PMID- 15723295
OWN - NLM
STAT- MEDLINE
DCOM- 20050509
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 134
IP  - 3
DP  - 2005 Apr 30
TI  - Use of targeted array-based CGH for the clinical diagnosis of chromosomal 
      imbalance: is less more?
PG  - 259-67
AB  - Chromosome analysis is an important component to the diagnosis of congenital 
      anomalies, developmental delay, and mental retardation. Routine chromosome 
      analysis identifies aneuploidy and structural rearrangements greater than 5 Mb 
      but cannot identify abnormalities of the telomeric regions or microdeletions 
      reliably. Molecular cytogenetic techniques were developed to overcome these 
      limitations. High-resolution comparative genomic hybridization (CGH)-based 
      microarrays (array CGH) were developed to increase the resolution of chromosomal 
      studies and to provide a comprehensive assay by using large-insert clones as the 
      target for analysis. We constructed a microarray for the clinical diagnosis of 
      medically significant and relatively common chromosomal alterations. Nine hundred 
      six bacterial artificial chromosome (BAC) clones were chosen, the chromosomal 
      locations of which were confirmed by fluorescence in situ hybridization (FISH). 
      FISH-testing showed that 7% of the clones were mismapped based on map locations 
      obtained from two publicly available databases (58 mapped to the wrong chromosome 
      and three mapped to a different locus on the same chromosome), 16% 
      cross-hybridized to other chromosomes, and 12% did not hybridize or showed poor 
      hybridization signals under uniform FISH conditions. Thus, from a total of 906 
      BAC clones that were evaluated, only 589 (65%) were deemed adequate for arraying 
      on this clinical device. The performance of this array was tested in a set of 
      blinded experiments on a cohort of phenotypically normal individuals and on 
      individuals with known chromosome abnormalities. The array identified 
      deletion/duplication polymorphisms not seen by FISH in the phenotypically normal 
      individuals and detected single copy dosage differences in all of the cases with 
      known chromosomal abnormalities. All abnormalities detected by the array were 
      confirmed by FISH with BACs from the appropriate loci. Our data demonstrate that 
      the rigorous assessment of BACs and their use in array CGH is especially 
      important when the microarray is used for clinical diagnosis. In addition, this 
      study illustrates that when constructed carefully with proper attention to the 
      quality of the BACs that are arrayed, array CGH is an effective and efficient 
      tool for delineating chromosomal aberrations and an important adjunct to FISH and 
      conventional cytogenetics.
FAU - Bejjani, Bassem A
AU  - Bejjani BA
AD  - Signature Genomic Laboratories, LLC, Spokane, WA 99204, USA. 
      bejjani@signaturegenomics.com
FAU - Saleki, Reza
AU  - Saleki R
FAU - Ballif, Blake C
AU  - Ballif BC
FAU - Rorem, Emily A
AU  - Rorem EA
FAU - Sundin, Kyle
AU  - Sundin K
FAU - Theisen, Aaron
AU  - Theisen A
FAU - Kashork, Catherine D
AU  - Kashork CD
FAU - Shaffer, Lisa G
AU  - Shaffer LG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Cell Line, Transformed
MH  - *Chromosome Aberrations
MH  - Chromosome Deletion
MH  - Chromosome Disorders/*diagnosis/genetics
MH  - Chromosome Mapping
MH  - Chromosomes, Artificial, Bacterial
MH  - Cytogenetic Analysis/methods/standards
MH  - Double-Blind Method
MH  - Female
MH  - Gene Duplication
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Nucleic Acid Hybridization/*methods
MH  - Polymorphism, Genetic
MH  - Reproducibility of Results
EDAT- 2005/02/22 09:00
MHDA- 2005/05/10 09:00
CRDT- 2005/02/22 09:00
PHST- 2005/02/22 09:00 [pubmed]
PHST- 2005/05/10 09:00 [medline]
PHST- 2005/02/22 09:00 [entrez]
AID - 10.1002/ajmg.a.30621 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2005 Apr 30;134(3):259-67. doi: 10.1002/ajmg.a.30621.