Validation of SNP Oligonucleotide Microarray Analysis (SOMA) for Clinical Cytogenetic Diagnosis. V. Jobanputra¹, O. Nahum², K. Anyane-Yeboa¹, W. Chung¹, Y. Sun², E. Bottinger², W. Zhang², D. Warburton¹, B. Levy¹. 1) Depts Genetics & Development, Obstetrics & Gynecology, Pathology and Pediatrics, Columbia University Medical Center, New York, NY; 2) Depts Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY.
   SNP arrays are high-density oligonucleotide-based arrays that can identify both loss of heterozygosity (LOH) at individual nucleotides and copy number alterations. In contrast to the CGH array approaches, in SNP arrays only one genomic sample is hybridized to the array, so copy number changes are identified by comparison with independent control hybridizations. In the current study, copy number gains and losses were determined by means of the Circular Binary Segmentation method. We are currently validating the Affymetrix 500K SNP Oligonucleotide microarray for clinical cytogenetic analysis (SOMA) and report on our first 18 cases. Cases were chosen to contain a variety of known cytogenetic aberrations, including whole chromosome aneuploidy, unbalanced rearrangements, marker chromosomes and microdeletions. All aberrations except one subtelomeric deletion were correctly identified by segmentation analysis of the SOMA data. With over half a million SNPs and a mean spacing of 5.8 kb, the 500K SNP array offers a comprehensive whole genome scan and has the potential to provide the highest resolution of copy number detection currently available. Since deletions and duplications can be precisely defined by using the SNP positions on the genome browser, SOMA will useful for the clinical interpretation of both visible and submicroscopic cytogenetic imbalances. Another advantage of using a SNP-based array lies in the concurrent availability of genotype information that would allow simultaneous DNA-based studies such as uniparental disomy (UPD), zygosity and maternal cell contamination. Further studies of normal populations are currently underway and these will be critical for delineating benign copy number variants. In addition, our ongoing study will also assess whether the coverage of the SNPs is adequate for most clinical cytogenetic diagnoses, including all known microdeletions and cryptic sub-telomeric gains and losses.