A high utility integrated map of the pig genome

Abstract

Background: The domestic pig is being increasingly exploited as a system for modeling human disease. It also has substantial economic importance for meat-based protein production. Physical clone maps have underpinned large-scale genomic sequencing and enabled focused cloning efforts for many genomes. Comparative genetic maps indicate that there is more structural similarity between pig and human than, for example, mouse and human, and we have used this close relationship between human and pig as a way of facilitating map construction.

Results: Here we report the construction of the most highly continuous bacterial artificial chromosome (BAC) map of any mammalian genome, for the pig (Sus scrofa domestica) genome. The map provides a template for the generation and assembly of high-quality anchored sequence across the genome. The physical map integrates previous landmark maps with restriction fingerprints and BAC end sequences from over 260,000 BACs derived from 4 BAC libraries and takes advantage of alignments to the human genome to improve the continuity and local ordering of the clone contigs. We estimate that over 98% of the euchromatin of the 18 pig autosomes and the X chromosome along with localized coverage on Y is represented in 172 contigs, with chromosome 13 (218 Mb) represented by a single contig. The map is accessible through pre-Ensembl, where links to marker and sequence data can be found.

Conclusion: The map will enable immediate electronic positional cloning of genes, benefiting the pig research community and further facilitating use of the pig as an alternative animal model for human disease. The clone map and BAC end sequence data can also help to support the assembly of maps and genome sequences of other artiodactyls.

Figure 1

Alignment between human chromosome 6 tilepath and pig chromosome 7 physical map via porcine BES matches. (a) Mb scale; (b) human sequence tilepath; (c) BES matches to human; (d) sequenced clone EMBL:CR956379 (CH242-196P11); (e) pig clone map - green indicate clones with BAC end sequence match to human; (f) UIUC RH map; (g) estimated Mb.

Figure 2

Blocks of conserved synteny between pig and human. (a) Pig SSC7 to human chromosomes 6, 14 and 15. (b) HSA13 compared to pig chromosome 11. Block inversions between pig and human are denoted with broken lines. Contig coverage is depicted by bars in the center of SSC7 and HSA13.

Figure 3

Comparison of homologous annotation between pig and human. Pig clone CH242-196P11 was aligned to HSA6 by BES matches, and the clone was then sequenced [EMBL:CR956379]. The resulting annotation showed the expected homologues to known human genes present in the pig sequence as in human sequences [EMBL:AL035587, EMBL:AL158815, EMBL:AL136304]. Full gene annotation for CH242-196P11 is available in the EMBL entry. Red lines indicate regions of sequence homology with a 75% sequence similarity over the whole region. Figure generated using Artemis Comparison Tool [57].