Multifactorial Disease Flashcards
Define Mendelian
Obeys Mendel’s laws of segregation- dominant, recessive, X-linked
Define complex
Tends to be used vaguely to describe something with an inherited but non-mendelian component
Define polygenic
The result of the action of multiple genes
Define multifactorial
The result of multiple factors, usually including both genetic & environmental
Does a multifactorial disease have a genetic component?
- Familial clustering
- Twin studies
What are problems with twin studies?
- Assumption that the degree of environmental sharing is the same for MZ twins- difference in birth weights, variation in time of splitting of the early embryo
- DZ twins can share more than half their genes
What congenital malformations show multifactorial inheritance
- Cleft lip/palate
- Congenital hip dislocation
- Congenital heart defects
- Neural tube defects
- Pyloric stenosis
- Talipes
What acquired disease of childhood & adult life show multifactorial inheritance?
- Asthma
- Autism
- Cancer
- Diabetes mellitus
- IDB
- Schizophrenia
- Parkinson disease
What is the likelyhood of a disease with a high magnitude of effect and high frequency in the population?
A disease with low magnitude of effect and frequency
High= unlikely to exist Low= function studies
What do genetic association studies look for?
- Seek to relate variation in human DNA sequence with a disease or trait
- Provides greater power to detect common genetic variants conferring susceptibility to complex phenotypes
- Estimates population attributable risk
- Controls should match cases and be a representative sample of the population
Describe the genetics of Alzheimer’s disease
- Sequence variants at a polymorphic locus have a large effect on age of onset
- Missense mutation in APP
- Much effect due to a gene implicated in heart disease- app-lipoprotein E (APOE) 3 haplotypes
What are the 3 haplotyes for alzheimer’s disease?
E4 = Increase in susceptibility
E2= Protective effect
E4/E4= Homozygous effected earlier than heterozygous
-Risk is increased further if there is high blood pressure
What are the risks for AMD?
- Genetics= CFH, ARMS2
- Environmental= smoking
