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In this review, the authors discussed the advances in mapping and sequencing …
Biology Articles » Genetics » Genomics » Canine Genomics and Genetics: Running with the Pack » Canine Genome Maps and Sequence
The high-quality draft sequence of the dog (http://www.genome.ucsc.edu; http://www.ncbi.nlm.nih.gov; http://www.ensembl.org) has illuminated many qualities of the canine genome only hinted at from previous work . The DAPI-banded karyotype of the dog's 40 chromosomes, combined with reciprocal chromosome paint studies from two independent groups, suggested that the canine genome was highly homologous to the human genome and comprised a limited number of conserved segments, intimating a low level of rearrangement between the two [5–7]. The size of the canine genome was initially estimated from maximum likelihood predictions to be 27 morgans in genetic distance . Estimates based on flow sorting of chromosomes suggest a physical size of 2.8 gigabases [9,10]. Predictions based on sequence analysis of euchromatic sequence suggest a size of 2.3–2.4 gigabases [1,11]. Integrated linkage, radiation hybrid (RH), and cytogenetic maps of the dog genome confirmed these general conclusions [12–15].
Most recently a comparative RH map of the dog genome containing 10,000 canine gene sequences has proven invaluable for identifying small rearrangements within the canine genome (http://www-recomgen.univ-rennes1.fr/doggy.html) , as well as assisting in the ordering of contigs for the draft assembly . The gene sequences used in construction of the 10,000-gene RH map were derived from a 1.5× sequence of the standard poodle. This initial sequence of the dog genome contained at least partial orthologs for 75% (18,473) of annotated human genes . Portions of 9,850 individual genes or about half of all dog genes were localized on an RH panel with 200 kilobase resolution . A total of 264 conserved segments less than 500 kilobases in size were identified from a comparison of the dog map and human genome sequence (National Center for Biotechnology Information Build 34), matching well with predictions from the draft assembly . This provided a clear snapshot of the order of canine genes relative to the human genome, and precise information about breakpoint position. Subsequent studies on breakpoint reuse across mammalian systems, utilizing RH maps from a variety of mammalian species, verify these data .
The 7.5× draft assembly of the canine genome was derived from a female boxer, selected because of her apparent lack of heterozygosity (H.G. Parker, unpublished data). The assembled sequence spans most of the dog's 2.4 gigabases and is derived from 31.5 million sequence reads (http://www.genome.ucsc.edu) . The quality of the assembly is extremely high compared to initial assemblies of other mammalian genomes [18–21]. Half of assembled bases (N50 contig size) are in contigs of 180 kilobases, and the N50 supercontig size is 45.0 megabases, which is considerably longer then the mouse genome at a similar point in its assembly. The reasons are 2-fold. First, technical advances in sequencing result in longer and higher-quality reads. Second, advances in bioinformatics have improved the accuracy with which genomes can be assembled. From a practical standpoint, this means that the majority of canine genes contain no sequence gaps and most canine autosomes are comprised of one to three supercontigs. The current gene count is listed as approximately 19,000, with about 75% representing 1:1:1 orthologs among dog, human, and mouse.
With the availability of the canine genome sequence, the research community is now ready to tackle goals stated nearly a decade ago, when the first arguments were put forth as to why the dog system offered unique advantages for mapping complex traits [22–24]. In general, researchers have focused on the dog as a system for advancing general medical knowledge. In addition, a small but growing number of groups have used the dog for tackling the genetics of morphology and behavior.
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