Chromosomal abnormality Flashcards
Chromosomal functions (2)
Genetic inheritance
Stabilises cellular DNA
Function of:
- Telomere
- Centromere
Telomere
- Protects ends
Centromere
- Holds chromatids together
- Segregates chromosomes
Chromosome classification (in relation to centromere:
- metacentric
- sub-metacentric
- acrocentric
Metacentric= middle
sub-metacentric= close to one telomere
Acrocentric= centromere near telomere.
Human karyotype
- Chromosome sets
2 haploid sets of 23
- 44 autosome, 2 sex chromosomes
Aneuploidy
Incorrect number of chromosomes (too many or few)
- Gametes can be generated via mitotic nondisjunction
- Most common cause= maternal meiosis
Balanced and unbalanced rearrangements
Balanced= translocation, inversions
Unbalanced= deletions, duplications
Nondisjunction
Failure of homologous chromosomes/ sister chromatids to separate during cell division
Post-zygotic nondisjunction and mosaicism
If post-zygotic, can lead to mosaicism
Can also occur in trisomic concepts and lead to anaphase lag
Anaphase lag
Sister chromatids to not separate properly.
- Due to spindle problems
- Leads to loss chromsome
Down’s syndrome
- Features
Most common autosomal abnormality
Presents
- Learning difficulties
- Dysmorphic features
- Heart defects
Down’s syndrome
- Karyotypes
Main= primary trisomy
- 47, XX + 21
1-2% mosicism= 46, XX/ 47 XX = 21
4%= translocation
der (14; 21)
Edward’s syndrome
- Defect
- Features
Trisomy 18
Features
- Dysmorphic
- Rocker bottom feet
- Congenital heat defects
- Die within weeks
Karyotype
- +18.
- 5% mosaicism
Patau’s syndrome
- Defect
- Features
Trisomy 13
Dysmorphic features
Renal abnormalities, cardiac defects
Most die within a year
Karyotype
- primary trisomy
- 20% translocation (13;14)
Klinerfelter syndrome
- Genetic defect
- Features
XXY
Features
- Tall
- Gynaecomastia
- Small tests
- Infertility
- Delayed/ incomplete puberty
Karyotype
- XXY
- Mosaicism XXY/ XY
- XXXY XXXXY
Turner syndrome
- Genetic defect
- Features
XO
Features
- Short
- infertile
- Maternal age NOT risk factor
Karyotype
- 40-60% monsomy
- Moasicism
XYY syndrome
Often asymptomatic
Features may include
- Learning disabilities
- Speech delay
- Hypotonia
Karyotype
- XXY, or mosaicism (XY)
Triple XXX syndrome
Mainly asymptomatic
- seizures and kidney abnormalities
XXX or mosaicism with XX
Lyonisation
Random activation of X chromosome in females
- Leads to less severity of sex chromosomal disorders.
Mechanism
- 2 weeks post-fertilisation
- Only one active X
X-inactivation mechanism
Occurs in X inactivation centre (XIC)
Xist (transcript RNa)
- expressed on inactive X
- Transcripts coat the X chromosome and lead to inactivation
Chromosomal translocations
- Definition
Rearrangement of chromosome segment transferred to non homologous chromosome or new site on same chromosome
Robertsonian translocation
Fusion of two acrocentric chromosomes
- Commonly 13;14 or 14;21
Phenotype is normal in balanced carriers but there is reproductive risks
Translocation down’s
fusion of long arms of chromsome 14 and chr 21
carrier= 46 xx, -14, -21 +t(14q21q)
downs= t(14;21) 21
Reciprocal translocation
two way exchange between non-homologous
- If balanced= normal
- Carrier= reproductive risks
isochromosome
Occurs from centromere fission
- where one arm is deleted, the other replicated
ring chromosome
when telomeric region is lost and the arms fuse
duplication
> 1 copy of chromosome segment
cru du chat
Genetic condition due to deletion on chr 5p
