BBOL- Molecular basis of human disease Flashcards
1
Q
What is genomics?
A
- Scientific study of genomes especially of their organisation and evolution, using nucleotide sequencing and gene mapping; branch of molecular biology that deals with this
2
Q
What genomic medicine?
A
- Individual patient’s genome will help determine the optimal approach to care, whether preventive, diagnostic or therapeutic, e.g. chromosome abnormalities, monogenetic disorders etc.)
3
Q
Describe cytogenetics
A
- Study of structure of chromosomes
- Alterations in chromosome number or structure (in all cells- constitutional abnormality, in some cells- somatic)
- Metaphase spread
- Rapidly dividing tissues, e.g. peripheral blood, amniotic fluid, chorionic villis
4
Q
Describe chronometer banding patterns
A
- Giemsa staining- gives rise to unique pattern
- Chromosome numbered in approx. order of size
- Chromosomal region identified by banding patterns
5
Q
Describe karyotyping
A
- Tissue samples cultures to induce proliferation
- Mitotic spindle disrupted and nuclear n=membrane lysed and stain applied
- Dye stains regions of chromosomes that are rich in A and T produce dark band
- Chromosomes counted, structure analysed, images captured and organised to a visual format
6
Q
Describe numerical chromosome abnormalities
A
- Involve gain or loss of complete chromosomes
(polyploidy- extra complete set of chromosomes, aneuploidy- one or more chromosomes extra/missing)
-Autosomal - Sex chromosomes
- Aneuploidy for most chromosomes is non-viable due to gene dosage changes, viable for smaller chromosomes
7
Q
How do structural chromosome abnormalities occur?
A
- Recombination btwn non-homologous chromosomes
- Double strand DNA breaks occurring in chromatids
- When centromere pair separates in wrong plane during meiosis
- Can be balanced (no loss of genetic material) or unbalanced
8
Q
How do disorders of imprinting occur?
A
- Karyotypes can be pathogenic with the wrong parental origin
- Methylation patterns can be male/female specific
- Only one copy of gene expressed
- UPD: uniparental disomy- 2 chromosomes from 1 parent- dosage problems
- Prader-Willi and Anglican syndromes
9
Q
What is a mutation?
A
A permanent transmissible change in the gemetic material, usually in a single gene- used to describe a genetic change with deleterious consequences
10
Q
What is polymorphism?
A
Existence of 2 or more alleles (variants) in the populations (typically > 1%) may be neutral or predispose towards disease
11
Q
What are the different types of point mutations?
A
- Single base pair change
- Silent- results in no change to amino acid sequence due to degenerate code
- Missense- reults in amino acid change
- Nonsense- introduces a new stop codon so no protein is made
12
Q
What are the different types of mutations?
A
- Point mutation
- Deletion
- Insertion
- Frame-shift
13
Q
What are the causes of mutation?
A
- Can be spontaneous (4 DNA molecules are somewhat unstable, DNA polymerase makes mistakes, imperfect meiosis)
- Can be induced- mutagens can alter DNA by chemicals covalently bonding to nucleotide bases, adding chemical groups to DNA bases, radiation can damage DNA
14
Q
How is DNA repaired?
A
- Process constantly operating in each cell; essential to survival because protects genome from damage
- Normal metabolic activities and environmental factor (such as UV) can cause DNA damage, resulting in as many as 500,000 individual molecular lesions/cell/day
15
Q
What happens when repair goes wrong?
A
- If rate of DNA damage exceeds capacity of cell to repair it, accumulation of errors is overwhelming, leads to senescence, apoptosis or cancer
- Inherited disease associated with faulty DNA repair result in premature ageing (Werner’s) and increased sensitivity to carcinogens
