Multifactorial Inheritance Flashcards
Qualitative trait
have or dont have eg parkinsons disease or cleft palate
quantitative
measurable such as blood pressure
familial aggregation
qualitative trait affected individuals affected tend to cluster in families if theres a genetic component relatives share a greater portion of their genes win one another than with unrelated individuals not always genetic component: chance cultural attitudes diets exposures ect..
concordance
if you are looking at two individuals they both have it
discordance
if you are looking at two individuals one has it one doesnt
genocopy
different genotypes but same condition eg diabities (different causes)
phenocopy
environmental or non genetic factor mimics genetically caused phenotype
relative risk
prevalence of the disease in a relative r of an affected person/population prevalece of disease r= class of relative ( siblings parents cousin ect)
allele sharing between relatives (siblings
- sibs share both alleles for a locus or no alleles 25%
- 50% of the time they share only one allele
- twins share 100% of alleles
- parent -sib
- share one allele all the time
case control studies
take individuals affected with diseas then look for family members without disease for factors such as family history
eg parkinsons disease 6.3% of affected indviduals have relatives affected vs only 1.2% of relative affected for the controls
ascertainment bias
increased awareness in proband family
recall bias
probands family more motivated to respond to a quenstionnair because of familiarity of disease
choice of controls
similarity in all other respects is important
for case contol studies an association may not prove causation eg. ethnicity and dietary habits may be related
twin studies
since MZ and DZ twins share the same environment and household share the same environmental and social backgrounds concordance with MZ vs DZ twin pairs is a good way to access a genetic component of a disease
limitations of MZ twin studies
- x inactivation is random
- somatic rearangments in the immunoglobin or t-cell receptor loci
- disparity in fetal blood supply
- results of concordance studies are avrages that do not
- reflect concordance for individual genotypes
- bias during recruitment
threshold effects
for qualitative traits there may be a complement of genetic and environmental factors predisposes to expression of the phenotype
some times multiple things must happen to have it show up
if threshold is lower then it is more likeley to have disease
continuous trait
- eg hight skin color blood sugar obesity ect
- in multigenetic trait each dominant allele contributes a specific quanity twords phenotype eg 3 in height to base value of height
- results in a bell shaped distribution of phenotypes
coefficient of correlation r
measurment of a pair of quantities : blood pressure of proband and the average BP of the probands siblings
positive correlation
the higher the probands blood pressure the hugher bp of the relative group being studied
negative
the higher the probands bp the lower the bo of the relative group being studied
multiple factor hypothesis
- t= u + g+e
- u= mean
- g = genetic factor
- e= environmental factor
variance in quantitative trait
- = square of the standard deviation =Vt(phenotypic variance)
- phenotypic variance
- Vt=Vg+ Ve
heritability
- H2= proportion of a populations phenotipic variance Vt that is attributable to genetic factors
- H2=Vg/Vt
- the higher H2 the greater contributions of genetic factors
*
heritability from twin studies
-h2=(variance in DZ twin-variance in MZ twin )/variance in DZ twins
complex inharutance factors
- does not exibit mendelian inheritance patterns
- demonstrates familial aggregation
- risk increases with increae in number of family memmbers affected
- magnitude of risk difference decreases as the incidence in the population increases
- for qualitative traits
- the risk of recurrence increases as severity of disease in relative increases
retinitis pigmentosa
- qualitative disorder (complex inheritance) has two magor genes (rom1=null and peripherin=missense)
- digenic inheritance
- either heterozygote is not affected: double heterozygote developes disease
- singlle gene homozygotes are not severyly affected
- *
coronary atery disease (CAD)
- hardening of the arteries on the surface of the heart
- major risk factors
- familial hypercholesterolemia type II( LDL receptor deficiency)
- elevation in plasma cholestoral and LDL or hyperlipoportenemias
- impropersynthesys /function of one ore more apolipoprtein levels of Lp(a)
- leves of homocystein chemoattractant and oxidizing agent
effect of Apo(a) on clot dissolution
alzheimer disease
familil aggregation ( 38% of relatives affected indiidual are affected) mono genic form
10% INDIVIDUALS HAVE MONOGENIC FORM
90% have sporadic form which may be caused by combination of genetic and environmental factors
genes that are know for riskfactors for alzhemire
Amyloid precursor protein (beta APP)
correlation of apolipoprotein E alleles and alzheimer disease
4/4 is the worst followed by 2/2 is protective steeper the curve the higher the risk
Heritability is a measurement that estimates the proportion of
phenotypic variation in a group that can be attributed to genes.
For a qualitative trait with a threshold effect:
males and females may have different thresholds
Disease concordance of less than 100% in MZ twins is strong evidence that:
non genetic factors play a role in the cause of disease
Comparing the frequency of the disease in relatives of an affected individual with its frequency in the general population is called:
Relative Risk
Siblings share ____% of their genes while fraternal twins share ____% and identical twins share ____% of their genes (on average).
50, 50, 100
What is familial aggregation?
Affected individuals tend to cluster in families if there is a genetic component.
The fact that two family members who share a genetic disease phenotype are more likely to participate in a family study than two who are discordant is a form of:
Ascertainment bias
Which of the following is the first known powerful, predisposing allele for common, late-onset Alzheimer disease?
Apo e4
If a complex disease has a high genetic component, the Relative risk ratios for monozygotic twins will be:
much higher compared to those for dizygotic twins
Assume a multifactorial disorder (disease X) is found around the world at a higher frequency among males than females. Which of the following is true?
The recurrence risk for disease X is highest for a couple with an affected daughter.
In an effort to identify the influence of genetic factors on both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, researchers calculated concordance rates for monozygotic (MZ) twins. Concordance rates of 30 –50% have been found for IDDM. Concordance rates of 80% were observed for NIDDM. For both types of diabetes, dizygotic (DZ) concordance rates were 15%. What does this information suggest concerning the relative effect of genetic and environmental factors for each type of diabetes?
Genetic influences exert a larger role in NIDDM than in IDDM
An adoption study was initiated in an attempt to determine whether depression has a genetic basis or is due strictly to environmental factors. Adults with depression who were adopted as infants were recruited into the study as cases. The frequency of depression was compared between the biological and non-biological adoptive relatives of the cases. If depression has a strong genetic component, what is the most likely finding of this study?
Depression rates are higher for biological relatives
