PURPOSE: The goal of this work was to test the ability of oligonucleotide-based arrays to reproduce the results of focused bacterial artificial chromosome (BAC)-based arrays used clinically in comparative genomic hybridization experiments to detect constitutional copy number changes in genomic DNA. METHODS: Custom oligonucleotide (oligo) arrays were designed using the Agilent Technologies platform to give high-resolution coverage of regions within the genome sequence coordinates of BAC/P1 artificial chromosome (PAC) clones that had already been validated for use in previous versions of clone arrays used in clinical practice. Standard array-comparative genomic hybridization experiments, including a simultaneous blind analysis of a set of clinical samples, were conducted on both array platforms to identify copy number differences between patient samples and normal reference controls. RESULTS: Initial experiments successfully demonstrated the capacity of oligo arrays to emulate BAC data without the need for dye-reversal comparisons. Empirical data and computational analyses of oligo response and distribution from a pilot array were used to design an optimized array of 44,000 oligos (44K). This custom 44K oligo array consists of probes localized to the genomic positions of >1400 fluorescence in situ hybridization-verified BAC/PAC clones covering more than 140 regions implicated in genetic diseases, as well as all clinically relevant subtelomeric and pericentromeric regions. CONCLUSIONS: Our data demonstrate that oligo-based arrays offer a valid alternative for focused BAC arrays. Furthermore, they have significant advantages, including better design flexibility, avoidance of repetitive sequences, manufacturing processes amenable to good manufacturing practice standards in the future, increased robustness because of an enhanced dynamic range (signal to background), and increased resolution that allows for detection of smaller regions of change.
PURPOSE: The goal of this work was to test the ability of oligonucleotide-based arrays to reproduce the results of focused bacterial artificial chromosome (BAC)-based arrays used clinically in comparative genomic hybridization experiments to detect constitutional copy number changes in genomic DNA. METHODS: Custom oligonucleotide (oligo) arrays were designed using the Agilent Technologies platform to give high-resolution coverage of regions within the genome sequence coordinates of BAC/P1 artificial chromosome (PAC) clones that had already been validated for use in previous versions of clone arrays used in clinical practice. Standard array-comparative genomic hybridization experiments, including a simultaneous blind analysis of a set of clinical samples, were conducted on both array platforms to identify copy number differences between patient samples and normal reference controls. RESULTS: Initial experiments successfully demonstrated the capacity of oligo arrays to emulate BAC data without the need for dye-reversal comparisons. Empirical data and computational analyses of oligo response and distribution from a pilot array were used to design an optimized array of 44,000 oligos (44K). This custom 44K oligo array consists of probes localized to the genomic positions of >1400 fluorescence in situ hybridization-verified BAC/PAC clones covering more than 140 regions implicated in genetic diseases, as well as all clinically relevant subtelomeric and pericentromeric regions. CONCLUSIONS: Our data demonstrate that oligo-based arrays offer a valid alternative for focused BAC arrays. Furthermore, they have significant advantages, including better design flexibility, avoidance of repetitive sequences, manufacturing processes amenable to good manufacturing practice standards in the future, increased robustness because of an enhanced dynamic range (signal to background), and increased resolution that allows for detection of smaller regions of change.
Authors: Heike Fiegler; Philippa Carr; Eleanor J Douglas; Deborah C Burford; Sarah Hunt; Carol E Scott; James Smith; David Vetrie; Patricia Gorman; Ian P M Tomlinson; Nigel P Carter Journal: Genes Chromosomes Cancer Date: 2003-04 Impact factor: 5.006
Authors: C Tyson; C Harvard; R Locker; J M Friedman; S Langlois; M E S Lewis; M Van Allen; M Somerville; L Arbour; L Clarke; B McGilivray; S L Yong; J Siegel-Bartel; E Rajcan-Separovic Journal: Am J Med Genet A Date: 2005-12-15 Impact factor: 2.802
Authors: B Menten; N Maas; B Thienpont; K Buysse; J Vandesompele; C Melotte; T de Ravel; S Van Vooren; I Balikova; L Backx; S Janssens; A De Paepe; B De Moor; Y Moreau; P Marynen; J-P Fryns; G Mortier; K Devriendt; F Speleman; J R Vermeesch Journal: J Med Genet Date: 2006-02-20 Impact factor: 6.318
Authors: Jonathan Sebat; B Lakshmi; Dheeraj Malhotra; Jennifer Troge; Christa Lese-Martin; Tom Walsh; Boris Yamrom; Seungtai Yoon; Alex Krasnitz; Jude Kendall; Anthony Leotta; Deepa Pai; Ray Zhang; Yoon-Ha Lee; James Hicks; Sarah J Spence; Annette T Lee; Kaija Puura; Terho Lehtimäki; David Ledbetter; Peter K Gregersen; Joel Bregman; James S Sutcliffe; Vaidehi Jobanputra; Wendy Chung; Dorothy Warburton; Mary-Claire King; David Skuse; Daniel H Geschwind; T Conrad Gilliam; Kenny Ye; Michael Wigler Journal: Science Date: 2007-03-15 Impact factor: 47.728
Authors: Yao-Shan Fan; Parul Jayakar; Hongbo Zhu; Deborah Barbouth; Stephanie Sacharow; Ana Morales; Virginia Carver; Paul Benke; Peter Mundy; Louis J Elsas Journal: Hum Mutat Date: 2007-11 Impact factor: 4.878
Authors: Paul van den Ijssel; Marianne Tijssen; Suet-Feung Chin; Paul Eijk; Beatriz Carvalho; Erik Hopmans; Henne Holstege; Dhinoth Kumar Bangarusamy; Jos Jonkers; Gerrit A Meijer; Carlos Caldas; Bauke Ylstra Journal: Nucleic Acids Res Date: 2005-12-16 Impact factor: 16.971
Authors: Paweł Stankiewicz; Shashikant Kulkarni; Avinash V Dharmadhikari; Srirangan Sampath; Samarth S Bhatt; Tamim H Shaikh; Zhilian Xia; Amber N Pursley; M Lance Cooper; Marwan Shinawi; Alex R Paciorkowski; Dorothy K Grange; Michael J Noetzel; Scott Saunders; Paul Simons; Marshall Summar; Brendan Lee; Fernando Scaglia; Florence Fellmann; Danielle Martinet; Jacques S Beckmann; Alexander Asamoah; Kathryn Platky; Susan Sparks; Ann S Martin; Suneeta Madan-Khetarpal; Jacqueline Hoover; Livija Medne; Carsten G Bonnemann; John B Moeschler; Stephanie E Vallee; Sumit Parikh; Polly Irwin; Victoria P Dalzell; Wendy E Smith; Valerie C Banks; David B Flannery; Carolyn M Lovell; Gary A Bellus; Kathryn Golden-Grant; Jerome L Gorski; Jennifer L Kussmann; Tracy L McGregor; Rizwan Hamid; Jean Pfotenhauer; Blake C Ballif; Chad A Shaw; Sung-Hae L Kang; Carlos A Bacino; Ankita Patel; Jill A Rosenfeld; Sau Wai Cheung; Lisa G Shaffer Journal: Hum Mutat Date: 2011-11-02 Impact factor: 4.878
Authors: Philip M Boone; Carlos A Bacino; Chad A Shaw; Patricia A Eng; Patricia M Hixson; Amber N Pursley; Sung-Hae L Kang; Yaping Yang; Joanna Wiszniewska; Beata A Nowakowska; Daniela del Gaudio; Zhilian Xia; Gayle Simpson-Patel; LaDonna L Immken; James B Gibson; Anne C-H Tsai; Jennifer A Bowers; Tyler E Reimschisel; Christian P Schaaf; Lorraine Potocki; Fernando Scaglia; Tomasz Gambin; Maciej Sykulski; Magdalena Bartnik; Katarzyna Derwinska; Barbara Wisniowiecka-Kowalnik; Seema R Lalani; Frank J Probst; Weimin Bi; Arthur L Beaudet; Ankita Patel; James R Lupski; Sau Wai Cheung; Pawel Stankiewicz Journal: Hum Mutat Date: 2010-11-02 Impact factor: 4.878
Authors: Zhishuo Ou; Paweł Stankiewicz; Zhilian Xia; Amy M Breman; Brian Dawson; Joanna Wiszniewska; Przemyslaw Szafranski; M Lance Cooper; Mitchell Rao; Lina Shao; Sarah T South; Karlene Coleman; Paul M Fernhoff; Marcel J Deray; Sally Rosengren; Elizabeth R Roeder; Victoria B Enciso; A Craig Chinault; Ankita Patel; Sung-Hae L Kang; Chad A Shaw; James R Lupski; Sau W Cheung Journal: Genome Res Date: 2011-01 Impact factor: 9.043
Authors: Przemyslaw Szafranski; Christian P Schaaf; Richard E Person; Ian B Gibson; Zhilian Xia; Sangeetha Mahadevan; Joanna Wiszniewska; Carlos A Bacino; Seema Lalani; Lorraine Potocki; Sung-Hae Kang; Ankita Patel; Sau Wai Cheung; Frank J Probst; Brett H Graham; Marwan Shinawi; Arthur L Beaudet; Pawel Stankiewicz Journal: Hum Mutat Date: 2010-07 Impact factor: 4.878
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Authors: Sung-Hae L Kang; Chad Shaw; Zhishuo Ou; Patricia A Eng; M Lance Cooper; Amber N Pursley; Trilochan Sahoo; Carlos A Bacino; A Craig Chinault; Pawel Stankiewicz; Ankita Patel; James R Lupski; Sau Wai Cheung Journal: Am J Med Genet A Date: 2010-05 Impact factor: 2.802