multifactorial disease Flashcards
how would you spot a multifactorial genetic disease?
twin studies and sibling relative tests
how would you spot genetic variants that contribute to multifactorial disease?
SNPs, halotyping, linkage disequilibrium, genome wide association studies
what are examples of multifactorial disease?
type 1 diabetes
schizophrenia
ageing muscular dystrophy
alzheimers
what does mendelian mean?
obeys mendels laws of segregation - dominant, recessive and X linked
what does complex mean?
tends to be used vaguely to describe something with an inherited but non mendelian component - multiple genes together with the environment
what is polygenic?
the result of the action of alleles of multiple genes - a disease that results from interaction of alleles of more than one gene
what does multifactorial mean?
the result of multiple factors including genetic and environmental factors
how can twin studies help to determine the genetic composition of multifactorial disease?
genetic characteristics should have a higher concordance in monozygotic twins than dizygotic
what is an atypical cluster headache?
a severe headache on one side of the head with a genetic component
how would familial clustering show the genetic composition of multifactorial disease?
look for the relative risk in those that are affected - take every individual known condition and look at siblings to see relative risk of sibling - see if there is an increased risk in those that share half a genome than those who do not
what would lambda s for siblings = 9 mean?
it would mean that if you are a sibling of someone with a disease who are 9 times more likely to get the disease than the general population
how can twin studies show there is an environmental risk?
for monozygotic if you share a genome there is only a 50% risk as there is also environmental factors
what is ascertainment bias?
when geneticists want to prove something is inherited so go out and look for a large family that this is the case for - may be a singular case and not standardised to population
why are genes known as additive instead of dominant or recessive?
they can combine with polygenic or complex or multifactorial inheritance and the different genes present add up - influenced by the environment, diseases can run in families but not simply in mendelian fashion
how are phenotypes determined?
determined by action of many different genes at different loci
what disorders how multifactorial inheritance?
congenital malformations, acquired disease of childhood and adult life, effects of the environment
what are some congenital malformations?
cleft lip/palate, congenital hip dislocation, congenital heart defects, NTDs, pyloric stenosis and talipes
what are acquired diseases of childhood and adult life?
asthma, autism, cancer, diabetes, epilepsy, glaucoma, hypertension, IBD, IHD and stroke, biploar, MS, PD, psoriasis, RA, schizophrenia
what is the effect of the environment on NTDs?
50-70% of NTDs can be prevented by maternal folic acid supplementation 1-3 months after conception
what do you inherit in alzheimers?
susceptibility
what is alzheimers?
it is the most common form of dementia over 40 years old resulting in the inability to cope, loss of memory and brain damage. It is due to the shrinkage of the brain, tangles of b-amyloid protein in nerve fibres of teh hippocampus.
what is familial clustering in alzheimers?
the relative risk to second sibling is 3-10
the early onset form of alzheimers is genetically heterogenous, what does this mean?
different genes may be involved in different families but will result in the same end stage symptoms.
what genes can be involved in genetic heterogenous alzheimers?
presenilin 1 and 2 both encode novel transmembrane aspartyl-proteases with g-secretase activity responsible for proteolytic cleavage of amyloid beta A4 precursor protein and NOTCH receptor proteins - missense mutation in APP
what has a large effect on the age of onset of alzheimers disease?
the sequence variants at the polymorphic locus - mostly due to apo-lipoprotein E which is implicated in heart disease
what are the three halotypes of APO-E proteins?
APO-EE2, APO-EE3, APO-E*E4