Day 5, Lecture 2 (Aug 26): Genetics VII: Multifactorial Disease

Question 1

Examples of Multifactorial/complex diseases

Answer 1

• Coronary artery disease
• Schizophrenia
• Autism
• Diabetes Mellitus
• Multiple sclerosis
• Epilepsy
• Rheumatoid arthritis
• Alzheimer disease
• Congenital malformations

Question 2

Spectrum of Genetic disease

Answer 2

Question 3

What is digenic

Answer 3

induced by two genes to cause phenotype

Question 4

Difference between Digenic expression and Digenic penetrance

Answer 4

• Digenic expression means that a mutation in two genes makes the expression of disease worse
• Digeneic penetrance means that you need a mutaiton in the second gene to actually express the trait

Question 5

How can discrete units like genes produce a continuous phenotype?

Answer 5

The cumulative effect of multiple genes can produce a continuous phenotype (polygenic trait)

Question 6

What is a polygenic trait?

Answer 6

Traits controlled by more than one gene

Question 7

Difference between a quantitative Trait loci (QTL) and disease susceptibility loci

Answer 7

• if the genes are contributing to a disease they are called disease susceptibility loci
• if they are contributing to a specific trait (such as height) then they are quantitative trait loci (QTL)

Question 8

Continuous phenotypes are determined by a combination of

Answer 8

• genes and environment
  
  • Example is height
    
    • not alot of genes have changed in the human genome over 100 years but environmental conditions have increased average height

Question 9

Question 10

a balance between ___ and ____ factors (and not a specific trigger) = multifactorial disease

Answer 10

Risky and beneficial factors

Question 11

What is a polygenic threshold

Answer 11

• This is the point were the level of phenotypical expression is high enough that disease is diagnosed

Question 12

Polygenic traits are

Answer 12

continuous and quantitative

Question 13

Heritability

Answer 13

The proportion of phenotypic variability explained by genetic variance- varies for different traits

Question 14

Characteristics of multifactorial diseases

Answer 14

• Familial aggregation w/o defined pattern of inheritance
• Empiric risks help determine the risk fo recurrence
• Recurrence risk is proportional to relatedness
• Recurrence risk is higher with multiple and more severely affected relatives
• There is often a sex-bias; recurrence risk is higher among relatives of the less prevalent sex

Question 15

Question 16

Empiric risk

Answer 16

The risk of a condition in a defined situation ascertained from simple observational data.

Question 17

Recurrence risk

Answer 17

The likelihood that a clinical disorder will occur in additional siblings of the same biological parents

Question 18

Question 19

Question 20

Recurrence risk of mutlifactorial traits depends on

Answer 20

Question 21

Explain Sex-specific thresholds

Answer 21

• Some diseases have a higher likely hood of being in one sex. This means that if a family member of the sex (which is in the general population is less likely to have the disease) has the disease than the risk goes up in the other members of the family
  
  • ex. Pyloric stenosis is 5 x more likely in men than women
    
    • so if a man has it then his relatives have about a 4% chance of having it but if a woman has it than her relatives have a 9% chance

Question 22

Question 23

What is an efficient way to analyze conditions that have a stong enviromental component

Answer 23

Question 24

Question 25

Familial aggregation

Answer 25

is the clustering of certain traits, behaviours, or disorders within a given family. Family aggregation may arise because of genetic or environmental similarities.