L16: Chromosomal Mutations Flashcards
What is a chromosome?
Threadlike structure of nucleic acid & protein found in the nucleus, carrying genetic information in the form of genes
Main components of the chromosome
1) Chromosome arms: short (p) & long (q) arms
2) Centromere
3) Kinetochore
4) Telomeres
5) Subtelomeres
What is kinetochore?
Protein complex at centromere where spindle fibres attach
What is a centromere?
link sister chromatids
Features of centromere
Multiple repeating sequences
What are telomeres?
Specialised repeated DNA sequences
Protect ends of chromosomes
What are subtelomeres?
Chromosome part between gene-rich areas & telomeres
Describe metacentric chromosome
centromere in the middle
telomere at the top
p & q arm
4 chromosome classification based on centromere position
1) Telocentric: centromere at end
2) Metacentric: centromere in the middle
3) Submetacentric: Centromere slightly off-center
4) Acrocentric: Centromere close to 1 end
What is cytogenetics the study of?
Chromosome variations & their link to traits/illnesses
How do cytogeneticists distinguish chromosome types by size & shape?
Use stains to contrast dark heterochromatic (repetitive DNA sequences) with lighter euchromatin (more protein encoding gene)
What is a karyotype?
An individual’s collection of chromosomes
What is karyotyping?
Process of pairing & ordering all chromosomes of an organism
Karyotype of a normal female & male
Female: 46, XX
Male: 46, XY
What is the G banding technnique?
Uses giemsa dye to stain chromosomes, highlighting euchromatin (light bands) & heterchromatin (dark bands)
How is chromosome nomenclature organised?
1st number/letter represent chromosome
2nd letter p/q describes arm
Then region/band number
What is Fluorescence In Situ Hybridisation (FISH)?
Uses fluorescent DNA probes to detect specific chromosomal abnormalities
How many fluorescently labelled DNA probes are used to analyse location in FISH?
2
What is the purpose of the 2 fluorescently labelled DNA probes in FISH?
1st probe: Control & hybridises with DNA on target chromosome (outside targeted region)
2nd probe: Hybridises to a target location on individual’s DNA sequence
What is chromosome painting?
Form of FISH where multiple probes label different chromsome regions
Procedure of FISH
1) Chromosomes fixed on a slide & denatured
2) Fluorescent probes hybridise to complementary sequences
3) Analysis under fluorescence micrscope
Constitutive vs acquired chromosome abnormalities
Constitutive: all the tissues hold the same anomaly
Acquired: only 1 organ is involvedm all others are normal
Homogeneous vs Mosaic chromosome abnormalities
Homogeneous: all cells (studied) carry anomaly
Mosaic: only some cells carry anomaly (cancer cells)
Numerical vs Structural chromosome abnormalities
Numerical: total no. of chromosomes in humans is not 46
Structural: defects including missing, extra genetic material within a chromosome
3 types of numerical chromosomal abnormalities
1) Euploidy
2) Polypoidy
3) Aneuploidy
What is euploidy?
Normal no. & sets of chromosomes
What is polypoidy?
Presence of 3 or more complete sets of chromosomes
What is aneuploidy?
Presence of additional/missing individual chromosomes
2 types of structural abnormalities
1) balanced chromosomal rearrangments
2) unbalanced rearrangments
What is balanced chromosmomal arrangments?
Type of chromosomal structural involving chromosmal rearrangements with gain/loss of chromatin
What is unbalanced rearrangements?
Include deletions, duplications of a chromosome segment when there is additional/missing genetic information
2 types of polypoidy
triploidy: 3 sets of chromosomes (23x3=69)
tetraploidy: 4 sets of chromosomes (23x4=92)
3 types of aneuploidy
1) monosomy: 1 less chromosome (23x2)-1=45
2) trisomy: 1 additional chromosome (23x2)+1=47
3) nullisomy: pair of homologous chromosome is missing (22x2=44)
Define nondisjunction
Failure of homologous chromosomes/sister chromatids to separate
What is autosomal aneuploidy?
All abnormalities that DO NOT involve sex chromosomes
What is sex chromosome aneuploidies?
All abnormalities that INVOLVE sex chromosomes
Karyotype of down syndrome
47, XY, +21
Karyotype of turner syndrome
45,X
Karyotype of Klinefelter Syndrome
47, XXY
4 type of structural chromosome abnormalities
deletion, duplication, inversion, translocation
What is submicroscopic deletions?
Too small to be detected by light microscopy
2 types of translocation in structural abnormalities
Reciprocal: segments from 2 different chromosomes have been exchanged
Robertsonian: entire chromosomal arm has been attached to another at/close to centromere
What is translocation?
Portion of 1 chromosome is transferred to another chromosome
What is inversion?
Portion of chromosome broken off, turned upside down, reattached, genetic material is inverted
2 types of inversions
Paracentric inversion: not including centromere
Pericentric inversion: INCLUDES centromere
What is a ring chromosome abnormality?
A portion of a chromosome has broken off & formed a circle/ring, as ends fuse together
What are isochromosomes abnormalities?
Formed by a mirror image copy of a chromosome segment including the centromere
What is uniparental disomy?
Both copies of a chromosome inherited from 1 parent
2 examples of uniparental disomy
Angelman Syndrome: maternal chromosome deletion
Prader-Willi Syndrome: paternal chromosome deletion
What are trinucleotide repeats?
Expansion of 3-nucleotide DNA sequences, leading to disorders
- cause dynamic/unstable mutation
Examples of trinucleotide repeats
1) Fragile X Syndrome: CGG repeat
2) Huntington’s Disease: CAG repeat
What genetic disorders does DNA repair defects lead to?
Xeroderma Pigmentosum (UV, skin cancer)
Werner Syndrome: premature aging
Fanconi Anemia: Bone marrow failure
What is a transposable element?
DNA sequence that can change its position within a genome
What is synteny?
Conservation of the relative order of genes/genetic markers across different species genomes
