DOE Human Genome Program
Contractor-Grantee Workshop VII
the Riches of Human Chromosome 19 Through Genomic
Jane E. Lamerdin,
Karolyn Burkhart-Schultz, Linda Danganan, Laurie
Gordon, Stephanie Stilwagen, Glenda Quan, Hoan Phan,
Nelson Velasco, Andre Arellano, Brent Kronmiller,
Long Do, Astrid Terry, Warren Regala, Vijay
Viswanathan, Jennifer Dias, Amy Brower, Tim Andriese,
Pat Poundstone, Julie Avila, Jackie Coefield, Susan
Lucas, Tina Attix, Stephenie Liu, Robert Bruce, Evan
Skowronski, Rick Colyaco, Arthur Kobayashi, David Ow,
Matt Nolan, Anthony V. Carrano, Anne. S. Olsen, and
Genomic sequencing of human chromosome 19 is well underway. Roughly 20% of the euchromatin of chromosome 19 is now available as finished genomic sequence in GenBank, with completion of most of the chromosome anticipated by 2001. Utilizing a high resolution physical map constructed largely in bacterial-based clones, we have seeded our current sequencing queue with many large (*1Mb) contigs from well-mapped regions, with representative contigs from almost every cytogenetic band on chromosome 19. As of Oct 30, we have finished over 11 Mb of genomic sequence, with roughly 10.5 Mb submitted to GenBank. Preliminary analyses of our data lend credence to the expectation that this GC-rich chromosome will be an excellent target for gene discovery through genomic sequencing. In this regard, several GC-rich regions (average GC content in excess of 58%) that have been sequenced on chromosome 19 exhibit a high gene density (on average, 1 gene per 20-25 kb) relative to the rest of the genome, and encode genes with compact genomic structure. Other regions with a slightly lower GC content (average GC= 50%) possess fewer genes which span larger genomic distances, e.g. the ryanodine receptor (RYR) region in 19q13.1.
One interesting feature of chromosome 19 is the large number of clustered gene families distributed throughout the length of the euchromatin. These include the pregnancy-specific glycoprotein family (PSG), multiple zinc finger families (ZNF), olfactory receptors (OLFR) and cytochrome P-450s (CYP). In order to understand their evolution and subsequent functional diversification, several of these clusters are current sequencing targets. Not surprisingly, the ages of these clusters differ significantly, with the PSG family having duplicated fairly recently in evolutionary time, while the OLFR and ZNF clusters appear much older, with many of their members possessing orthologs in mice and rats. One common feature of the genomic structure of these disparate families is the prevalence of specific repeat families, which may have contributed to the evolution and expansion of these regions. We are undertaking a more detailed comparison of the genomic content of these gene family regions on chromosome 19, as well as their orthologous counterparts in mouse. These comparisons will no doubt expand our recognition of the fluidity of the mammalian genome.
This work was performed by Lawrence Livermore National Laboratory under the auspices of the U.S. Department of Energy, Contract No. W-7405-Eng-48.
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