Module 7

Question 1

List the 6 causes of monogenetic obesity.

Answer 1

• Leptin deficiency – ob/ob mouse
• Leptin receptor deficiency – db/db mouse
• Prohormone convertase (PC1) defect
• Melanocortin – 4-receptor (MC4R) defect
• POMC deficiency
• PPAR-γ defect

Question 2

What is the most common cause of monogenetic obesity?

Answer 2

Melanocortin-4-receptor (MC4R) defect

Question 3

How is the FTO gene locus SNP linked with obesity?

Answer 3

• May modulate feeding through leptin/STAT3 signalling pathway
• May impact processes of browning of WAT
• May affect adipogenesis
• Highly expressed in hypothalamus

Question 4

Explain how Genetic Investigation of Anthropometric Traits (GIANT) studies work.

Answer 4

• Hypothesis-free analysis of genome variation
• Uses genetic database
• Looks for highly-replicable associations using a very high statistical significance threshold

Question 5

What was the finding of the GIANT study?

Answer 5

BMI loci genes were found in in neuronal genes (especially those associated with appetite)

Question 6

List the 3 ways that modifications are made in epigenetics.

Answer 6

• Methylation/demethylation ⇒ usually supresses expression
• Histone modification ⇒ compactness of DNA wound around histones impacts expression
• Non-coding RNA (micro-RNA)

Question 7

What is meant by the expression, “genetics loads the gun, our environment pulls the trigger” in relation to obesity?

Answer 7

Our genetics predisposes us to risk for obesity, however it is our environment that makes it possible for the disease to thrive.