With the recent completion of the human genome sequence, the sequencing of other vertebrate genomes has taken center stage. The sequencing of widely studied model organisms (e.g., mouse, rat, and zebrafish) is providing a valuable resource for future experimentation and important insights into vertebrate biology. Less clear is the relative value of other candidate genomes being considered for systematic sequencing, especially with regard to their potential contribution to the annotation and interpretation of the human sequence. To investigate such issues, we are generating large blocks of orthologous sequence from multiple vertebrates for detailed comparative analyses. Specifically, the same targeted genomic regions from multiple vertebrate specie are being isolated in large-insert clones and then sequenced. Efficient methods for designing orthologous hybridization probes and isolating bacterial artificial chromosome (BAC) clones from the different species have been developed and implemented. Following characterization by several mapping methods, tiling paths of BACs are then selected and systematically sequenced. In total, >200 Mb of comparative sequencing data is being generated each year. The establishment of this comparative sequence resource is facilitating the development of new computational tools for multi-species sequence comparisons, providing insight about the appropriate degrees of sequencing finishing that should be pursued in the sequencing of other vertebrate species, and revealing the benefits of sequencing species from a range of evolutionary distances. These efforts are being extensively focused on the recently launched ENCODE project, which aims to identify all functional in a targeted 1% of the human genome.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000196-04
Application #
6988877
Study Section
(DIR)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Human Genome Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
(2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816
Nikolaev, Sergey; Montoya-Burgos, Juan I; Margulies, Elliott H et al. (2007) Early history of mammals is elucidated with the ENCODE multiple species sequencing data. PLoS Genet 3:e2
Margulies, Elliott H; Cooper, Gregory M; Asimenos, George et al. (2007) Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome. Genome Res 17:760-74
Zhang, Wei; Bouffard, Gerard G; Wallace, Susan S et al. (2007) Estimation of DNA sequence context-dependent mutation rates using primate genomic sequences. J Mol Evol 65:207-14
Hurle, Belen; Swanson, Willie; NISC Comparative Sequencing Program et al. (2007) Comparative sequence analyses reveal rapid and divergent evolutionary changes of the WFDC locus in the primate lineage. Genome Res 17:276-86
Cretekos, Chris J; Deng, Jian-Min; Green, Eric D et al. (2007) Isolation, genomic structure and developmental expression of Fgf8 in the short-tailed fruit bat, Carollia perspicillata. Int J Dev Biol 51:333-8
Keebaugh, Alaine C; Sullivan, Robert T; NISC Comparative Sequencing Program et al. (2007) Gene duplication and inactivation in the HPRT gene family. Genomics 89:134-42
Morin, Ryan D; Chang, Elbert; Petrescu, Anca et al. (2006) Sequencing and analysis of 10,967 full-length cDNA clones from Xenopus laevis and Xenopus tropicalis reveals post-tetraploidization transcriptome remodeling. Genome Res 16:796-803
Margulies, Elliott H; Chen, Christina W; Green, Eric D (2006) Differences between pair-wise and multi-sequence alignment methods affect vertebrate genome comparisons. Trends Genet 22:187-93
She, Xinwei; Liu, Ge; Ventura, Mario et al. (2006) A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications. Genome Res 16:576-83

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