Structural Chromosomal Abnormalities Flashcards
Three types of balanced structural abnormalities
Inversions
Reciprocal translocations
Robertsonian translocations
Name and briefly describe the two primary types of structural abnormalities.
Balanced: normal complement of chromosomal material
Unbalanced: abnormal chromosomal content
Four types of unbalanced structural abnormalities
Deletions
Duplications
Isochromosomes
Marker (ring) chromosomes
What sort of DNA damage is required for all types of structural rearrangements?
Double strand breaks
Define pericentric inversion
An inversion of a section of the chromosome which spans the centromere.
e.g. 46,XX,inv(5)(p12q14)
Note p and q present in the notation
Consequences of gamete formation in carriers of pericentric inversions
Normal, balanced and unbalanced chromosomes may all result.
All are monocentric.
Define paracentric inversions
An inversion of a section of the chromosome that does not span the centromere.
e.g. 46,XY,inv(3)(q22q24)
Note only q (or p) present in notation
Consequences in gamete formation for carriers of paracentric inversions.
Normal, balanced and unbalanced chromosomes may all result.
Produces dicentric and acentric chromosomes, causing cell cycle arrest or apoptosis.
Paracentric inversions are more deleterious than pericentric.
What unusual feature do peri and para centric inversions cause during meiosis?
Form chromosomal “loops” to align gene loci with homologous chromosomes. Recombinations in the looped regions lead to duplications and deletions of genes/centromeres.
Define reciprocal translocation
The exchange of chromosomal regions between two non-homologous chromosomes. Also called derivatized (der).
Results in no loss of genetic information, carriers likely have normal phenotypes.
What is the significance of chronic myelogenous leukemia in regards to chromosomal abnormalities?
It is one known occurrence of reciprocal translocation that causes disease in the carriers.
46,XX,t(9;22)(q34;q11.2)
Define Robertsonian Translocation
The fusion of two acrocentric chromosomes at the centromere.
e.g. 45,XX,der(14;21)(q10;q10)
How can a Robertsonian translocation lead to trisomy?
Fusion of two chromosomes (i.e. 14;21) leads to a single chromosome which may independently assort into a daughter cell along with the unfused homologue. (Trivalent segregation)
What features must a chromosome possess to be stably transmissible through cell divisions?
Centromere
Telomeres
At least one replication origin
Define “isochromosome”.
A chromosome in which one arm is missing and the other arm is duplicated in a mirror like fashion.
What does a carrier of isochromosome 21 (21q21q) cause?
A carrier may have normal phenotype, but 100% of offspring will have trisomy 21 (Down syndrome).
Name five mechanisms that can lead to Down syndrome.
Meiosis I non-disjunction (95% of cases) 47,XY,+21
Robertsonian translocation (4% of cases) 46,XX,der(14;21)+21
Isochromosome 21 46,XY,i(21)+21
Mosaic Down syndrome (non-disjunction in early zygotic division)
Partial Down syndrome (partial duplication of 21 genes)
Define non-allelic homologous recombination (NAHR)
If alleles are not properly aligned during homologous recombination chromosomes will result with duplicated sequences on one and deleted sequences on the other. Unbalanced chromosomal rearrangements.
How are Charcot-Marie-Tooth disease and Hereditary neuropathy to liability to pressure palsies related?
CMT disease is caused by the duplication (producing 3 copies) of the gene for peripheral myelinated protein-22, while HNPP is caused by the deletion (leaving 1 copy) of the same gene. 17p11.2
How are Velocardialfacial syndrome and DiGeorge syndrome related?
Both are contiguous gene syndromes resulting from the a deletion at the same locus. (del 22q11)
What percentage of miscarriages are due to chromosomal abnormalities?
50%
What is the impact of repetitive patterns in DNA on chromosome structural integrity?
Repetitive patterns tend to cause deletions.
What is the impact of repetitive patterns in DNA on chromosome structural integrity?
Repetitive patterns tend to cause deletions.
What is contiguous gene syndrome?
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