Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Mar 6;9(6):e90852. doi: 10.1371/journal.pone.0090852. eCollection 2014.

Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.

Author information

1
Human Genetics, Genome Institute of Singapore, Singapore, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
2
Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
3
Stem Cells and Developmental Biology, Genome Institute of Singapore, Singapore, Singapore.
4
Computational and Mathematical Biology, Genome Institute of Singapore, Singapore, Singapore.
5
Scientific & Research Computing, Genome Institute of Singapore, Singapore, Singapore.
6
Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
7
Eye and Developmental Genetics Research, The Children's Hospital at Westmead, Children's Medical Research Institute and Save Sight Institute, Sydney, New South Wales, Australia; Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
8
Department of Cytogenetics, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
9
Department of Clinical Genetics, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
10
Department of Immunology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
11
Unité de Génétique, Centre Hospitalier, Blois, France.
12
Service de Genetique INEM UMR7355 CNRS-University, Centre Hospitalier Régional d'Orléans, Orléans, France.
13
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
14
Genome Technology and Biology, Genome Institute of Singapore, Singapore, Singapore.
15
Eye and Developmental Genetics Research, The Children's Hospital at Westmead, Children's Medical Research Institute and Save Sight Institute, Sydney, New South Wales, Australia.

Abstract

Delineating candidate genes at the chromosomal breakpoint regions in the apparently balanced chromosome rearrangements (ABCR) has been shown to be more effective with the emergence of next-generation sequencing (NGS) technologies. We employed a large-insert (7-11 kb) paired-end tag sequencing technology (DNA-PET) to systematically analyze genome of four patients harbouring cytogenetically defined ABCR with neurodevelopmental symptoms, including developmental delay (DD) and speech disorders. We characterized structural variants (SVs) specific to each individual, including those matching the chromosomal breakpoints. Refinement of these regions by Sanger sequencing resulted in the identification of five disrupted genes in three individuals: guanine nucleotide binding protein, q polypeptide (GNAQ), RNA-binding protein, fox-1 homolog (RBFOX3), unc-5 homolog D (C.elegans) (UNC5D), transmembrane protein 47 (TMEM47), and X-linked inhibitor of apoptosis (XIAP). Among them, XIAP is the causative gene for the immunodeficiency phenotype seen in the patient. The remaining genes displayed specific expression in the fetal brain and have known biologically relevant functions in brain development, suggesting putative candidate genes for neurodevelopmental phenotypes. This study demonstrates the application of NGS technologies in mapping individual gene disruptions in ABCR as a resource for deciphering candidate genes in human neurodevelopmental disorders (NDDs).

PMID:
24603971
PMCID:
PMC3946304
DOI:
10.1371/journal.pone.0090852
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center