Title
Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Leiden ,
Subject
Chemistry
Biology
Human medicine
Source (journal)
European journal of human genetics / European Society of Human Genetics. - Leiden
Volume/pages
22(2014) :5 , p. 652-659
ISSN
1018-4813
ISI
000334600400015
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs. published online 9 October 2013
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