title: SNP array analysis in constitutional and cancer genome diagnostics--copy number variants, genotyping and quality control.
abstract: Array-based comparative genomic hybridization analysis of genomic DNA was first applied in postnatal diagnosis for patients with intellectual disability (ID) and/or congenital anomalies (CA). Genome-wide single-nucleotide polymorphism (SNP) array analysis was subsequently implemented as the first line diagnostic test for ID/CA patients in our laboratory in 2009, because its diagnostic yield is significantly higher than that of routine cytogenetic analysis. In addition to the detection of copy number variations, the genotype information obtained with SNP array analysis enables the detection of stretches of homozygosity and thereby the possible identification of recessive disease genes, mosaic aneuploidy, or uniparental disomy. Patient-parent (trio) information analysis is used to screen for the presence of any form of uniparental disomy in the patient and can determine the parental origin of a de novo copy number variation. Moreover, the outcome of a genotype analysis is used as a final quality control by ruling out potential sample mismatches due to non-paternity or sample mix-up. SNP array analysis is now also used in our laboratory for patients with disorders for which locus heterogeneity is known (homozygosity pre-screening), in prenatal diagnosis in case of structural ultrasound anomalies, and for patients with leukemia. In this report, we summarize our array findings and experiences in the various diagnostic applications and demonstrate the power of a SNP-based array platform for molecular karyotyping, because it not only significantly improves the diagnostic yield in both constitutional and cancer genome diagnostics, but it also enhances the quality of the diagnostic laboratory workflow.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. n.deleeuw@antrg.umcn.nl
authors.forename: N
authors.initials: N
authors.lastname: de Leeuw
authors.forename: J Y
authors.initials: JY
authors.lastname: Hehir-Kwa
authors.forename: A
authors.initials: A
authors.lastname: Simons
authors.forename: A
authors.initials: A
authors.lastname: Geurts van Kessel
authors.forename: D F
authors.initials: DF
authors.lastname: Smeets
authors.forename: B H W
authors.initials: BH
authors.lastname: Faas
authors.forename: R
authors.initials: R
authors.lastname: Pfundt
mesh_terms: D055028:Comparative Genomic Hybridization / Q000379:methods* / Q000592:standards; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics; D056915:DNA Copy Number Variations; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D012016:Reference Values