A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
Researchers are studying the inheritance pattern of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, the gene responsible for cystic fibrosis. It is believed that, in addition to the commonly found ΔF508 mutation, a novel mutation in this gene is found in a particular population under study. Which of the following would most likely suggest that these two loci have a high probability of being closely linked?
-
A
LOD Score < 1Incorrect. A LOD score less than 1 is below the threshold and does not support linkage; it suggests the loci are likely independent or the data are inconclusive.
-
B
LOD Score < 2Incorrect. A LOD score less than 2 is still inconclusive or below the linkage threshold (3) used in pedigree analysis.
-
C
LOD Score > 3Correct. A LOD score greater than 3 corresponds to odds of linkage of at least 1000:1 and is the accepted threshold for declaring two loci genetically linked.
-
D
LOD Score = 0Incorrect. A LOD score of 0 indicates the data are equally likely under linkage or no linkage, providing no evidence for linkage.
-
E
LOD Score = 1Incorrect. A LOD score of 1 corresponds to 10:1 odds favoring linkage, which is below the conventionally accepted threshold of 3 (1000:1 odds) required to declare two loci genetically linked.
↑ Tap an answer to reveal the reasoning
Answer: C. Logarithm of the odds (LOD) score is a statistical test for linkage between two genetic loci, comparing the likelihood of observing the pedigree data if the loci are linked versus if they are inherited independently. A LOD score greater than 3 (corresponding to odds of linkage of 1000:1) is the conventional threshold for accepting linkage between two loci, while a LOD score less than -2 is the threshold for rejecting linkage.
In this scenario, the researchers want to know whether a novel mutation cosegregates with the CFTR gene (and therefore lies near it on chromosome 7). A LOD > 3 in their pedigree data would strongly support physical linkage of the two loci, useful both for mapping the new mutation and for genetic counseling within affected families.
Key teaching points: LOD > 3 = linked; LOD < -2 = unlinked; LOD between is inconclusive. The threshold of 3 corresponds to a p-value of approximately 0.05 after accounting for the prior probability of linkage in genome-wide testing.
**Why each option:**
**A.** A LOD score less than 1 is below the threshold and does not support linkage; it suggests the loci are likely independent or the data are inconclusive.
**B.** A LOD score less than 2 is still inconclusive or below the linkage threshold (3) used in pedigree analysis.
**C.** Correct. A LOD score greater than 3 corresponds to odds of linkage of at least 1000:1 and is the accepted threshold for declaring two loci genetically linked.
**D.** A LOD score of 0 indicates the data are equally likely under linkage or no linkage, providing no evidence for linkage.