Week 3 - Gene Environment Interactions in Health and Disease Flashcards
Variation of Rhodepsin
- The Glu134 and Arg135 residues are part of the highly conserved D/ERY motif an important interaction site with transducin
- Mutations at codon 135 are associated with severe autosomal dominant RP
- R135L and R135W are both class IIb mutants which is classified defective in ability to bind II-cis retinal, folding and stability and transportation to cell surface
- In vitro studies of bovine rhodopsin mutants have shown that both R135L and R135W bound retinal almost in a wild-type like fashion but were unable to activate the associated protein.
Gene Replacement Therapy
Can be used for people suffering with Retinitis Pigmentosa type II (RP) and Leber’s Congenital Amaurosis type II (LCA).
Mitochondrial Replacement Therapy
Mechanism
* Three parent babies
* The technique involves using DNA from three people in order to prevent serious inherited disease.
* The mother’s nucleus with abnormal mitochondria is removed and is placed into a donor cell with normal mitochondria and is then fertilised in-vitro with the father’s sperm cell
Unknown Risks
* Interaction between donor’s mitochondrial DNA and mother’s nucleus
Expressivity
The degree to which a particular genotype expresses its phenotype
What is a de novo mutation?
An alteration in a gene that is present for the first time as a result of a mutation in a germ cell (egg or sperm) as one of the paretns or soon after fertilisation
What is mosaicism?
Occurs when someone has two or more genetically different sets of cells within his/her body
What is penetrance?
The likelihood of the gene generating its associated phenotype
BRCA1 gene
- Acts as a tumour suppressor, controls cell death and cell growth
- Involved in DNA repair, particularly double stranded break repair
- Possible role in embryonic development
Breast cancer environmental risk factors - Obesity
- Smoking
- Alcohol consumption
- Menopause
- Childbirth
- Oral contraception
- Radiation exposure
- Insufficient exercise
- Genetics
Polygenic traits/disorders
Ones whose phenotype is influenced by more than one gene
Complex traits/disorders
Result from a variation within multiple genes and their interaction with behavioural and environmental factors
Polygenic risk scores
- An estimate of an individuals genetic liability or relative risk of a trait or disease
- The score uses risk data for variants showing association to the trait/disease to calculate a combined score for the relative risk of the individual dependant on which of these genetic variants they carry
- Doesn’t explain all risk
Tau protein
Abnormal chemical changes cause tau to detatch from microtubules and stick to other tau molecules forming threads that eventually join to form tangles in neurons
Amyloid plaques
Abnormal levels of this naturally occuring protein clump together to form plaques that collect between neurons and disrupt cell function
Apoliprotein E (ApoE)
- Binds to a specific peripheral cell receptors and plays a role in lipid metabolism
- Polymorphic
1. APOE - E2 (cys112, cys158)
2. APOE - E2 (cys112, arg158)
3. APOE - E4 (arg112, arg158) - 40 - 65% of AD patients have at least one copy of the E4 allele
Gene dosage: sex differences
X chromosome contains over 1,000 genes that are essential for proper development and cell viability
