James R. Mickelson

e-mail: micke001@umn.edu

295 Animal Science/Veterinary Medicine
1988 Fitch Avenue
University of Minnesota
St. Paul, MN 55108

Education

 
B.S., University of Wisconsin—Madison
M.S., University of Wisconsin—Madison
Ph.D., University of Wisconsin—Madison
Post-Doctoral, University of Minnesota

Research Interests

 
The primary goal of Dr. Mickelson's research program is to identify the molecular bases of inherited neurologic and neuromuscular disorders in domestic animals. In order to achieve this goal, his group played a significant role in the development of genetic linkage, physical, and comparative maps of the canine and equine genomes, as well as the development of high throughput genetic analysis tools. Multidisciplinary studies, in which his group performed the genetic and molecular genetic analyses have identified the genetic basis for the overo coat color gene in Paint horses that also causes lethal white foal syndrome, a gene that causes a form of canine malignant hyperthermia, and the gene responsible for glycogen storage disease IV in Quarter Horses.  More recently, a dominant mutation in the skeletal muscle glycogen synthase gene responsible for a glycogen storage disease known as polysaccharide storage myopathy in many breeds of horses has been identified.  And most recently, a recessive mutation in the dynamin 1 gene responsible for synaptic vesicle endocytosis at synaptic junctions has been discovered that is responsible for the highly prevalent condition known as exercise-induced in Labrador Retrievers and related breeds.

Many of these heritable disorders are homologous to those found in humans and other species, while others appear to be novel diseases found only in that species.  In addition to defining the basic molecular pathobiology, genetic tests to specifically diagnose the conditions are developed, and used to recommend breeding strategies to eliminate or control the spread of these genetic disorders.  Future goals of the laboratory are to define functional bases for these mutations on the protein function and to determine the overall frequency of these mutations in the respective breeds.  His laboratory is currently mapping the loci for epilepsy in a number of different breeds of dog, polyneuropathy in Leonbergers, recurrent exertional rhabdomyolysis in Thoroughbred race horses, and a new form of polysaccharide storage myopathy in Quarter Horses.  Dr Mickelson is the lead investigator responsible for developing the equine SNP genotyping chip that will enable large scale genotyping of these genetic markers in genetic case:control association studies to map genes for traits in horses.

Mickelson Canine and Equine Genetics Laboratory

Selected Publications 
(For a comprehensive list of   Dr. Mickelson's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

McCue ME, Valberg SJ, Miller MB, Wade CM, DiMauro S, Akman HO, and Mickelson JR.  (2008). Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics 91, 458- 466.

Patterson EE, Minor KM, Tchernatynskaia AV, Taylor SM, Shelton GD, and Mickelson JR. (2008). Dynamin 1 (DNM1) mutation is highly associated with the syndrome of exercise-induced collapse in the Labrador retriever dog. Nature Genetics 40, 1235-1239.

McCue ME, Valberg SJ, Luccio M and Mickelson JR.  (2008). Glycogen synthase 1 mutation in diverse breeds with polysaccharide storage myopathy. J Vet Intern Med 22, 1228 – 1233.

Raudsepp T, Gustafson-Seabury A, Durkin K, Wagner ML, Goh G, Seabury CM, Brinkmeyer-Langford C, Lee EJ, Agarwala R, Rice ES, Schäffer AA, Tozaki T, Yasue H, Penedo MCT, Lyons LA, Khazanehdari KA, Leeb T, Distl O, Binns MM, MacLeod JN, Mickelson JR, Chowdhary BP.  (2008).  A 4103 marker integrated map of the horse genome.   Cytogenetics and Genome Research 122, 28-36.

Tryon RC, Penedo MCT, McCue, ME PhD, Valberg SJ, Mickelson JR, Famula TR, Wagner ML, Jackson M, Hamilton M, Noteboon S, Bannasch DL. (2009).  Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses.  J Am Vet Med Assoc 234. 120-125.

Herszberg B, McCue ME, Larcher T, Mata X, Vaiman A, Chaffaux S, Chérel Y, Valberg SJ, Mickelson JR, Guérin G.  (2008).  A GYS1 gene mutation is highy associated with polysaccharide storage myopathy in Cob Normand draft horses.  Animal Genetics 40, 94-96.

McCue ME, Valberg SJ, Jackson M, Lucio M and Mickelson JR. (2009).  Polysaccharide Storage Myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation.  Neuromuscular Disorders 19, 37-43.

Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear T, Adelson DL, Penedo MCT , Bellone RR, Bailey E,  Mauceli E, Garber M, MacLeod JN, Sharpe T, Vogel J,  Andersson L, Antczak DF, Biagi T, Binns MM1, Blöcker H, Chowdhary BP, Coleman SJ, Della Valle G, Distl O, Edgar RC, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Leeb T, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze  SG, Onofrio R, Pedroni S, Piras MF, Raison J, Raudsepp T, Rocchi M,  Røed KH, Ryder O, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JS, Zody MC,  Broad Institute Genome Sequencing Platform, Broad Institute Whole Genome Assembly Team, Lander ES, and Lindblad-Toh K.  (2009).  Genome sequence, comparative analysis and population genetics of the domestic horse (Equus caballus).  Science 326, 865-867.

Stanley RL, Valberg SJ, McCue ME, Mickelson JR, McGowan C, Hahn C, Patterson-Kane J and Piercy RJ. (2009). A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds. Equine Veterinary Journal 41, 597-601.

McCue ME, Armién AG, Lucio M, Mickelson JR, and Valberg SJ, (2009). Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses. Vet Pathology 46, 1281-1291.

Beggs AH, Bohm J, Snead E, Kozlowski M, Maurer M, Minor K, Childers MK, Taylor SM, Hitte C, Mickelson JR, Guo LT, Mizisin AP, Bug-Bello A, Tiret L, Laporte J and Shelton GD. (2010). MTM1 mutation Associated With X-Linked Myotubular Myopathy In Labrador Retrievers. Proc Nat Acad Sci 107, 14697–14702.

Baird JD, Valberg SJ, Anderson SM, McCue ME, and Mickelson JR. (2010). Presence of the Glycogen Synthase 1 (GYS1) mutation causing Polysaccharide Storage Myopathy in Continental European Draught horse breeds. Vet Rec 167, 781-784.

McCue ME, Anderson SM, Valberg SJ, Piercy R, Binns MM, Distl O, Penedo MCT, and Mickelson JR. (2010). Estimated prevalence of the Type 1 Polysaccharide Storage Myopathy mutation in selected North American and European breeds. Animal Genetics 41, Supplement 2, 145-149.

Lykkjen S, Dolvik NI, McCue ME, Rendahl AK, Mickelson JR, and Roed KH. (2010). Genome-Wide Association Analysis and Identification of SNPs Related to Osteochondrosis in Norwegian Standardbred Trotters. Animal Genetics 41, Supplement 2, 111-120.

Johlig L, Valberg SJ, Mickelson JR, Klukowska J, Reusser HR, Straub R, and Gerber V. (2011). Epidemiologic and genetic study of exertional rhabdomyolysis in a Warmblood horse family in Switzerland. Equine Veterinary Journal 43, 240-245.

Minor KM, Patterson EE, Keating MK, Gross SD, Ekenstedt KJ, Taylor SM, and Mickelson JR. (2011). Presence and Impact of the Exercise-Induced Collapse Associated DNM1 Mutation in Labrador Retrievers and Other Breeds. Veterinary Journal 189, 214-219.

Ekenstedt, KJ, Patterson EE, Johnson GS, Minor KM, and Mickelson JR. (2011). Candidate genes for idiopathic epilepsy in four dog breeds. BMC Genetics 12, 38.

McCue ME, Bannasch DL, Petersen JL, Bailey E, Binns MM, Distl O, Guérin G, Hasegawa T, Hill EW, Leeb T, Lindgren G, Penedo, Røed KH, Ryder OA, Swinburne JE, Tozaki T, Valberg SJ, Vaudin M, Lindblad-Toh K, Wade CM, and Mickelson JR. (2012). A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity and Phylogeny Studies. A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity and Phylogeny Studies. PLoS Genetics, 2012 Jan;8(1):e1002451,  Epub 2012 Jan 12.

Ekenstedt KJ, Patterson EE, Mickelson JR. (2012). Canine epilepsy genetics. Mamm Genome 23: 28-39.

Fritz KL, McCue ME, Valberg SJ, Rendahl AK, Mickelson JR. (2012). Genetic mapping of recurrent exertional rhabdomyolysis in a population of North American Thoroughbred horses. Animal Genetics Mar 23, doi: 10.1111/j.1365-2052.2012.02351.x. Epub 2012 Mar 23

Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren L, Andersson L and Kullander K. (2012). Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Article selected for the cover. Nature 2012 Aug 30;488 (7413):642-6.

Petersen JL, Mickelson JR, Valberg SJ, lots of others, and McCue ME (2013). Signatures of selection in domestic horse populations. PLOS Genetics10.1371/journal.pgen.1003211

Petersen JL, Mickelson JR, lots of others, and McCue ME Genetic diversity in the horse derived from whole genome SNP data. PLoS One, accepted.

Furrow E, Minor K, Taylor SM, Mickelson JR, and Patterson EE. (2012). Relationship between dynamin 1 mutation and phenotype in 109 Labrador retrievers with collapse during exercise. JAVMA, accepted.

Lykkjen S, Dolvik NI, Mccue ME, Rendahl AK, Mickelson JR, and Røed KH. Equine developmental orthopaedic diseases – a GWAS of first phalanx plantar osteochondral fragments in Standardbred trotters. Animal Genetics, Accepted.

Bruun CS, Jadelund KH, Berendt M, Jensen KB, Spodsberg EH, Gredal HB, SheIton D, Mickelson JR, Minor KM, Lohi H, Bjerkaas I, Stigen O, Espensen A, Rohdin C, Cizinauskas S, Leifsson PS, Drogemuller C, Moe L, Cirera S, and Fredholm M. A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy PLoS One, accepted.

Current Funding

“Mapping the recurrent exertional rhabdomyolysis gene in Thoroughbred horses”; Morris Animal Foundation and University of Minnesota Equine center.

 “Canine Epilepsy: inheritance, genes, and linkage test”; American Kennel Club, Canine Health Foundation

“Genetic basis of polyneuropathy in Leonberger dogs”; American Kennel Club, Canine Health Foundation

 “Genetic analysis of glycogen storage disorders in Quarter Horses”; American Quarter Horse Association

 “Development and distribution of equine SNP chips: USDA NRICGP and Morris Animal Foundation

“Genetic basis for polyneuropathy in Leonberger dogs”

Honors and Awards 

College of Veterinary Medicine Collegiality Award, 1997, 1998.

Molecular Veterinary Biosciences Graduate Program Teaching Award, 2001.

Pfizer Research Excellence Award, 2004.

MVB Courses and Activities

Director of Graduate Studies, Molecular Veterinary Biosciences, 1994 - 1997.

Program Advisory Committee, Molecular Veterinary Biosciences, 1997 - 2001.

Sponsor of Laboratory Rotations