Polygenic inheritance Flashcards
Define polygenic inheritance?
Inheritance of single train that is controlled by 2 or more genes
Define multifactorial disease
Disease that has resulted from interaction of genetic & environmental factors
E.g. of characteristics that follow polygenic inheritance?
Height
weight
skin colour
If polygenic characteristic was plotted on a graph, what shape would the graph be? Why?
Continuous, normal distribution, bell shaped curve
Phenotype is determined by many genes at different lotion a chromosome- each alley has small additive effect
Leeds to different variations= continuous
Define concordance rate
The probability that 2 people w/ shared genes will develop same disease
Used to examine how genetically linked disease is
High concordance rate= trait has strong genetic influence
Low concordance= high environmental influence i.e epigenetic
How to interpret concordance rates?
MZ concordance higher than DZ concordance= disorder has genetic component
MZ concordance same or similar to DZ- disorder is environmentally caused
MZ concordance is 100%- disorder is genetically caused
MZ concordance is less than 100%- disorder has environmental component
Common multifactorial diseases?
Diabetes- Type 1 &2
Hypertension
Heart disease- caused by coronary heart disease
Stroke
Breast cancer
What is the concordance rate for MZ twins & DZ twins for Type 1 diabetes?
MZ= 30-70%- suggests diabetes 1 has significant genetic factor.
DZ= 5-10%
Which alleles & genes are linked to causing Type 1 diabetes?
HLA class II alleles- involved in T cell recognition
Insulin gene- tandem repeat polymorphism in this gene affects transcription
Tandem repeat= sequence of.2 or more DNA base pairs that are next to each other
What is concordance rate for MZ twins * DZ twins for Type 2 diabetes?
MZ= 35-60%
Mz is higher than DZ
Which alleles & genes are linked to causing type 2 diabetes?
TCF7L2 gene- codes for transcription factor involved in secreting insulin
variant of this gene increases risk of type 2 by 50%
What environmental factor plays role in Type 2 diabetes ?
Obesity- significant risk factor
influenced by diet & exercise levels
although genes can play role in obesity too
What is the heritability estimate for hypertension w/in families? What does value suggest?
Heritability estimates= 30-50%
This is less than 100%= so environmental factors contribute to high blood pressure
What environmental factors add to risk of getting hypertension?
Sodium intake
reduce physical activity
obesity
psychosocial stress
What genetic factors lead to Increased risk of hypertension?
Blood pressure is regulated by many systems- kidney function, cellular ion transport & heart function- these systems are controlled by genes
more than 20 genes linked to hypertension- many affect reabsorption of water & salt in kidney, affects blood vol & pressur
Give general heritability estimate for heart disease
Person w/ positive family history of CAD is X@ likely to suffer w/ CAD compared w/ someone with no history
What environmental factors increase risk of heart disease?
Diet- obesity, cholesterol
Smoking
Hypertension
What genetic factor adds to risk of getting heart disease?
LDL receptor gene mutations- doubles cholesterol levels in body
Condition called familial hypercholesterolemia
High levels of LDL lead to atheroma- causes blockages in coronary artery
What is risk of having strokes if you have positive family history? Concordance rates?
Risk of having a stroke increases by x 2-3 if 1 parent has had a stroke.
Twin studies show concordance rate for MZ was 10% & for DZ twins it was 5%
- Suggests that environmental factors are important too
What genetic factors add to risk of stroke?
More than 12 single-gene disorders can cause a stoke
- e.g. Sickle Cell Disease - caused by mutation of HBB gene - causes RBCs to get stuck in blood vessels.
- e.g. Haemophilia- mutation of F8 causes Heamophilia A which causes altered or missing coagulation factor VIII.
What environmental factors can increase risk of stroke?
-Diabetes
Hypertension
Obesity
What is risk of getting breast cancer is relative has it?
risk doubles
What environmental factors influence cancer?
EF can induce mutations
Tobacco accounts for 1/3 of all cancer deaths in HIC
Radiation
chemicals- carcinogens
What genetic mutations are linked to breast cancer?
Mutations in BRCA1 & BRCA2 genes- involved in DNA repair
