Comparison of genome-wide array genomic hybridization platforms for the detection of copy number variants in idiopathic mental retardation.
BMC Med Genomics
; 4: 25, 2011 Mar 25.
Article
in En
| MEDLINE
| ID: mdl-21439053
ABSTRACT
BACKGROUND:
Clinical laboratories are adopting array genomic hybridization as a standard clinical test. A number of whole genome array genomic hybridization platforms are available, but little is known about their comparative performance in a clinical context.METHODS:
We studied 30 children with idiopathic MR and both unaffected parents of each child using Affymetrix 500 K GeneChip SNP arrays, Agilent Human Genome 244 K oligonucleotide arrays and NimbleGen 385 K Whole-Genome oligonucleotide arrays. We also determined whether CNVs called on these platforms were detected by Illumina Hap550 beadchips or SMRT 32 K BAC whole genome tiling arrays and tested 15 of the 30 trios on Affymetrix 6.0 SNP arrays.RESULTS:
The Affymetrix 500 K, Agilent and NimbleGen platforms identified 3061 autosomal and 117 X chromosomal CNVs in the 30 trios. 147 of these CNVs appeared to be de novo, but only 34 (22%) were found on more than one platform. Performing genotype-phenotype correlations, we identified 7 most likely pathogenic and 2 possibly pathogenic CNVs for MR. All 9 of these putatively pathogenic CNVs were detected by the Affymetrix 500 K, Agilent, NimbleGen and the Illumina arrays, and 5 were found by the SMRT BAC array. Both putatively pathogenic CNVs identified in the 15 trios tested with the Affymetrix 6.0 were identified by this platform.CONCLUSIONS:
Our findings demonstrate that different results are obtained with different platforms and illustrate the trade-off that exists between sensitivity and specificity. The large number of apparently false positive CNV calls on each of the platforms supports the need for validating clinically important findings with a different technology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Dosage
/
Oligonucleotide Array Sequence Analysis
/
Comparative Genomic Hybridization
/
Intellectual Disability
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Child
/
Humans
Language:
En
Journal:
BMC Med Genomics
Year:
2011
Document type:
Article