DOE Human Genome Program Contractor-Grantee Workshop VIII
February 27-March 2, 2000  Santa Fe, NM

1. Sequence Analysis of Human Chromosome 19

Anne Olsen¹, Paul Predki², Ken Frankel², Laurie Gordon¹, Astrid Terry¹, Matt Nolan¹, Mark Wagner¹, Amy Brower¹, Andrea Aerts², Marnel Bondoc², Kristen Kadner², Manesh Shah³, Richard Mural³, Miriam Land³, Denise Schmoyer³, Sergey Petrov³, Doug Hyatt³, Morey Parang³, Jay Snoddy³, Ed Uberbacher³, and the JGI Production Sequencing Team

¹Lawrence Livermore National Laboratory and ²Lawrence Berkeley National Laboratory, DOE Joint Genome Institute, Production Sequencing Facility, Walnut Creek, CA; ³Genome Annotation Consortium, Oak Ridge National Laboratory, Oak Ridge, TN

olsen2@llnl.gov

Chromosome 19 has an estimated size of ~65 Mb and is the most GC-rich human chromosome. The higher than expected proportion of genes and ESTs mapped to this chromosome suggests that it is exceptionally gene-rich, consistent with its high GC content. Sequencing of chromosome 19 will thus be especially rewarding in terms of gene discovery and elucidation of higher order gene organization. The sequence-ready BAC/cosmid map of chromosome 19 constructed at Lawrence Livermore National Laboratory currently consists of 17 ordered, restriction mapped BAC/cosmid contigs of average size 3.3 Mb spanning 56.3 Mb, or approximately 97% of the estimated 58 Mb comprising the p- and q-arms. A minimally overlapping set of clones (468 cosmids and 290 BACs) spanning the chromosome has been selected for sequencing. About 15 Mb of unique sequence has been finished and submitted to Genbank. Draft sequence (minimum coverage 3X) has been generated for about 68% of the remaining territory with an average depth of 7.7X. Sequence contigs have been ordered and oriented for about 5.2 Mb of the draft sequence. Updated map and sequence data is available from the LLNL web site and the JGI web site. Sequence is being analyzed through the Genome Annotation Pipeline at Oak Ridge National Laboratory. The analysis of 15 Mb of finished genomic sequence yielded 719 gene models predicted by Genscan, and 766 gene models predicted by GRAIL-EXP. About two-thirds of the gene models predicted by GRAIL-EXP were aligned with one or more ESTs. 500 of the Genscan predicted proteins and 456 GRAIL-EXP predicted proteins had homologs with BLAST E-values <1.0e-5. Annotation summaries are available from the ORNL Genome Catalog and Genome Channel at http://genome.ornl.gov. Detailed analyses of specific chromosomal regions will be presented.

Supported by USDOE under Contracts W-7405-Eng-48 (LLNL), DE AC0376SF00098 (LBNL) and DE-AC05-96OR22464 (ORNL).