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Facilitating genome navigation: survey sequencing and dense radiation-hybrid gene mapping


Accurate and comprehensive sequence coverage for large genomes has been restricted to only a few species of specific interest. Lower sequence coverage (survey sequencing) of related species can yield a wealth of information about gene content and putative regulatory elements. But survey sequences lack long-range continuity and provide only a fragmented view of a genome. Here we show the usefulness of combining survey sequencing with dense radiation-hybrid (RH) maps for extracting maximum comparative genome information from model organisms. Based on results from the canine system, we propose that from now on all low-pass sequencing projects should be accompanied by a dense, gene-based RH map-construction effort to extract maximum information from the genome with a marginal extra cost.

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Figure 1: Marker order for canine chromosome 1, as determined by radiation-hybrid mapping and sequence assembly.
Figure 2: Integration of the canine radiation-hybrid map with the dog sequence assembly and human data: the example of canine chromosome 1.
Figure 3: Simulation of the number of radiation-hybrid markers required for optimal comparative genome-mapping studies.
Figure 4: Mammals in the genome-sequencing pipeline.


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We acknowledge the American Kennel Club Canine Health Foundation (E.A.O. and F.G.) and the US National Institutes of Health (E.A.O., E.K., F.G. and K.L.-T.). E.A.O. is the recipient of a Burroughs Wellcome Award in Functional Genomics; F.G. is supported by the Centre National Recherche Scientifique, the Université de Rennes1 and Conseil Régional de Bretagne (France). The canine high-quality draft sequence was supported by the National Human Genome Research Institute. D.T., C.S. and P.D. were supported by the Wellcome Trust.

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Correspondence to Elaine A. Ostrander or Francis Galibert.

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Dog Genetics and Whole Genome Mapping


National Human Genome Research Institute Genome Sequencing Proposals web page

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A monophyletic group of related organisms that share a common ancestor, and therefore share similar features.


An abbreviation for contiguous sequence; used to indicate a set of DNA segments that overlap.


A cytogenetic technique used to analyse specific chromosomal regions. Typically, large flourescently labelled pieces of DNA are used as probes in hybridization experiments to determine the presence, absence or orientation of chromosomal material in a region of interest.


Di-, tri-, or tetranucleotide repeat sequences that are composed of large numbers of tandem repeats. Microsatellites are widespread throughout mammalian genomes. Large numbers of alleles are generally associated with each microsatellite within most populations. Therefore, they are frequently used as markers for carrying out family-based linkage analysis.


A method for carrying out sequence comparisons. The method uses the BLAST algorithm to identify the best match for a given query sequence. The mutual-best BLAST method is frequently used to identify orthologous genes from different species.


The Reference Sequence project. A database of annotated human genes. The overall goal of the project is to produce a reference sequence for all naturally occurring molecules.


A genomic sequencing strategy that involves random fragmentation of large DNA segments. The fragments are sequenced, and programs with highly refined algorithms are used to reassemble the original DNA sequence.


A single gene or marker that identifies the comparable region in a target genome, but does not cluster with other genes or markers to form a segment.


The propery of being located on the same chromosome. Conserved synteny is revealed by the localization of orthologous genes between species.

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Hitte, C., Madeoy, J., Kirkness, E. et al. Facilitating genome navigation: survey sequencing and dense radiation-hybrid gene mapping. Nat Rev Genet 6, 643–648 (2005).

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