The mouse t-complex on chromosome 17 has long been a focus of interest for developmental biologists. Because many embryonic lethal mutations are localized in the region, and corresponding genes of importance in development are therefore inferred to reside there, it is a prime target for high priority sequence analysis. The findings of our collaborators that the region contains a large number of otherwise unknown genes, including many expressed selectively in the ectoplacental cone, both underlines the importance of the region and provides probes to screen for substrates for long-range sequence analysis. We have thus started to analyze a multimegabase portion of the t-complex. From the initially targeted 1 Mb of overlapping bacterial artificial chromosomes, the sequencing of 500 kb of clones has been done with greater than 99.9% accuracy. Our main tools for the analysis are comparison with the Genbank EST database, the exon- predicting program GRAIL, the repetitive sequence finding program CENSOR, and the use of CpG content as an assay for CpG islands and genes. Thus far, 12 genes have been identified, including the known genes for ALS (which binds and stabilizes the IGF/IGFBP3 complex in serum), the 3exons homologous to the rat round spermatid gene (RSP29), Chloride channnel 7 gene, gene for Ubiquitin conjugating enzyme and among the remaining newly discovered genes, one of which (Nubps) shows significant sequence similarity to a human nucleotide-binding protein. Much of the region contains an average of 1 gene/ 15 kb, making this zone of the t-complex part of the highest gene density fraction (2 to 5%) of the genome. - Development; genomic sequencing; embryonic lethals; sequence analysis; gene discovery; mapping; imprinting

National Institute of Health (NIH)
National Institute on Aging (NIA)
Intramural Research (Z01)
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National Institute on Aging
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Abe, Kuniya; Yuzuriha, Misako; Sugimoto, Michihiko et al. (2004) Gene content of the 750-kb critical region for mouse embryonic ectoderm lethal tcl-w5. Mamm Genome 15:265-76
Kargul, G J; Nagaraja, R; Shimada, T et al. (2000) Eleven densely clustered genes, six of them novel, in 176 kb of mouse t-complex DNA. Genome Res 10:916-23