Detection of two equine trisomies using SNP-CGH

Abstract

Chromosomal aberrations in the horse are known to cause congenital abnormalities, embryonic loss, and infertility. While diagnosed mainly by karyotyping and FISH in the horse, the use of SNP array comparative genome hybridization (SNP-CGH) is becoming increasingly common in human diagnostics. Normalized probe intensities and allelic ratios are used to detect changes in copy number genome-wide. Two horses with suspected chromosomal abnormalities and six horses with FISH-confirmed aberrant karyotypes were chosen for genotyping on the Equine SNP50 array. Karyotyping of the first horse indicated mosaicism for an additional small, acrocentric chromosome, although the identity of the chromosome was unclear. The second case displayed a similar phenotype to human disease caused by a gene deletion and so was chosen for SNP-CGH due to the ability to detect changes at higher resolutions than those achieved with conventional karyotyping. The results of SNP-CGH analysis for the six horses with known chromosomal aberrations agreed completely with previous karyotype and FISH analysis. The first undiagnosed case showed a pattern of altered allelic ratios without a noticeable shift in overall intensity for chromosome 27, consistent with a mosaic trisomy. The second case displayed a more drastic change in both values for chromosome 30, consistent with a complete trisomy. These results indicate that SNP-CGH is a viable method for detection of chromosomal aneuploidies in the horse.

Whole genome analysis reveals aneuploidies in early pregnancy loss in the horse

“…Of the 20 individuals with autosomal aneuploidy reported to date (combining reports in the literature with our study), it is of note that approximately 45% involve chromosome 27 or 30 (5 trisomy live born [28–30, 41], two monosomy 27 EPLs, and 2 trisomy 30 EPLs). The underlying mechanisms of why certain chromosomes would be more susceptible to aneuploidy is not known with further studies warranted.…”

“…In the horse, there are only 8 individual case reports of aneuploid live borns, involving chromosomes 23, 26, 27, 28, 30, and 31. These presented with variable congenital abnormalities involving the musculoskeletal, neurological, and vasculature systems [28–30, 39–42]. Of these six equine aneuploidy types tolerated to term, only trisomy 30 was also identified in EPL conceptuses.…”

“…Chromosomes 27 and 30 are among the most gene poor equine autosomes (6 genes/Mb each), possibly explaining their higher incidence. The difference in lethality of chromosome 27 is interesting as it appears that trisomies of this chromosome are viable to term, and display varying characteristics within 24 months of birth including cryptorchidism, bilateral carpal flexural deformity and an inability to suck [28], skeletal abnormalities and a failure to thrive [30], and atypical gait and reduced social skills [29]. Our study has added to the list of chromosome 27 aneuploidies by documenting 2 monosomies in early failed pregnancies.…”

“…While more commonly reported in humans, aneuploidy has also been noted occasionally in domesticated species including live born calves [24–26], dogs [27] and live born foals [28–30]. Equines reported to survive to term are often euthanised at a young age due to extreme developmental defects [28–30]. In species with reported live born individuals with autosomal aneuploidies, all are trisomies with no reported monosomies in the literature [31].…”

“…Single Nucleotide Polymorphism (SNP) Arrays are a lower cost, high throughput method that may offer an answer. A low-density SNP array (Equine SNP50 BeadChip) has previously been used to detect aneuploidy in two live born horses suspected of chromosomal abnormalities [30], offering evidence for the validity of this methodology.…”