Showing papers by "Richard K. Wilson published in 1999"

The DNA sequence of human chromosome 22

Abstract: Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana

Abstract: The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

A map for sequence analysis of the Arabidopsis thaliana genome

Abstract: Arabidopsis thaliana has emerged as a model system for studies of plant genetics and development, and its genome has been targeted for sequencing1 by an international consortium (the Arabidopsis Genome Initiative; http://genome-www.stanford.edu/Arabidopsis/agi.html ). To support the genome-sequencing effort, we fingerprinted more than 20,000 BACs (ref. 2) from two high-quality publicly available libraries3,4,5, generating an estimated 17-fold redundant coverage of the genome, and used the fingerprints to nucleate assembly of the data by computer. Subsequent manual revision of the assemblies resulted in the incorporation of 19,661 fingerprinted BACs into 169 ordered sets of overlapping clones ('contigs'), each containing at least 3 clones. These contigs are ideal for parallel selection of BACs for large-scale sequencing and have supported the generation of more than 5.8 Mb of finished genome sequence submitted to GenBank; analysis of the sequence has confirmed the integrity of contigs constructed using this fingerprint data. Placement of contigs onto chromosomes can now be performed, and is being pursued by groups involved in both sequencing and positional cloning studies. To our knowledge, these data provide the first example of whole-genome random BAC fingerprint analysis of a eucaryote, and have provided a model essential to efforts aimed at generating similar databases of fingerprint contigs to support sequencing of other complex genomes, including that of human.

An encyclopedia of mouse genes.

Abstract: The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis1 possible (see also the Jackson Laboratory web site, http://www.jax.org/ ) and the ever–expanding collection of molecular tools2,3. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes4,5,6,7,8,9,10,11,12,13,14,15,16. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects7,12. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5´ end sequences from directionally cloned, oligo–dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification17, comparative sequence analysis18,19, comparative gene mapping and candidate disease gene identification20, genome sequence annotation21,22, microarray development23 and the development of gene–based map resources24.

Identification, characterization, and mapping of a mouse homolog of the gene mutated in Nijmegen breakage syndrome

Abstract: . The rare autosomal recessive disorder Nijmegen breakage syndrome (NBS) results from mutations in the NBS1 gene on human chromosome 8q21. A mouse homolog of the NBS1 gene was iso