Progress 10/01/03 to 09/30/08
Outputs
OUTPUTS: Map Development: When the horse genome was sequenced in 2006 by the Broad Institute under the auspices of the National Human Genome Research Institute (NHGRI), the role of map development became support for the assembly of the horse genome. In February 2007, the Broad Institute reported a first assembly of the horse genome based on computational analysis of the horse genome sequence. During 2007, work by members of the horse genome technical committee included mapping to resolve questions that arose during genome assembly. Toward that goal, scientists at the University of Kentucky, Texas A&M University, University of California, University of Minnesota and the Animal Health Trust in Newmarket, United Kingdom, shared information from previously completed radiation hybrid maps, linkage maps and FISH mapped markers to facilitate assembly. Under the direction of the Broad Institute, additional BACs were FISH mapped at the University of Kentucky. At the end of 2007 a second assembly of the horse genome was published on the internet. During 2008, that information was used to develop a tool for genome scanning based on SNP analyses, as described below. Shared Resources: The coordinator has held and distributed DNA from reference horse families for genetic mapping and related studies. In addition, a set of fluorescent dye labeled primers are available through the coordinator for genome scanning studies. DNA and relevant analyses for radiation hybrid mapping are available through NRSP8 member scientists at Texas A&M. BAC library clones are available through a commercial enterprise at the Children's Hospital of Oakland Institute as well as through the INRA at Jouy-en-Josas, France and Texas A&M University. A commercial SNP assay system for 55,000 SNPs was developed by a commercial enterprise (Illumina) with support from grants by Morris Animal Foundation, the USDA and by funds independently raised by the University of Kentucky, University of Berne, Animal Health Trust (United Kingdom) and Royal Veterinary College (London). That assay is currently being used and early results indicate that it is an effective and powerful tool for discovery research. In parallel, there are several efforts to develop tools for investigation of gene expression, including hybridization and sequencing methods. Travel and Meeting Support: Some conferences have received support funding from the Coordinator. During 2008, the main meetings including the Plant and Animal Genome Conference in San Diego in January 2008. Particular emphasis was placed on supporting student and postdoctoral participation. In addition, the coordinator and other workshop committee members were invited to make presentations at several meetings to explain and promote the use of horse genomics in research. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Scientists working on horses, veterinarians, animal scientists, horse owners, horse breeders. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
A community of scientists was created that collaborated to make a genome map for the horse and ultimately to obtain a whole genome sequence. The whole genome sequence enables further research to identify the genetic bases of performance and health in horses. The work in individual labs led to the identification of the genetic basis for several diseases and other traits of interest, including horse coat color. During 2008, numerous studies were published or presented at scientific meetings by scientists from NRSP8 member stations on the topics of developmental bone diseases (osteochondrosis and related diseases), muscle diseases (polysaccharide storage myopathy), skin disease (JEB), coat color (appaloosa, champagne dilution, dominant white, tobiano) and aspects of performance and infectious disease. The work was clearly made possible by the quality of the genetic marker maps produced under the auspices of the workshop participants in previous years. Information about obtaining access to these resources is available at the website for the Horse Genome Workshop: http://www.uky.edu/AG/Horsemap. Database Activities: Two databases compile published genetic data for horses: http://locus.jouy.inra.fr/cgi-bin/lgbc/mapping/common/intro2.plBASE= horse; http://www.thearkdb.org/. BAC map data is available: http://www.tiho-hannover.de/einricht/zucht/hgp/index.htm. Several genome browsers have been developed: http://www.genome.ucsc.edu/cgi-bin/hgGatewayhgsid=95987985&clade=ver tebrate&org=Horse&db=0; http://www.equinegenome.org/Equinegenome.org.html; http://pbrowse2.abcc.ncifcrf.gov/cgi-bin/gbrowse/horse.1/; http://pre.ensembl.org/Equus_caballus/index.html. A SNP database is available: http://www.broad.mit.edu/mammals/horse/. A major entry point for databases and other relevant information is the workshop website: http://www.uky.ledu/AG/Horsemap.
Publications
- No publications reported this period
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: Meetings were supported at the Plant and Animal Genome Conference in San Diego in January 2007 and at the Havemeyer Horse Genome Conference at Lake Tahoe in August 2007. Travel for scientists and their students working in connection with horse genomics was supported for these meetings. Work was supported to assist the Broad Institute or at MIT/Harvard in the assembly of the horse genome. The first assembly was reported, online, in February 2007 and the second is in progress. In addition, work was supported to develop genome research tools in connection with a research project funded by the Morris Animal Foundation (equine medical genetics). The website for the workshop (http://www.uky.edu/ag/horsemap) was redesigned to promote the use of the newly developed horse genome sequence and associated tools. The coordinator also made presentations to animal science meetings in Maryland and Ireland and to a Veterinary Respiratory Disease Conference in Indiana to explain and promote
the use of the horse genome information for research. Shared resources, including DNA from reference families, primer sets for investigation of genetic markers and information on databases and reports were distributed to workshop participants, worldwide.
PARTICIPANTS: Ernest Bailey, Teri Lear, James N. MacLeod
TARGET AUDIENCES: Scientists conducting research on all aspects of horse biology, especially veterinary scientists and animal scientists; horse owners and breeders; news media serving the horse industry
Impacts
Collaborative teams have been established within the United States and between scientists within the United States and abroad to conduct research on genetic and physiological traits of horses, including those pertaining to diseases and performance. These teams have already identified specific genes and established tests for coat color traits and several diseases of horses. Work is underway to use measurements of gene transcription to assess hereditary and non-hereditary aspects of disease and performance. We anticipate the extension of these studies in areas of equine nutrition and management as well as the discovery of yet additional genetic markers for hereditary traits.
Publications
- No publications reported this period
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Progress 01/01/06 to 12/31/06
Outputs
Three meetings were conducted during 2006 in connection with this project. The first, in January at the Plant and Animal Genome Conference in San Diego, consisted of presentations by scientists on accomplishments of the preceding year. Of particular note were additions to the half sib and full sib linkage maps and the RH maps for several of the chromosomes. In addition, discoveries and applications to several diseases were presented. A plan to sequence the horse genome by the National Human Genome Research Institute (NHGRI) was also discussed and applications considered with reference to the recently completed genome sequence for dogs. Other points of discussion and activity were coordination of a consortium research proposal by workshop participants to the Morris Animal Foundation for support of Veterinary Genetics research and two applications to the USDA for support of SNP use and gene expression microarray research. The second meeting occurred at the Broad
Institute of MIT and Harvard in April to discuss the progress on horse genome sequencing and make choices for future tests.. The plan from the NHGRI included 7X genome sequencing of a female thoroughbred horse, discovery of single nucleotide repeats (SNP) in horses from 7 other breeds, comparison of SNPs among equids from 24 different populations and investigation of linkage disequilibrium for the SNPs among 12 diverse horse breeds. The third meeting occurred in connection with the International Society of Animal Genetics in Porto Seguro, Brazil in August at which discussions took place on additions to the map, plans for sequencing and applications of the genome information to solve problems interfering with the health and welfare of horses. The genome sequencing was completed in July with all sequence information available through the internet. The assembly was conducted with plans for completion in early 2007. The assembly would then be compared to the existing maps for validation.
Coordinator support funds were provided for travel to meetings by workshop participants, provision of BAC libraries to participants and other activities to encourage and facilitate research on the horse genome.
Impacts
The complete genome sequence for the horse will empower all areas of equine research. Many projects begin with investigations for genes or DNA sequences, costing tens of thousands of dollars and taking months to complete. With the completion of this project, these expenses will no longer be necessary. Furthermore, for many projects, having accurate genome information is the primary expense. Therefore, this information will make it possible for scientists to quickly and cheaply conduct preliminary investigations on genes that influence diseases. Beyond using this specific information, the workshop scientists will continue to collaborate on projects that are sufficiently complex that no one laboratory could complete. These are probably the most interesting projects.
Publications
- No publications reported this period
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Progress 01/01/05 to 12/31/05
Outputs
Objective: 1. Increase Resolution of Genome Maps for Horses. New markers were added to the half sibling linkage map (766 markers spanning 3740 cM) (Penedo et al, 2005 Cytogenetics and Genome Research 111:5-15), the full sibling linkage map (742 markers spanning 2772 cM) (Swinburne et al., 2006, Genomics 87: 1-29) and the RH map for the horse (Chowdhary et al., 2003, Genome Research 13: 742-751) and additional markers not yet published but exceeding 2000. In addition, significant efforts were made to integrate the existing horse genome maps. Objective: 2. Facilitate integration of genomic approaches toward better understanding economically important traits. ESTs were identified by laboratories at Cornell University, University of Kentucky and Texas A&M University and the data pooled with the objective of creating microarray tools for investigating gene expression in horse tissues. Over 45,000 ESTs were evaluated and approximately 10,000 unique genes were identified for
incorporation into a microarray chip. Partial funding was obtained from one agency and preliminary work has been done on development of this tool for the benefit of the horse genome research community. A grant application from a German laboratory (workshop participant) for the end-sequencing and fluorescent fingerprinting of 150,000 CHORI-241 clones has been approved by the Volkswagen Foundation. This project should result in a high-resolution physical map and genome-wide BAC contigs of the horse genome that can facilitate the assembly of the horse genome sequence. The project is estimated to be completed in 2007. In July 2005, a proposal was submitted to the National Human Genome Research Institute for a 2X genome sequence for the horse (see at http://www.uky.edu/AG/Horsemap/). At the Sixth International Havemeyer Horse Genome Workshop meeting, a committee was formed to develop a plan for deeper (5x) coverage for horse genome sequencing. Objective: 3. Facilitate and implement
bioinformatic tools to extract, analyze, store and disseminate information. 1. Primers for a Genome Scanning Panel: panel of 100 markers isavailable. 2. Websites and Databases: A website is maintained with information describing the workshop efforts and developments for the horse gene map:http://www.uky.edu/Ag/Horsemap/ 3. Reference Family DNA: 13 sires and their 500 offspring. 4. Full-sibling Family for Linkage Mapping. 5. Bacterial Artificial Chromosome (BAC) Libraries: An 11X BAC library has been created by Pieter DeJong, under the auspices of the USDA NRI program, and is available. 6. Radiation Hybrid Panel: A radiation hybrid panel at Texas A&M is subject of collaborative work. 7. Funds from the horse species coordinator were used during 2005 to support the radiation mapping panel, travel support for technical committee members to attend the PAGXIV meeting in San Diego, coordinator travel to support gene mapping work, resources for development and distribution of the BAC library,
use of the linkage family materials, support of marker development for linkage mapping and support of several conferences for gene mapping research in domestic animals.
Impacts
During 2006, the workshop participants will participate in a workshop conducted at the Conference of the International Society of Animal Genetics and in concert with the NRSP8 horse technical committee. A meeting is being planned to discuss development and application of genome tools for the horse at the Banbury Center in May 2006. The primary activities of the workshop will continue to be: further development of the linkage map, comparison of the linkage map to the RH map, development of the RH map and other comparative approaches to gene mapping, formation of an effective collaboration on functional genomics and, most importantly, development of whole genome sequencing for the horse. The genome map and genome sequence will underpin all biological research on horses and enable the participating scientists to make discoveries that will solve health problems of horses.
Publications
- No publications reported this period
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Progress 01/01/04 to 12/31/04
Outputs
Progress towards Objective 1. Enhance and integrate genetic and physical maps of agriculturally important animals for cross species comparisons and sequence annotation. A single linkage map was composed for the horse using all published linkage maps, plus new data plus family data from studies in independent laboratories. The map was constructed from a total of 766 markers distributed on the 31 equine autosomes. It has a higher marker density than that of previously reported maps with 626 markers linearly ordered and 140 other markers assigned to a chromosomal region. Fifty-nine markers (7%) failed to meet the criteria for statistical evidence of linkage and remain unassigned. The map spans 3740 cM with an average distance of 6.3 cM between markers. Fifty-five percent of the intervals are less than 5 cM and only 3% are greater than 20 cM. The current map provides a single source for genome scan analyses and integration with the radiation hybrid map. [Penedo M.C.T et
al. (in press) Cytogenetics and Genome Research) ] In 2003 a first generation radiation hybrid map was published with 730 markers on a 5000 rad panel. (Chowdhary et al., 2003 Genome Research 13:742-751). Markers are being added to that resource, principally by the scientists at Texas A&M but also by scientists elsewhere. The RH panel is has been offered by the Texas A&M scientists as a mapping resource available to scientists elsewhere. At present, approximately 3000 markers have been mapped, including over 1000 known genes. High resolution maps have been created for 14 chromosomes and others are in progress. Extensive use is being made of BAC end sequencing for mapping. Maps have been published for ECA17 (Lee et al., 2004 Genomes 82:203-215), X (Raudsepp et al., 2004, PNAS 101:2386-2391) and Y (Raudsepp et al, 2004 PNAS 101:9321-9326). Publications of other chromosomes maps are in preparation or under review. As described in the report of the horse technical committee, other work has
been conducted by committee members to discover and map new genetic markers, construct a BAC contig for the MHC region and to determine BAC end sequences for use in mapping. Progress towards Objective 2. Facilitate integration of genomic, transcriptional, proteomic and metabolomic approaches toward better understanding of biological mechanisms underlying economically important traits. This work and these tools remain in early stages and are being developed a the University of Georgia, University of Kentucky, Texas A&M University and Cornell University in connection with the NRSP8 workshop. Coordination and organization are a primary point of discussion at the current meeting. Progress towards Objective 3. Facilitate and implement bioinformatic tools to extract, analyze, store and disseminate information. A genome viewer was created by Lee Millon and co-workers at the University of California Davis for comparison of linkage, RH and cytogenetic maps of the horse.
www.vgl.ucdavis.edu/equine/caballus/
Impacts
During 2005 the workshop participants will participate in a workshop conducted by the Dorothy Russell Havemeyer Foundation and in concert with the NRSP8 horse technical committee. The primary activities of the workshop will be: further development of the linkage map, comparison of the linkage map to the RH map using the program Carthagene, development of the RH map and other comparative approaches to gene mapping and formation of an effective collaboration on functional genomics.
Publications
- No publications reported this period
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