Deletion:
-Cri Du Chat (5p-)
>microencephaly, moon face, retard, cat like cry

2) Interstitial Deletion:
-Williams Sydnrome (7q-)
> deletion of Elastin gene

Question 4

Uneven Crossing over

Answer 4

-leads to Duplication + Deletion

Question 5

Insertion

Answer 5

• ranges from Microsatellites (DNA Pol slipping) to Section of Chromosomes being inserted into others
• Uneven crossing over most common cause

Question 6

Types of Insertion

Answer 6

1) N-Region Addition:
- Non coded NT are added during crossing over by Terminal Deoxynucleotidyl transferase

2) P-Region Addition:
- addition of plaindromic NT

Question 7

Inversion

Answer 7

• piece breaks -> fragment is inverted and rejoined

- unless breakpoint disrupts imp gene -> phenotype may be normal

Question 8

Types of Inversion

Answer 8

1) Pericentric Inversion:
- centromere is involved
- cross over produces monocentric Chrs

2) Paracentric Inversion:
- Centromere is not involved
- issue arises in Meiosis

Question 9

Problem in Meiosis with paracentric Inversion

Answer 9

-chrs line up –> chrs most form loop region where the other chrs has inversion –> loop no problem –> unless there is cross over then there may be physical linkage –> subsequent Deletion -> Dicentric + Acentricchrs

Question 10

Translocation

Answer 10

-chrs break and fragment rejoins other chrs
-no loss of genetic material but breakpoint can:
> disrupt critical gene
> fusion gene creation
-Reduce FERTILITY

Question 11

Types of Translocation

Answer 11

1) Reciprocal Translocation
2) Robertsonian (Centric Fusion)
3) Insertional

Question 12

Reciprocal Translocation

Answer 12

• 2 Non-Homologous chrs break and exchange fragments
• balanced complement of Chrs + normal Phenotype
• Subfertility -> due to problem in pairing/segregation in meiosis
• trnsl chrs + homologues form -> Quadrivalents
• formation of unbalanced gamates and offspring with unbalanced genome -> lethal

Question 13

Example of Reciprocal Translocation

Answer 13

Ph Chrs

• T(9:22) (q34:q11)
• ABL (9) + BCR (22) -> incr tyr kinase –> CML + ALL

Question 14

Burkitt’s Lymphoma

Answer 14

T(8;14) (q21;32)

• reciprocal translocation
• overexpression of C-MYC

Question 15

Robertsonian Translocation

Answer 15

• takes place btween ACROCENTRIC chrs
• karyotype -> one less than normal diploid numeber of chrs
• mild reduction in fertility (less severe than recirpocal)

Question 16

Mechanism of Robertsonian Translocation

Answer 16

-centromere of 2 non-homologous acrocentric chrs fuse

Question 17

Example of Robertsonian Translocation

Answer 17

Down Syndrome

• Centric fusion in parents yields 4% of Downsyndrome cases
• usually: T(14;21)

Question 18

Ring Chromosomes

Answer 18

• Breakremoves both telemores –> repaired by sealing ends together forming a ring chromosome
• Deleted genes at both ends of the chromosome (symptoms depend on extent of deletion)
• Mitotically stable)

Question 19

Example of diseases associated with Ring chromsomes

Answer 19

• Epilepsy- 20
• ment retard - 14
• turner - x

Question 20

Isochromsome

Answer 20

• chrs split in “wrong way” during Mitosis or Meiosis II
• both long arms go one pole/both short arms go one pole
• isochrs are duplicated for genes in retained arm –> poor prognosis

Question 21

Which Isochromosome does not have poor prognosis

Answer 21

iXq (isochromosome of long arm of the x)