Term
| Do genes contribute to diseases with complex inheritance? Are these diseases single gene disorders? Do these diseases demonstrate a simple mendelian pattern of inheritance? |
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Definition
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Term
| Complex diseases result from interactions between a number of genetic and environmental factors, because of this they are said to follow what sort of inheritance pattern? |
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Definition
| multifactorial (or complex) inheritance pattern |
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Term
| Why do diseases with complex inheritance often demonstrate familial aggregation? What is familial aggregation? |
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Definition
Familial aggregation means that these diseases cluster and run in families
They tend to do so because relatives of an affected individual are more likely to experience the same gene-gene and gene-environment interactions that led to disease in the proband than are individuals unrelated to the proband |
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Term
| Define concordant and discordant. |
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Definition
Concordant is when two related individuals in a family have the same disease
Discordant is when only one member of the pair of relatives is affected and the other is not |
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Term
| Complex diseases are more common among the close relatives of the pro band and become less common in relatives who are less closely related and therefore share fewer predisposing alleles. Based on this what would you think of the concordance expected between monozygotic and dizygotic twins? |
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Definition
| greater concordance for the disease is expected among monozygotic versus dizygotic twins |
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Term
| Pairs of relatives who share disease-predisposing genotypes at relevant loci may still be discordant for the phenotype (show lack of penetrance), why is this? What is the most extreme example of this? |
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Definition
Because of the crucial role of non-genetic factors in disease causation
*the most extreme example of this is discordant monozygotic twins |
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Term
| The complex phenotypes of multifactorial disorders can be divided into two major categories: qualitative traits and quantitative traits. Define each. |
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Definition
-Qualitative traits= a genetic disease that is either present or absent. For qualitative traits we use concordance as an estimate of heritability (alzheimer's, schizophrenia)
-Quantitative trait: a measurable physiological or biochemical quantity, such as height , BP, serum cholesterol concentration, and BMI. For quantitative traits we can measure heritability. |
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Term
| There are two types of phenotype variation, genetic variance and environmental variance. Explain them. |
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Definition
-Genetic variance= the phenotypic variance of a trait in a population that is attributed to genotypic differences
-Environmental variance= the phenotypic variance of a trait in a population that is attributed to differences in the environment |
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Term
| What is Heritability (h^2)? What is its range? |
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Definition
-An expression of how much of the observed variation in a phenotype is due to differences in genotype
-Ranges from 0 to 1
-If a trait has a variability of 1.0, it means that all phenotypic variation in the population is caused by genotypic differences |
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Term
| What is the equation to compute the relative risk ratio when measuring familial aggregation in qualitative traits? |
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Definition
| (prevalence of the disease in the relatives of an affected person)/(prevalence of the disease in the general population) |
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Term
| What are case-control studies in relation to measuring familial aggregation in qualitative traits? |
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Definition
| Patients with a disease (the case) are compared to suitably chosen individuals without the disease (the controls) with respect to family hx, environmental exposures, other illnesses, and so forth |
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Term
| The more closely related two individuals are in a family, the more _________ they have in common. The more distantly related the relative is to the proband, the fewer ________ they share |
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Definition
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Term
| What is one approach to dissecting the contribution of genetic influences from environmental effects in multifactorial disease? |
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Definition
| compare disease concordance in relatives who are more or less closely related to the proband |
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Term
| When genes are important contributors to a disease, the frequency of disease concordance (increases/decreases) as the degree of relatedness (increases/decreases) |
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Definition
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Term
| What are unrelated family member controls in relation to determining the relative contributions of genes and environment in complex disease? |
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Definition
| comparing the incidence of disease in unrelated family members (adoptees, spouses) with that in biological relatives |
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Term
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Definition
They study MZ and DZ twins; the degree of concordance for a trait is compared in MZ and DZ twins reared together and apart
-the greater the difference, the greater the heritability |
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Term
| DZ twins share about ______% of their genes |
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Definition
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Term
| The concordance in MZ twins for nontraumatic epilepsy is 70% and for DZ twins its 6%. What does this tell you about the heritability of the trait? |
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Definition
| The large difference between the two shows that there is a huge heritable component, but since the MZ concordance is not 100% it means that there must be some environmental factors as well |
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Term
| What is the normal distribution with respect to genetic analysis of quantitative disease traits? |
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Definition
| quantitative traits can be graphed, with the number of individuals in the population on the y-axis and the quantitative trait on the x-axis, which produces a normal distribution of the trait that is governed by mean and variance of the trait |
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Term
| How is the normal range computed? |
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Definition
| it is determined from the normal distribution with limits of the normal range usually defined by +/- two SD of the mean |
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Term
| How can family studies be used to determine the role of heredity in quantitative traits? |
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Definition
| by measuring the correlation of particular physiological quantities among relatives. That is, the tendency for the actual values of a physiological measurement to be more similar among relatives than among the general population |
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Term
| What is the coefficient of correlation (r) with respect to measuring familial aggregation in quantitative traits? |
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Definition
| It is a statistical measure applied to a pair of measurements. The objective is to find out whether the pair of measurements show relationships to each other more consistently than we would expect from chance alone. r can range from 0 for no correlation, to +1 for a perfect positive correlation, to -1 for a perfect negative correlation |
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Term
| What is the equation for estimating heritability from twin studies? |
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Definition
| h^2= (variance in DZ pairs- variance in MZ pairs)/ variance in DZ pairs |
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Term
| What does it mean if the heritability measurement from twin studies is 0? |
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Definition
| it means the variability of a quantitative trait is caused mainly by the environment, therefore the variance between DZ and MZ will be about the same and the numerator and heritability will be 0 |
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Term
| What does it mean if the heritability from a twin study is 1? |
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Definition
| the variability of the quantitative trait is caused only by genes, then the variance of MZ twins will be 0 and the heritability will be 1. |
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