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W J Kent

Publications and source records attributed to W J Kent.

6 recordsLinked to original sources

Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Animals↗

The UCSC Genome Browser Database.

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.

Animals↗

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗

Assembly of the working draft of the human genome with GigAssembler.

The data for the public working draft of the human genome contains roughly 400,000 initial sequence contigs in approximately 30,000 large insert clones. Many of these initial sequence contigs overlap. A program, GigAssembler, was built to merge them and to order and orient the resulting larger sequence contigs based on mRNA, paired plasmid ends, EST, BAC end pairs, and other information. This program produced the first publicly available assembly of the human genome, a working draft containing roughly 2.7 billion base pairs and covering an estimated 88% of the genome that has been used for several recent studies of the genome. Here we describe the algorithm used by GigAssembler.

Algorithms↗

The intronerator: exploring introns and alternative splicing in Caenorhabditis elegans.

The Intronerator (http://www.cse.ucsc.edu/ approximately kent/intronerator/ ) is a set of web-based tools for exploring RNA splicing and gene structure in Caenorhabditis elegans. It includes a display of cDNA alignments with the genomic sequence, a catalog of alternatively spliced genes and a database of introns. The cDNA alignments include >100 000 ESTs and almost 1000 full-length cDNAs. ESTs from embryos and mixed stage animals as well as full-length cDNAs can be compared in the alignment display with each other and with predicted genes. The alt-splicing catalog includes 844 open reading frames for which there is evidence of alternative splicing of pre-mRNA. The intron database includes 28 478 introns, and can be searched for patterns near the splice junctions.

Alternative Splicing↗

Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment.

A new algorithm, WABA, was developed for doing large-scale alignments between genomic DNA of different species. WABA was used to align 8 million bases of Caenorhabditis briggsae genomic DNA against the entire 97-million-base Caenorhabditis elegans genome. The alignment, including C. briggsae homologs of 154 genetically characterized C. elegans genes and many times this number of largely uncharacterized ORFs, can be browsed and searched on the Web (http://www.cse.ucsc.edu/ approximately kent/intronerator). The alignment confirms that patterns of conservation can be useful in identifying regulatory regions and rarely expressed coding regions. Conserved regulatory elements can be identified inside coding exons by examining the level of divergence at the wobble position of codons. The alignment reveals a bimodal size distribution of syntenic regions. Over 250 introns are present in one species but not the other. The 3' and 5' intron splice sites have more similarity to each other in introns unique to one species than in C. elegans introns as a whole, suggesting a possible mechanism for intron removal.

Algorithms↗