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Exome Pool-Seq in neurodevelopmental disorders
- Source :
- European Journal of Human Genetics
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14765438 and 10184813
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....30a16d226c24ba96e63c1a149a12583f