Exome Pool-Seq in neurodevelopmental disorders
Autor: | Antje Wiesener, Juliane Hoyer, Cornelia Kraus, André Reis, Arif B. Ekici, Christian Thiel, Christiane Zweier, Bernt Popp |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Candidate gene Sialoglycoproteins Nerve Tissue Proteins Computational biology medicine.disease_cause Sensitivity and Specificity Article DNA sequencing MED12 03 medical and health sciences 0302 clinical medicine Exome Sequencing Genetics GNAS complex locus medicine Humans Genetic Testing Exome Genetics (clinical) ATRX biology Antigens Nuclear 030104 developmental biology KMT2A Genetic Loci Neurodevelopmental Disorders Costs and Cost Analysis biology.protein Female KRAS Carrier Proteins 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | European Journal of Human Genetics |
ISSN: | 1476-5438 1018-4813 |
Popis: | High throughput sequencing has greatly advanced disease gene identification, especially in heterogeneous entities. Despite falling costs this is still an expensive and laborious technique, particularly when studying large cohorts. To address this problem we applied Exome Pool-Seq as an economic and fast screening technology in neurodevelopmental disorders (NDDs). Sequencing of 96 individuals can be performed in eight pools of 12 samples on less than one Illumina sequencer lane. In a pilot study with 96 cases we identified 27 variants, likely or possibly affecting function. Twenty five of these were identified in 923 established NDD genes (based on SysID database, status November 2016) (ACTB, AHDC1, ANKRD11, ATP6V1B2, ATRX, CASK, CHD8, GNAS, IFIH1, KCNQ2, KMT2A, KRAS, MAOA, MED12, MED13L, RIT1, SETD5, SIN3A, TCF4, TRAPPC11, TUBA1A, WAC, ZBTB18, ZMYND11), two in 543 (SysID) candidate genes (ZNF292, BPTF), and additionally a de novo loss-of-function variant in LRRC7, not previously implicated in NDDs. Most of them were confirmed to be de novo, but we also identified X-linked or autosomal-dominantly or autosomal-recessively inherited variants. With a detection rate of 28%, Exome Pool-Seq achieves comparable results to individual exome analyses but reduces costs by >85%. Compared with other large scale approaches using Molecular Inversion Probes (MIP) or gene panels, it allows flexible re-analysis of data. Exome Pool-Seq is thus well suited for large-scale, cost-efficient and flexible screening in characterized but heterogeneous entities like NDDs. |
Databáze: | OpenAIRE |
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