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Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays
Author(s) -
Ming Jeffrey E.,
Geiger Elizabeth,
James Alison C.,
Ciprero Karen L.,
Nimmakayalu Manjunath,
Zhang Yi,
Huang Andrew,
Vaddi Madhavi,
Rappaport Eric,
Zackai Elaine H.,
Shaikh Tamim H.
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20322
Subject(s) - biology , subtelomere , karyotype , fluorescence in situ hybridization , microarray , chromosomal rearrangement , genetics , copy number variation , breakpoint , genome , comparative genomic hybridization , gene duplication , chromosome , dna microarray , computational biology , gene , gene expression
Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytogenetic tests currently used for the detection of such chromosomal rearrangements are low resolution and limited coverage of the genome. Thus, it is likely that children with MCA may have submicroscopic chromosomal rearrangements that are not detectable by current techniques. We report the use of a commercially available, oligonucleotide‐based microarray for genome‐wide analysis of copy number alterations. First, we validated the microarray in patients with known chromosomal rearrangements. Next, we identified previously undetected, de novo chromosomal deletions in patients with MCA who have had a normal high‐resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH) analysis. These findings indicate that high‐density, oligonucleotide‐based microarrays can be successfully used as tools for the detection of chromosomal rearrangement in clinical samples. Their higher resolution and commercial availability make this type of microarray highly desirable for application in the diagnosis of patients with multiple congenital defects. Hum Mutat 27(5), 467–473, 2006. © Published 2006 Wiley‐Liss, Inc.