Multifactorial Diseases, Founder Effect and Genetic Drift

Question 1

What is a multifactorial disease?

Answer 1

A multifactorial disease is caused by a combination of genetic and environmental factors rather than a single gene mutation. These diseases do not follow Mendelian inheritance patterns and often involve multiple genetic variants with small effects​

Question 2

What are some key characteristics of multifactorial diseases?

Answer 2

• Caused by multiple genes (polygenic) + environmental factors.
• Do not follow Mendelian inheritance, but risk can be inherited.
• Follow a threshold model—disease develops when genetic + environmental factors cross a certain level.
• Variable expressivity—not everyone with risk factors develops the disease.

Question 3

Give examples of multifactorial diseases.

Answer 3

✔ Crohn’s disease (immune-related, affected by gut microbiota).
✔ Diabetes mellitus (influenced by both genetic predisposition and lifestyle).
✔ Cardiovascular diseases (genetic risk + diet/smoking/stress).
✔ Cleft lip and palate (threshold model of inheritance).

Question 4

How are multifactorial diseases studied?

Answer 4

Twin Studies → Compare disease concordance in monozygotic (MZ) vs. dizygotic (DZ) twins.
🔬 Genome-Wide Association Studies (GWAS) → Identify common genetic variants associated with disease risk.
🔬 Linkage Studies → Analyze inheritance patterns in families to locate disease-associated genes​

Question 5

What is the “liability threshold model” in multifactorial diseases?

Answer 5

Some diseases develop only if an individual crosses a certain threshold of genetic and environmental risk factors.
Example: Cleft lip and palate only occurs when a combination of genetic predisposition and environmental factors (e.g., smoking, malnutrition) exceeds the liability threshold​

Question 6

What is the founder effect?

Answer 6

The founder effect occurs when a small group of individuals colonizes a new population, leading to reduced genetic diversity and an increased frequency of certain alleles that were present in the founding population.

Example: The Amish population in the U.S. has a higher incidence of Ellis-van Creveld syndrome due to a small group of ancestors carrying the mutation.

Question 7

What is genetic drift?

Answer 7

Genetic drift is the random fluctuation of allele frequencies in a population due to chance events, rather than natural selection. It is most significant in small populations.

Question 8

How does genetic drift differ from natural selection?

Answer 8

Genetic drift is random and can reduce genetic variation, leading to allele fixation or loss.
Natural selection is non-random and favors adaptive traits that enhance survival and reproduction.

Question 9

What is the bottleneck effect? How is it related to genetic drift?

Answer 9

The bottleneck effect occurs when a large population undergoes a drastic reduction in size, leading to a loss of genetic variation.
Example: Cheetahs have very low genetic diversity due to past population bottlenecks​

Question 10

How can the founder effect and genetic drift impact human disease prevalence?

Answer 10

• Founder Effect: Increases the frequency of rare genetic disorders in isolated populations (e.g., Tay-Sachs in Ashkenazi Jews).
• Genetic Drift: Can cause random changes in allele frequencies, sometimes reducing beneficial genetic diversity.