B&B Genetics Flashcards
inheritance that does not follow one of the mendelian patterns seen in single-gene disorders but complex diseases; arises from genetic factors and environmental factors
-empirically-derived risk figures are given to patients, because geneticists do not have an explanation for the underlying mechanisms of gene-gene and gene-environment interactions
multifactorial inheritance
disease is present or absent
-discrete trait
qualitative trait
measurable, physiological or biochemical quantities such as height, bp, cholesterol, BMI, factors underlie many of the devastating illnesses
quantitative trait
affected individuals cluster in families
familial aggregation
two related individuals in a family have the disease
concordance
only one family member of a pair has the disorder/disease
discordance
λr = (prevalence of disease in the relatives of an affected person)/(prevalence of disease in general population)
relative risk ratio
indicates that a relative is NOT more likely than any other individual in the population to develop the disorder
relative risk ratio = 1
disease concordance < 100% in MZ twins
strong evidence nongenetic factors play a role in disease
greater concordance in MZ twins versus DZ twins
strong evidence the disease has a genetic component
limitation of twin studies
- MZ twins do not have identical gene expression, despite starting with identical copy
(ex: random X inactivation, disparity of conditions within the womb, somatic rearrangements in immunoglobulin & T cell receptor loci) - MZ twins who volunteer for a study are more likely to be in concordance than those MZ twins asked to participate in a study
the square of the standard deviation
variance
the spread of values on either side of the mean
standard deviation
the variance of a measured quantity in the population
total phenotypic variance
quantifies the role of genetic differences in determining the variability of quantitative traits
-Reflects the measure of the extent to which different alleles at various loci are responsible for the variability in a given quantitative trait seen across a population
value = 0 means genes contribute nothing
value = 1 means the genes are totally responsible for phenotypic variance
= (variance in DZ pairs - variance in MZ pairs)/ variance in DZ pairs
heritability (h^2)
relationship exists
range 0 to +1
positive correlation
no similarity
range 0 to -1
negative correlation
limitations of heritability
- relatives share environment as well as genes
- high heritability does not reveal the number of loci involved or how those loci interact
- cannot be considered in isolation from the population group (ex: living conditions)
Common errors in risk calculation
- if children only share one parent, they are second-degree relatives, not first
- when an uncle or aunt asks about the risk of the defect in their offspring, the relevant risk is specific to the offspring & they are third-degree relatives
- be suspicious that diseases with unusual pattern are caused by a single gene with mendelian inheritance pattern, masked by small family size and incomplete penetrance
- protein component of LDL particle involved in clearing LDL through interaction with high affinity receptors in the liver
- participates in lipid transport between tissues and cells
- function in brain is unknown
- constituent of amyloid plaques that binds AB-peptide in Alzheimer’s disease
ApoE
mutations associated with early onset Alzheimer’s disease
- APP
- PSEN1
- PSEN2
Note: ApoE mutations not associated with monogenic AD but its presence increases risk
cofactor for gamma secretase
PSEN1
maintains neuronal integrity, influences microtubule assembly maintaining polarity and axonal transport
tau protein
fully penetrant mutations in Alzheimer’s disease
APP
PSEN1
*PSEN1 is associated with early onset at age 45 with rapid progression
not fully penetrant mutation in Alzheimer’s disease that is associated with slow progression
PSEN2
