Genetic Variation and Disease II. Whole Chromosomes to Single Bases Flashcards
Genome structure
Single bases –> DNA strand –> Whole chromosome
Chromosome Notation (__XY/XX)
46XX
- Total number of chromosomes
- Sex chromosome complement
How a Chromosome is recognised
Telomere - protective cap
Short arm (p)
Centromere
Long arm (q)
Telomere
Acrocentric Chromosomes
Centromere not central
Near end of chromosome
Balanced Chromosome Rearrangement
All chromosomal material present
Unbalanced Chromosome Rearrangement
Extra or missing chromosomal material
Aneuploidy
Whole extra or missing chromosome
Translocation
Rearrangement of chromosomes
Insertions and Deletions
Missing or duplicated material
Microdeletions
chromosomal deletions that are too small to be detected by light microscopy using conventional cytogenetic methods
Trisomy 21
Gives rise down syndrome
Robertsonian Translocation
Two acrocentric chromosomes stuck end to end
Balanced Translocation
A type of genetic variant where part of one chromosome has moved, usually to another, non-homologous, chromosome
Trisomy 14
Miscarriage
Turner Syndrome
45X
Triple X
47XXX
Klinefelter syndrome
47XXY
Reciprocal Translocations
occur due to the exchange of chromosome material between two nonhomologous chromosomes
Reproductive Risks
- Roughly 50% of conceptions will have either normal chromosomes or balanced translocations
-Unbalanced products - miscarriage, dysmorphic delayed child
DiGeorge Syndrome
A condition present from birth that can cause a range of lifelong problems, including heart defects and learning difficulties
22q11 deletion
Molecular Cytogenetics
No longer need to see chromosomes to count them
You will only detect imbalance
You can detect tiny changes
Some small changes are polymorphisms
Where do mutations come from?
Germ line mutation
- One parent has this
New mutation in gametogenesis
One patient is mosaic
Mutation is post-zygotic (child is mosaic)
Mosaicism
Different cells have a different genetic constitution
Could be mosaic chromosome abnormality or mosaicism for a point mutation
Somatic Mosaicism
Genetic variation that is present in the genomes of cells that make up the body of the organism and do not contribute to gametes produced by the individual
All cells suffer mutations as they divide - meiosis and mitosis
Repair mechanisms exist
Chromosome changes could (2)
Activate an oncogene
Delete a tumour supressor
E.g. HER2 amplification and protein expression
Philadelphia Chromosome
Bcr-Abl
Chromosome 9 and 22 Translocation
Increased proliferation, decreased apoptosis
