Question

7. Students are analyzing data from several patients. Patient X has no mutations in LDLR, PCSK9, or APOB but still has high LDL cholesterol and a family history of heart disease. Patient Y has a mutation in LDLR and high cholesterol. Patient Z has normal cholesterol levels despite carrying a PCSK9 mutation. The students also learn that height, like cholesterol, is a complex trait influenced by many genes.

Which explanation best summarizes why Patient X still has high cholesterol?

Responses

A. Patient X’s high cholesterol must be due to poor nutrition and lack of exercise.
A. Patient X’s high cholesterol must be due to poor nutrition and lack of exercise.

B. Because Patient X has no monogenic mutations, their cholesterol levels are unrelated to genetics.
B. Because Patient X has no monogenic mutations, their cholesterol levels are unrelated to genetics.

C. Only mutations in LDLR, PCSK9, or APOB can ever increase cholesterol levels.
C. Only mutations in LDLR, PCSK9, or APOB can ever increase cholesterol levels.

D. Patient X likely has a high polygenic risk score, where many small-effect mutations collectively raise LDL levels.
D. Patient X likely has a high polygenic risk score, where many small-effect mutations collectively raise LDL levels.

E. Patient X must have inherited the trait in a simple dominant-recessive pattern.
E. Patient X must have inherited the trait in a simple dominant-recessive pattern.

Answer 1

D.

Patient X likely has high polygenic risk: many common, small-effect variants can add up to substantially raise LDL cholesterol even when no single high-impact mutation (LDLR/PCSK9/APOB) is found. This fits the family history and parallels how height is a complex, polygenic trait. (Other choices are wrong because they ignore polygenic genetics or over-attribute the trait to environment or simple Mendelian inheritance.)