Prevalence of Sex-Related Chromosomal Abnormalities in a Large Cohort of Spanish Purebred Horses

SIMPLE SUMMARY: Horses are well known for the increased number of individuals carrying chromosomal abnormalities related to the sex pair, which have been identified as a major cause of idiopathic infertility. However, large-scale populational studies evaluating the occurrence of these chromosomal aberrations in commercial or wild populations are extremely scarce. We, therefore, performed a cytogenetic analysis on a large dataset of 25,237 individuals, gathered over a period of 24 months, using a two-step genomic-based diagnostic methodology. We first screened the entire population, analyzing the results of short tandem repeats parentage testing to determine individuals showing abnormal results. Thereafter, the positive samples, together with the individuals showing morphological abnormalities in the reproductive tract, were reanalyzed using a single nucleotide polymorphism (SNP)-based procedure to determine the occurrence of chromosomal abnormalities. Our results showed that the overall prevalence of individuals carrying chromosomal alterations was close to 0.05%, with blood chimerism and 64,XY sex-reversed mares the most common type of aberrations detected. In addition, one case of Turner and one of Klinefelter syndrome, as well as a small number of individuals carrying complex karyotypes, were also detected. However, these results should be taken with caution since the occurrence of X chromosome monosomy, a sex-related chromosomal aberration commonly reported in mares, cannot be screened using the methodology employed in this study. To our knowledge, this is the largest study performed aimed at determining the prevalence of the most important chromosomal abnormalities in the domestic horse. ABSTRACT: Chromosomal abnormalities are largely associated with fertility impairments in the domestic horse. To date, over 600 cases of individuals carrying abnormal chromosome complements have been reported, making the domestic horse the species with the highest prevalence. However, studies analyzing the prevalence of chromosomal diseases in whole populations are scarce. We, therefore, employed a two-step molecular tool to screen and diagnose chromosomal abnormalities in a large population of 25,237 Pura Raza Español horses. Individuals were first screened using short tandem repeats parentage testing results and phenotypic evaluations. Those animals showing results suggesting chromosomal abnormalities were re-tested using a single nucleotide polymorphism (SNP)-based diagnostic methodology to accurately determine the chromosomal complements. Thirteen individuals showed a positive screening, all of which were diagnosed as chromosomally abnormal, including five 64,XY mares with sex development disorders (DSD) and four cases of blood chimerism (two male/female and two female/female cases). In addition, we detected one Turner and one Klinefelter syndrome and two individuals carrying complex karyotypes. The overall prevalence in the entire population was ~0.05%, with the prevalence of 64,XY DSD and blood chimerism ~0.02% and ~0.016%, respectively. However, the overall results should be taken with caution since the individuals carrying Turner syndrome (in full (63,X) or mosaic (mos 63,X/64,XX) forms) cannot be detected due to limitations in the methodology employed. Finally, the lack of agreement between populational studies performed using karyotyping or molecular methods is discussed. To our knowledge, this is the largest populational study performed evaluating the prevalence of the most common chromosomal abnormalities in the domestic horse.