González, Juan R.Carrasco Jordan, Josep LluísArmengol, LluísVillatoro, SergiJover Armengol, Lluís deYasui, YutakaEstivill, Xavier, 1955-2009-03-202009-03-2020081471-2105https://hdl.handle.net/2445/7321Background: 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 to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.15 p.application/pdfengcc-by, (c) González et al., 2008http://creativecommons.org/licenses/by/2.0/Genètica molecularBiotecnologiaGene dosageMolecular probe techniquesinfo:eu-repo/semantics/article562817info:eu-repo/semantics/openAccess18522760