Identification of aneuploidy in dogs screened by a SNP microarray.

Microarray analysis is an efficient 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 identified 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 proprietary SNP array that represents approximately 650,000 loci across the domestic dog genome. During the validation of this microarray prior to clinical use, we identified three cases of aneuploidy after screening 2053 dogs of various breeds including monosomy X, trisomy X, and an apparent mosaic trisomy of canine chromosome 38 (CFA38). This study represents the first 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.

37,X/38,XY Mosaicism in a Cryptorchid Bengal Cat with Müllerian Duct Remnants.

A 23-month-old tomcat was referred to our clinic because of male behavioral problems, cryptorchidism, and an undefined intra-abdominal organ resembling a uterus. Ultrasonography and computed tomography showed 2 fluid-filled tubular structures dorsolaterally to the bladder and connected to the pelvic urethra. The cat was castrated, and the tubular structures were surgically removed. Histology identified them as Müllerian duct remnants. The testes were hypoplastic, the epididymes and deferent ducts were normal. Cytogenetic analyses revealed the presence of a mosaic 37,X/38,XY karyotype which explains the clinical findings.

Disorders of sexual development in the domestic horse, Equus caballus.

Abnormalities of sexual development causing infertility in horses have been investigated since the early 1970's. Conventional cytogenetic analysis by karyotyping has been the primary tool used to investigate these horses. Abnormalities have a broad range, from a phenotypically normal mare with gonadal dysgenesis to a horse with ambiguous external genitalia and internal male and female organs. Cytogenetic analysis can determine genetic sex but cannot identify mutations or deletions of genes involved in the sex determination pathway. Molecular technologies have been developed to confirm cytogenetic results and to aid in identifying the genetic causes of abnormal sex determination in horses. In this paper, we review the historical development of methods used to understand abnormal sexual development in the horse as well as summarize cases reported over the last 40-50 years.

Disorders of sexual development in wild and captive exotic animals.

Disorders of sexual development (DSDs) are an increasing concern in both captive and free-ranging wildlife species. Partial or complete reduction in fertility that results from intersex conditions or gonadal dysgenesis is detrimental to the reproductive potential of wildlife populations, and consequently, to their long-term survival. Compared to the wealth of information available on humans and domestic species, a better understanding of the factors influencing sexual development in wildlife is essential for developing and improving population management or conservation plans. This review attempts to bring together the different facets of DSDs as studied in the fields of reproductive physiology, endocrinology, ecotoxicology, wildlife biology, and environmental health.

Gonadal and sex differentiation abnormalities of dogs and cats.

The molecular steps in normal sexual development were largely discovered by studying patients and animal models with disorders of sexual development (DSD). Although several types of DSD have been reported in the cat and dog, which are often strikingly similar to human DSD, these have been infrequently utilized to contribute to our knowledge of mammalian sexual development. Canine and feline cases of DSD with sufficient evidence to be considered as potential models are summarized in this report. The consensus DSD terminology, and reference to previous terminology, is used to foster adoption of a common nomenclature that will facilitate communication and collaboration between veterinarians, physicians, and researchers. To efficiently utilize these unique resources as molecular tools continue to improve, it will be helpful to deposit samples from valuable cases into repositories where they are available to contribute to our understanding of sexual development, and thus improve human and animal health.

Trisomy-X with estrous cycle anomalies in two female dogs.

Two female dogs were presented with a history of abnormal estrous cycles and infertility, despite multiple breedings. Medical therapy to correct the cycle anomalies did not result in pregnancy. Cytogenetic analysis of blood lymphocyte cultures in each dog revealed three copies of the X chromosome in each cell, constituting a 79,XXX karyotype (trisomy-X). Both dogs were eventually ovariohysterectomised and histological evaluation revealed hypoplastic ovaries and an absence of normal follicular structures. However, partial or immature follicles were noted, which may have been sufficient to cause both females to initiate cycling. The history and clinical characteristics found in these dogs were compared to those described in three other dogs reported with trisomy-X, as well as those reported in other species. These findings highlighted the importance of cytogenetic studies in fertility evaluation and achieving a definitive diagnosis for infertility in the bitch.