title: An efficient screening method for simultaneous detection of recurrent copy number variants associated with psychiatric disorders.
abstract: Several recurrent copy number variants (CNVs) increasing risk to neuropsychiatric diseases have been identified in recent years. They show variable clinical expressivity, being associated with different disorders, and incomplete penetrance. However, due to its very low frequency, the full variety of clinical outcomes associated with each one of these CNVs is unknown. Current methods for detection of CNVs are labor intensive, expensive or not suitable for high throughput analysis. Quantitative interspecies competitive PCR linked to variant minisequencing and detection by mass-spectrometry may overcome these limitations. Here, we present two multiplex assays based on this method to screen for eleven psychiatric risk CNVs, such as 1q21, 16p11.2, 3q29, or 16p13.11 regions, among others. The assays were tested in our collection of 514 schizophrenia patients. Results were compared with MLPA at two CNVs. Additional positive results were confirmed by exome sequencing. A total of fourteen patients were CNV carriers. The method presents high sensitivity and specificity, showing its utility as a cheap, accurate, high throughput screening tool for recurrent CNVs. The method may be very useful for management of psychiatric patients as well as screening of different collections of samples to better identify the full spectrum of clinical variability.
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors: Julio
authors: J
authors: Rodriguez-Lopez
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors: Noa
authors: N
authors: Carrera
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Manuel
authors: M
authors: Arrojo
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors: Jorge
authors: J
authors: Amigo
authors: Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors: Beatriz
authors: B
authors: Sobrino
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Mario
authors: M
authors: Páramo
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Eduardo
authors: E
authors: Paz
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Santiago
authors: S
authors: Agra
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Ramón
authors: R
authors: Ramos-Ríos
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
authors: Julio
authors: J
authors: Brenlla
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors: Ángel
authors: Á
authors: Carracedo
authors: Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain. Electronic address: javier.costas.costas@sergas.es.
authors: Javier
authors: J
authors: Costas
mesh_terms: D000818:Animals; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1 / Q000737:chemistry; D002885:Chromosomes, Human, Pair 16 / Q000737:chemistry; D002893:Chromosomes, Human, Pair 3 / Q000737:chemistry; D056915:DNA Copy Number Variations; D059472:Exome; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D057166:High-Throughput Screening Assays; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D002679:Pan troglodytes / Q000235:genetics; D019683:Penetrance; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
keywords: Autism; Copy number variants; Psychiatric genetics; Quantitative interspecies competitive PCR; Schizophrenia