Design Considerations for Massively Parallel Sequencing Studies of Complex Human Disease
2011

Design Considerations for Massively Parallel Sequencing Studies of Complex Human Disease

publication Evidence: moderate

Author Information

Author(s): Feng Bing-Jian, Tavtigian Sean V., Southey Melissa C., Goldgar David E.

Primary Institution: University of Utah School of Medicine

Hypothesis

How can we best use new sequencing capabilities to find rare high-penetrance disease-associated variants for common/complex diseases?

Conclusion

The study provides important guidelines for designing sequencing studies to identify disease susceptibility genes while minimizing false positives.

Supporting Evidence

  • Massively Parallel Sequencing (MPS) allows for cost-effective sequencing of entire genomes.
  • Careful sample selection and filtering strategies are crucial for identifying true disease susceptibility genes.
  • Simulations indicate that while requiring variants in multiple pedigrees reduces false positives, it may also miss true susceptibility genes.

Takeaway

This study helps scientists figure out the best ways to use new DNA sequencing technology to find genes that might cause diseases.

Methodology

Simulation-based analyses were performed to compare several strategies for massively parallel sequencing in complex diseases.

Limitations

The study assumes certain genetic architectures and may not account for all variations in human diseases.

Digital Object Identifier (DOI)

10.1371/journal.pone.0023221

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