The Second Case of Non-Mosaic Trisomy of Chromosome 26 with Homologous Fusion 26q;26q in the Horse

SIMPLE SUMMARY: We present chromosome and DNA analysis of a normal Thoroughbred mare and her abnormal foal born with neurologic defects. We show that the foal has an abnormal karyotype with three copies of chromosome 26 (trisomy chr26), instead of the normal two. However, two of the three chr26 have fused, forming an unusual derivative chromosome. Chromosomes of the dam are normal, suggesting that the chromosome abnormality found in the foal happened during egg or sperm formation or after fertilization. Analysis of the foal and the dam with chr26 DNA markers indicates that the extra chr26 in the foal is likely of maternal origin and that the unusual derivative chromosome resulted from the fusion of two parental chr26. We demonstrate that although conventional karyotype analysis can accurately identify chromosome abnormalities, determining the mechanism and parental origin of these abnormalities requires DNA analysis. Most curiously, this is the second case of trisomy chr26 with unusual derivative chromosome in the horse, whereas all other equine trisomies have three separate copies of the chromosome involved. Because horse chr26 shares genetic similarity with human chr21, which trisomy causes Down syndrome, common features between trisomies of horse chr26 and human chr21 are discussed. ABSTRACT: We present cytogenetic and genotyping analysis of a Thoroughbred foal with congenital neurologic disorders and its phenotypically normal dam. We show that the foal has non-mosaic trisomy for chromosome 26 (ECA26) but normal 2n = 64 diploid number because two copies of ECA26 form a metacentric derivative chromosome der(26q;26q). The dam has normal 64,XX karyotype indicating that der(26q;26q) in the foal originates from errors in parental meiosis or post-fertilization events. Genotyping ECA26 microsatellites in the foal and its dam suggests that trisomy ECA26 is likely of maternal origin and that der(26q;26q) resulted from Robertsonian fusion. We demonstrate that conventional and molecular cytogenetic approaches can accurately identify aneuploidy with a derivative chromosome but determining the mechanism and parental origin of the rearrangement requires genotyping with chromosome-specific polymorphic markers. Most curiously, this is the second case of trisomy ECA26 with der(26q;26q) in the horse, whereas all other equine autosomal trisomies are ‘traditional’ with three separate chromosomes. We discuss possible ECA26 instability as a contributing factor for the aberration and likely ECA26-specific genetic effects on the clinical phenotype. Finally, because ECA26 shares evolutionary homology with human chromosome 21, which trisomy causes Down syndrome, cytogenetic, molecular, and phenotypic similarities between trisomies ECA26 and HSA21 are discussed.