4 Multifactorial diseases Flashcards
What is λs?
Risk of a person developing a disease if a sibling has it, compared to the population at large.
What are the problems with using twin studies to show genetic component of diseases?
MZ twins have large differences in birth weight, and vary in when the early embryo split.
Diamniotic monozygotics survive better than monochorionic.
DZ twins share more than 50% of genes, and 1 in 10 undergoes a blood transfusion during pregnancy.
What are adoption studies commonly used to study?
Psychiatric conditions.
How do genetic association studies work?
Patient and matched control group. Estimates population attributable risk (effect size).
When are linkage analysis performed compared to association studies?
Linkage - large gene effect, small frequency.
Association - small gene effect, large frequency.
What are linkage disequilibrium studies?
Inheritance of mutation is surrounded by inheritance of ‘normal’ patch of chromosome. Variations surrounding it will be significantly associated. Needs GWAS with large sample and careful control selection.
Explain one of the most common genetic and molecular basis of Alzheimer’s disease:
Presnilin 1 and 2 (PSEN1/2) encode transmembrane aspartyl-proteases with γ-secretase which cleaves APP and NOTCH receptor proteins.
Which gene has a large effect on the age of onset of Alzheimers?
What are the protective and risky alleles?
APOE (apo-lipoprotein E).
APOE2 = protective.
APOE4 = increased susceptibility (homozygotes affected earlier than hetero).
Which polymorphism increase schizophrenia risk?
COMT gene.
Catechol-O-Methylase Gene.
Which disease are these genes implicated in the development of?
UBE2E2. CDKAL2. KCNQ1. C2CD4A-C2CD4B.
Type 2 diabetes.
What is the thrifty phenotype hypothesis? (Type 2 diabetes).
Maternal malnutrition -> foetal malnutrition, decreased beta cells mass and function -> non-insulin dependant diabetes.
Which condition do these genes play a major role in?
CFH, ARMS2, CFB/C2, CFC3
Age related macular degeneration.
What is age-related macular degeneration?
Early deposition of drusen leading to central blindness.
