Lecture 23

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Questions and Answers

What proportion of genetic variations in the human genome can explain differences in phenotypes and susceptibilities to diseases in a population?

10%

50%

0.1% (correct)

What is the term for the proportion of phenotypic variation in a quantitative trait that is due to genetic factors?

Genetic variation

Phenotypic variation

Genomic contribution

Heritability (correct)

What can studying the prevalence and incidence of a disease in a population help explain?

Environmental factors only

Migration patterns only

Cultural differences in a population

Genetics of a disease (correct)

What is the formula used to calculate heritability (h2) in twin studies?

h2 = 2 [r(MZ)-r(DZ)] Signup and view all the answers

What happens to the disease incidence in the migrant group over time if there is a genetic component to the disease?

It rises to the same level as the host population Signup and view all the answers

Why are monozygotic twins useful in studying the genetic susceptibility to diseases?

Because they have the same genotype Signup and view all the answers

What is the assumption made when using twin studies to calculate heritability?

Environmental variation is identical Signup and view all the answers

What does a high concordance in monozygotic twins and a low concordance in dizygotic twins indicate?

A strong genetic influence Signup and view all the answers

What is the range of values for heritability (h2) in a population?

0 to 1 Signup and view all the answers

What is the purpose of comparing identical twins separated at birth in twin studies?

To estimate heritability more accurately Signup and view all the answers

What is the purpose of twin studies in assessing genetic susceptibility to diseases?

To assess the contribution of genetics and environmental factors Signup and view all the answers

What does the correlation coefficient (r) represent in twin studies?

The correlation between monozygotic and dizygotic twins Signup and view all the answers

What can be concluded if rMZ > rDZ in a twin study?

Genetic factors are important Signup and view all the answers

How similar are humans in terms of their genome?

They differ by 0.1% Signup and view all the answers

Who first proposed the concept of polygenic inheritance in 1918?

Ronald Fisher Signup and view all the answers

What type of distribution do the variations in certain traits follow in polygenic inheritance?

Normal distribution Signup and view all the answers

Which of the following human characteristics shows a continuous normal distribution?

Blood Pressure Signup and view all the answers

What would be the result if height was determined by two loci?

A discontinuous phenotype of 5 groups Signup and view all the answers

What is the effect of increasing the number of loci involved in a trait?

The distribution starts to resemble a normal curve Signup and view all the answers

How many genes are involved in controlling skin pigmentation in humans?

Many genes Signup and view all the answers

What are the dark alleles for each gene controlling skin pigmentation?

A, B, and C Signup and view all the answers

What is the author of the book 'Medical Genetics'?

Jorde, Carey and Bamshad Signup and view all the answers

What is the genotype of the darkest skin in the model?

AABBCC Signup and view all the answers

How many possible phenotypes can result from mating between an AaBbCc couple?

Seven Signup and view all the answers

What is the correlation between first-degree relatives for a polygenic trait?

0.5 Signup and view all the answers

Why can tall parents have short children?

All of the above Signup and view all the answers

What is the name of the model proposed by Sewall Wright in 1934?

Liability/Threshold Model Signup and view all the answers

What is the term for the accumulation of all influencing factors, genetic or environmental, in a population?

Liability Signup and view all the answers

What determines whether an individual is a disease case in the Liability/Threshold Model?

The threshold value Signup and view all the answers

What can be revealed by comparing the distribution of liabilities in the general population versus relatives of affected individuals?

The genetic component of the disease Signup and view all the answers

What is the purpose of association studies in genetics?

To compare the frequency of a particular variant in affected patients vs a control group Signup and view all the answers

What is the odds ratio in association studies?

A measure of the strength of association between a variant and a disease Signup and view all the answers

What is the limitation of association studies?

Association does not prove causation Signup and view all the answers

Why may many of the associations discovered through the candidate gene approach not be replicated in independent studies?

All of the above Signup and view all the answers

What is the purpose of figure 10.7 in the context of association studies?

To compare the mean trait values for each genotype group Signup and view all the answers

What is the typical range of odds ratio for most markers in a multifactorial disease?

1.1-1.5 Signup and view all the answers

What is the consequence of a variant being associated with a disease?

Both a and b Signup and view all the answers

What is the term for the false positive results in association studies due to poorly designed studies?

False positive Signup and view all the answers

Study Notes

Studying Disease Prevalence and Incidence

Migrating groups can help explain the genetics of a disease: if a group with low incidence of a disease moves to a population with high incidence, the disease incidence may rise to the same level as the host population.
If the disease incidence remains the same in the migrant group, it suggests that genetic factors play a significant role in the disease.

Approaches to Demonstrating Genetic Susceptibility

Family and Twin studies:
- Problem: familial aggregation of a disease can be due to shared environment or genetics.
- Solution: study frequency of disease in dizygotic vs monozygotic twins.
- High concordance in monozygotic twins but low concordance in dizygotic twins indicates genetic susceptibility.
Twin studies:
- Assess the contribution of genetics and environmental factors to traits.
- Monozygotic twins are genetically identical (100%), while dizygotic twins share 50% of their genetics.
- If rMZ > rDZ, genetic factors are important; if rDZ > ½ rMZ, shared environment is important.
Polymorphism association studies:
- Humans differ by 0.1% in their genome, which can explain differences in phenotypes and disease susceptibility.
- Single nucleotide polymorphisms (SNPs) can be associated with diseases.
- However, SNP association does not equal SNP causation.

Estimating the Genetic Contribution in Common Diseases

Heritability (h2): the proportion of phenotypic variation in a quantitative trait that is due to genetic factors.
Calculating h2 using Falconer's formula: h2 = 2 [r(MZ)-r(DZ)].
Comparing identical twins separated at birth can provide more accurate results.
h2 values range from 0 to 1, with higher values indicating a greater genetic contribution.

Polygenic Inheritance and the Normal Distribution

Polygenic inheritance: the additive effects of multiple genes explain variations in certain traits that follow a continuous/normal distribution.
Examples of traits that follow a normal distribution: blood pressure, height, intelligence, body mass index, and skin color.
The more loci involved, the more the distribution resembles a normal curve.

Skin Pigmentation

Skin pigmentation is controlled by many separately inherited genes.
A simplified model: three genes with dark alleles A, B, and C, and light alleles a, b, and c.
Each dark allele contributes to one unit of darkness, with the darkest skin being AABBCC and the lightest being aabbcc.

Multifactorial Inheritance and the Liability/Threshold Model

Disorders like cleft lip involve the contribution of many genetic loci but do not follow a continuous distribution.
The liability/threshold model: all influencing factors are considered a single entity known as liability.
Liabilities form a continuous normal distribution, and an individual is a disease case only if the underlying accumulated liability lies above a certain threshold.
The genetic burden of a disease can be revealed by comparing distribution in the general population vs relatives of affected individuals.

Associating Genetic Variants with Disease

Association studies: compare the frequency of a particular variant in affected patients vs frequency in a control group.
Evidence of association: if the frequencies in the two groups differ significantly.
Odds ratio: gives an indication of how much more frequently a disease occurs in individuals with a specific variant/marker.

Limitations of Association Studies

Association does not prove causation.
Many associations discovered through the candidate gene approach could not be replicated in independent studies (FALSE POSITIVES).
Reasons for false positives include small sample size, weak statistical support, and low prior probability of a selected variant being genuinely associated with the disease.

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Description

This quiz explores the relationship between disease prevalence and incidence in a population, and how it relates to migration and genetics. It also covers the conclusions that can be drawn from changes in disease incidence over time.