Principles of multifactorial disease Flashcards
mitochondrial inheritance
- mitochondria only inherited from mother (maternal inheritance)
- e.g. if the father is affected by condition it wont be passed on
- relatively rare conditions
- involved around neurological, cardiac, skeletal muscle (high energy systems)
mitochondrial replacement therapy
- 3 parent embryo
- a female donor donates egg with healthy mitochondria
- nucleus of mothers egg is removed and placed into donor egg and fertilised by sprem from father
- egg and mitochondrial DNA from donor mother but nuclear DNA from biological mother
multifactorial diseases
- non-mendelian (e.g. not autosomal domiant or recessive etc)
- occur in families more frequently than by chance
- shows no clear classical pattern of inheritance
- is an interaction between environmental and genetic predisposition factors
e. g. Parkinson’s, hypertension, diabetes, stroke
pathology of multifactorial inheritance
- excluding the interaction between genes and the environment
- inheritance of common alleles that are too small alone to cause affects of a disease
- interaction of several different genes that together have a greater effect (polygenic trait)
- could be a genetic factor that doesn’t cause the disease but having it worsens the phenotype (modify gene)
- the interaction between genes and epigenetics
modify genes
doesn’t influence the risk of getting the disease but once disease susceptibility is present or developed, these genes modify the severity of the phenotype
threshold model for polygenic traits
assumes that in the general population we all have a number of these genetic risk factors combined with environmental risk factors but threshold must be reached before its expressed
- in families with an increased predisposition, the curve moves to the right and they have a lower threshold (due to familial risk)
identification of multifactorial threshold trait
- disorders run in families, but no distinct pattern
- concordance rate greater in identical twins than non-identical twins
- frequency higher in 1st degree than 2nd-degree relatives
- recurrence risk proportional to number of family members affected
- recurrence risk proportional to severity of condition
linkage
- is the tendency of DNA sequences that are close together on a chromosome to be inherited together
- linkage analysis looks for co-transmission of disease with polymorphism of possible linked genetic markers
genome-wide association studies (GWAS)
looks at the association between single nucleotide polymorphisms and multifactorial diseases
examines a set of genetic variants in different individuals to see if any variant is associated with a trait
opportunities following gene identification
improved understanding of disease pathology and diagnosis
- advanced understanding of pathophysiology
- reclassification of disease
- ability to examine gene-environment interactions
- increased accuracy in risk prediction
- allow for preventive strategies e.g. change diet
- identify new drug targets
personalised medicine
the use of an individual’s genetic information to make decisions aimed at health, prevention of disease or improving the outcome of diseases
precision medicine
is the next step from personalised medicine where all of a patients health information (blood tests, genetics, past medical history) are assessable to the scientist to optimize management of patient
- common in cancer
personalized/precision medicine examples
drug efficacy = identify patients who will receive greatest benefit
drug tolerance = patients likely to experience side-effects
screening= identify high-risk individuals
prevention= identify those at higher risk due to adverse lifestyle
