WK2 - Cytogenetics Part I & II Flashcards
What is a chromosomal abnormality?
abnormality in:
- number of chromosomes
- deletion or duplication of part of a chromosome
- rearrangement between two chromosomes resulting in imbalance - ie. an unbalanced rearrangement
What does a centromere do?
attaches the DNA molecule to the mitotic spindle
What is a telomere?
DNA sequence of repeats at each end of the chromosome
What is euchromatin?
- relatively high frequency of coding regions or genes
- bands define alternating partitions of euchromatin
- transcriptionally active
What is heterochromatin?
- area devoid of genes or containing inactive genes; ie. transcriptionaly inactive areas
- these areas tend to remain highly condensed throughout cell cycle
- contains highly repetitive elements
- demonstrate with C banding or fluorescent staining
What is constitutive heterochromatin? And where are they found in chromosomes?
- always in the inactive state
- composed largely of certain repetitive DNA sequences
- found in centromeres, Yq, p arms of acrocentric chromosomes
What is facultative heterochromatin? Give an example.
- can be genetically active or inactive
- specialized case is mammalian X which may undergo chromosome inactivation
What is X inactivation?
- most genes on the X chromosome do not have a counterpart on the Y chromosome
- needs to be a mechanism for dosage compensation; ie. turn off the genes that have more than 1 copy
- early in embryogenesis, one X chromosome in each cell randomly inactivates (some genes stay active)
- the initial inactivation persists in all the subsequent mitotic divisions of that original cell
- each normal female is then a mosaic for the active X chromosome
What is a Barr body?
- the inactivated X chromosome is seen in the cell as a Barr body
What type of banding are there?
- G (Giemsa) banding
- R (reverse) banding
- C banding (highlights centromere, long arm, etc.)
What is the order you get the least chromosome band to the most in the following harvesting time:
- routine preparation
- amniocentesis
- prometaphase
- amniocentesis - 400-500 bands (can miss things because don’t get too much info)
- routine preparation - 550 bands
- prometaphase - 750 to 800 bands ( generally used to look at detail)
Define fluorescent in-situ hybridization (FISH), when it hybridize and what it help look for.
- specific single-stranded DNA probes labelled to fluoresce
- can be hybridized to metaphase chromosomes or to interphase nuclei
- can paint or look for specific deletions (but cannot differentiate whether a mutation is a consequence of nondisjunction or translocation)
What is microarray comparative genomic hybridization and what does it look for?
- compares normal to patient DNA analyzing multiple area on the chromosome
- look for imbalances such as duplicates or deletions
What is copy number variants (CNVs)?
- fewer or more than the expected number of copies of a genomic region
- the molecular equivalent of aneuploidy
- may contain few to many genes whose function may or may not be known
- benign CNVs are frequent
- most benign CNVs are inherited polymorphisms
What is polyploidy?
multiples of haploid set of chromosomes
What is triploidy and what does the phenotype look like?
3 sets of chromosomes - almost never seen in live births
What is aneuploidy?
- fewer or more chromosomes than the exact multiple of the haploid set
- this includes trisomy and monosomy
- trisomies are the most frequent; monosomies (other than monosomy X) are often lethal
What is nondisjunction and when can it happen during cell division?
- failure of a pair of chromosomes to disjoin in the normal way
- may happen in MI or MII of meiosis or in mitosis
What is the consequence of MI error?
- gamete contains 24 chromosomes instead of 23
- contains both pat and mat members of the pair
What is the consequence of MII error?
- gamete contains 24 chromosomes instead of 23
- contains both copies of either mat or pat chromosomes
At what maternal age does the risk of aneuploidy start to increase?
32 year old
What is monosomy?
- all of a chromosome missing
- lethal unless 45, X
- can be the consequence of anaphase lag, less often nondisjunction
- NOT associated with advanced maternal age
What is Turner syndrome?
- about half of Turner syndrome is 45, X
- others have one normal X and one abnormal X (with deletions or other rearrangements)
What is an isochromosome?
- choromosome with one arm missing, one arm duplicated; sister chromatid exchange likely
- individual is partially monosomic; partially trisomic
- most commonly seen as subtype of Turner syndrome when X involved
- karyotype: 46. X.i(X)(q10)
What can result in deletion?
- chromosome breakage with loss of segment
- unequal crossing over
- abnormal segregation of translocation
What are micro deletion syndromes? What methods can be used to detect them?
- recognizable syndrome secondary to a specific microdeletion (not seen in metaphase chromosomes)
- sometimes seen in high resolution banding, with FISH probes or Array CGH
What are inversions? What are the two types?
- single chromosome undergoes two breaks
- reconstituted with segment between breaks inverted
- paracentric - beside the centromere (2 breaks occur in one arm)
- pericentric - around the centromere (2 breaks occur in both arms)
What are translocations?
- exchange of 2 chromosomal segments between two usually non-homologous chromosomes
Define reciprocal translocation.
- reciprocal exchange of the broken off segments between two chromosomes
- the derivative chromsomes are the products of the exchange
Define Robertsonian translocation.
Fusion of two acrocentric chromosomes near the centromere
What are acrocentric chromosomes and which chromosomes are they?
- chromosomes 13, 14, 15, 21 and 22
- satellited short arms which carry genes for rRNA
What are the age related risk for trisomy 13, 18 or 21 in any pregnancy?
- 1 to 2 %
- or age related risk if over 35 years old
What are the age related risk for trisomy 21 in a Robertsonian t(14;21) female carrier?
10%
What are the age related risk for trisomy 21 in a Robertsonian t(14;21) male carrier?
2%
What are the age related risk for trisomy 21 in a t(21;21) male carrier?
100%
What are the age related risk for trisomy 21 in a t(21;21) female carrier?
100%
What are the risk for trisomy in a carrier with reciprocal translocations?
30 to 40 %
What are the indications for Karyotyping?
- Problems of early growth and development – failure to thrive, development delay, multiple malformations, short stature
- Stillbirth and Neonatal death
- Infertility or recurrent spontaneous abortions
- Family history of chromosome problem
- Tumors (the tumor itself)
- Advanced maternal age (the pregnancy)
What are the risk for trisomy in a carrier with inversions?
up to 5 to 10 %
