Molecular heterogeneity of XY sex reversal in horses

Authors

  • T. Raudsepp,

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
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  • K. Durkin,

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
    2. Unit of Animal Genomics, GIGA-R, Department of Animal Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
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  • T. L. Lear,

    1. M.H. Gluck Equine Research Center, Veterinary Science Department, University of Kentucky, Lexington, KY, USA
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  • P. J. Das,

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
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  • F. Avila,

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
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  • P. Kachroo,

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
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  • B. P. Chowdhary

    1. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA
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T. Raudsepp and B. P. Chowdhary, Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX-77843-4458, USA.
E-mails: traudsepp@cvm.tamu.edu and bchowdhary@cvm.tamu.edu

Summary

Male-to-female 64,XY sex reversal is a frequently reported chromosome abnormality in horses. Despite this, the molecular causes of the condition are as yet poorly understood. This is partially because only limited molecular information is available for the horse Y chromosome (ECAY). Here, we used the recently developed ECAY map and carried out the first comprehensive study of the Y chromosome in XY mares (n = 18). The integrity of the ECAY in XY females was studied by FISH and PCR using markers evenly distributed along the euchromatic region. The results showed that the XY sex reversal condition in horses has two molecularly distinct forms: (i) a Y-linked form that is characterized by Y chromosome deletions and (ii) a non-Y-linked form where the Y chromosome of affected females is molecularly the same as in normal males. Further analysis of the Y-linked form (13 cases) showed that the condition is molecularly heterogeneous: the smallest deletions spanned about 21 kb, while the largest involved the entire euchromatic region. Regardless of the size, all deletions included the SRY gene. We show that the deletions were likely caused by inter-chromatid recombination events between repeated sequences in ECAY. Further, we hypothesize that the occurrence of SRY-negative XY females in some species (horse, human) but not in others (pig, dog) is because of differences in the organization of the Y chromosome. Finally, in contrast to the Y-linked SRY-negative form of equine XY sex reversal, the molecular causes of SRY-positive XY mares (5 cases) remain as yet undefined.

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