Lecture 7 - Multifactorial Inheritance

Question 1

What are polygenic traits?

Answer 1

Traits thought to be caused by multiple genes

Question 2

What are multifactorial traits?

Answer 2

Polygenic traits that are also influenced by environmental factors. Many quantitative traits are multifactorial (BP, heart rate, etc)

Question 3

What type of distribution is caused by multifactorial traits?

Answer 3

A normal distribution, as they are caused by additive effects of the environment and genetics

Question 4

How do genetic diseases compare to environmental diseases?

Answer 4

Genetic diseases in comparison are:

Rare, simple genetics, unifactorial, high recurrence rate

Question 5

Why would multifactorial disorders have a low recurrence rate?

Answer 5

Because you would need to inherit more genes as they are polygenic, and it is much easier to inherit a single gene

Question 6

What is the liability model?

Answer 6

It is a model that applies to most multifactorial disorders, which assumes that a threshold must be passed before the disease is expressed.

Question 7

If the liability model’s threshold is more towards the right for a female than a male, what does this mean?

Answer 7

It means that females will generally need to have more “problems” before they actually show the disease

Question 8

What factors increase the chance of having a multifactorial disorder?

Answer 8

1. Having a close relation to the proband (1st person identified)
2. High heritability of disorder
3. Proband is of more rarely affected sex (probably more things wrong with them)
4. Severe/early onset of disease
5. Multiple family members affected

Question 9

What does it mean if a disease has a high heritability?

Answer 9

It means that the disease is more dependant on genetics, and there aren’t too many genes involved (more chances of passing it on)

Question 10

How is data gathered about genetic risks for multifactorial diseases?

Answer 10

1. Family studies
2. Twin studies
3. Adoption studies
4. Population and Migration studies

Question 11

Why is it that the more severe the manifestation of a multifactorial condition, the greater the recurrence risk?

Answer 11

Because more genetics are involved and it will be easier to pass them on to the next generation

Question 12

What is the difference between a monozygotic twin and a dizygotic twin?

Answer 12

In monozygotic twins, there is a single sperm and egg, and a shared placenta.
In dizygotic twins, there are two sperms and two eggs, and 2 placentas

Question 13

What does concordant and discordant mean?

Answer 13

Concordance is when both twins show the same trait, and when they don’t they are discordant

Question 14

What is a consideration for determining concordance rates in dizygotic twins?

Answer 14

If the twins are different sex, then there is probably different thresholds for certain diseases, so those need to be considered

Question 15

Approximately how much of the DNA between twins are similar?

Answer 15

Monozygotic = 100% ; Dizygotic = 50%

Question 16

What are some complications in concordance studies of twins?

Answer 16

Reduced penetrance
MZ twins are often treated more alike than DZ
Environmental and developmental conditions
Somatic mutations may occur
Methylation patterns based on behaviors

Question 17

When there is a large percentage of concordance between MZ twins vs. DZ twins, what does it tell you?

Answer 17

It tells you that the disorder is probably heavily genetic

Question 18

What are some identifiable but uncontrollable risk factors for diseases?

Answer 18

Age, gender, race, family history

Question 19

What is a phenocopy?

Answer 19

The same phenotype as one that is caused by a disease gene, but it is caused by the environment

Question 20

Why is it difficult to identify specific genes for a disease?

Answer 20

1. Locus heterogeneity
2. Interaction between multiple genes
3. Decreased penetrance
4. Age-dependant onset
5. Phenocopies

Question 21

What is a major, good method to identify disease-causing genes?

Answer 21

Look for markers in people in a diseased population, and we can assume that it is inherited along with the gene

Question 22

What is an LOD score?

Answer 22

It is the logarithm of the likelihood of the two loci being linked at x% recombination frequency divided by likelihood at 50%.
A score >3 = 1000:1 chance of linkage
A score<-2 = 100:1 chance not linked

Question 23

What are some ways you can identify a disease-causing gene?

Answer 23

Linkage analysis of family studies
Affected sibling method
GWAS

Question 24

What is an SNP?

Answer 24

Single nucleotide polymorphism; must occur in 1% of population to be considered an SNP

Question 25

What is the HapMap project?

Answer 25

It is a multi-country effort to find disease causing genes

Question 26

What is a haplotype map?

Answer 26

A haplotype is a combination of alleles at adjacent loci on chromosomes that are inherited together

Question 27

What is QTL? What does it allow us to do and how?

Answer 27

Quantitative trait locus (QTL)
Breed using extreme values of trait (eg. hypertension) cross with a normal to get a heterozygote. Do this until we can figure out the smallest part of the chromosome it can be on

Question 28

One member of a pair of MZ twins is affected by an autosomal dominant disease, and the other is not. List two different ways this could happen.

Answer 28

Reduced penetrance

Somatic mutation