Catherine André

Publications of Catherine André

• 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.

• LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs.

  Authors: Anne-Sophie Lequarré, Leif Andersson, Catherine André, Merete Fredholm, Christophe Hitte, Tosso Leeb, Hannes Lohi, Kerstin Lindblad-Toh, Michel Georges

  Veterinary journal (London, England : 1997). 08/2011; 189(2):155-9.

  The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal modelThe domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend.

• Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies.

  Authors: Gonzalo Rincon, Katarina Tengvall, Janelle M Belanger, Laetitia Lagoutte, Juan F Medrano, Catherine André, Anne Thomas, Cynthia Taylor Lawley, Mark St Hansen, Kerstin Lindblad-Toh, Anita M Oberbauer

  BMC research notes. 06/2011; 4:226.

  ABSTRACT: The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs) for the canine genome has expanded the opportunities to undertake genome-wide associationABSTRACT: The availability of array-based genotyping platforms for single nucleotide polymorphisms (SNPs) for the canine genome has expanded the opportunities to undertake genome-wide association (GWA) studies to identify the genetic basis for Mendelian and complex traits. Whole blood as the source of high quality DNA is undisputed but often proves impractical for collection of the large numbers of samples necessary to discover the loci underlying complex traits. Further, many countries prohibit the collection of blood from dogs unless medically necessary thereby restricting access to critical control samples from healthy dogs. Alternate sources of DNA, typically from buccal cytobrush extractions, while convenient, have been suggested to have low yield and perform poorly in GWA. Yet buccal cytobrushes provide a cost-effective means of collecting DNA, are readily accepted by dog owners, and represent a large resource base in many canine genetics laboratories. To increase the DNA quantities, whole genome amplification (WGA) can be performed. Thus, the present study assessed the utility of buccal-derived DNA as well as whole genome amplification in comparison to blood samples for use on the most recent iteration of the canine HD SNP array (Illumina). In both buccal and blood samples, whether whole genome amplified or not, 97% of the samples had SNP call rates in excess of 80% indicating that the vast majority of the SNPs would be suitable to perform association studies regardless of the DNA source. Similarly, there were no significant differences in marker intensity measurements between buccal and blood samples for copy number variations (CNV) analysis. All DNA samples assayed, buccal or blood, native or whole genome amplified, are appropriate for use in array-based genome-wide association studies. The concordance between subsets of dogs for which both buccal and blood samples, or those samples whole genome amplified, was shown to average >99%. Thus, the two DNA sources were comparable in the generation of SNP genotypes and intensity values to estimate structural variation indicating the utility for the use of buccal cytobrush samples and the reliability of whole genome amplification for genome-wide association and CNV studies.

• Toward understanding dog evolutionary and domestication history.

  Authors: Francis Galibert, Pascale Quignon, Christophe Hitte, Catherine André

  Comptes rendus biologies. 03/2011; 334(3):190-6.

  Dog domestication was probably started very early during the Upper paleolithic period (~35,000 BP), thus well before any other animal or plant domestication. This early process, probably unconscious,Dog domestication was probably started very early during the Upper paleolithic period (~35,000 BP), thus well before any other animal or plant domestication. This early process, probably unconscious, is called proto-domestication to distinguish it from the real domestication process that has been dated around 14,000 BC. Genomic DNA analyses have shown recently that domestication started in the Middle East and rapidly expanded into all human populations. Nowadays, the dog population is fragmented in several hundreds of breeds well characterized by their phenotypes that offer a unique spectrum of polymorphism. More recent studies detect genetic signatures that will be useful to highlight breed history as well as the impact of domestication at the DNA level.

• Screening for a canine model of choroideremia exclusively identifies nonpathogenic CHM variants.

  Authors: Lorenne Robert, Audrey Sénéchal, Béatrice Bocquet, Laetitia Herbin, Gilles Chaudieu, Vasiliki Kalatzis, Catherine André, Christian P Hamel

  Ophthalmic research. 01/2011; 45(3):155-63.

  Choroideremia is an X-linked, progressive photoreceptor degeneration disorder due to mutations in CHM. In addition to an atrophy of the outer retina, affected individuals present with aChoroideremia is an X-linked, progressive photoreceptor degeneration disorder due to mutations in CHM. In addition to an atrophy of the outer retina, affected individuals present with a characteristic atrophy of the choroid. To search for a canine model, we screened the CHM gene of 37 dogs (22 breeds) with various forms of retinal dystrophies. We found 21 variations in 13 breeds (17 detected in only one breed and 4 shared by two or more) with 43% segregating in the same pedigree, a Great Dane female and a female offspring. Of particular interest were an exonic missense variation and a 3-bp intronic deletion near a splice acceptor site. However, although not detected in unrelated healthy Great Danes, these variants were nonpathogenic since they did not segregate with the disease phenotype in the pedigree. These results suggest that a CHM dog model may not be viable, as is the case for mouse and zebrafish.

• A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis.

  Authors: Marie Abitbol, Jean-Laurent Thibaud, Natasha J Olby, Christophe Hitte, Jean-Philippe Puech, Marie Maurer, Fanny Pilot-Storck, Benoit Hédan, Stéphane Dréano, Sandra Brahimi, Delphine Delattre, Catherine André, Françoise Gray, Françoise Delisle, Catherine Caillaud, Florence Bernex, Jean-Jacques Panthier, Geneviève Aubin-Houzelstein, Stéphane Blot, Laurent Tiret

  Proceedings of the National Academy of Sciences of the United States of America. 08/2010; 107(33):14775-80.

  Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motorNeuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs' disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.

• Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes.

  Authors: Edouard Cadieu, Mark Neff, Pascale Quignon, Kari Walsh, Kevin Chase, Heidi G Parker, Bridgett M Vonholdt, Alison Rhue, Adam Boyko, Alexandra Byers, Aaron Wong, Dana S Mosher, Abdel G Elkahloun, Tyrone C Spady, Catherine André, K Gordon Lark, Michelle Cargill, Carlos D Bustamante, Robert K Wayne, Elaine A Ostrander

  Science (New York, N.Y.). 09/2009;

  Coat color and type are essential characteristics of domestic dog breeds. While the genetic basis of coat color has been well characterized, relatively little is known about the genes influencingCoat color and type are essential characteristics of domestic dog breeds. While the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5 and keratin-71, respectively), which together account for the majority of coat phenotypes in purebred dogs in the United States. This work illustrates that an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.

• Epidemiology, Pathology, and Genetics of Histiocytic Sarcoma in the Bernese Mountain Dog Breed.

  Authors: Jérôme Abadie, Benoit Hédan, Edouard Cadieu, Clotilde De Brito, Patrick Devauchelle, Catherine Bourgain, Heidi G Parker, Amaury Vaysse, Patricia Margaritte-Jeannin, Francis Galibert, Elaine A Ostrander, Catherine André

  The Journal of heredity. 07/2009;

  Histiocytic sarcoma (HS) refers to a highly aggressive and frequently disseminated neoplastic disease belonging to the class of canine histiocytic proliferative disorders. Disseminated HS (previouslyHistiocytic sarcoma (HS) refers to a highly aggressive and frequently disseminated neoplastic disease belonging to the class of canine histiocytic proliferative disorders. Disseminated HS (previously called malignant histiocytosis) is highly breed specific, with Bernese mountain dogs (BMDs), rottweilers, and retrievers having a high prevalence with a frequency of approximately 25% in the BMD breed. We collected DNA samples and clinical information from 800 BMDs, of which 200 are affected by HS. To better characterize the physiopathology and epidemiology, an in-depth analysis of 89 BMD cases has been performed. The mean age of onset was 6.5 years, males and females being equally affected. The clinical features, biochemical parameters, and pathological features have been determined. The life span after diagnosis has been estimated to be 49 days. A large BMD pedigree of 327 dogs, 121 of which are affected, was assembled. Using a subset of 160 BMDs, encompassing 21 complete sibships, we now propose an oligogenic transmission mode of the disease. Whole-genome linkage scans as well as association studies using a case/control analysis, in parallel with expression profiling of neoplastic versus normal histiocytes, are all underway. Altogether, these complementary approaches are expected to localize the genes for HS in the BMD, leading to advances in our knowledge of histiocyte diseases in dogs and humans.

• Ancestral T-Box Mutation Is Present in Many, but Not All, Short-Tailed Dog Breeds.

  Authors: Marjo K Hytönen, Anaïs Grall, Benoît Hédan, Stéphane Dréano, Samuel J Seguin, Delphine Delattre, Anne Thomas, Francis Galibert, Lars Paulin, Hannes Lohi, Kirsi Sainio, Catherine André

  The Journal of heredity. 11/2008;

  Dogs differ greatly in their morphological characteristics including various tail phenotypes. Congenitally short-tailed dogs are present in many breeds; however, the causative mutation located in theDogs differ greatly in their morphological characteristics including various tail phenotypes. Congenitally short-tailed dogs are present in many breeds; however, the causative mutation located in the T-box transcription factor T gene (C189G) had only been described in the bobtailed Pembroke Welsh Corgis. We investigated here the presence of the T gene mutation in 23 other breeds (360 dogs, including 156 natural short tailed) in which natural bobtailed dogs exist. In the 17 breeds in which the C189G mutation was observed, there was a perfect correlation between this mutation and the short-tail phenotype. However, 6 breeds did not carry the known substitution or any other mutations in the T gene coding regions. No dogs were found to be homozygous for the C189G mutation, suggesting that the homozygous condition is lethal. In order to study the effect of the T gene mutation on litter size, we compared the number of puppies born from short-tailed parents to that born from long-tailed parents. In the Swedish Vallhund breed, we observed a 29% decrease in the litter size when both parents were short tailed. Given that the T gene mutation is not present in all breeds of short-tailed dog, there must be yet other genetic factors affecting tail phenotypes to be discovered.

• The dog: A powerful model for studying genotype-phenotype relationships.

  Authors: Francis Galibert, Catherine André

  Comparative biochemistry and physiology. Part D, Genomics & proteomics. 03/2008; 3(1):67-77.

  Within the last two years, series of studies have focused on the structure of the dog genome (Canis familiaris) and the characteristics of the dog population as it evolved since being domesticatedWithin the last two years, series of studies have focused on the structure of the dog genome (Canis familiaris) and the characteristics of the dog population as it evolved since being domesticated from wolves about 14,000 years ago. In this review, we explain why the dog is a unique and promising model for determining genotype/phenotype relationships and why it should be easier with this model to identify the genes responsible for many genetic diseases. We also revisit the last ten years of developments in canine molecular genetics that culminated in the release of the entire genome sequence.

• Progressive retinal atrophy in the Border Collie: a new XLPRA.

  Authors: Thierry Vilboux, Gilles Chaudieu, Patricia Jeannin, Delphine Delattre, Benoit Hedan, Catherine Bourgain, Guillaume Queney, Francis Galibert, Anne Thomas, Catherine André

  BMC veterinary research. 02/2008; 4:10.

  BACKGROUND: Several forms of progressive retinal atrophy (PRA) segregate in more than 100 breeds of dog with each PRA segregating in one or a few breeds. This breed specificity may be accounted forBACKGROUND: Several forms of progressive retinal atrophy (PRA) segregate in more than 100 breeds of dog with each PRA segregating in one or a few breeds. This breed specificity may be accounted for by founder effects and genetic drift, which have reduced the genetic heterogeneity of each breed, thereby facilitating the identification of causal mutations. We report here a new form of PRA segregating in the Border Collie breed. The clinical signs, including the loss of night vision and a progressive loss of day vision, resulting in complete blindness, occur at the age of three to four years and may be detected earlier through systematic ocular fundus examination and electroretinography (ERG). RESULTS: Ophthalmic examinations performed on 487 dogs showed that affected dogs present a classical form of PRA. Of those, 274 have been sampled for DNA extraction and 87 could be connected through a large pedigree. Segregation analysis suggested an X-linked mode of transmission; therefore both XLPRA1 and XLPRA2 mutations were excluded through the genetic tests. CONCLUSION: Having excluded these mutations, we suggest that this PRA segregating in Border Collie is a new XLPRA (XLPRA3) and propose it as a potential model for the homologous human disease, X-Linked Retinitis Pigmentosa.

• 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.

• Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies.

  Authors: Pascale Quignon, Laetitia Herbin, Edouard Cadieu, Ewen F Kirkness, Benoit Hédan, Dana S Mosher, Francis Galibert, Catherine André, Elaine A Ostrander, Christophe Hitte

  PLoS ONE. 02/2007; 2(12):e1324.

  BACKGROUND: In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogsBACKGROUND: In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity. CONCLUSIONS: These data provide new guidelines for association studies using purebred dogs that take into account population structure.

• [The dog and its genome]

  Authors: Francis Galibert, Catherine André

  Médecine sciences : M/S. 11/2006; 22(10):806-8.

• 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.

• Expanded repeat in canine epilepsy.

  Authors: Hannes Lohi, Edwin J Young, Susan N Fitzmaurice, Clare Rusbridge, Elayne M Chan, Mike Vervoort, Julie Turnbull, Xiao-Chu Zhao, Leonarda Ianzano, Andrew D Paterson, Nathan B Sutter, Elaine A Ostrander, Catherine André, G Diane Shelton, Cameron A Ackerley, Stephen W Scherer, Berge A Minassian

  Science (New York, N.Y.). 02/2005; 307(5706):81.

  Epilepsy afflicts 1% of humans and 5% of dogs. We report a canine epilepsy mutation and evidence for the existence of repeat-expansion disease outside humans. A canid-specific unstable dodecamerEpilepsy afflicts 1% of humans and 5% of dogs. We report a canine epilepsy mutation and evidence for the existence of repeat-expansion disease outside humans. A canid-specific unstable dodecamer repeat in the Epm2b (Nhlrc1) gene recurrently expands, causing a fatal epilepsy and contributing to the high incidence of canine epilepsy. Tracing the repeat origins revealed two successive events, starting 50 million years ago, unique to canid evolution. A genetic test, presented here, will allow carrier and presymptomatic diagnosis and disease eradication. Clinicopathologic characterization establishes affected animals as a model for Lafora disease, the most severe teenage-onset human epilepsy.

• 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.