Molecular Cytogenetic and Y Copy Number Analysis of a Reciprocal ECAY-ECA13 Translocation in a Stallion with Complete Meiotic Arrest

SIMPLE SUMMARY: We present a detailed molecular cytogenetic analysis of a translocation between horse (ECA) chromosomes Y and 13 in a Friesian stallion with complete meiotic arrest and azoospermia. We use two-color fluorescence in situ hybridization with select ECAY and ECA13 markers and show the location of translocation breakpoints in ECAY and in ECA13. The translocation generates two abnormal chromosomes: one comprised of the short arm of ECA13 and the proximal gene-poor 2/3 of ECAY and another, the long arm of ECA13 and the distal 1/3 of ECAY containing most of the single copy and ancestral genes. A copy number (CN) analysis of select ECAY multicopy genes shows that the Friesian stallion has significantly reduced CNs of TSPY, ETSTY1, and ETSTY5, suggesting some genetic loss due to the translocation. We discuss likely meiotic behavior of abnormal chromosomes and theorize about the possible effect of the aberration on Y regulation and the progression of meiosis. The study adds a unique case to equine clinical cytogenetics and contributes to understanding the role of the Y chromosome in male meiosis. ABSTRACT: We present a detailed molecular cytogenetic analysis of a reciprocal translocation between horse (ECA) chromosomes Y and 13 in a Friesian stallion with complete meiotic arrest and azoospermia. We use dual-color fluorescence in situ hybridization with select ECAY and ECA13 markers and show that the translocation breakpoint in ECAY is in the multicopy region and in ECA13, at the centromere. One resulting derivative chromosome, Y;13p, comprises of ECAY heterochromatin (ETSTY7 array), a small single copy and partial Y multicopy region, and ECA13p. Another derivative chromosome 13q;Y comprises of ECA13q and most of the single copy ECAY, the pseudoautosomal region and a small part of the Y multicopy region. A copy number (CN) analysis of select ECAY multicopy genes shows that the Friesian stallion has significantly (p < 0.05) reduced CNs of TSPY, ETSTY1, and ETSTY5, suggesting that the translocation may not be completely balanced, and genetic material is lost. We discuss likely meiotic behavior of abnormal chromosomes and theorize about the possible effect of the aberration on Y regulation and the progression of meiosis. The study adds a unique case to equine clinical cytogenetics and contributes to understanding the role of the Y chromosome in male meiosis.