title: High-resolution SNP arrays in mental retardation diagnostics: how much do we gain?
abstract: We used Affymetrix 6.0 GeneChip SNP arrays to characterize copy number variations (CNVs) in a cohort of 70 patients previously characterized on lower-density oligonucleotide arrays affected by idiopathic mental retardation and dysmorphic features. The SNP array platform includes approximately 900,000 SNP probes and 900,000 non-SNP oligonucleotide probes at an average distance of 0.7 Kb, which facilitates coverage of the whole genome, including coding and noncoding regions. The high density of probes is critical for detecting small CNVs, but it can lead to data interpretation problems. To reduce the number of false positives, parameters were set to consider only imbalances >75 Kb encompassing at least 80 probe sets. The higher resolution of the SNP array platform confirmed the increased ability to detect small CNVs, although more than 80% of these CNVs overlapped to copy number 'neutral' polymorphism regions and 4.4% of them did not contain known genes. In our cohort of 70 patients, of the 51 previously evaluated as 'normal' on the Agilent 44K array, the SNP array platform disclosed six additional CNV changes, including three in three patients, which may be pathogenic. This suggests that about 6% of individuals classified as 'normal' using the lower-density oligonucleotide array could be found to be affected by a genomic disorder when evaluated with the higher-density microarray platforms.
authors.affiliation: CSS Hospital, IRCSS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Viola
authors.initials: V
authors.lastname: Alesi
authors.forename: Sara
authors.initials: S
authors.lastname: Loddo
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Irene
authors.initials: I
authors.lastname: Bottillo
authors.forename: Agatino
authors.initials: A
authors.lastname: Battaglia
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zampino
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.forename: Saul
authors.initials: S
authors.lastname: Surrey
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D022981:Allelic Imbalance; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D007621:Karyotyping; D019656:Loss of Heterozygosity; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results