American Journal of Medical Genetics 134A:282–289 (2005) Rapid Array-Based Genomic Characterization of a Subtle Structural Abnormality: A Patient With Psychosis and der(18)t(5;18)(p14.1;p11.23) Carolyn M. Drazinic, 1,5,6 Adife G. Ercan-Sencicek, 1,2 Laura M. Gault, 1,5,6 Fuki M. Hisama, 3 Mazin B. Qumsiyeh, 4 Norma J. Nowak, 7 Joseph F. Cubells, 5,6 and Matthew W. State 1,2,4 * 1 Child Study Center, Yale University School of Medicine, New Haven, Connecticut 2 Yale Center for Human Genetics and Genomics, Yale University School of Medicine, New Haven, Connecticut 3 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 4 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 5 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 6 Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, Connecticut 7 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York Array-based copy number analysis has recently emerged as a rapid means of mapping complex and/or subtle chromosomal abnormalities. We have compared two such techniques, using bac- terial artificial chromosome (BAC) and single nucleotide polymorphism (SNP) arrays in the evaluation of a 45-year-old woman with dys- morphic features, mental retardation, psychosis, and an unbalanced derivative chromosome 18, (46,XX, der(18)t(18;?)(p12;?)). Both array-based methods demonstrated that the additional mate- rial on chromosome 18 was of 5p origin. The 5p duplication mapped telomeric to 25.320 Mb (BAC array) and 25.607 Mb (SNP array), corresponding to the band 5p14.1. Both BAC and SNP arrays also showed a deletion involving chromosome 18p extending telomeric from 8.437 Mb (BAC array) and 8.352 Mb (SNP array), corresponding to the band 18p11.23. Molecular cytogenetic mapping using fluorescence in situ hybridization (FISH) supported the array findings and further refined the breakpoint regions, confirming that the BAC and SNP chips were both useful in this regard. Both case reports and linkage analyses have implicated these chromosomal intervals in psy- chosis. The array-based experiments were com- pleted over the course of several days. While these methods do not eliminate the requirement for traditional fine-mapping, they provide an effi- cient approach to identifying the origin and extent of deleted and duplicated material in chro- mosomal rearrangements. ß 2005 Wiley-Liss, Inc. KEY WORDS: chromosome abnormality; unba- lanced translocation; psychosis; schizophrenia; trisomy 5p; mono- somy 18p; microarray; FISH; mapping INTRODUCTION Recent findings in the genetics of schizophrenia [Brzustowicz et al., 2000] and autism [Jamain et al., 2003] emphasize the value of mapping chromosomal abnormalities as a means of identifying disease-related genes. Although considerable advances have been made over the past decade that allow for precise mapping of cytogenetic abnormalities using fluores- cence in situ hybridization (FISH), the characterization of complex and/or subtle chromosomal rearrangements, particu- larly those involving duplications and deletions, has remained a time-consuming and laborious task. Now, with the advent of microarray technology, it is possible to efficiently characterize a range of cytogenetic abnormalities in a single hybridization. This study compares two array-based methods, the bacterial artificial chromosome (BAC) array and the single nucleotide polymorphism (SNP) array, for genomic copy number assess- ments in the characterization of a patient presenting with psychosis and a cytogenetic abnormality. Both methods rapid- ly produce useful and generally comparable information about cytogenetic abnormalities, and both approaches facilitate the subsequent mapping of breakpoints. This patient was of interest as a result of her G-banded karyotype, which showed involvement of the p-arm of chromosome 18, a region pre- viously suggested to have a role in schizophrenia and bipolar disorder [Schwab et al., 1998; McInnes et al., 2001; Segurado et al., 2003; Babovic-Vuksanovic et al., 2004]. Grant sponsor: Shepherd Foundation; Grant sponsor: NIH Career Development Award; Grant number: RR-16118; Grant sponsor: NIH K award; Grant number: K02 DA 015766; Grant sponsor: National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award; Grant sponsor: NIMH Research Training Program in Childhood Neuropsychia- tric Disorders; Grant number: 5 T32-MH18268; Grant sponsor: Veterans Administration Neuroscience Research Fellowship; Grant sponsor: NIMH Clinical Neuroscience Research Training; Grant number: T32-MH19961; Grant sponsor: Paul Beeson Scholar Award from the American Federation for Aging Research; Grant sponsor: NCI Extramural Cancer Chromosome Aberration Project; Grant number: CA80270; Grant sponsor: RPCI Cancer Center Support; Grant number: P30 CA16056. Joseph F. Cubells’s present address is Department of Human Genetics and Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA *Correspondence to: Matthew W. State, M.D., Ph.D., Yale Child Study Center, Department of Genetics, and Yale Center for Human Genetics and Genomics, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520. E-mail: matthew.state@yale.edu Received 17 September 2004; Accepted 28 November 2004 DOI 10.1002/ajmg.a.30616 ß 2005 Wiley-Liss, Inc.