Multifactorial diseases Flashcards
What are multifactorial diseases?
Complex disorders.
- many genetic and environmental factors
- non-Mendelian inheritance
What is the difference between polygenic and multifactorial?
POLYGENIC - multiple genes
MULTIFACTORIAL - multiple factors, both genetic and environmental
What does familial clustering mean?
Occurring more in a family than would be expected by chance.
-still environmental
What does the statistic (lambda)s show?
The relative risk to 2nd sibling compared to general population.
-familial disease
Is schizophrenia inherited?
Familial; inherited but not Mendelian.
-closer relation»_space; higher risk
What is the relative risk to siblings and identical twins of schizophrenia?
Siblings - 9%.
Identical twins - 48%.
What sort of disease are cluster headaches?
Multifactorial.
-run in families
What is a major environmental factor for twins?
The uterus (pregnancy).
If multifactorial diseases have a genetic component, should there be a higher concordance in monozygotic (MZ) or dizygotic (DZ) twins?
Higher concordance in monozygotic (MZ) twins.
-MZ twins = identical
Do twins share the same placenta?
- Monozygotic twins share the same placenta.
- Dizygotic twins either share the same placenta, or have separate placentas.
Do MZ have the same environmental exposure before birth?
MZ twins share placenta, but not necessarily same environment (»different birth weights).
-still environmental influences
How can adoption studies be used to determine the genetic influences of conditions?
Child shares environment but different genetics to adoptive parents.
-ethical issues though
What type of inheritance is shown by genes in polygenic / multifactorial inheritance?
ADDITIVE.
- not dominant / recessive
- phenotypes determined by many genes
What is usually the distribution of polgenic / multifactorial genes in the general population?
Tend to be normally-distributed.
-Gaussian curve
Give some examples of disorders that show multifactorial inheritance.
CONGENITAL - cleft lip, neural tube defects, heart defects
ACQUIRED - asthma, cancer, diabetes (type 2), IBD
What is the purpose of genetic association studies?
To relate DNA variation with a disease / trait.
-estimates population risk and phenotype susceptibility
What are in the 2 groups for association studies?
One group of affected individuals, one control group representing normal population (some affected individuals).
Which type of inheritance is usually more common; multifactorial or Mendelian?
Multifactorial inheritance is normally more common than Mendelian, but less severe.
What are single nucleotide polymorphisms (SNPs)?
Variation in a single nucleotide at a specific position in the genome.
How common are single nucleotide polymorphisms?
Very common.
- everyone has many
- usually no effect
What are used to detect single nucleotide polymorphisms?
SNP chips.
-‘light up’ means a base is present
What is linkage disequilibrium?
The occurrence of combinations of linked genes in non-random proportions.
-DNA surrounding mutation is often similar
What sort of graph is show linkage disequilibrium?
Manhattan plot.
-scatter graph
What is the thrifty phenotype hypothesis?
States that reduced fetal growth is strongly associated with a number of chronic conditions later in life.
-initially involved maternal malnutrition and metabolic syndrome
What is the pathology of Alzheimer’s?
- Shrinkage of brain
- Beta-amyloid protein accumulation in nerves
Is Alzheimer’s inherited?
Inherit susceptibility, not condition itself.
-environmental factors too
Familial clustering; what is the sibling relative risk in Alzheimer’s?
3-10.
What is the inheritance of early onset Alzheimer’s thought to be?
Genetically heterogenous.
- different genes involved
- e.g. PSEN1, PSEN2»_space; cleave amyloid precursor
- e.g. amyloid precursor mutation
What gene has an effect on the age of onset of Alzheimer’s?
Apo-lipoprotein E (APOE).
Which haplotype of APOE increases the susceptibility of Alzheimer’s, and which has a protective effect?
APOE*E4 - increased susceptibility.
APOE*E2 - protective effect.
What is deposited in age-related macular degeneration?
Drusen.
-early deposition = main risk factor
What is the simplest “multifactorial” genetic condition?
Ageing macular dystrophy.
-smoking/light exposure and genetic defect»_space; 70x increased risk
What are the genetic and environmental causes of ageing macular dystrophy?
GENETIC - CFH, ARMS2
ENVIRONMENT - smoking, light exposure
What is the purpose of screening in multifactorial diseases?
Identifies individuals at increased risk.
- does not confirm disease
- e,g. BRCA
