Aneuploidy in dizygotic twin sheep detected using genome-wide single nucleotide polymorphism data from two commonly used commercial vendors

Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would

not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now

being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the

allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of

aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM

AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X

sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on

1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on

383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR),

were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from

their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele

intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females

monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or

Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the

population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this

was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective

autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In

both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle

development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species

that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach

proposed in the present study was agnostic to genotype platform.