Lectures 13 & 14: Quantitative Genetics

Question 1

What is Quantitative Genetics?

Answer 1

The study of the inheritance of characteristics that do not fall into distinct classes.

Question 2

What are quantitative trait loci, QTLs?

Answer 2

Quantitative trait loci (QTLs) are stretches of DNA containing or linked to the genes that underlie a quantitative trait.

Question 3

Define Heritability

Answer 3

The proportion of total variation in the population that is due to genetic variation

Question 4

What does a high heritability indicate?

Answer 4

That there is a high proportion of the phenotype which can be attributed to shared genes, shared environments or both. High heritability does not indicate that the characters with high heritability are insulated from environmental effects

Question 5

Define broad sense heritability

Answer 5

the proportion of total phenotypic variation which is due to genetic variation

Question 6

Define narrow sense heritability

Answer 6

The proportion of total phenotypic variation that is due to additive genetic variation

Question 7

Narrow sense heritability is easily measured in humans; T/F

Answer 7

False; applies more to animal and plant breeder because it determines responses to selection

Question 8

T/F: Heritability is a ratio

Answer 8

True

Question 9

What type of distribution is seen with quantitative traits?

Answer 9

Normal Distribution

Question 10

What is “regression to the mean”?

Answer 10

When two people with similar quantitative characteristics mate and the offspring have the characteristic closer to the mean rather than the same measure of that characteristic

Question 11

Why don’t quantitative diseases follow the pattern expected of single-gene disorders?

Answer 11

There is an underlying liability in the distribution of complex diseases in a given population

Question 12

What does liability mean?

Answer 12

The factors that contribute to the disease manifestation

Question 13

What are the facts about multifactorial inheritance?

Answer 13

Most affected children have normal parents, Recurrence risk increases with the number of children affected in a family, Recurrence risk increases with severity of defect, rick of affected relatives falls off very quickly with the degree of relationship

Question 14

Why does the affected relatives fall off quickly with the degree of relationship?

Answer 14

The many genes and environmental factors must combine to produce the disease-phenotype

Question 15

What is correlation?

Answer 15

The tendency of two measures on different individuals, or two different measures on the same one, to vary in parallel.

Question 16

Which two statistical measures are taken into account when calculating correlation?

Answer 16

Mean and Variance

Question 17

What is covariance?

Answer 17

The multiplying of the deviation of a point on the x axis from the mean x and its deviation on the y axis from the mean y

Question 18

What is the range for covariance?

Answer 18

-1 to 1

Question 19

What does covariance measure?

Answer 19

Only the precision of the relationship between two variables but not the extent to which one increases given a unit increase in the other

Question 20

What is the equation for heritability?

Answer 20

H^2 = Vg/Vp

Question 21

What is the equation for Vp?

Answer 21

Vp = Vg + Ve + Vge

Question 22

Does a strong genetic correlation disprove the importance of the environment in multifactorial traits?

Answer 22

No

Question 23

Monozygotic twins are the result of..

Answer 23

One fertilization event followed by the separation of blastomeres into two groups during cleavage

Question 24

Separation before trophoblast tissue formation at day 5 =

Answer 24

embryos have two separate chorions and amnions

Question 25

Separation between day 5 and 9 is when

Answer 25

the amnion lining forms and thus the embryos have one shared chorion and two amnions

Question 26

Separation after day 9 =

Answer 26

embryos share one chorion and one amnion

Question 27

T/F Dichorionic MZs survive better than monochorionics

Answer 27

True, the later the embryo splits the more likely the twins are to be monochorionic or even conjoined

Question 28

What is twin-twin transfusion?

Answer 28

When blood supplies are shared in the womb and one twin begins to take blood from the other. Donors grow to be anaemic and underweight whilst recipients are overweight and have heart problems.

Question 29

What are adoption studies?

Answer 29

These are studies which compare adopted children with their biological parents and their adoptive parents. They share genes with their biological parents but not environments, but they share environments but not genes with their adoptive parents.

Question 30

What was the conclusion of the adopted-away children studies of schizophrenia?

Answer 30

The incidence of schizophrenia in adopted-away children of schizophrenic mothers was ~10%, roughly the same as that of the children of schizophrenic mothers who bring up children in their own home.

Question 31

What is the family method adoption design?

Answer 31

Using schizophrenia as an example; Do a large survey of all adopted children and find those that become schizophrenic. Take a control group of the same size of adopted children who do not become schizophrenic. The question is how many of the biological parents of the schizophrenic children get the disease compared to the biological parents of the control (adopted but not schizophrenic) group?

Question 32

What is the candidate gene approach?

Answer 32

This is the search for genes that might perhaps be involved because we know their function and see if they are associated with the disease we are interested in.

Question 33

What is the case-control approach?

Answer 33

Take a large number of people with a disease (heart disease, schizo-) and a large matched group of unaffected people for the control group and scan the whole genome, either with HapMap or sequencing technology.

Question 34

Why is there a lack of power to detect genome-wide association?

Answer 34

There is highly stringent significance thresholds required as a result of multiple testing and the unrealistic assumption that by testing each SNP one at a time one of the markers in the genotyping platform used will either be the causal or in almost complete linkage disequilibrium with the causal variant.

Question 35

In GWAs, what is the problem with large study numbers?

Answer 35

Data sets often include cases with variable disease onset, variable phenotype definition and sample collection in different geographic regions. This increases probability of a causal variant to be missed.

Question 36

What is the likely mode if inheritance for Very early onset AD

Answer 36

simple dominant

Question 37

Why are the genetics of AD difficult to establish?

Answer 37

A question of penetrance; symptoms do not come until advanced age.