Background: Using different array techniques it was recently shown that about 10% of patients with mental retardation of unknown origin harbour cryptic chromosomal aneusomies. Nevertheless, data analysis is currently not standardized and little is known about its sensitivity and specificity.
Methods: We developed an electronic data analysis tool for GeneChip Mapping SNP arrays, which we called copy number variation finder (CNVF). Using the CNVF we analysed 104 unselected patients with mental retardation of unknown origin with the GeneChip Mapping 100K SNP array and established an optimized set of analysis parameters.
Results: We detected deletions as small as 20 kb when covered by at least 3 SNPs and duplications as small as 150 kb when covered by at least 6 SNPs with only one false positive signal per 6 patients. In 9.1% of patients we detected apparently disease-causing or de novo aberrations sizing 0.4-14 Mb. Morphological anomalies in patients with de novo aberrations were equal to that of unselected patients when measured with de Vries score.
Conclusion: Our standardized data analysis tool CNVF is easy to use and has a high sensitivity and specificity. As some genomic regions are covered more densely than others the actual genome wide resolution of the 100 K array is about 400-500 kb for deletions and 900-1000 kb for duplications. Detection rate of about 10% de novo aberrations is independent from selection of patients for certain features. The incidental finding of heterozygosity for the 250 kb recurrent deletion at the NPH1 locus associated with autosomal recessive juvenile nephronophthisis in two patients being inherited from a healthy parent highlights the fact that inherited aberrations might be disease-related although not causal for mental retardation.
- 100 K SNP arrays
- copy number variation
- mental retardation
- molecular karyotyping
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