Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (ML

Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample. Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace. Conclusion: Using the proposed mixed-model, we are able to determine thresholds t...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Juan R. González, Josep L. Carrasco, Lluís Armengol, Sergi Villatoro, Lluís Jover, Yutaka Yasui, Xavier Estivill
• Keywords: BMCBI 2008, Copy Number, Human Genome, Useful Semi-quantitative Method