Source: UNIVERSITY OF KENTUCKY submitted to
NATIONAL ANIMAL GENOME RESEARCH PROGRAM
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0216927
Grant No.
(N/A)
Project No.
KY014035
Proposal No.
(N/A)
Multistate No.
NRSP-_OLD8
Program Code
(N/A)
Project Start Date
Oct 1, 2008
Project End Date
Sep 30, 2013
Grant Year
(N/A)
Project Director
Bailey, E.
Recipient Organization
UNIVERSITY OF KENTUCKY
500 S LIMESTONE 109 KINKEAD HALL
LEXINGTON,KY 40526-0001
Performing Department
Veterinary Science
Non Technical Summary
Biological research is best conducted in context of the most complete genomic information available for the species in question. The horse benefits from the strong homology that exists among mammals and the recent completion of a whole genome sequence for the horse. This information is a valuable tool that will enhance and enable new research in diverse areas of horse health and welfare including genetics, infectious disease investigations, reproductive physiology, therapeutics, nutrition and general physiology. Although a genome sequence has been completed, research in this area is needed to make the information more readily available through bioinformatics portals, create new tools to take advantage of this resource and to provide expertise in collaborative activities to harvest the fruit of these new tools. Success of this activity will be apparent as the creation of new information that will be published in scientific and lay media as well as the development of new diagnostic tests and therapeutic treatments to benefit the health and welfare of horses.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30438101080100%
Knowledge Area
304 - Animal Genome;

Subject Of Investigation
3810 - Horses, ponies, and mules;

Field Of Science
1080 - Genetics;
Goals / Objectives
Create shared genomic tools and reagents and sequence information to enhance the understanding and discovery of genetic mechanisms affecting traits of interest. Facilitate the development and sharing of animal populations and the collection and analysis of new, unique and interesting phenotypes. Develop, integrate and implement bioinformatics resources to support the discovery of genetic mechanisms that underlie traits of interest.
Project Methods
NRSP-8 fosters communication among its members and stakeholders through, among other things, several email newsletters and participation in meetings and conferences. The horse technical committee will have one or more industry representatives, selected in consultation with appropriate national industry organizations. Industry representatives will be invited to attend all technical committee meetings and serve as liaisons between animal industries and both the committee and the species coordinators. Species coordinators will continue to present and interact at national and regional producer meetings. They will also facilitate communication of research outcomes to the general public. The most important measurements of impact of the project will be the scientific milestones. Information on these milestones will be disseminated through peer-reviewed articles in scientific journals, as well as scientific presentations, books, book chapters, and popular press articles. These milestones and the resulting information will be summarized each year in an annual report compiled by chairs of the species committees. In addition, a generation of new scientists will be trained by NRSP-8 members in animal genomics and bioinformatics, while contributing to NRSP-8 projects. A competitive award for graduate students that supports travel to the annual PAG conference has been established by each of the species coordinators; participation by students at this conference ensures early exposure to animal genomics research and its applications.

Progress 10/01/08 to 09/30/13

Outputs
Target Audience: Target audiences included scientists engaged in research on horses and other livestock, practicing veterinarians, horse owners and horse managers. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Seven PhD students and 4 Master of Science students conducted research and received training in connection with this project. How have the results been disseminated to communities of interest? Seminars were present annually in the Veterinary Science Department a the University of Kentukcy, at other universities (University of Delaware, Washington State University, Iowa State University, Southern Indiana University, University of Louisville, University of Sydney) and to horse interest groups (Thoroughbred, Akhal-Teke, Egyptian Arabian, Equine Affaireincluding research presentations and presentations about applications of the results. Reviews were also published in lay-journals and professional veterinary journals including The Horse, Journal of the American Saddlebred, Equine Veterinary Journal, Veterinary Record and Bluegrass Equine Digest. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Objective 1. This project began immediately after the whole genome sequencing of the reference horse Twilight. This station contributed to the development of the Equine50SNP chip used for investigation of performance, color and diseases among horses. The SNPs were selected from the sequence but evaluated using horses provided by this and other stations. Analysis of the data validated the use of the chip but also suggested changes that were applied to the next generation chip, the Equine70SNP chip. Before the end of this grant period, fund were applied to development of a new technology for SNP analysis with 670,000 SNPs. This tool will be available in 2014. Use of these tools made possible many discoveries reported and published by this and other stations during the period from 2008-2013. Sequence information and investigation of gene expression identified some errors in the assembly and annotation of the genome. While the horse genome assembly is reputed to be among the best of domestic animals, work has begun on a new assembly and annotation for the reference genome. Objective 2. During this period, one of the major questions addressed was the extent of variation among different horse breeds. DNA samples were collected from this and other laboratories for a common analysis leading to characterization of diverse breeds. The results of these studies were published in two studies in 2013 and in one study in 2012 and one study in 2009. Common collections were not created however the workshop facilitated sharing resources among laboratories under cooperative agreements. Objective 3. No contributions were made in the bioinformatics area from this laboratory, however other participants in the workshop conducted RNA-SEQ studies to characterize the expression of genes in various tissues at various times for the horse. This information was useful in guiding the plans for creating a new assembly of the reference genome.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, Machado AC, Capomaccio S, Cappelli K, Cothran EG, Distl O, , Fox-Clipsham L, Graves KT, Gu�rin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MCT, Piercy RJ, Raekallio M, Rieder S, R�ed KH, Swinburne J, Tozaki T, Vaudin M, Wade CM , McCue. (2013) Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLOS Genetics 9: e1003211
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Petersen JL , Mickelson JR, Cothran EG, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, Machado AC, Distl O, Felicetti M, Fox-Clipsham L, Graves KT, Gu�rin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MCT, Piercy RJ, Raekallio M, Rieder S, R�ed KH, Silvestrelli M, Swinburne J, Tozaki T, Vaudin M, Wade CM , McCue M. (2013) Genetic diversity in the modern horse illustrated from genome-wide SNP data. PLOS One 8: e54997.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Go YY, Bailey E, Timoney PJ, Shuck KM and Balasuriya UBR (2012) In vitro susceptibility of CD3+ T lymphocytes to equine arteritis virus infection reflects genetic predisposition of naturally infected stallions to become carriers of the virus. Journal of Virology 86: 12407-12410.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Holl H, Lear T, Nolen-Walston R, Slack J, Brooks S (2013). Detection of two equine trisomies using SNP-CGH. Mammalian Genome, 23:252-256.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2013 Citation: Lear TL, Raudsepp T, Lundquist JM, Brown S. Repeated early embryonic loss in a Thoroughbred mare with a chromosomal translocation [64,XX,t(2;13)]. Journal of Equine Veterinary Science. (in press)
  • Type: Book Chapters Status: Awaiting Publication Year Published: 2013 Citation: Lear TL. Equine cytogenetics. In, JJ Dascanio, PM McCue, eds. Wiley-Blackwell, Hoboken, NJ. Equine Reproductive Procedures. (in press)
  • Type: Books Status: Published Year Published: 2013 Citation: Bailey, E & S A Brooks (2013) Horse Genetics, 2nd Edition. CABI publisher, Oxford, UK.


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: During 2012 scientists from the horse genome workshop committee met formally on two occasions, first at the Plant and Animal Genome Conference in San Diego during January 2012 and again at the Conference of the International Society of Animal Genetics in Cairns, Australia. Presentations at the two meeting described discoveries related to genetics of performance, conformation, musculoskeletal disease, immunology and infectious diseases. In addition, considerable discussion concerned the importance of developing the infrastructure and informatics for horse genomics. During 2012 approximately 30 horses have been sequenced using Nextgen sequencing approaches. Committees formed during the Havemeyer Conference in 2011 discussed plans for creation of a new assay tool that would include 685,000 SNPs. This would represent a 10-fold increase in the capability over the previous SNP assay (65.000 SNPs) but the cost of the assay would remain approximately the same (around $200 per horse). In research at the University of Kentucky collaborative works with the workshop group were published regarding the genetic structure among horse breeds as well as projects which 1) used the distribution of SNPs among horses of different ages to determine that inbreeding has increased among Thoroughbred horses during the last few decades, 2) determined that the genetic haplotype responsible for aspects of equine arteritis infection may play a role in development of persistent carrier states in stallions. Work being prepared for publication or submitted included discovery of additional mutations causing dwarfism among miniature horses and use of SNP arrays to identify chromosome abnormalities among mares. Information has been disseminated by presentations at scientific and lay meetings by workshop scientists and in lay and scientific publications. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: The horse genome workshop iTarget audiences include veterinarians, horse owners, horse breeders and associations of breeders and veterinarians. ncludes over 100 scientists worldwide. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The horse industry has an indirect economic impact of $102 billion according to a 2005 study by the American Horse Council. The value resides in consumer confidence with respect to the health and athletic abilities of horses for their diverse uses. The American horse industry is respected internationally as evidenced by export of Thoroughbred, Standardbred, Quarter Horse, Miniature Horse, Saddlebred and horses of other breeds. We are able to promote our breeds through demonstrations of genetic superiority in aspects of performance. Conversely, major threats to promotion and marketing of horses include fears of genetic weaknesses affecting muscle, bone, respiratory system and immune system of our livestock. Work in connection with the NRSP8 horse genome project has produced resources for genetically characterizing the different horse breeds, identified genes responsible for discrete genetic diseases affecting horse performance and is being focused on complex genetic problems related to bone development, muscle diseases and respiratory diseases. At the same time, genomics provides tools being used to characterize the host aspects of infectious diseases for the first time, especially as evidenced by the discoveries in the area of equine viral arteritis and ongoing work with equine herpesviruses. The information is being used by horse owners to make choices regarding choices of breeding stock as well as by breed registries for protecting the genetic integrity of their horses. In addition, genes have been identified for coat colors, racing performance and gait allowing breeders to apply the information from this program in a very positive way.

Publications

  • Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, Bailey E, et al. (2012) Genome-wide analysis reveals selection for important traits in domestic horse breeds. PLOS Genetics (in press, 11/15/2012.
  • Go YY, Bailey E, Timoney PJ, Shuck KM and Balasuriya UBR (2012) In vitro susceptibility of CD3+ T lymphocytes to equine arteritis virus infection reflects genetic predisposition of naturally infected stallions to become carriers of the virus. Journal of Virology 86: 12407-12410.
  • McCue, ME, Bannasch DL, Petersen JL, Bailey E, et al. (2012) A high density SNP array for the domestic horse and extant perissodactyla: utility for association mapping, genetic diversity and phylogeny studies. PLoS Genetics: 10.1371/journal.pgen.1002451
  • Binns M., Boehler D., Bailey E., Lear T., Cardwell J., Lambert D. (2012) Inbreeding in the Thoroughbred horse. Animal Genetics 43: 340-342.
  • Lear TL, McGee RB (2012). Disorders of sexual development in the domestic horse, Equus caballus. Sexual Development 6:61-71.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: During 2011 scientists from the horse genome workshop committee met on three occasions, specifically at the Plant and Animal Genome (PAG) meeting in San Diego during January 2011, at the Equine Science Society Meeting, May 30-June 3, in Murfreesboro, TN and at the Dorothy Russell Havemeyer Horse Genome Conference in Minnesota during July 27-29. Scientists presented the results of research activities at their stations and discussed collaborative research. The three meetings involved different scientists but there was some overlap in participation. The focus of discussions was on the need for improved bioinformatics resources, improved infrastructure of the horse genome and sequencing of additional horses using NEXTGEN technology. Committees were formed and we anticipate plans to coordinate sequencing of additional horses and improved annotation of the horse genome. In addition presentations were made to industry stakeholders including groups representing the Thoroughbred industry, Arabian horse industry and practicing veterinarians. At a general meeting of the Dorothy Russell Havemeyer workshops including scientists working in the areas of infectious diseases, reproduction, immunology, sports medicine and genomics scientists presented research using the genomics tools in each of the areas as well as discussed using the technology for future research. In research at the University of Kentucky, genomics was applied to investigations of equine infectious anemia virus, parasite infestations of foals and cytogenetics. Genetic markers were discovered and reported for equine arteritis virus. PARTICIPANTS: Participants in the horse genome project include over 100 scientists worldwide. TARGET AUDIENCES: Target audiences for this work include veterinarians, horse breeders, horse trainers, horse owners and associations of horse owners and veterinarians. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
During 2011 scientists participating in the workshop made numerous reports on genetic influences on performance and disease in horses as a consequence of resources developed in the workshop or through collaborations. Several project continue at the University of Kentucky into 2012 however during 2011 we reported on genes associated with susceptibility to Equine Arteritis Virus (EAV)pathology, inbreeding levels among Thoroughbred horses and sex reversal syndromes in horses. The work on EAV should lead to improved vaccines or therapies designed to eliminate the virus carrier state in stallions. The information about inbreeding levels in Thoroughbred horses will be beneficial to The Jockey Club in determining breeding policies. The information about sex reversal will be useful to breeders and veterinarians in managing horses.

Publications

  • Bailey, E. (2011) Screening for Foal Immunodeficiencey Syndrome. Veterinary Record 169: 653-654
  • Go , Y.Y., Bailey E., Cook D., Coleman S., MacLeod J., Chen K-C, Timoney P., and Balasuriya U.B. (2011) Genome-Wide Association Study Among Four Horse Breeds Identifies a Common Haplotype Associated with the In Vitro CD3+ T Cell Susceptibility/Resistance to Equine Arteritis Virus Infection. J. Virol. 85:13174-13184.
  • Lear, T.L., McGee, R.B. (2011). Disorders of sexual development in the domestic horse, Equus caballus: a review. Sexual Development DOI: 10.1159/000334048.
  • Villagomez, D.A.F., Lear, T.L., Chenier, T., Lee, S., Cahill, J., Foster, R.A., Reyes, E., St John, E., King, W.A. (2011). Equine disorders of sex development; XX SRY-negative, XY SRY-negative and XY SRY-positive genotypes in mares. Sexual Development, 15:16-25.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: During 2010 scientists met in connection with horse genomics studies at the Plant and Animal Genome Conference in San Diego, the International Society of Animal Genetics Conference in Edinburgh and at the World Congress on Genetics Applied to Livestock in Germany. At the conferences, scientists presented outputs in terms of tests for several diseases and phenotypic traits of horses including racing performance, developmental bone diseases, white color markings, dwarfism and muscle diseases. A special issue of the journal, Animal Genetics, was jointly published by workshop participants. A website was maintained and industry questions regarding genetics and genomics were fielded by experts. PARTICIPANTS: Participants in the horse genome workshop include over 100 scientists, worldwide. TARGET AUDIENCES: Target audiences for this work include veterinarians, horse breeders, horse trainers, horse owners and associations of veterinarians and horse owners. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Applications of the Whole Genome Association studies were effective in identifying genetic principles for swayback in Saddlebred horses, dwarfism in miniature horses, susceptibility genes for viral diseases in horses. Specific tests were developed for appaloosa color pattern and dwarfism and for another variant of dominant white coloration in horses. Evidence was found for a role of mast cells in causing laminitis in horses. In addition, a method was developed to test for major histocompatibility complex haplotypes in horses using microsatellite markers. These reports demonstrate the ease of discovery of useful information using genomics tools for horses.

Publications

  • Bellone, R.B., Forsyth, G., Leeb, T., Archer, S., Sigurdsson, S., Mauceli, E., Enquensteiner, M., Bailey, E., Sandmeyer, L., and Grahn, B. (2010) Fine mapping and mutation analysis of TRPM1, a candidate gene for Leopard Complex (LP) spotting and congential stationary Night Blindness (CNSB) in horses. Briefings in Functional Genomics and Proteomics Advance Access published on March 29, 2010; doi: doi:10.1093/bfgp/elq002
  • Tseng, C.T., Miller, D. Cassano, J., Bailey, E. and Antczak, D.F. (2010) Molecular identification of equine major histocompatibility complex haplotypes using polymorphic microsatellites. Animal Genetics 41(supl 2):150-153.
  • Cook, D., Gallagher, P.C. and Bailey, E. (2010) Genetics of swayback in American Saddlebred Horses. Animal Genetics 41(supl 2):64-71.
  • Brooks, S.A., and Bailey, E. (2010) RT-qPCR comparison of mast cell populations in whole blood from healthy horses and those with laminitis. Animal Genetics 41(supl 2):16-22.
  • Holl, H., Brooks, S. and Bailey, E. (2010) De novo mutation of KIT discovered as a result of non-hereditary white coat color pattern. Animal Genetics 41(supl 2):196-198.
  • Binns, M., Boehler, D., Bailey, E., Lear, T., Cardwell, J., and Lambert, D. (2010) Inbreeding in the Thoroughbred horse. Animal Genetics (in press).
  • Bailey, E. (2010) Relevance of genomics to equine reproduction. In A.O. McKinnon (ed), Equine Reproduction. Blackwell Publishing. In press.
  • Bailey, E. (2010) Equine Parentage. In A.O. McKinnon (ed), Equine Reproduction. Blackwell Publishing. In press.
  • Eberth, J., Swerczek, T., and Bailey, E. (2009) Investigation of dwarfism among miniature horses using the Illumina Horse SNP50 Bead Chip. Journal of Equine Veterinary Science 29:315.
  • Cook, D. , Gallagher, P., and Bailey, E. (2009) Illumina Equine SNP50 Bead Chip investigation of adolescent idiopathic lordosis among American Saddlebred Horses. Journal of Equine Veterinary Science 29:315-316.


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: During 2009, scientists from the horse genome workshop community met on three occasions, specifically, at the Plant and Animal Genome Conference (PAG) in San Diego in January, at the Equine Science Society (ESS) Meeting in Colorado in June and at the Dorothy Russell Havemeyer Workshop near Newmarket, UK in July. The PAG meeting included research activities at each research station and deliberations regarding a manuscript describing the whole genome sequence (WGS) for the horse. The ESS meeting provided an opportunity for students to present their research and to develop collaborations with the Animal Science community. The Havemeyer Meeting was noteworthy because it was the first in this series in which the focus was the application of the WGS and discussion of research approaches. In addition, scientists made presentations to lay audiences including presentations by the coordinator to groups of breeders (Arabian, Thoroughbred, Saddlebred), Veterinarians (Kentucky Equine), and other scientists (Iowa State, University College Dublin). PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The primary product from the workshop used during 2009 was the Illumina Equine SNP50 chip, used to assay approximately 50,000 DNA variants distributed on all autosomes and the X chromsome of horses. This was enabled by the information generated in connection with the whole genome sequencing. The use of the tool was the focus of research presented at the three meetings. The applications made in Kentucky concerned 1) discovery of a recessive gene for extreme lordosis among Saddlebred horses 2) discovery of three mutations responsible for dwarfism among miniature horses 3) discovery of two possible genes conferring an immune characteristic in response to equine arteritis virus infection in horses. Work at other research stations identified genetic influences on developmental bone diseases, muscle diseases and Lavender Foal Syndrome of Arabian Horses. In addition, work continued on development of tools to investigate gene expression for horses. At least three vehicles have been developed and annotation is underway. This work is a product of the whole genome sequence.

Publications

  • Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F., Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Blocker H., Distl O., Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T., Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T., Binns M.M., Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guerin G, Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G., Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R., Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roed K.H., Ryder O.A., Searle S., Skow L., Swinburne J.E., Syvanen A.C., Tozaki T., Valberg S.J., Vaudin M., White J.R., Zody M.C. (2009) Genome sequence, comparative analysis and population genetics of the domestic horse (Equus caballus.). Science 326: 865-867.