A tiling resolution DNA microarray with complete coverage of the human genome

• Published in: Nature genetics Vol. 36; no. 3; pp. 299 - 303
• Main Authors: Lam, Wan L, Ishkanian, Adrian S, Malloff, Chad A, Watson, Spencer K, deLeeuw, Ronald J, Chi, Bryan, Coe, Bradley P, Snijders, Antoine, Albertson, Donna G, Pinkel, Daniel, Marra, Marco A, Ling, Victor, MacAulay, Calum
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-03-2004
• Subjects: Biological and medical sciences; Boundaries; Chromosome mapping; Chromosomes, Artificial, Bacterial; Deoxyribonucleic acid; Diverse techniques; DNA; DNA microarrays; Fundamental and applied biological sciences. Psychology; Gene Dosage; Genome, Human; Genomics; Human genome; Humans; Hybridization; Methods; Molecular and cellular biology; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis - methods; Physiological aspects; Sensitivity and Specificity; Tumor Cells, Cultured; Tumors; Canada; Chromosomal aberration; Human; Genome; DNA chip
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1307

We constructed a tiling resolution array consisting of 32,433 overlapping BAC clones covering the entire human genome. This increases our ability to identify genetic alterations and their boundaries throughout the genome in a single comparative genomic hybridization (CGH) experiment. At this tiling resolution, we identified minute DNA alterations not previously reported. These alterations include microamplifications and deletions containing oncogenes, tumor-suppressor genes and new genes that may be associated with multiple tumor types. Our findings show the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers. Our submegabase resolution tiling set for array CGH (SMRT array) allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease.