Multifactorial Disorders (4) Flashcards
Mendelian
Obeys Mendel’s laws of segregation - dominant, recessive, X-linked
Complex
Tends to be used vaguely to describe something with an inherited but non-mendelian component
Polygenic
The result of the action of multiple genes
Multifactorial
The result of multiple factors, usually including both genetic and environmental factors
Familial clustering
λs (relative risk to 2nd sibling)
Schizophrenia
Inherited, but not mendelian
Phenotypes are determined
by action of may genes at different loci
Polygenic/complex/multifactorial inheritance
- Genes are additive (not recessive/dominant)
- Blood pressure, head circumference, height, intelligence
- Gaussian distribution (normal)
- Influenced by environment
Congenital malformations with multifactorial inheritance
Cleft lip/palate, congenital hip dislocation, congenital heart defects, neural tube defects, pyloric stenosis, talipes/club foot
Acquired diseases of childhood & adult life with multifactorial inheritance
Asthma, autism, cancer, diabetes mellitus, epilepsy, glaucoma, hypertension, inflammatory bowel disease (Crohn disease), ischaemic heart disease & stroke, bipolar disorder, multiple sclerosis, Parkinson disease, psoriasis, rheumatoid arthritis, schizophrenia
NTDs prevented by
400ug/day of maternal folic acid supplementation 1-3 months in pregnancy (50-70% prevention)
SNPs
- Single nucleotide polymorphism
- Common, usually binary
- Easy and quick to test (computer)
- Change in one single nucleotide
How many SNPs identified?
> 10 milion
Population association studies and linkage disequilibrium
- Most disease bearing chromosomes are descended from ancestral chromosomes
- Can detect association to
Alzheimer’s
Inheriting susceptibility rather than the condition
What age does Alzheimer’s effect?
Most common form of dementia >40 years
Symptoms of Alzheimer’s
Inability to cope, loss of memory, brain damage
Neurology of Alzheimer’s
Shrinkage of brain, tangles of B-amyloid protein in nerve fibres of hippocampus
Familial clustering of Alzheimers
3 to 10
Much of the effect of Alzheimers is due to the gene…
Api-Lipoprotein E (APOE) - APOEE2, APOEE3 and APOE*E4
*E4 halotype confers
Increase in susceptibility (affected much earlier if homozygote E4/E4)
*E2 halotype confers
A protective effect
Age-related Macular Degeneration
- Leading cause of irreversible central visual dysfunction caused by degeneration of the macula
- Early deposition of drusen
Major genetic effects for AMD
CFH (1q), ARMS2 (10q)
Major environment effect on AMD
Smoking
Genetic and smoking major effects increase risk for AMD by how much?
70 fold
