TBL Multifactorial inheritance and Risk Application

Question 1

Multifactorial inheritance

Answer 1

refers to the idea that both genetic AND environmental factors are involved in influencing gene expression

Question 2

Simple Mendelian traits

Answer 2

are inherited and determined solely by dominant/recessive patterns

Question 3

Complex traits

Answer 3

controlled by polygenic or quantitative inheritance

Question 4

Polygenes

Answer 4

normal distribution generated by many genes

Question 5

 Polygenic/quantitative inheritance

Answer 5

inheritance and expression of a phenotype is determined by many genes at different loci, with each gene exerting a small additive effect

Question 6

additive

Answer 6

effects of genes are cumulative

Question 7

Characteristics that show a continuous normal distribution

Answer 7

Blood pressure Dermatoglyphics (ridge count)
Head circumference Height
Intelligence
Skin color

Question 8

Type 1 Diabetes

Answer 8

Greater evidence for familial clustering. Age of onset: Childhood/adolescence. Inheritance: Polygenic. B-Cell Dystfunction

Irreversibel destruction of insulin-producing islet Beta cells in the pancreas by the body’s own immune system
• Greater evidence for familial clustering but there are environmental factors as well.
• HLA region on chromosome 6p21 with TIDM association via B8, B15 and DR3, DR4
• Insulin gene on chromosome 11p15 via the INS VNTR where normally it may protect insulin-producing B cells viewed as foreign by immune system.
• Another near CTLA4

Question 9

Type 2 Diabetes

Answer 9

Age of onset: Middle/old age. Inheritance: Polygenic. Insulin secretion/resistance.

Prone to macro/microvascular diabetic complications
• Candidate mutation genes: PPARG, KCNJ11, WFS1, HNF1B, HNF1A
• Individuals who inherit two risk alleles are twice at risk to develop T2DM via the TCF7l2 Locus.

Question 10

Crohn’s Disease

Answer 10

Inflamatory Bowel Disease.
• CARD15 gene.
• IRGM and aTG16L1 genes have explaiend a deletion which change the autophagy fo bacteria inside cells.

Question 11

Hypertension

Answer 11

Two groups: (1) as the consequence of another disorder (2) Essential hypertension

Environment: High diet sodium levels, obesity, alcohol intake, reduced exercise.
Genetic Factors: Familial
Susceptibility Genes:SLC12A3, SLC12A1, KCNJ1, chromosome 12q24

Question 12

Coronary Artery Disease

Answer 12

High level of LDLs, First degree relative risk

Question 13

Schizophrenia

Answer 13

Grossly disorganized thought processes and behavior
Genetic contribution unclear. But there is a suggested importance of environemtnal factors.
Mutation deletions associated with condition
Immune system component to the risk of the disease.

Question 14

Alzheimer’s Disease

Answer 14

Postmortem examination we find amyloid deposits in neurofibrillary tangles and neuronal/senile plaques
Environmental factors important. May be invovled with tau proteins

Question 15

First Degree relatives and proportion

Answer 15

Parents, Siblings, Children

1/2 (0.5)

Question 16

Second Degree relatives and proportion

Answer 16

Uncles/Aunts, Nephews/Nieces, Grandparents, Grandchildren, Half-siblings
1/4 (0.25)

Question 17

Third Degree relatives and proportion

Answer 17

First cousins, great-grandparents, great-grandchildren

1/8 (0.125)

Question 18

Heritability

Answer 18

proportion of the total variance of a trait that is caused by genes (h2), higher the heritability the more likely to inherit the disease

Question 19

λs

Answer 19

the ratio of risk to SIBLINGS of affected individuals compared to the general population incidence.

A Lower λs indicates a lower heritability factor, and suggests more environmental factor involvement.

Question 20

Law of addition

Answer 20

: if events are mutually exclusive, then the probability that either one or the other will occur equals the sum of their individual probabilities

Question 21

Law of Multiplication

Answer 21

: if two or more events or outcomes are independent, then the probability that both the first and the second will occur equals the product of their individual probabilities

Question 22

Concordance rate

Answer 22

the presence of the same trait in both members of a pair of twins.

Question 23

Purely genetic trait

Answer 23

• monozygotic twins (from same embryo and genetically “identical”) would share the trait 100% of the time; this would be 100% concordance
• dizygotic twins (essentially siblings because they share 50% of their genes), there would be a 50% concordance rate

Question 24

For a trait that is purely determined by the environment

Answer 24

expect the SAME concordance in mono and dizygotic twins

Question 25

Prior probability

Answer 25

: The initial probability of an event, based on ancestral or anterior information

Question 26

Conditional probability

Answer 26

: Observations or tests that can be used to modify prior probabilities using Bayesian calculation in risk estimations. “The chance that certain observed events would have happened if each possibility were true.” Based on posterior information

Question 27

Joint probability

Answer 27

The resulting product event for each event/outcome.

Question 28

Posterior/Relative probability

Answer 28

dividing the joint probability for that event by the sum of all the join probabilities.

Question 29

1 standard deviation

Answer 29

68%

Question 30

2 standard deviations

Answer 30

95%

Question 31

3 standard deviation

Answer 31

99%