What is the primary benefit of sequencing a proband and both parents in a genetic test (a trio)?

• A. It reduces cost
• B. It helps identify de novo variants and inheritance patterns, improving diagnostic yield
• C. It eliminates the need for follow-up testing
• D. It reduces the turnaround time

Answer: (B)

Sequencing the affected child together with both parents creates a trio that reveals how a variant is transmitted in the family. This allows detection of de novo variants—mutations that are present in the child but not in either parent—which are a common cause of many pediatric disorders. It also clarifies inheritance patterns, showing whether a variant is inherited from a single affected parent in a dominant way, or whether two parental variants come together in the child to cause a recessive condition, or whether X-linked inheritance is involved. This segregation information helps distinguish potentially disease-causing variants from benign inherited variants and improves the diagnostic yield, because variants are interpreted in the context of how they segregate with disease in the family. It also aids in interpreting variants of uncertain significance: a variant found in a parent who is unaffected may be benign or have reduced penetrance, while a de novo finding in the child strengthens evidence for pathogenicity. In short, trio sequencing provides the inheritance framework needed to prioritize clinically relevant variants and reach a more accurate diagnosis.