Genetics Flashcards
What does multifactorial mean in genetic terms?
Traits which show variation caused by multiple genes and environmental factors e.g. BP, Height or IQ
The additive effects of multiple genes and environmental
factors give rise to what sort of distribution?
Bell shaped curve - normal distribution
What is the threshold model of polygenic disease?
Some polygenic diseases do not show a normal distribution but are either present or absent (mimicking a single gene trait)
These show a liability distribution
Those with few disease associated alleles or limited exposure to environmental factors have a limited chance of developing disease
Those with more disease associated alleles or more exposure to environmental factors have increased chance of developing disease
Threshold of liability must be crossed before disease is expressed
Describe how the difference in liability threshold for pyloric stenosis between males and females can result in different recurrence risk for future offspring
Fewer disease causing factors (genetics and environmental) are required to generate the disease in males
When calculating recurrence risk in a family it is important to
consider any factors which alter the liability threshold
If proband is female then recurrence risk is higher than if the proband is a male as more disease causing factors must be present
Why is recurrence risk calculation difficult for multifactorial disease?
Number of genes contributing to a disease is usually not known
Precise allelic constitution of the parents is usually not known
Impact of environmental factors is difficult to quantify
How are recurrence risks calculated for multifactorial disease?
Usually empirical
Based on direct observation of large numbers of probands and their relatives e.g. if 3% of siblings of probands develop disease X then the empirical recurrence risk is 3%
What are recurrence risk values specific to in multifactorial disease?
Each multifactorial disease
The population being looked at
What factors increase recurrence risk in multifactorial disease?
Higher if more than one family member is affected
If expression of disease in proband is more severe, recurrence risk is higher eg bilateral cleft palate, more severe than unilateral
Higher if proband is of less commonly affected sex
Recurrence risk for disease usually decreases rapidly in more remotely related relatives, much more quickly than in single gene disease
If prevalence of disease in a population is f, risk of disease in offspring and siblings of probands is…?
Square root of f
What studies can be used to determine effects of genes and environment on disease?
Twin studies: Environment is a significant confounder
Adoption studies: Risk of developing disease in offspring of affected individuals who are adopted v not-adopted
List some common multifactorial diseases of childhood
Congenital malformations, pyloric stenosis, Hirschsprung disease, cleft palate, neural tube defects, club foot
List some common multifactorial diseases of adulthood
Coronary artery disease: Impact of lipid metabolism, Family history of CAD doubles risk especially if early age of onset and several family members affected, Environmental factors also key, diet, exercise
Stroke
Hypertension
Cancer: Breast, Colorectal, Prostate
Endocrine disease: Diabetes mellitus, variants with familial clustering: type 1, type 2 and MODY (maturity onset diabetes of the young)
Psychiatric diseases: Alzheimers, Alcoholism, Schizophrenia, Bipolar
What does polygenic mean?
Traits which are caused by the effects of multiple genes
What factors does normal skeletal muscle function require?
Metabolic demands of the tissue are met
Muscle is used
Innervation
What is in a motor unit?
Lower motor neuron, axon, neuromuscular junction
Muscle fibres
