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Linkage mapping of the locus for inherited ovine arthrogryposis (IOA) to sheep Chromosome 5

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Abstract

Arthrogryposis is a congenital malformation affecting the limbs of newborn animals and infants. Previous work has demonstrated that inherited ovine arthrogryposis (IOA) has an autosomal recessive mode of inheritance. Two affected homozygous recessive (art/art) Suffolk rams were used as founders for a backcross pedigree of half-sib families segregating the IOA trait. A genome scan was performed using 187 microsatellite genetic markers and all backcross animals were phenotyped at birth for the presence and severity of arthrogryposis. Pairwise LOD scores of 1.86, 1.35, and 1.32 were detected for three microsatellites, BM741, JAZ, and RM006, that are located on sheep Chr 5 (OAR5). Additional markers in the region were identified from the genetic linkage map of BTA7 and by in silico analyses of the draft bovine genome sequence, three of which were informative. Interval mapping of all autosomes produced an F value of 21.97 (p < 0.01) for a causative locus in the region of OAR5 previously flagged by pairwise linkage analysis. Inspection of the orthologous region of HSA5 highlighted a previously fine-mapped locus for human arthrogryposis multiplex congenita neurogenic type (AMCN). A survey of the HSA5 genome sequence identified plausible candidate genes for both IOA and human AMCN.

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Acknowledgments

This study was supported by grants from Enterprise Ireland (No. SC/01/453) and Science Foundation Ireland (Nos. 05/RFP/Gen0060 and 02-IN.1-B256). The authors thank Mr. Pat Duffy, Dr. Dimitris Rizos, Ms. Ciara O’Meara, Ms. Mary Duane, Mr. Eoin Ryan, Mr. William Fitzgerald, Ms. Laura Mitchell, and all of the Staff at the UCD Lyons Research Farm for assistance with sheep management and reproduction. They also thank Prof. Noelle Cockett and Ms. Tracy Shay of the Animal, Dairy and Veterinary Sciences Department, Utah State University for valuable advice and provision of microsatellite primers.

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Authors and Affiliations

  1. Animal Genomics Laboratory, School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland

    Angela M. Murphy, David E. MacHugh, Stephen D.E. Park, Erik Scraggs & Maurice P. Boland

  2. Department of Genetics and Genomics, Roslin Institute (Edinburgh), Roslin, Midlothian, EH25 9PS, Scotland, UK

    Chris S. Haley

  3. Department of Genetics, Smurfit Institute, Trinity College, Dublin 2, Ireland

    David J. Lynn

  4. Centre for Clinical Studies, School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland

    Michael L. Doherty

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  1. Angela M. Murphy
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  2. David E. MacHugh
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  3. Stephen D.E. Park
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  4. Erik Scraggs
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  8. Michael L. Doherty
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Correspondence to David E. MacHugh.

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Murphy, A.M., MacHugh, D.E., Park, S.D. et al. Linkage mapping of the locus for inherited ovine arthrogryposis (IOA) to sheep Chromosome 5. Mamm Genome 18, 43–52 (2007). https://doi.org/10.1007/s00335-006-0016-8

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  • DOI: https://doi.org/10.1007/s00335-006-0016-8

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