Multifactoral Disorders Flashcards
Complex traits or multifactorial diseases result from what
complex interactions of genetic & enviornmental factors
Describe family clustering
“running in families”
families share genetic & environmental risk factors
are multifactoral disorders genetic?
combined affect of different genes but there is also environmental comnponene
Most phenotypic traits in humans are:
multifactorial traits
in fully penetrant diseases, other genes and enviornmental factors:
have no affect
describe penetrance in multifactorial diseases
each gene has reduced penetrance, and a lot of genes play a small part in the disease
what are polygenic traits
many different genes having affect on phenotype
what is susceptibility gene
some genes having larger effect on phenotype
what is oligogenic traits
multiple genes, but less (like 4-5 genes instead of 20)
what is variable expressivitiy
A common feature of multifactorial disorders, due to the interactions of these multiple genes with multiple environmental factors
what are quantitative traits
traits that have continuous variability
like height, body mass, cholesterol levels
what are qualitative traits
they are either present or absent
they have disease or they don’t have diseaes
height is example of what kind of trait
quantitative
what measures the spread of the curve
variance or standard deviation
quantitative traits generall folly what in the population
normal distribution
how do many genes lead to bell shaped curve (what theory)?
polygenic theory
what is polygenic theory
every gene has additive affect on phenotype, as you add more genes the distribuation will form a bell shaped curve, the more genes the more like a bell shaped curve it gets
what will give total risk person has for disease
add the genetic and enviornmental risk and protective factors
What is “Liability”
total risk that a person has, combined affect of all the differnent enviornmental and genetic factors
AKA susceptibility
Describe population/migration studies
look at different incidence rates among different populations - try to see what is enviornmental and what is genetic
Describe Adoption studies
compare adoptive family to biological family
adoptive family you can look at enviornment effects
biological family you can look at genetic effects
Describe Affected Family Studies
related family members at higher risk, this looks at the affected family members and try to see what they have in common vs. the unaffected family members
What are case-control studies
look at correlation b/w genetic and environmental factors
what is a good control that is not genetically related but same enviornment
spouses
What is one way to measure (empirically) relative risk ratio
sibling risk ratio
what is the sibling risk ratio telling you
risk sibilng has compared to everyone else in population
if sibling risk ratio = 1 what does it mean
sibilng of affected person no more likely to have disease than anyone else in population
if sibling risk ratio >1 what does it mean
sibilng more likely than other people in pop. to have disease
what is the sibilng risk ratio
prevalence of disease in the sibilngs of affected person/ prevalence of diseases in the general population
in general, the greater the number of affected relatives, the:
greater the genetic effect
what are the advantages of twins
age matched
genetic similarity
intrauterine and early childhood environments similarity
what are thw two types of twins
monozygotic & dizygotic twins
wht are monozygotic twins
genetically identical, same intrautrering enviornment
what are dizygotic twins
no more genetically identical than sibs
share intrauterine enironment
how many common genes do monozygotic twins have
100% of genes in common
what is concordance
measure of when 2 individuals share the same trait
what is discordance
individuals do not share the same trait
what are concordance rates for monozygotic twins
100%
what is the strongest indicator of genetic vs. enviornmental contribution
monozygotic concordance
the higher the monozygotic concordance rate, the:
higher the genetic component
If MZ > DZ concordance rates what does it mean
genetic component
If there are low concordance in MZ and DZ twins what does it suggest
stronger contribution of environmental factors
what is the bias in twin studies
MZ twins are treated more the same than DZ twins, so enviornment is more similar than DZ twins
can you do concordance studies with quantitative traits
no
can’t do it with something like height
what do you use to study quantitative traits
heritability
what does heritability measure
compares degree of variance (spread of curve) b/w MZ & DZ twins
If h^2 = 1 what does it mean
condition is only genetically determined
If h^2 = 0 what does it mean
condition is only determined by enviornmental factors
the greater the h^2 number, the:
greater the genetic influence
how do quantitative traits determine qualitative traits
liability threshold model
describe liability threshold model
if person’s liability exceeds some threshold, then disease will present
once person is beyond threshold, the further they are beyond the threshold - the greater the severity of the presentation of disease
what happens to liability curve of family members of affected individual
the curve shifts to the right
how far curve is shifted to right in liability threshold model depends on what
the degree they are related - so first degree relatives will shift far to the right.
there is greater ____ in family members (regarding liability threshold model)
liability
the more severely the family member is, what happens to the liability curve
shifted further to right for them and family members
if uncommon gender is affected, what does that mean**
if uncommon gender is affected, their children are at higher risk of being affected, esp if their children are the common gender
are children of uncommon or common gender more at risk
uncommon gender
In a bell graph will the uncommon gender be the line to the right or the left
the left - the uncommon gender isn’t the one who is usually affected, so when they are it is more severe
What are the two clinical types of Alzheimers
early onset
late onset
What is the MOI of alzheiemer (early onset)
AD
Which form of alzheimer is the sporadic form/multifactoral
late onset
What are the three genes that could lead to the familial form of alzheimers (they are mendelia AD)
amyloid precursor protein (APP) presenilin 1 (PSEN1) presenilin 2 (PSEN2)
What form in extracellular space in alzheimer
plaques
What does APP mutation lead to
more amyloid beta precurosr proteins - greater risk for alzherimer
What kind of mutation causes amyloid precursor protein (APP)
presenilin 1 (PSEN1)
presenilin 2 (PSEN2)
to make alzheimer
Gain of function
What does ApoE stand for
Apolipoprotein E
What does ApoE do?
related to cholesterol
what are the three common alleles of APOE
epsilon2, 3, 4
what is result of epsilon 2 allele of APOE
protective
what does epsilon 3 do of APOE
wildtype
What does epsilon 4 of APOE do
greater risk of late-onset an sporadic form of AD
Alleles of APOE are associated with what
greater risk for alzheimers depending on which allele
