Lecture 43: Multifactorial

Question 1

Multifactorial

Answer 1

-Disease caused by both Gene and environment

Question 2

Types of genetic disorders

Answer 2

1) Single gene
(Think AR, AD, X-linked dom/rec Diseases)
2) Chromosomal abnormalities
3) Mitochondrial

Question 3

Genetic liability

Answer 3

• Liability= Factors (genes/environment) that contribute to a disease
• There is a threshold of liability variables that must be reached to cause expression of abnormal phenotype (Disease)
• Good genes or environment= curve shifts left (less likely to get disease)
• Bad genes or environment= curve shifts right (more likely to get disease)

Question 4

Familial relative risk

Answer 4

• Closer you are to disease relative = high risk for getting disease
• Drops by 1/2 ever distance from affected person
• But sometimes environmental factors can have a bigger effect than genetic with developing a disease

Equation
(Ar) Relative Risk Ratio= prevalence of disease in affected person/prevalence of disease in general population

Question 5

Characteristics of Multifactorial Inheritance

Answer 5

1) Doesn’t follow medenlian pattern of inheritance
2) Families aggregation
3) More common in close relatives (developing disease)
4) Effects by genes and environment

Question 6

Liability Threshold Model

Answer 6

Risk higher if:
1) Individual severely affected

2) Closer Relative
3) Multiple affected (more genes)

4) Sex biased traits
(Ex: Pylorus stenosis- more common in males)

Question 7

Pylorus Stenosis

Answer 7

• Males more prone
• Threshold differs in males and females (females need to be at high end of curve aka right)

Symptoms:

• Hypertrophy stomach
• Impeding gastric emptying
• Projectile vomiting in babies
• Dehydration, salt/fluid imbalances

Question 8

Determining Heritability of a disease

Answer 8

1) Population/migration studies
- Disease incidence diff in populations = genetic factor

2) Family studies
- more genetic variability

3) Twin studies
Monozygotic (MZ) twins- (Identically genetic)
Dizygotic (DZ) twins - Controls- (50% genetically different)
-Concordance = twins have same disease (100% genetically determined)
-Discordance = one twin has it and other doesn’t (environment changed it)

4) Adoption studies
- Separation of identical twins
- Changes= environmental factors

5) Association studies
- Case control studies
- Test co-occurences of specific allele at a marker locus and a trait in a population by comparing the frequency of an allele in pt’s and controls
- Genome-Wide Association studies (GWAS) = association studies w microarray

Question 9

Anencephaly

Answer 9

• Neural tube defects
• multifactorial inheritance

Symptoms:

• Underdeveloped brains/incomplete skulls
• Brain stem functioning
• Usually fatal

Question 10

Spina Bifida

Answer 10

• Neural tube defects
• multifactorial inheritance

Symptoms:

• Incomplete Closure of spine
• Variable severity
• Repair can be done in utero or postnatally

Evidence for Genetics:
-Much higher risk for mother having a child w disorder when she already has one with a neural tube defect (higher than population risk)

Evidence for Environment:
-Mother taking folate can reduce risk of neural tube defects

Question 11

Polygenic Theory of quantitative trait

Answer 11

-Mutations in more than one gene contribute to a trait
(Ex: more than 1 gene changes height)

-Produces a normal shaped bell curve aka (distribution) = more genes that can display the phenotype

Question 12

Some human polygenic traits

Answer 12

-Produce normal distribution

1) Height
2) Weight
3) Skin color
4) Intelligence
5) BP

All influenced by environment as well