Segmental copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component of our phenotypic diversity. In this study, using a whole-genome array comparative genomic hybridization assay, we identified 3,654 autosomal segmental CNVs, 800 of which appeared at a frequency of at least 3%. Of these frequent CNVs, 77% are novel. In the 95 individuals analyzed, the two most diverse genomes differed by at least 9 Mb in size or varied by at least 266 loci in content. Approximately 68% of the 800 polymorphic regions overlap with genes, which may reflect human diversity in senses (smell, hearing, taste, and sight), rhesus phenotype, metabolism, and disease susceptibility. Intriguingly, 14 polymorphic regions harbor 21 of the known human microRNAs, raising the possibility of the contribution of microRNAs to phenotypic diversity in humans. This in-depth survey of CNVs across the human genome provides a valuable baseline for studies involving human genetics.

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.Identification of chromosomal imbalances and variation in DNA copy-number is essential to our understanding of disease mechanisms and pathogenesis. Array CGH 1 or matrix CGH 2 offers the highest resolution for practical genome-wide detection of chromosomal alterations. This technique is derived from the concept of conventional CGH 3 , which has contributed greatly to the molecular characterization of both somatic and constitutional genomic DNA mutations over the last decade 4-6 . The primary limitation of conventional CGH is its resolution (∼20 Mb), as this method detects segmental copy-number changes on metaphase chromosomes 3 . In array CGH, the metaphase chromosome spread is replaced by BACs, PACs or YACs containing human DNA as targets, increasing the resolution to the distance between the selected marker DNA clones 1,2 . Genome screening using array CGH has great potential in the characterization of numerous chromosomal disorders.Efforts to construct DNA arrays spanning the human genome consisted of spotting 2,460 (ref. 7) or 3,500 (ref. 8) marker BAC clones representing the sequenced genome at an average interval of ∼1 Mb.These studies showed that sufficient target-DNA printing solution could be generated from individual BACs using PCR-based protocols. Because the target product is PCR-derived, it is easily replenishable, obviating the need for multiple rounds of laborious large-scale BAC DNA preparations. These arrays are sensitive enough to detect singlecopy changes, but the technique is limited by the small number of BAC markers representing the genome on the slide, rather than the methodology. Even at this resolution, array CGH is useful for detecting chromosomal aberrations associated with congenital abnormalities and somatic malignancies [9][10][11][12] .Recent studies focused on higher-density regional arrays for fine mapping and identifying new genes in specific chromosomal regions [13][14][15][16][17][18] . For example, a candidate oncogene for association with

Early identification of high-risk disease could greatly reduce both mortality and morbidity due to oral cancer. We describe a simple handheld device that facilitates the direct visualization of oral-cavity fluorescence for the detection of high-risk precancerous and early cancerous lesions. Blue excitation light (400 to 460 nm) is employed to excite green-red fluorescence from fluorophores in the oral tissues. Tissue fluorescence is viewed directly along an optical axis collinear with the axis of excitation to reduce inter- and intraoperator variability. This robust, field-of-view device enables the direct visualization of fluorescence in the context of surrounding normal tissue. Results from a pilot study of 44 patients are presented. Using histology as the gold standard, the device achieves a sensitivity of 98% and specificity of 100% when discriminating normal mucosa from severe dysplasia/carcinoma in situ (CIS) or invasive carcinoma. We envisage this device as a suitable adjunct for oral cancer screening, biopsy guidance, and margin delineation.

Once thought to be a part of the ‘dark matter’ of the genome, long non-coding RNAs (lncRNAs) are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE) libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer.