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The Use of a Whole Genome Scan to Find a Genetic Marker for Degenerative Suspensory Ligament Desmitis in the Peruvian Paso Horse

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The Use of a Whole Genome Scan to Find a Genetic Marker for Degenerative Suspensory Ligament Desmitis in the Peruvian Paso Horse View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Kentucky University of Kentucky UKnowledge University of Kentucky Master's Theses Graduate School 2005 THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE Diane I. Strong University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Strong, Diane I., "THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE" (2005). University of Kentucky Master's Theses. 419. https://uknowledge.uky.edu/gradschool_theses/419 This Thesis is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Master's Theses by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF THESIS Diane I. Strong The Graduate School University of Kentucky 2005 ii THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE ABSTRACT OF THESIS A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the College of Agriculture at the University of Kentucky By Diane I. Strong Sadieville, Kentucky Director: Dr. E. Gus Cothran, Department of Veterinary Science Lexington, Kentucky 2005 iii ABSTRACT OF THESIS THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE Degenerative suspensory ligament desmitis (DSLD) is a debilitating disease of connective tissues seen in many breeds but has become prevalent in the Peruvian Paso horse. DSLD is believed to be a genetic disorder caused by one primary founder and most likely has a recessive mode of inheritance although a dominant or co-dominant mode of inheritance has not been ruled out. A genome scan using 259 microsatellite markers was used to test for linkage disequilibrium between one or more markers and DSLD. Two groups of Peruvian Paso horses were selected from one population including the US and Canada. The only difference between the two groups of horses besides the size of the two groups was the presence of DSLD in the affected group and the absence of DSLD in the unaffected group. It was assumed that differences seen between the two groups in homozygosity and or common allele frequency could be an indication of linkage to DSLD. As a connective tissue disorder, there were a large number of candidate genes for DSLD to consider, yet no identical human or animal model exists. The genome scan identified five chromosomal regions where statistically significant differences were seen between affected and unaffected sample populations that could be indications of linkage to DSLD. Those chromosomes were: ECA 6, 7, 11, 14, and 26. iv Sequencing of a portion of the G domain in the Chondroitin Sulfate Proteoglycan 2 (CSPG2) gene has mostly ruled out that segment of chromosome 14 as having linkage to DSLD. Further research needs to be conducted in the regions of ECA 6,7,11 and 26 where statistically significant differences were seen between the affected and unaffected groups, especially on ECA 6 and 11 since possible candidate genes are located in those regions based on the human comparative map. Key Words: Degenerative Suspensory Ligament Desmitis, Peruvian Paso, whole genome scan, connective tissue diseases, linkage disequilibrium v THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE By Diane I. Strong ________________________________ (Director of Dissertation) ________________________________ (Director of Graduate Studies) vi RULES FOR THE USE OF THE THESES Unpublished dissertations submitted for the Master’s degree and deposited in the University of Kentucky Library are as a rule open for inspection, but are to be used only with due regard to the rights of the authors. BiblioFigureical references may be noted, but quotations or summaries of parts may be published only with the permission of the author, and with the usual scholarly acknowledgments. Extensive copying or publication of the thesis in whole or in part also requires the consent of the Dean of the Graduate School of the University of Kentucky. A library that borrows this thesis for use by its patrons is expected to secure the signature of each user. NAME DATE __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ __________________________________________________________________________ vii THESIS Diane I. Strong The Graduate School University of Kentucky 2005 viii THE USE OF A WHOLE GENOME SCAN TO FIND A GENETIC MARKER FOR DEGENERATIVE SUSPENSORY LIGAMENT DESMITIS IN THE PERUVIAN PASO HORSE THESIS A dissertation submitted in partial fulfillment of the requirements for the degree of Master of Science in the College of Agriculture at the University of Kentucky By Diane I. Strong Sadieville, Kentucky Director: Dr. E. Gus Cothran, Department of Veterinary Science Lexington, Kentucky 2005 ix x This thesis is dedicated to my Mother who believed I could do it, my father whom never thought I would do it, my husband who stuck by me while I did it and my daughter who happened along the way. xi ACKNOWLEDGEMENTS I would like to take a moment to thank the many people who made this thesis a reality. First I would like to thank my thesis Chair, Dr Gus Cothran who offered me this opportunity over 5 years ago and has stood by me through process that has led to its completion. I would also like to thank the other members of my thesis committee, Dr. Kathryn T. Graves, Dr. Teri L. Lear, and silent member Dr. Ernest Bailey (whom thankfully, is seldom silent). All of which have guided me, challenged me and given incite to this project. I would like to thank Pam Henney who is priceless. Her knowledge of all things scientific and ability to teach have added to my abilities enormously. I would also like to thank Lyn Ennis for teaching me to sequence. I thank Dr. Rytis Juras for his help on many aspects of the genome scan, and knowledge of data analysis programs. I want to thank Doris Gabbard and her computer wizardry for compiling all of my data into usable sets, painstaking work. I would like to thank Hua Liu from the statistics department for dealing with my data sets at the last minute. I would like to thank Arlynda Castro of the North American Peruvian Horse Association for materials and information pertaining to Peruvian Paso horses. I would like to recognize and personally thank the concerned Peruvian Paso horse owners who have provided horses, blood, histories, and most importantly brought the DSLD problem to the surface so it could be looked at from a scientific point of view. I especially want to thank those Peruvian Paso horse owners who have funded this research. I need to thank Dr. Donald E. Moore of Adobe Creek Animal Clinic in Fruita, Colorado, who is the finest Veterinarian I have ever known and was instrumental in me xii coming to the University of Kentucky. I would also like to thank my friends and family who have never quite understood what I have been doing for the last five years, but have supported me anyway. I especially thank my sister, Deborah Baker, who taught me how to study in 10th grade. Until then, education was a four-letter word. I want to say thank you to my husband Danny who has stood by me, sacrificed his goals at times so I could succeed and most importantly taken care of our sweet baby Emma while I was in the lab so she wouldn’t have to go into daycare. I have to thank my father who never thought an 8-year-old girl would really save her allowance for two years to buy herself a pony, but never the less honored his promise to let me have a pony if I bought it myself. No regrets Pa. Finally, I owe a great big thank you to Jo, my first love. He was the most beautiful palomino Quarter Horse. He taught me many things, but most recently he taught me what it was like to loose a horse you love before their time due to a genetic flaw. I’m so sorry Jo. I never meant to hurt you. God speed. xiii TABLE OF CONTENTS Acknowledgments......................................................................................................xi List of Tables .............................................................................................................xv List of figures.............................................................................................................xvi Chapter One: Introduction and Background.............................................................01 The History of DSLD.....................................................................................02 The Biology and Pathology of DSLD............................................................04 History of the Peruvian Paso .........................................................................11 The Purpose of this Research.........................................................................12 Review of Genetic Literature.........................................................................12
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