Thomas Derrien

Publications of Thomas Derrien

• Annotation of the domestic dog genome sequence: finding the missing genes.

  Authors: Thomas Derrien, Amaury Vaysse, Catherine André, Christophe Hitte

  Mammalian genome : official journal of the International Mammalian Genome Society. 11/2011; 23(1-2):124-31.

  There are over 350 genetically distinct breeds of domestic dog that present considerable variation in morphology, physiology, and disease susceptibility. The genome sequence of the domestic dog wasThere are over 350 genetically distinct breeds of domestic dog that present considerable variation in morphology, physiology, and disease susceptibility. The genome sequence of the domestic dog was assembled and released in 2005, providing an estimated 20,000 protein-coding genes that are a great asset to the scientific community that uses the dog system as a genetic biomedical model and for comparative and evolutionary studies. Although the canine gene set had been predicted using a combination of ab initio methods, homology studies, motif analysis, and similarity-based programs, it still requires a deep annotation of noncoding genes, alternative splicing, pseudogenes, regulatory regions, and gain and loss events. Such analyses could benefit from new sequencing technologies (RNA-Seq) to better exploit the advantages of the canine genetic system in tracking disease genes. Here, we review the catalog of canine protein-coding genes and the search for missing genes, and we propose rationales for an accurate identification of noncoding genes though next-generation sequencing.

• Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

  Authors: Amaury Vaysse, Abhirami Ratnakumar, Thomas Derrien, Erik Axelsson, Gerli Rosengren Pielberg, Snaevar Sigurdsson, Tove Fall, Eija H Seppälä, Mark S T Hansen, Cindy T Lawley [......] Carles Vilà, Hannes Lohi, Francis Galibert, Merete Fredholm, Jens Häggström, Ake Hedhammar, Catherine André, Kerstin Lindblad-Toh, Christophe Hitte, Matthew T Webster

  PLoS genetics. 10/2011; 7(10):e1002316.

  The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysisThe extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

• [Long non-coding RNAs with enhancer-like function in human cells].

  Authors: Thomas Derrien, Roderic Guigó

  Médecine sciences : M/S. 04/2011; 27(4):359-61.

• Revisiting the missing protein-coding gene catalog of the domestic dog.

  Authors: Thomas Derrien, Julien Theze, Amaury Vaysse, Catherine Andre, Elaine Ostrander, Francis Galibert, Christophe Hitte

  BMC genomics. 03/2009; 10(1):62.

  ABSTRACT: BACKGROUND: Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000,ABSTRACT: BACKGROUND: Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000, compared to over 20,000 reported for other mammalian species. Of particular interest are the ~400 genes annotated in primates and rodent genomes which are missing in the dog. RESULTS: Using over 14,000 orthologous genes between human, chimpanzee, mouse, rat and dog, we built multiple pairwise synteny maps to infer short orthologous intervals that were targeted for characterizing the canine missing genes. Based on gene prediction and a functionality test using the ratio of silent to replacement nucleotide substitution rates (dN/dS), we provide compelling structural and functional evidence for the identification of 232 new protein-coding genes in the canine genome and 69 gene losses, characterized as undetected gene or pseudogenes. Gene loss phyletic pattern analysis using ten species from chicken to human allowed us to characterize 28 canine-specific gene losses that have functional orthologs continuously from chicken or marsupials through human, and 10 genes that arose specifically in the evolutionary lineage leading to rodent and human. In addition, we identified a set of 10 genes that have been independently lost in canine as well as other lineages. CONCLUSIONS: This study demonstrates the central role of comparative genomics for refining gene catalogs and exploring the evolutionary history of gene repertoires, particularly as applied for the characterization of species-specific gene gains and losses.

• AutoGRAPH: an interactive web server for automating and visualizing comparative genome maps.

  Authors: Thomas Derrien, Catherine André, Francis Galibert, Christophe Hitte

  Bioinformatics (Oxford, England). 03/2007; 23(4):498-9.

  AutoGRAPH is an interactive web server for automatic multi-species comparative genomics analyses based on personal datasets or pre-inserted public datasets. This program automatically identifiesAutoGRAPH is an interactive web server for automatic multi-species comparative genomics analyses based on personal datasets or pre-inserted public datasets. This program automatically identifies conserved segments (CS) and breakpoint regions, assesses the conservation of marker/gene order between organisms, constructs synteny maps for two to three species and generates high-quality, interactive displays facilitating the identification of chromosomal rearrangements. AutoGRAPH can also be used for the integration and comparison of several types of genomic resources (meiotic maps, radiation hybrid maps and genome sequences) for a single species, making AutoGRAPH a versatile tool for comparative genomics analysis. AVAILABILITY: http://genoweb.univ-rennes1.fr/tom_dog/AutoGRAPH/. SUPPLEMENTARY INFORMATION: A description of the algorithm and additional information are available at http://genoweb.univ-rennes1.fr/tom_dog/AutoGRAPH/Tutorial.php.

• Analysis of the unassembled part of the dog genome sequence: chromosomal localization of 115 genes inferred from multispecies comparative genomics.

  Authors: Thomas Derrien, Catherine André, Francis Galibert, Christophe Hitte

  The Journal of heredity. 02/2007; 98(5):461-7.

  The identification of dog genes and their accurate localization to chromosomes remain a major challenge in the postgenomics era. The 132 annotated canine genes with human orthologs remaining in theThe identification of dog genes and their accurate localization to chromosomes remain a major challenge in the postgenomics era. The 132 annotated canine genes with human orthologs remaining in the unassembled part (chrUnknown) of the dog sequence assembly (CanFam1) are of limited use for candidate gene approaches or comparative mapping studies. We used a two-step comparative analysis to infer a canine chromosomal interval for localization of the chrUn genes. We first constructed a human-dog synteny map, using 14,456 gene-based comparative anchors. We then mapped the 132 chrUn genes onto the reference (human) synteny map and identified the corresponding, orthologous segment on the canine map, based on conserved gene order. Our results show that 110 chrUn genes could be localized to short intervals on 18 dog chromosomes, whereas 22 genes remained assigned to 2 possible intervals. We extended this comparative analysis to multiple species, using the chimpanzee, mouse, and rat genome sequences. This made it possible to narrow down the intervals concerned and to increase the number of canine chrUn genes with an inferred chromosome location to 115. This study demonstrates that dog chromosomal intervals for chrUn genes can be rapidly inferred, using a reference species, and indicates that comparative strategies based on larger numbers of species may be even more effective.

• A comparative genome approach to marker ordering.

  Authors: Thomas Faraut, Simon de Givry, Patrick Chabrier, Thomas Derrien, Francis Galibert, Christophe Hitte, Thomas Schiex

  Bioinformatics. 01/2007; 23:50-56.

• Coat colour in dogs: identification of the merle locus in the Australian shepherd breed.

  Authors: Benoit Hédan, Sébastien Corre, Christophe Hitte, Stéphane Dréano, Thierry Vilboux, Thomas Derrien, Bernard Denis, Francis Galibert, Marie-Dominique Galibert, Catherine André

  BMC veterinary research. 02/2006; 2:9.

  BACKGROUND: Coat colours in canines have many natural phenotypic variants. Some of the genes and alleles involved also cause genetic developmental defects, which are also observed in humans and mice.BACKGROUND: Coat colours in canines have many natural phenotypic variants. Some of the genes and alleles involved also cause genetic developmental defects, which are also observed in humans and mice. We studied the genetic bases of the merle phenotype in dogs to shed light on the pigmentation mechanisms and to identify genes involved in these complex pathways. The merle phenotype includes a lack of eumelanic pigmentation and developmental defects, hearing impairments and microphthalmia. It is similar to that observed in microphthalmia mouse mutants. RESULTS: Taking advantage of the dog as a powerful genetic model and using recently available genomic resources, we investigated the segregation of the merle phenotype in a five-generation pedigree, comprising 96 sampled Australian shepherd dogs. Genetic linkage analysis allowed us to identify a locus for the merle phenotype, spanning 5.5 megabases, at the centromeric tip of canine chromosome 10 (CFA10). This locus was supported by a Lod score of 15.65 at a recombination fraction theta = 0. Linkage analysis in three other breeds revealed that the same region is linked to the merle phenotype. This region, which is orthologous to human chromosome 12 (HSA12 q13-q14), belongs to a conserved ordered segment in the human and mouse genome and comprises several genes potentially involved in pigmentation and development. CONCLUSION: This study has identified the locus for the merle coat colour in dogs to be at the centromeric end of CFA10. Genetic studies on other breeds segregating the merle phenotype should allow the locus to be defined more accurately with the aim of identifying the gene. This work shows the power of the canine system to search for the genetic bases of mammalian pigmentation and developmental pathways.

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

  Authors: Christophe Hitte, Jennifer Madeoy, Ewen F Kirkness, Catherine Priat, Travis D Lorentzen, Fabrice Senger, Dan Thomas, Thomas Derrien, Christina Ramirez, Carol Scott [......] David B Jaffe, Sandrine Tacher, Stéphane Dréano, Nadia Berkova, Catherine André, Panagiotis Deloukas, Claire Fraser, Kerstin Lindblad-Toh, Elaine A Ostrander, Francis Galibert

  Nature reviews. Genetics. 09/2005; 6(8):643-8.

  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 yieldAccurate 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.

• CRH_Server: an online comparative and radiation hybrid mapping server for the canine genome.

  Authors: Christophe Hitte, Thomas Derrien, Catherine André, Elaine A Ostrander, Francis Galibert

  Bioinformatics (Oxford, England). 01/2005; 20(18):3665-7.

  SUMMARY: CRH_Server is an on line Comparative and Radiation Hybrid mapping Server dedicated to canine genomics. CRH_Server allows users to compute their own RH data using the current canine RH map,SUMMARY: CRH_Server is an on line Comparative and Radiation Hybrid mapping Server dedicated to canine genomics. CRH_Server allows users to compute their own RH data using the current canine RH map, and allows comparative dog/human mapping analyses. Finally, it suggests multiple options for storage and queries of the dog RH database. AVAILABILITY: http://idefix.univ-rennes1.fr:8080/Dogs/rh-server.html. SUPPLEMENTARY INFORMATION: All information is available at http://idefix.univ-rennes1.fr:8080/Dogs/help_rh-server.html.