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Flashcards in Chromosomal Abnormalities I Deck (23)
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Describe the normal human chromosome number 

46 Chromosomes  

22 pairs and 1 pair of sex Chromosomes 


What is a karyotype 

Is the chromosomal constitution of the cell nucleus (photomicrograph of the chromosomes arranged)

  • G-bandings allows us to look at the karyotype 
  • Stain chromosomes with Gisema stain in METAPHASE 
    • - Euchromatin = GC-rich, loosely packed, genes active 
    • - Heterochromatin = AT-rich, tightly packed, genes inactive 
    • Stain differently allowing us to see the banding pattern 

Line up based on: 

  • Size 
  • Banding 
  • Centromere position 



Describe the normal structure of chromosomes

  • Chromosomes will require a centromere and telomere to survive 
  • Chromosomes are called p (petite) and q arm 
    • P =short arm, q = long arm 
  • Chromosomes will usually exist as chromatin 
  • DNA double helix bound to histones 
  • Octamer of histones form nucleosome 
  • Chromosomes will exist as homologous parts and have a maternal and paternal copy 
    • Homologs will have the same genes on them however they may have different allelic forms 


Why do we visuallise chromosomes at the metaphase stage? 

Because they are most condensed 


What are metacentric, submetacentric and acrocentric chromsomes? 

Metacentric (p and q same length) 

  • 1-3, 16-18 

Submetacentric (p arm shorter than q) 

  • 4-12, 19-20, X

Acrocentric (long q, small p) 

  • p contains no unique DNA 
    • genes on satellite arms code for same set of rRNA molecules) 
  • 13-15, 21-22, Y 


What type of chromosomes are the X and Y chromosome? 

X chromosome = Submetacentric 

Y chromosome = Acrocentric 


What are the two types of chromosomal abnormalities which can occur? 

How can they be detected? 

  1. Numerical - can detect through karyotyping, FISH, QF-PCR, NGS
  2. Structural - detect through karyotyping and FISH 


Define Haploid, Diploid and Polyploid 

    • one set of chromosomes (n=23) as in a normal gamete.
    • cell contains two sets of chromosomes (2n=46; normal in human)
    • multiple of the haploid number (e.g. 4n=92)


Define Aneuploidy

Chromosome number that is not an exact multiple of haploid number due to extra or missing chromosomes e.g a cell having 45 or 47 chromosomes 


Define three classic autosomal aneuploidies

  • Trisomy 13 (Patau Syndrome) 
  • Trisomy 18 (Edward's Syndrome) 
  • Trisomy 21 (Down's Syndrome) 


List some examples of aneuploid numerical abnormalities 

  • Trisomy - three chromosomes in a cell (2n+1) 
  • Monosomy - one chromosome in a cell 
  • Mosaicism - two or more populations of cells with different genotypes in one individual 
    • E.g turner syndrome, some cells will be XO and some will be XX 


Via what mechanism does aneuploidy arise? 

Aneuploidy arises via NON-DISJUNCTION 


This is where the homologues will not pull apart and both go onto the same cell 

In meiosis I = Two diploid cells 

In meiosis II = 2 haploid cell and 1 diploid cell 


What are the two mechanisms of mosaicism? 

  • Post-zygotic nondisjunction/mitotic non-disjunction 
    • All cells start as 2n and go to a mixture of 2n and 2n+1
  • Anaphase lag 
    • Trisomic rescue = all cells start as 2n+1 then go to a mxture of 2n+1 and 2n 


Describe mitotic/ post-zygotic non-disjunction 

  • Occurs as a result of the chromatids which are not seperating properly in mitosis resulting in a mixed population of cells with respect to the genomic material 
  • Some cells are trisomic and other cells are disomic 


Describe anaphase lag? 

  • In the process of anaphase there may be a delay/pause in the pulling part of one of the chromosomes
  • A membrane will form around this individual chromosome which will essentially be rescued from trisomy due to the delay (note: its not a repair process) this will then be degraded
  • This allows for a mixed population of cells where some are disomic and other cells are trisomic
  • This essentially rescues some of the cells from being trisomic (hence trisomic rescue)


What is the clinical relevance of mosaicism? 

  • Mosaic forms are thought to be less severe


  • However difficult to asses 
    • What are the proportions of the different cell types?
    • Which tissues/organs are affected? 
  • Examples 
  • Downs = 2% Trisomy 21
  • Klinefelter = 15% (48XY/ 47XXY)
  • Turner = Up to 25%




Describe the different types of monosomies

  • Autosomal monosomies are very rare 
    • This is because they are not consistent with life 
  • Sex Chromosome monosomy is very common e.g Turner's XO 
  • All full monosomies arise via non-disjunction 
  • Partial monosomies (microdeletion syndromes (more common) thought to arise via a different mechanism) 


Considering how Turner's arises (45X), what are some possible combinations of chromosomes in monosomies 

    • + X Chr = XO = Turner’s (physically female)
    • + Y Chr = lethal (not consistent with life)
  • XX
    • + X Chr = XXX = Triple X syndrome
    • + Y Chr = XXY = Klinefelter’s (physically male)
  • XY
    • + X Chr = XXY = Klinefelter’s
    • + Y Chr = XYY = XYY Syndrome


What are the ways of analysing chromosomal abnormalities? 


  • Blood samples 
    • Take blood and look at chromosomes in the metaphase stage


  • CVS, aminocentesis or cffDNA & NGS 


Describe chorionic villus and aminocentesis sampling 

→ Chorionic Villus Sampling (cells removed from placenta) 

11-14 weeks, Miscarriage rate 0.5%-1%, can be Maternal Contamination and can cause Transverse Limb defects

→ Aminocentesis

>16 weeks, extraction of amniotic fluid, biochemical diagnosis possible, miscarriage risk (0.5-1%)


How can FISH and qPCR be used for analysis? 

  • quantitative flouorescence PCR 
    • Primers are designed for specific microsatellitemarkers on chromosome 21
    • These regions are amplified and copies will be assesed on their size 
    • In diagram you can see three peaks = 3 chromosomes 
  • FISH 
    • Flurorescent probes will bind to target DNA on chromosomes 


What are some ways we can get pre-natal diagnosis which is not invasive? 


(Aminocentesis and Chorionic Villus sampling can increase the risk of a miscarriage) 

Cell free foetal DNA (cffDNA) 

  • DNA fragments in maternal plasma (10 weeks onwards) 
  • Foetal DNA seperated and further tests are carried out such as 
    • PCR
    • NGS 


List common trisomies including their karyotype

  • Patau 47 - trisomy 13
    • XX+ 13, XY+ 13 
  • Edwards 47 - trisomy 18
    • XX+ 18, XY + 18 
  • Downs 47 - trisomy 21
    • XX + 21, XY + 21
  • Turner's = 45 XO 
  • Klinefelter 47 XXY 

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