Presented here are hypothetical findings from studies of heterokaryons formed from seven human xeroderma pigmentosum cell strains:

These data are measurements of the occurrence or nonoccurrence of unscheduled DNA synthesis in the fused heterokaryon. None of the strains alone shows any unscheduled DNA synthesis. Which strains fall into the same complementation groups? How many different groups are revealed based on these data? What can we conclude about the genetic basis of XP from these data?

Verified step by step guidance

1. Step 1: Understand the meaning of complementation in this context. Complementation (+) indicates that when two different XP strains are fused, the heterokaryon shows unscheduled DNA synthesis, meaning the mutations are in different genes. No complementation (-) means the mutations are in the same gene, so the defect is not rescued by fusion.
2. Step 2: Identify groups of strains that do not complement each other (marked with '-') to determine which strains belong to the same complementation group. For example, XP1, XP2, and XP3 show no complementation among themselves, so they likely belong to the same group.
3. Step 3: Look for strains that complement all others except themselves and their group members. For instance, XP4 complements XP1, XP2, and XP3 but not itself, indicating it forms a separate complementation group.
4. Step 4: Repeat this analysis for XP5, XP6, and XP7. Notice that XP5 complements XP1, XP2, XP3, and XP4 but not XP6 or XP7, suggesting XP5 is in a different group from XP6 and XP7. XP6 and XP7 do not complement each other, so they form another group.
5. Step 5: Summarize the findings: group the strains into distinct complementation groups based on the pattern of complementation (+) and non-complementation (-). Count the number of groups and conclude that xeroderma pigmentosum is genetically heterogeneous, caused by mutations in multiple different genes.

Key Concepts

Complementation Testing

Complementation testing is a genetic technique used to determine whether two mutations causing a similar phenotype are in the same gene or in different genes. If two mutant strains complement each other (show a wild-type phenotype when combined), their mutations are in different genes. Lack of complementation indicates mutations in the same gene.

Unscheduled DNA Synthesis (UDS)

Unscheduled DNA synthesis is a measure of DNA repair activity, specifically nucleotide excision repair, occurring outside of normal DNA replication. In xeroderma pigmentosum (XP) cells, UDS is absent due to defective repair. Restoration of UDS in heterokaryons indicates complementation and functional repair.

Genetic Heterogeneity in Xeroderma Pigmentosum

Xeroderma pigmentosum is genetically heterogeneous, meaning mutations in different genes can cause the disease. Complementation groups represent distinct genes involved in DNA repair. Identifying multiple complementation groups reveals the complexity and multiple genetic causes underlying XP.