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1. Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi.

Author

Cavazza, A., Hendel, A., Bak, R.O., Rio, P., Güell, M., Lainšček, D., Arechavala-Gomeza, V., Peng, L., Hapil, F.Z., Harvey, J., Ortega, F.G., Gonzalez-Martinez, C., Lederer, C.W., Mikkelsen, K., Gasiunas, G., Kalter, N., Gonçalves, M.A.F.V., Petersen, J., Garanto, A., Montoliu, L., Maresca, M., Seemann, S.E., Gorodkin, J., Mazini, L., Sanchez, R., Rodriguez-Madoz, J.R., Maldonado-Pérez, N., Laura, T., Schmueck-Henneresse, M., Maccalli, C., Grünewald, J., Carmona, G., Kachamakova-Trojanowska, N., Miccio, A., Martin, F., Turchiano, G., Cathomen, T., Luo, Y, Tsai, S.Q., Benabdellah, K., Cavazza, A., Hendel, A., Bak, R.O., Rio, P., Güell, M., Lainšček, D., Arechavala-Gomeza, V., Peng, L., Hapil, F.Z., Harvey, J., Ortega, F.G., Gonzalez-Martinez, C., Lederer, C.W., Mikkelsen, K., Gasiunas, G., Kalter, N., Gonçalves, M.A.F.V., Petersen, J., Garanto, A., Montoliu, L., Maresca, M., Seemann, S.E., Gorodkin, J., Mazini, L., Sanchez, R., Rodriguez-Madoz, J.R., Maldonado-Pérez, N., Laura, T., Schmueck-Henneresse, M., Maccalli, C., Grünewald, J., Carmona, G., Kachamakova-Trojanowska, N., Miccio, A., Martin, F., Turchiano, G., Cathomen, T., Luo, Y, Tsai, S.Q., and Benabdellah, K.

Abstract

Item does not contain fulltext, The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing's potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

Published
2023

2. Sequence assembly

Author

Scheibye-Alsing, K., Hoffmann, S., Frankel, A., Jensen, P., Stadler, P.F., Mang, Y., Tommerup, N., Gilchrist, M.J., Nygård, A.-B., Cirera, S., Jørgensen, C.B., Fredholm, M., and Gorodkin, J.

Published
2009
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4. FRETraj: integrating single-molecule spectroscopy with molecular dynamics

Author

Gorodkin, Jan, Gorodkin, J ( Jan ), Steffen, Fabio D; https://orcid.org/0000-0001-8795-2212, Sigel, Roland K O; https://orcid.org/0000-0002-1307-7993, Börner, Richard; https://orcid.org/0000-0001-8407-6624, Gorodkin, Jan, Gorodkin, J ( Jan ), Steffen, Fabio D; https://orcid.org/0000-0001-8795-2212, Sigel, Roland K O; https://orcid.org/0000-0002-1307-7993, and Börner, Richard; https://orcid.org/0000-0001-8407-6624

Abstract

Quantitative interpretation of single-molecule FRET experiments requires a model of the dye dynamics to link experimental energy transfer efficiencies to distances between atom positions. We have developed FRETraj, a Python module to predict FRET distributions based on accessible-contact volumes (ACV) and simulated photon statistics. FRETraj helps to identify optimal fluorophore positions on a biomolecule of interest by rapidly evaluating donor-acceptor distances. FRETraj is scalable and fully integrated into PyMOL and the Jupyter ecosystem. Here, we describe the conformational dynamics of a DNA hairpin by computing multiple ACVs along a molecular dynamics trajectory and compare the predicted FRET distribution with single-molecule experiments. FRET-assisted modeling will accelerate the analysis of structural ensembles in particular dynamic, non-coding RNAs and transient protein-nucleic acid complexes.

Published
2021

11. CellBench: R/Bioconductor software for comparing single-cell RNA-seq analysis methods

Author

Gorodkin, J, Su, S, Tian, L, Dong, X, Hickey, PF, Freytag, S, Ritchie, ME, Gorodkin, J, Su, S, Tian, L, Dong, X, Hickey, PF, Freytag, S, and Ritchie, ME

Abstract

MOTIVATION: Bioinformatic analysis of single-cell gene expression data is a rapidly evolving field. Hundreds of bespoke methods have been developed in the past few years to deal with various aspects of single-cell analysis and consensus on the most appropriate methods to use under different settings is still emerging. Benchmarking the many methods is therefore of critical importance and since analysis of single-cell data usually involves multi-step pipelines, effective evaluation of pipelines involving different combinations of methods is required. Current benchmarks of single-cell methods are mostly implemented with ad-hoc code that is often difficult to reproduce or extend, and exhaustive manual coding of many combinations is infeasible in most instances. Therefore, new software is needed to manage pipeline benchmarking. RESULTS: The CellBench R software facilitates method comparisons in either a task-centric or combinatorial way to allow pipelines of methods to be evaluated in an effective manner. CellBench automatically runs combinations of methods, provides facilities for measuring running time and delivers output in tabular form which is highly compatible with tidyverse R packages for summary and visualization. Our software has enabled comprehensive benchmarking of single-cell RNA-seq normalization, imputation, clustering, trajectory analysis and data integration methods using various performance metrics obtained from data with available ground truth. CellBench is also amenable to benchmarking other bioinformatics analysis tasks. AVAILABILITY AND IMPLEMENTATION: Available from https://bioconductor.org/packages/CellBench.

Published
2020

12. Good guide, bad guide: spacer sequence-dependent cleavage efficiency of Cas12a

Author

Creutzburg, S.C.A., Wu, Wen, Mohanraju, P., Swartjes, Thomas, Alkan, F., Gorodkin, J., Staals, R.H.J., van der Oost, J., Creutzburg, S.C.A., Wu, Wen, Mohanraju, P., Swartjes, Thomas, Alkan, F., Gorodkin, J., Staals, R.H.J., and van der Oost, J.

Abstract

Genome editing has recently made a revolutionary development with the introduction of the CRISPR–Cas technology. The programmable CRISPR-associated Cas9 and Cas12a nucleases generate specific dsDNA breaks in the genome, after which host DNA-repair mechanisms can be manipulated to implement the desired editing. Despite this spectacular progress, the efficiency of Cas9/Cas12a-based engineering can still be improved. Here, we address the variation in guide-dependent efficiency of Cas12a, and set out to reveal the molecular basis of this phenomenon. We established a sensitive and robust in vivo targeting assay based on loss of a target plasmid encoding the red fluorescent protein (mRFP). Our results suggest that folding of both the precursor guide (pre-crRNA) and the mature guide (crRNA) have a major influence on Cas12a activity. Especially, base pairing of the direct repeat, other than with itself, was found to be detrimental to the activity of Cas12a. Furthermore, we describe different approaches to minimize base-pairing interactions between the direct repeat and the variable part of the guide. We show that design of the 3′ end of the guide, which is not involved in target strand base pairing, may result in substantial improvement of the guide's targeting potential and hence of its genome editing efficiency.

Published
2020

17. A mini-greedy algorithm for faster structural RNA stem-loop search

Author

Gorodkin, J., Lyngsø, R.B., and Stormo, G.D.

Abstract

When a set of coregulated genes share a common structural RNA motif, e.g. a hairpin, most motif search approaches fail to locate the covarying but structurally conserved motif. There do exist methods that can locate structural RNA motifs, like FOLDALIGN, but the main problem with these methods is that they are computationally expensive. In FOLDALIGN, a major contribution to this is the use of a greedy algorithm to construct the multiple alignment. To ensure good quality many redundant computations must be made. However, by applying the greedy algorithm on a carefully selected subset of sequences, near full greedy quality can be obtained. The basic idea is to estimate the order in which the sequences entered a good greedy alignment. If such a ranking, found from all pairwise alignments, is in good agreement with the order of appearance in the multiple alignment, the core structural motif can be found by performing the greedy algorithm on just the top sequences in the ranking. The ranking used in this mini-greedy algorithm is found by using two complementing approaches: 1) When interpreting the FOLDALIGN score as an inner product (kernel), the sequences can be ranked according to their distance to their center of mass; 2) We construct an algorithm that attempts to find the K closest sequences in the vector space associated with the inner product, and the remaining sequences can be ranked by their minimum distance to any of the sequences, or to the center of mass in this set. The two approaches arecompared and merged, and the results discussed. We also show that structural alignments of near full greedy quality can found in significantly reduced time, using these methods. The algorithm is being included in the SLASH (Stem-Loop Align SearcH) server available at http://www.bioinf.au.dk/slash.

Published
2016

19. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

Author

Hölzer, M., Krähling, V., Amman, F., Barth, E., Bernhart, S.H., Carmelo, V.A.O., Collatz, M., Doose, G., Eggenhofer, F., Ewald, J., Fallmann, J., Feldhahn, Lasse, Fricke, M., Gebauer, J., Gruber, A.J., Hufsky, F., Indrischek, H., Kanton, S., Linde, J., Mostajo, N., Ochsenreiter, R., Riege, K., Rivarola-Duarte, Lorena Soledad, Sahyoun, A.H., Saunders, S.J., Seemann, S.E., Tanzer, A., Vogel, B., Wehner, S., Wolfinger, M.T., Backofen, R., Gorodkin, J., Grosse, Ivo, Hofacker, I., Hoffmann, S., Kaleta, C., Stadler, P.F., Becker, S., Marz, M., Hölzer, M., Krähling, V., Amman, F., Barth, E., Bernhart, S.H., Carmelo, V.A.O., Collatz, M., Doose, G., Eggenhofer, F., Ewald, J., Fallmann, J., Feldhahn, Lasse, Fricke, M., Gebauer, J., Gruber, A.J., Hufsky, F., Indrischek, H., Kanton, S., Linde, J., Mostajo, N., Ochsenreiter, R., Riege, K., Rivarola-Duarte, Lorena Soledad, Sahyoun, A.H., Saunders, S.J., Seemann, S.E., Tanzer, A., Vogel, B., Wehner, S., Wolfinger, M.T., Backofen, R., Gorodkin, J., Grosse, Ivo, Hofacker, I., Hoffmann, S., Kaleta, C., Stadler, P.F., Becker, S., and Marz, M.

Abstract

The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.

Published
2016

20. Adipocyte gene expression and DNA methylation patterns differ significantly between lean and obese pigs

Author

Jacobsen, Mette Juul, Havgaard, Jakob Hull, Mentzel, Caroline M. Junker, Sørensen, P. M., Pundhir, Sachin, Anthon, Christian, Karlskov-Mortensen, Peter, Bruun, Camilla Vibeke Sichlau, Cirera Salicio, Susanna, Gorodkin, J., Jorgensen, C. B., Barrès, Romain, Fredholm, M., Jacobsen, Mette Juul, Havgaard, Jakob Hull, Mentzel, Caroline M. Junker, Sørensen, P. M., Pundhir, Sachin, Anthon, Christian, Karlskov-Mortensen, Peter, Bruun, Camilla Vibeke Sichlau, Cirera Salicio, Susanna, Gorodkin, J., Jorgensen, C. B., Barrès, Romain, and Fredholm, M.

Published
2016

21. P2019 Adipocyte gene expression and DNA methylation patterns differ significantly between lean and obese pigs

Author

Jacobsen, M. J., primary, Havgaard, J. H., additional, Mentzel, C. M. Junker, additional, Sørensen, P. M., additional, Pundhir, S., additional, Anthon, C., additional, Karlskov-Mortensen, P., additional, Bruun, C. S., additional, Cirera, S., additional, Gorodkin, J., additional, Jørgensen, C. B., additional, Barrès, R., additional, and Fredholm, M., additional

Published
2016
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22. Fast local fragment chaining using sum-of-pair gap costs

Author

Otto, C., Hoffmann, S., Gorodkin, J., Stadler, P.F., and Publica

Subjects
lcsh:Genetics, lcsh:Biology (General), lcsh:QH426-470, Computational Theory and Mathematics, Structural Biology, Applied Mathematics, lcsh:QH301-705.5, Molecular Biology, Software Article
Abstract

Background Fast seed-based alignment heuristics such as BLAST and BLAT have become indispensable tools in comparative genomics for all studies aiming at the evolutionary relations of proteins, genes, and non-coding RNAs. This is true in particular for the large mammalian genomes. The sensitivity and specificity of these tools, however, crucially depend on parameters such as seed sizes or maximum expectation values. In settings that require high sensitivity the amount of short local match fragments easily becomes intractable. Then, fragment chaining is a powerful leverage to quickly connect, score, and rank the fragments to improve the specificity. Results Here we present a fast and flexible fragment chainer that for the first time also supports a sum-of-pair gap cost model. This model has proven to achieve a higher accuracy and sensitivity in its own field of application. Due to a highly time-efficient index structure our method outperforms the only existing tool for fragment chaining under the linear gap cost model. It can easily be applied to the output generated by alignment tools such as segemehl or BLAST. As an example we consider homology-based searches for human and mouse snoRNAs demonstrating that a highly sensitive BLAST search with subsequent chaining is an attractive option. The sum-of-pair gap costs provide a substantial advantage is this context. Conclusions Chaining of short match fragments helps to quickly and accurately identify regions of homology that may not be found using local alignment heuristics alone. By providing both the linear and the sum-of-pair gap cost model, a wider range of application can be covered. The software clasp is available at http://www.bioinf.uni-leipzig.de/Software/clasp/.

Published
2011

23. Sequence assembly. Review

Author

Scheibye-Alsing, K., Hoffmann, S., Frankel, A., Jensen, P., Stadler, P.F., Mang, Y., Tommerup, N., Gilchrist, M.J., Nygard, A.B., Cirera, S., Jorgensen, C.B., Fredholm, M., Gorodkin, J., and Publica

Subjects
shothun, high-throughput sequencing, EST, assembly method, genomes
Abstract

Despite the rapidly increasing number of sequenced and re-sequenced genomes, many issues regarding the computational assembly of large-scale sequencing data have remain unresolved. Computational assembly is crucial in large genome projects as well for the evolving high-throughput technologies and plays an important role in processing the information generated by these methods. Here, we provide a comprehensive overview of the current publicly available sequence assembly programs. We describe the basic principles of computational assembly along with the main concerns, such as repetitive sequences in genomic DNA, highly expressed genes and alternative transcripts in EST sequences. We summarize existing comparisons of different assemblers and provide a detailed descriptions and directions for download of assembly programs at: http://genome.ku.dk/resources/assembly/methods.html.

Published
2009

28. Analyses of pig genomes provide insight into porcine demography and evolution

Author

Groenen, M. A., Archibald, A. L., Uenishi, H., Tuggle, C. K., Takeuchi, Y., Rothschild, M. F., Rogel-Gaillard, C., Park, C., Milan, D., Megens, H. J., Li, S., Larkin, D. M., Kim, H., Frantz, L. A., Caccamo, M., Ahn, H., Aken, B. L., Anselmo, A., Anthon, C., Auvil, L., Badaoui, B., Beattie, C. W., Bendixen, C., Berman, D., Blecha, F., Blomberg, Jonas, Bolund, L., Bosse, M., Botti, S., Bujie, Z., Byström, M., Capitanu, B., Carvalho-Silva, D., Chardon, P., Chen, C., Cheng, R., Choi, S. H., Chow, W., Clark, R. C., Clee, C., Crooijmans, R. P., Dawson, H. D., Dehais, P., De Sapio, F., Dibbits, B., Drou, N., Du, Z. Q., Eversole, K., Fadista, J., Fairley, S., Faraut, T., Faulkner, G. J., Fowler, K. E., Fredholm, M., Fritz, E., Gilbert, J. G., Giuffra, E., Gorodkin, J., Griffin, D. K., Harrow, J. L., Hayward, Alexander, Howe, K., Hu, Z. L., Humphray, S. J., Hunt, T., Hornshoj, H., Jeon, J. T., Jern, Patric, Jones, M., Jurka, J., Kanamori, H., Kapetanovic, R., Kim, J., Kim, J. H., Kim, K. W., Kim, T. H., Larson, G., Lee, K., Lee, K. T., Leggett, R., Lewin, H. A., Li, Y., Liu, W., Loveland, J. E., Lu, Y., Lunney, J. K., Ma, J., Madsen, O., Mann, K., Matthews, L., McLaren, S., Morozumi, T., Murtaugh, M. P., Narayan, J., Nguyen, D. T., Ni, P., Oh, S. J., Onteru, S., Panitz, F., Park, E. W., Park, H. S., Pascal, G., Paudel, Y., Perez-Enciso, M., Ramirez-Gonzalez, R., Reecy, J. M., Rodriguez-Zas, S., Rohrer, G. A., Rund, L., Sang, Y., Schachtschneider, K., Schraiber, J. G., Schwartz, J., Scobie, L., Scott, C., Searle, S., Servin, B., Southey, B. R., Sperber, Göran, Stadler, P., Sweedler, J. V., Tafer, H., Thomsen, B., Wali, R., Wang, J., White, S., Xu, X., Yerle, M., Zhang, G., Zhang, J., Zhao, S., Rogers, J., Churcher, C., Schook, L. B., Groenen, M. A., Archibald, A. L., Uenishi, H., Tuggle, C. K., Takeuchi, Y., Rothschild, M. F., Rogel-Gaillard, C., Park, C., Milan, D., Megens, H. J., Li, S., Larkin, D. M., Kim, H., Frantz, L. A., Caccamo, M., Ahn, H., Aken, B. L., Anselmo, A., Anthon, C., Auvil, L., Badaoui, B., Beattie, C. W., Bendixen, C., Berman, D., Blecha, F., Blomberg, Jonas, Bolund, L., Bosse, M., Botti, S., Bujie, Z., Byström, M., Capitanu, B., Carvalho-Silva, D., Chardon, P., Chen, C., Cheng, R., Choi, S. H., Chow, W., Clark, R. C., Clee, C., Crooijmans, R. P., Dawson, H. D., Dehais, P., De Sapio, F., Dibbits, B., Drou, N., Du, Z. Q., Eversole, K., Fadista, J., Fairley, S., Faraut, T., Faulkner, G. J., Fowler, K. E., Fredholm, M., Fritz, E., Gilbert, J. G., Giuffra, E., Gorodkin, J., Griffin, D. K., Harrow, J. L., Hayward, Alexander, Howe, K., Hu, Z. L., Humphray, S. J., Hunt, T., Hornshoj, H., Jeon, J. T., Jern, Patric, Jones, M., Jurka, J., Kanamori, H., Kapetanovic, R., Kim, J., Kim, J. H., Kim, K. W., Kim, T. H., Larson, G., Lee, K., Lee, K. T., Leggett, R., Lewin, H. A., Li, Y., Liu, W., Loveland, J. E., Lu, Y., Lunney, J. K., Ma, J., Madsen, O., Mann, K., Matthews, L., McLaren, S., Morozumi, T., Murtaugh, M. P., Narayan, J., Nguyen, D. T., Ni, P., Oh, S. J., Onteru, S., Panitz, F., Park, E. W., Park, H. S., Pascal, G., Paudel, Y., Perez-Enciso, M., Ramirez-Gonzalez, R., Reecy, J. M., Rodriguez-Zas, S., Rohrer, G. A., Rund, L., Sang, Y., Schachtschneider, K., Schraiber, J. G., Schwartz, J., Scobie, L., Scott, C., Searle, S., Servin, B., Southey, B. R., Sperber, Göran, Stadler, P., Sweedler, J. V., Tafer, H., Thomsen, B., Wali, R., Wang, J., White, S., Xu, X., Yerle, M., Zhang, G., Zhang, J., Zhao, S., Rogers, J., Churcher, C., and Schook, L. B.

Abstract

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

Published
2012
Full Text
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29. Analyses of pig genomes provide insight into porcine demography and evolution

Author

Groenen, MAM, Archibald, AL, Uenishi, H, Tuggle, CK, Takeuchi, Y, Rothschild, MF, Rogel-Gaillard, C, Park, C, Milan, D, Megens, H-J, Li, S, Larkin, DM, Kim, H, Frantz, LAF, Caccamo, M, Ahn, H, Aken, BL, Anselmo, A, Anthon, C, Auvil, L, Badaoui, B, Beattie, CW, Bendixen, C, Berman, D, Blecha, F, Blomberg, J, Bolund, L, Bosse, M, Botti, S, Zhan, B, Bystrom, M, Capitanu, B, Carvalho-Silva, D, Chardon, P, Chen, C, Cheng, R, Choi, S-H, Chow, W, Clark, RC, Clee, C, Crooijmans, RPMA, Dawson, HD, Dehais, P, De Sapio, F, Dibbits, B, Drou, N, Du, Z-Q, Eversole, K, Fadista, J, Fairley, S, Faraut, T, Faulkner, GJ, Fowler, KE, Fredholm, M, Fritz, E, Gilbert, JGR, Giuffra, E, Gorodkin, J, Griffin, DK, Harrow, JL, Hayward, A, Howe, K, Hu, Z-L, Humphray, SJ, Hunt, T, Hornshoj, H, Jeon, J-T, Jern, P, Jones, M, Jurka, J, Kanamori, H, Kapetanovic, R, Kim, J, Kim, J-H, Kim, K-W, Kim, T-H, Larson, G, Lee, K, Lee, K-T, Leggett, R, Lewin, HA, Li, Y, Liu, W, Loveland, JE, Lu, Y, Lunney, JK, Ma, J, Madsen, O, Mann, K, Matthews, L, McLaren, S, Morozumi, T, Murtaugh, MP, Narayan, J, Dinh, TN, Ni, P, Oh, S-J, Onteru, S, Panitz, F, Park, E-W, Park, H-S, Pascal, G, Paudel, Y, Perez-Enciso, M, Ramirez-Gonzalez, R, Reecy, JM, Rodriguez-Zas, S, Rohrer, GA, Rund, L, Sang, Y, Schachtschneider, K, Schraiber, JG, Schwartz, J, Scobie, L, Scott, C, Searle, S, Servin, B, Southey, BR, Sperber, G, Stadler, P, Sweedler, JV, Tafer, H, Thomsen, B, Wali, R, Wang, J, White, S, Xu, X, Yerle, M, Zhang, G, Zhang, J, Zhao, S, Rogers, J, Churcher, C, Schook, LB, Groenen, MAM, Archibald, AL, Uenishi, H, Tuggle, CK, Takeuchi, Y, Rothschild, MF, Rogel-Gaillard, C, Park, C, Milan, D, Megens, H-J, Li, S, Larkin, DM, Kim, H, Frantz, LAF, Caccamo, M, Ahn, H, Aken, BL, Anselmo, A, Anthon, C, Auvil, L, Badaoui, B, Beattie, CW, Bendixen, C, Berman, D, Blecha, F, Blomberg, J, Bolund, L, Bosse, M, Botti, S, Zhan, B, Bystrom, M, Capitanu, B, Carvalho-Silva, D, Chardon, P, Chen, C, Cheng, R, Choi, S-H, Chow, W, Clark, RC, Clee, C, Crooijmans, RPMA, Dawson, HD, Dehais, P, De Sapio, F, Dibbits, B, Drou, N, Du, Z-Q, Eversole, K, Fadista, J, Fairley, S, Faraut, T, Faulkner, GJ, Fowler, KE, Fredholm, M, Fritz, E, Gilbert, JGR, Giuffra, E, Gorodkin, J, Griffin, DK, Harrow, JL, Hayward, A, Howe, K, Hu, Z-L, Humphray, SJ, Hunt, T, Hornshoj, H, Jeon, J-T, Jern, P, Jones, M, Jurka, J, Kanamori, H, Kapetanovic, R, Kim, J, Kim, J-H, Kim, K-W, Kim, T-H, Larson, G, Lee, K, Lee, K-T, Leggett, R, Lewin, HA, Li, Y, Liu, W, Loveland, JE, Lu, Y, Lunney, JK, Ma, J, Madsen, O, Mann, K, Matthews, L, McLaren, S, Morozumi, T, Murtaugh, MP, Narayan, J, Dinh, TN, Ni, P, Oh, S-J, Onteru, S, Panitz, F, Park, E-W, Park, H-S, Pascal, G, Paudel, Y, Perez-Enciso, M, Ramirez-Gonzalez, R, Reecy, JM, Rodriguez-Zas, S, Rohrer, GA, Rund, L, Sang, Y, Schachtschneider, K, Schraiber, JG, Schwartz, J, Scobie, L, Scott, C, Searle, S, Servin, B, Southey, BR, Sperber, G, Stadler, P, Sweedler, JV, Tafer, H, Thomsen, B, Wali, R, Wang, J, White, S, Xu, X, Yerle, M, Zhang, G, Zhang, J, Zhao, S, Rogers, J, Churcher, C, and Schook, LB

Abstract

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

Published
2012

31. Pigs in sequence space: A 0.66X coverage pig genome survey based on shotgun sequencing

Author

Wernersson, Rasmus, Schierup, M.H., Jorgensen, F.G., Gorodkin, J., Panitz, F., Stærfeldt, Hans Henrik, Christensen, O.F., Mailund, T., Hornshoj, H., Klein, A., Wang, J., Liu, B., Hu, S.N., Dong, W., Li, W., Wong, G.K.S., Yu, J., Bendixen, C., Fredholm, M., Brunak, Søren, Yang, H.M., Bolund, L., Wernersson, Rasmus, Schierup, M.H., Jorgensen, F.G., Gorodkin, J., Panitz, F., Stærfeldt, Hans Henrik, Christensen, O.F., Mailund, T., Hornshoj, H., Klein, A., Wang, J., Liu, B., Hu, S.N., Dong, W., Li, W., Wong, G.K.S., Yu, J., Bendixen, C., Fredholm, M., Brunak, Søren, Yang, H.M., and Bolund, L.

Abstract

Background: Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls. Results: We have generated similar to 3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis. The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human. Conclusion: The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing.

Published
2005

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