Identification of chromosomal regions associated with cranial cruciate ligament rupture in a population of Newfoundlands

Vicki L. Wilke Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Shu Zhang Departments of Biochemistry, Biophysics and Molecular Biology and Statistics, College of Liberal Arts and Sciences, Iowa State University, Ames, IA 50011.

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Richard B. Evans Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.

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Michael G. Conzemius Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

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Max F. Rothschild Department of Animal Science, College of Agriculture and Life Sciences, Iowa State University, Ames, IA 50011.

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DOI:
https://doi.org/10.2460/ajvr.70.8.1013
Volume/Issue:
Volume 70: Issue 8
Online Publication Date:
01 Aug 2009
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Abstract

Objective—To identify chromosomal regions associated with cranial cruciate ligament rupture (CCLR) in a population of Newfoundlands.

Animals—90 client-owned Newfoundlands.

Procedures—A pedigree was constructed for dogs that did or did not have CCLR (determined on the basis of physical examination and radiographic findings). From this pedigree, affected and unaffected dogs were selected for genotyping on the basis of their predicted statistical likelihood of being homozygous CCLR-unaffected (n = 53) or homozygous CCLR-affected (37) dogs. Genotyping was performed for 532 microsatellite markers (MSATs). Comparisons of genotypes and allele frequencies were made between CCLR-affected and CCLR-unaffected dogs.

Results—In the selected population, 495 MSATs were informative with a mean interval between markers of 5.5 centimorgans. Eighty-six MSATs were significantly associated with the CCLR trait, whereas 4 markers (located on 4 chromosomes) were significantly associated with the trait when false discovery rate (q value) was controlled at the 0.05 level. Subsequent initial validation confirmed significant trait association for 3 of the 4 MSATs.

Conclusions and Clinical Relevance—In the population of Newfoundlands, 4 MSATs that were located on 4 chromosomes were significantly associated with the CCLR trait. Three of those markers were validated in part via genotyping additional closely located markers. The MSATs that were associated with the CCLR trait were identified in all regions (except for those on chromosome 24). Newfoundlands with CCLR could be used to study the disease process associated with anterior cruciate ligament injuries that occur in young female human athletes.

Abstract

Objective—To identify chromosomal regions associated with cranial cruciate ligament rupture (CCLR) in a population of Newfoundlands.

Animals—90 client-owned Newfoundlands.

Procedures—A pedigree was constructed for dogs that did or did not have CCLR (determined on the basis of physical examination and radiographic findings). From this pedigree, affected and unaffected dogs were selected for genotyping on the basis of their predicted statistical likelihood of being homozygous CCLR-unaffected (n = 53) or homozygous CCLR-affected (37) dogs. Genotyping was performed for 532 microsatellite markers (MSATs). Comparisons of genotypes and allele frequencies were made between CCLR-affected and CCLR-unaffected dogs.

Results—In the selected population, 495 MSATs were informative with a mean interval between markers of 5.5 centimorgans. Eighty-six MSATs were significantly associated with the CCLR trait, whereas 4 markers (located on 4 chromosomes) were significantly associated with the trait when false discovery rate (q value) was controlled at the 0.05 level. Subsequent initial validation confirmed significant trait association for 3 of the 4 MSATs.

Conclusions and Clinical Relevance—In the population of Newfoundlands, 4 MSATs that were located on 4 chromosomes were significantly associated with the CCLR trait. Three of those markers were validated in part via genotyping additional closely located markers. The MSATs that were associated with the CCLR trait were identified in all regions (except for those on chromosome 24). Newfoundlands with CCLR could be used to study the disease process associated with anterior cruciate ligament injuries that occur in young female human athletes.

Contributor Notes

Dr. Wilke's present address is the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108.

Dr. Evans' present address is the Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61852.

Supported by the American Kennel Club Canine Health Foundation (grant No. 247); Newfoundland Club of America; Orthopedic Research Laboratory—College of Veterinary Medicine, Iowa State University; Iowa State University Biotechnology Council; Department of Animal Science, Iowa State University; Special Research Initiation Grant, the Iowa Agriculture and Home Economics Experiment Station; Hatch and State of Iowa funds; and the Veterinary Genetics Laboratory, University of California, Davis.

Presented in part at the 17th American College of Veterinary Surgeons Symposium, Chicago, October 2007.

The authors thank Amalie DiMiceli for for assistance with microsatellite genotyping.

Address correspondence to Dr. Wilke.
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Aug 2009
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