Identification of aneuploidy in dogs screened by a SNP microarray

Abstract

Microarray analysis is an e cient approach for screening and identifying cytogenetic imbalances in humans. SNP arrays, in particular, are a powerful way to identify copy number gains and losses representing aneuploidy and aneusomy, but moreover, allow for the direct assessment of individual genotypes in known disease loci. Using these approaches, trisomies, monosomies and mosaicism of whole chromosomes have been identi ed in human microarray studies. For canines, this approach is not widely used in clinical laboratory diagnostic practice. In our laboratory, we have implemented the use of a propriety SNP array that represents approximately 650,000 loci across the domestic dog genome. During the validation of this microarray prior to clinical use, we identi ed three cases of aneuploidy after screening 2,053 dogs of various breeds including monosomy X, trisomy X and an apparent, mosaic trisomy of canine chromosome 38 (CFA 38). This study represents the rst use of microarrays for copy number evaluation to identify cytogenetic anomalies in canines. As microarray analysis becomes more routine in canine genetic testing, more cases of chromosome aneuploidy are likely to be uncovered.

Non-mosaic X monosomy (77,X) in a female dog with signs of virilization

“…This suggests that mosaic and non-mosaic types of X monosomy may occur with similar incidences in dogs, as has also been observed in TS patients (Zhong and Layman 2012). Interestingly, a total of three canine cases (42%) have thus far been diagnosed in Poodle breeds: namely, a Toy Poodle (Mayenco-Aguirre et al 1999), a cross of a Miniature Poodle with a Goldendoodle (Shaffer et al 2021), and a Miniature Poodle (the present case).…”

“…Seven cases of X monosomy have been reported in dogs to date, including the present case (Smith et al 1989;Löfstedt et al 1992;Mayenco-Aguirre et al 1999;Switonski et al 2003;Shaffer et al 2021). Six of these were studied cytogenetically; three cases were non-mosaics and three were mosaics (77,X/78,XX), with the proportion of the monosomic cell line varying from 5 to 95% (Szczerbal and Switonski 2021).…”

“…On the other hand, a small number of the diagnosed cases could also be the result of the limited number of laboratories performing cytogenetic diagnosis of dogs. Recently, a random cohort of 2053 dogs, including 1281 females and 964 males, was screened with the use of an SNP microarray; a single case of X monosomy and a single case of X trisomy were found (Shaffer et al 2021). This finding shows that the frequency of X monosomy in dogs may be even higher than the incidence of this aneuploidy in humans, where it is called Turner syndrome (TS), which varies between 1/2500 and 1/4000 in live-born female infants (Dawkins et al 2018).…”

Special issue on companion animal genetics: Novel variants discovered in wide variety of diseases in dogs, identification and further characterization of traits in dogs and cats, and the use of microarrays in the detection of aneuploidy in dogs

“…The last paper in this issue uses microarray technologies to identify copy-number variation and the identification of the first autosomal aneuploidy in dogs (Shaffer et al 2021b).…”