Genetics & Human Disease Flashcards
Each person is estimated to carry how many deleterious genes?
5-8
Define Pleiotropism
A mutation in a single gene can lead to many effects
CF
Define Genetic Heterogeneity
Mutations at several loci may produce the same trait
Diabetes, PKU
Define Autosomal Dominant
Only need 1 parent to carry defective gene
Define Autosomal Recessive
Both parents must carry defective gene
Two Austosomal Dominant diseases?
Huntington’s disease
Familial hypercholesterolemia
Define Huntington’s disease
Triplet repeat on chromosome 4
Dysfunctional protein builds up leading to toxicity at the GABA neurons
Define Familial hypercholesterolemia
Defective LDL receptor –> inability to bind LDL and transport to liver
Three Autosomal Recessive Disease
PKU
CF
Sickle cell anemia
Define PKU
Defective phenylalanine hydroxylase –> build up in the CNS leading to mental retardation
Define CF
Defective chloride ion channel –> thickened mucus secretion
Define Sickle Cell Anemia
Defective hemoglobin which precipitates at low O2 tension
Who is most effect by X-linked disease and why?
Males
They only have only one X (always from the father)
Three X-Linked Recessive Diseases
Hemophilia A&B
G6PD deficiency
Diabetes insipidus
Define Hemophilia A&B
Defect in clotting factors (8&9) –> prolonged bleeding
Define G6PD deficiency
Most common enzyme defect
RBC are unable to repair
Define Diabetes insipidus
Mutation in AVPR2 gene –> defective vasopressin receptor
Majority of disease are?
Polygenic: different places for a mutation to occur
Define Non-disjunction
Failure to separate
Example of Non-disjunction
If you have non-disjunction in meiosis II then you could have one cell with two copies of chromosomes 21, then when it is fertilized there will be another making 3 copies of chromosomes 21
Why do genetic diseases exist?
- We are living longer now
- Mutations may protect us from other disease
Define Positive Selection
Heritable mutation which confers a survival advantage
Examples of Positive Selection
Alcohol tolerance
Lactose tolerance
How is Sickle Cell Anemia a beneficial mutation?
Heterozygotes protected from malaria
How is CF a beneficial mutation?
Protects against typhoid
How is Tay Sachs a beneficial mutation?
Protects against TB
How is Type AB blood a beneficial mutation?
Highly resistant to chlorea
Development of disease examples?
Multiple sclerosis, asthma
Development of drug complications examples?
Factor V Leden and OCP’s
Define Multiple Sclerosis
Incidence is higher in countries far from the equator (US, Canada, N. Europe)
- Both gene and environment
What is the most common CV event in young women?
Venous Thrombosis
How does Venous Thrombosis manifest?
Thrombosis of deep leg veins or PE
Venous thrombosis interact with?
Oral contraceptives (estrogen) and the highest risk is in the first year of exposure
Define Factor V Leiden Mutation
Position 506 Arginine is replaced with glutamine –> at the cleavage site so it cannot be cleaved leading to no activation of Factor 5 aka excess clotting
What type of mutation is Factor V Leiden Mutation?
Non-conservative missense mutation
Factor V Leiden Mutation is more common in?
Caucasians 2-10%
Factor V Leiden Mutation in individuals with VT?
14-21%
Testing for Factor V Leiden Mutation if:
Age <50 with MI and smoker
Routinely you test for?
Trisomy 21 or 18
Sicle cell, GALT, biotinidase deficiency, CF, Beta thalassemia, G6PD deficiency and PKU
