An integrated 4249 marker FISH/RH map of the canine genome.

Matthew Breen,Edouard Cadieu,Leah Sabacan,Richard Guyon,Claire M Fraser,Heidi G Parker,Rachael Thomas,Ewen F Kirkness,Gwenaelle Evanno,Ruth Hudson,Catherine André,Travis D Lorentzen,Francis Galibert,Allyson Scott,Boris Gelfenbeyn,Elaine A Ostrander,Christophe Hitte,Gregory G Mahairas

doi:10.1186/1471-2164-5-65

Abstract

BackgroundThe 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology.ResultsTo facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS.ConclusionsThese results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps.

Highlights

The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation
The typing of 4249 markers resulted in an radiation hybrid (RH) map containing 4106 markers that were eventually grouped and assigned to each of the canine chromosomes, leaving only 143 unlinked markers
Even when markers of the same type are co-localized, they are likely to be of value; any given microsatellite is not informative in every pedigree, and closely localized bacterial artificial chromosome clones (BACs) may represent the beginning of an overlapping contig

Summary

Introduction

The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Three major advances in the development of resources for mapping canine disease genes have been: 1) the development of a radiation hybrid (RH) map composed of large numbers of microsatellite markers and genes that link the canine and human genomes [1], 2) the development of canine specific whole chromosome paints that have allowed preliminary assignment of conserved segments between human and dog [3,4,5]; and 3) the publication of a 1.5x genome sequence of the dog [2]. The most recently published RH map of the dog comprises 3270 markers including 1596 microsatellite-based markers, 900 caninespecific cloned gene sequences and expressed sequence tags (ESTs), and an initial set of 668 canine-specific BACends [1]. The current alignment supports most of the proposed comparative segments, but suggests that the final comparative dog-human map will be composed of at least 160 comparative blocks [2]

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Conclusion